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Identification of sucrose non-fermenting related kinase (SNRK) as a suppressor of adipocyte inflammation

Yujie Li1,2, Yaohui Nie1,3, Ynes Helou4, Guoxian Ding2, Bin Feng1, Gang Xu3, Arthur Salomon5,6, Haiyan Xu1,7

1 Hallett Center for Diabetes and Endocrinology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903 2 Department of Geriatric Endocrinology, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China 3 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China 4 Department of Molecular Pharmacology and Physiology, Brown University, Providence, RI 02903 5 Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02903 6 Department of Chemistry, Brown University, Providence, RI 02903 7 Pathobiology Program, Brown University, Providence, RI 02903

Running title: SNRK and adipocyte inflammation

Correspondence to be addressed to: Haiyan Xu MD, PhD, Hallett Center for Diabetes and Endocrinology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, 55 Claverick St., Rm 318, Providence, RI 02903, Tel: 4014440347; Fax: 4014443784; Email: [email protected]

Word count: 4302 Tables: 2 Figures: 6 Supplementary tables: 3 Supplementary figures: 0

1

Diabetes Publish Ahead of Print, published online March 21, 2013 Diabetes Page 2 of 603

ABSTRACT

In this study, the role of sucrose nonfermenting related kinase (SNRK) in white adipocyte biology was investigated. SNRK is abundantly expressed in adipose tissue and the expression level is decreased in obese mice. SNRK expression is repressed by inflammatory signals but increased by insulin sensitizer in cultured adipocytes. In vivo, adipose tissue SNRK expression can be decreased by lipid injection but enhanced by macrophage ablation. Knocking down SNRK in cultured adipocytes activates both JNK and IKKβ pathways as well as promotes lipolysis. Insulinstimulated Akt phosphorylation and glucose uptake are impaired in SNRK knockdown adipocytes. Phosphoproteomic analysis with SNRK knock down adipocytes revealed significantly decreased phosphorylation of 49 by 25% or more, which are involved in various aspects of adipocyte function with a clear indication of attenuated mTORC1 signaling. Phosphorylation of 43 proteins is significantly increased by 1 fold or higher, among which several proteins are known to be involved in inflammatory pathways. The inflammatory responses in SNRK knock down adipocytes can be partially attributable to defective mTORC1 signaling since rapamycin treatment activates IKKβ and induces lipolysis in adipocytes. In summary, SNRK may act as a suppressor of adipocyte inflammation and its presence is necessary for maintaining normal adipocyte function.

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INTRODUCTION

Sedentary lifestyle and excessive energy intake have caused obesity epidemics. Extensive studies

have demonstrated that obesityrelated insulin resistance and type 2 diabetes are associated with a

low degree of inflammation in adipose tissue (1). Obese adipose tissue secretes a variety of

inflammatory markers, cytokines and chemokines at elevated levels. Some of these factors, such

as TNFα, IL6, IL1β and MCP1, have been reported to impair insulin signaling (25).

Dysregulation of adipocyte lipolysis, induced by increased expression of adipose inflammatory

cytokines, contributes to systemic insulin resistance through elevated circulating free fatty acid

(FFA) levels. Multiple types of immune cells have been identified to regulate inflammatory

pathways in obese adipose tissue, such as macrophages, neutrophils, T cells and mast cells (6; 7).

Potent antiinflammatory effects, such as suppression of adipose macrophage expression in

vitro and in vivo and inhibition of proinflammatory mononuclear cells, have been reported for the

only class of insulin sensitizer thiozolidinediones (811). Curbing inflammation of obese patients

with salsalate, a prodrug of salicylate for treating arthritis, has been reported to improve glycemic

control (12). These results indicate that obesityrelated adipose inflammation plays an important

role for the development of insulin resistance. However, the molecular pathways involved in the

development of adipose inflammation in response to overnutrition are not fully understood.

Being the most extensively studied member of the family, AMPK has been described as a master

energy sensing enzyme activated by increased AMP/ATP ratio. Activation of AMPK turns on

catabolic pathways that generate ATP while switching off ATPconsuming anabolic pathways.

Recent studies also indicate an antiinflammatory role for AMPKα1 in macrophages through

diminishing inflammasome formation and activation of SIRT1 (13; 14). Extensive research

efforts have established a clear role for AMPK in energy metabolism in muscle, liver and

macrophages. In contrast, limited and contradictory information is available on the role of AMPK

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in adipocytes. AMPK phosphorylates Ser565 of hormone sensitive lipase (HSL), which was proposed to exert an antilipolytic effect through preventing phosphorylation of Ser563 by

kinase A (PKA) (15). However, the significance of this mechanism has been questioned because

of the recent finding that Ser563 is not essential for HSL activation (16). In addition, both pro

and antilipolytic effects have been described for AMPK in adipocytes (17; 18). Although the

AMPK activator AICAR stimulates glucose uptake in both muscle cells and adipocytes, AMPK

only appears to mediate AICARinduced glucose uptake in muscle cells, not in adipocytes (19).

AMPKα2 knockout mice have unchanged fat mass despite impaired glucose tolerance when fed

on a normal chow diet, suggesting that AMPKα2 is not important for energy metabolism in

adipose tissue of normal mice (20). Interestingly, AMPKα2 knockout mice develop adipocyte

hypertrophy when fed on a high fat diet, indicating that AMPKα2 may be able to prevent excess

lipogenesis in states of nutrition surplus (21). However, it is unclear whether this is due to the

deficiency of AMPKα2 in adipocyte or due to the secondary effects of AMPKα2 deficiency in liver or muscle because AMPKα2 is expressed at a low level in fat. AMPKα1 has been reported

to be the major isoform of AMPK in adipose tissue yet global AMPKα1 knock out mice derived

from the same founders were reported to increase adiposity from one laboratory and decrease

adiposity from another (18; 22). These results raise questions regarding the importance of

AMPKα1 in adipocyte function.

The biological functions of many AMPK related family members have not been clearly defined.

In this study, we describe the potential role of an AMPK related kinase, sucrose nonfermenting

related kinase (SNRK), as a potential suppressor of inflammation in adipocytes. As a family

member of AMPK related kinases, the function of SNRK has not been previously studied in

adipose tissue. SNRK was initially cloned from fat cell cDNA library (23). The Nterminus

catalytic domain has a low homology to AMPKα but the non catalytic domain is unique (23).

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SNRK can be activated by LKB1, the same upstream kinase that activates AMPK (24). Gene

knockdown study in zebrafish indicates that SNRK may play a role in angioblast development

(25; 26). A recent study reported that SNRK inhibits colon cancer cell proliferation (27). It is

worthy to note that SNRK is a completely different protein from sucrose nonfermenting AMPK

related kinase (SNARK), which is also a member of the AMPK/SNF1 family and can be

activated by LKB1(28; 29).

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RESEARCH DESIGN AND METHODS

Cells, reagents, and treatments. 3T3L1 cells were obtained from American Type Tissue

Culture Collection. 3T3L1 CAR cells, a 3T3L1 subline stably expressing the truncated

adenovirus receptor, were provided by Dr. David Orlicky (University of Colorado Health

Sciences Center) (30). Preadipocytes were differentiated as previously described (31). Free fatty acid mixture, dexamethasone, insulin, and IBMX were purchased from Sigma. Liposyn II was purchased from Webster Veterinary. JNK, ACC and IKKβ antibodies were purchased from

Santa Cruz Biotechnology. PhosphoJNK and phosphoIKKβ antibodies were purchased from

Cell Signaling Technology. SNRK antibody was purchased from University of Dundee (24).

Tubulin antibody was purchased from Abcam. PhosphoACC antibody was purchased from

Millipore. LC3 antibody was purchased from Novus Biologicals. Raptor expression constructs

and antibodies were provided by Dr. Diane Finger (University of Michigan Medical School).

Clodronate liposomes were purchased from clodronateliposomes.org (Vrije Universiteit,

Netherlands) as previously described (32). Stable isotope labeling with amino acids in cell

culture (SILAC) medium was purchased from Thermo Scientific. Rapamycin was purchased

from Calbiochem. Adenoviruses expressing inducible myrAkt1 and the tetracycline

transactivator (tTA) were purchased from Cell Biolabs Inc.

Mouse models. Male ob/ob mice and littermate controls were purchased from The Jackson

Laboratory. These mice were fed standard chow and sacrificed at 9 weeks of age for tissue

collection. For DIO mice, C57BL/6J mice were purchased from The Jackson Laboratory at 3

weeks of age, acclimated for a week and fed on either a chow diet (5% Kcal from fat) or a high

fat diet (60% Kcal from fat, D12492, Research Diets Inc.) for up to 20 weeks. For macrophage

ablation experiment, mice were injected with clodronate liposomes at the dose of 110mg/kg. At

the end of the study, mice were sacrificed by CO2 inhalation and epididymal fat pads were

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collected. All animal experiments were approved by the Institutional Animal Care and Use

Committee of Rhode Island Hospital.

Isolation of primary adipocytes. Epididymal white fat pads from DIO mice were excised,

weighed, and rinsed in isolation buffer. Fat pads were then cut into small pieces in isolation

buffer supplemented with 1mg/ml type I collegenase and digested at 37°C in shaking water bath

at 100 rpm for 45 min. Digested tissues were filtered through 400M mesh to get single cell

suspension. After centrifugation, floating adipocytes were rinsed twice with isolation buffer.

Adenovirus construction. To construct adenoviral vector for mouse SNRK, the coding sequence

was amplified by PCR, cloned into the entry vector and sequence confirmed. The coding

sequence was then recombined into the Gatewaybased pAdCMV DESTTM vector (Invitrogen)

according to the manufacturer’s instructions. To construct adenoviral vector for short hairpin

interfering RNA against SNRK, six short hairpin oligonucleotides and complementary strands

were designed to target SNRK and ligated into the Gatewaybased pENTR/U6 vector (Invitrogen)

and recombined into the BLOCKiTTM RNAi system after sequence confirmation. As a negative

control, adenovirus expressing shGFP was used as previously described (33). Amplification of

recombinant adenovirus was performed according to the manufacturer’s instructions using HEK

293A cells.

RNA isolation and real time PCR analysis. RNA samples were extracted using the TRIZOL

reagent. was measured using realtime PCR analysis. Random hexamers were

used for reverse transcription. Realtime PCR analysis was performed in a 15l reaction on 96

well clear plate using Power SYBR Green RTPCR Reagents Kit on ABI Prism thermal cycler

model StepOnePlus. The relative mRNA expression levels were normalized to expression of β

actin or 28S rRNA. The sequences of primers are shown in supplemental table 1.

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Immunoprecipitation and western-blot analysis. To immunoprecipitate endogenous SNRK

from adipose tissue, thirty microliters of A/G plus matrix (Santa Cruz Biotechnology) slurry were

used to preclear 1mg protein lysates at 4°C for 30 min. Then 3g of SNRK antibody was added for 1h followed by forty microliters of A/G plus matrix slurry for overnight incubation at 4ºC. For immunoblot analysis, immunoprecipitated protein or one hundred micrograms of protein lysates from each sample were used. Following PAGE on 412% gel (BioRad Laboratories), the resolved proteins were transferred onto PVDF membranes. Membranes were blocked in 1%

BSA/1x TBST or 5% milk/1xTBST for 1hr then incubated with the appropriate primary antibodies in the presence of 1% BSA/1x TBST or 5% milk/1xTBST followed by incubation with appropriate horseradish peroxidaselinked secondary antibodies for 1hr in 5% milk/ 1x TBST.

Protein bands were detected by ECL western blotting detection reagent (Perkin Elmer).

Phosphoproteomic study. 3T3L1 CAR preadipocytes were cultured in SILAC medium for eight doublings and then seeded on 6well plates for differentiation in SILAC medium. Half of the cells were labeled with light arginine and lysine and infected with adenovirus expressing shSNRK. The other half were labeled with heavy arginine and lysine and infected with adenovirus expressing shGFP. For each sample, 2.5mg of light arginine and lysinelabeled protein lysates were mixed with 2.5mg of heavy arginine and lysinelabeled protein lysates.

Samples were reduced with 45mM DTT at 60ºC for 20 minutes, alkylated with 100mM iodoacetimide for 15 min in the dark, and digested overnight with TPCKtreated trypsin. Peptides were then desalted using SepPak C18 columns and enriched for phosphopeptides using

Titansphere PhosTio kit before loading to Orbitrap Velos ETD mass spectrometer. Results from four biological replicates were used for data analysis. Q values for multiple hypothesis tests

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were also calculated based on the determined p values using the R package QVALUE as

previously described (34).

Statistical analysis. Student T test was used to analyze experiments involving two groups. Two

way ANOVA and Bonferroni posttests were used to analyze multiple experimental groups. Error

bars represent mean ± standard errors.

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RESULTS

Expression and regulation patterns of SNRK in adipocyte and adipose tissue. By studying

tissue distribution patterns of more than 300 human kinases including all family members of

AMPK/SNF1 related kinases, SNRK gene was found to be abundantly and predominantly

expressed in white adipose tissue in human and in both white and brown adipose tissue in mouse

(Figure 1AB). SNRK protein expression pattern confirmed its predominant presence in adipose

tissue (Figure 1C). AMPKα1 has been shown to be the major isoform of AMPK in adipose tissue

(18). However, the relative mRNA expression level of SNRK is 74% higher than that of

AMPKα1 in human white adipose tissue and 2.1 fold higher than that of AMPKα1 in mouse adipose tissue. Expression levels of AMPKα2 are very low in both human and mouse adipose

tissue, supporting the hypothesis that AMPKα2 may not play an important role in adipocyte

energy metabolism. SNRK has a nuclear localization signal and has been shown to be localized in

nucleus of cultured rat cerebellar granule neurons by immunohistochemistry (35). To localize

SNRK in adipocyte, SNRKGFP fusion protein was expressed via adenoviral mediated gene

transfer and reveals a large overlapping with lysosomal tracker (Figure 1D), indicating that

SNRK may have different cellular localization patterns in different cell types. SNRK expression

in white adipose tissue is significantly reduced in both ob/ob and DIO mice at both mRNA and protein levels (Figure 2AC). Further analysis indicates that the decrease of SNRK gene expression in adipose tissue of DIO mice occurs in adipocyte, not in stromal vascular cells

(Figure 2D). Interestingly, SNRK mRNA and protein levels can be induced by fasting in adipose tissue of lean mice but this regulation is lost in DIO mice (Figure 2A and 2C, bottom graphs), suggesting that SNRK may be involved in regulating metabolism in response to fasting in lean mice.

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It is well established that FFA release and production of inflammatory factors are increased in

adipose tissue of obese state, which contribute to the development of insulin resistance and

hyperglycemia. To explore whether these factors are potentially responsible for downregulating

SNRK expression in adipose tissue, free fatty acids and proinflammatory factor TNFα were used

to treat cultured adipocytes. As shown in figure 3AB, SNRK gene expression was significantly

reduced by treatment with both FFA and TNFα, indicating that activation of inflammatory

pathways suppresses SNRK expression. The constitutively active form of IκB kinase β (IKKβ

SE), a master kinase that turns on transcription of many inflammatory , was also over

expressed in 3T3L1 CAR adipocytes by adenovirusmediated gene transfer. IKKβ SE

significantly repressed SNRK gene expression (Figure 3C). In addition, significantly decreased

SNRK gene expression is observed in isolated adipocytes prepared from lean mice treated with

intravenous injection of liposyn II (Figure 3D), suggesting that the decreased SNRK expression in

obese adipose tissue is likely due to the occurrence of obesityinduced adipose inflammation

and/or lipid toxicity. In contrast, treatment with rosiglitazone, an insulin sensitizer with potent

antiinflammation effect, increased SNRK gene expression in cultured adipocytes (Figure 3E).

Ablation of adipose macrophages, an important source of inflammatory factors in obesity, by

clodronate liposomes significantly increased SNRK gene expression in adipose tissue of DIO

mice (Figure 3F). Further experiments confirmed that SNRK protein expression levels are also

decreased by inflammatory signals and increased by rosiglitazone in cultured adipocytes (Figure

3GJ).

Effect of SNRK knockdown in cultured adipocytes. To understand the function of SNRK,

adenovirusmediated short hairpin interfering RNA was used to knock down SNRK expression in

3T3L1 CAR adipocytes. Expression levels of SNRK mRNA and protein were significantly

reduced by interfering RNA against SNRK compared to control adipocytes expressing interfering

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RNA against GFP (Figure 4A). Reduction of SNRK expression in 3T3L1 CAR adipocytes

activated IKKβ and JNK pathways as shown by increased phosphorylation (Figure 4B), which is

accompanied by increased basal lipolysis as reflected by elevated glycerol release (Figure 4C).

Consistent with activation of inflammatory pathways, markedly increased expression levels of proinflammatory cytokines, including TNFα and IL6, were observed in SNRK knockdown 3T3

L1 CAR adipocytes compared to control cells (Figure 4DF). TNFα is a potent inducer of lipolysis, which may contribute to increased lipolysis. It has been previously reported that multiple monocyte chemotactic factors are upregulated in adipose tissue and adipocytes of diet induced obese mice (31). Reduction of SNRK expression in cultured adipocytes also led to increased gene expression of three monocyte chemotactic factors, MCP1, MCP2 and MCP3, indicating that decreased SNRK expression in adipocytes may potentially enhance macrophage infiltration in obesity. Reduced SNRK expression also increased expression of chop gene. In contrast, mRNA expression levels of insulinresponsive 4 () and insulin sensitizing adiponectin are significantly decreased upon SNRK knockdown (Figure 4G). Insulin stimulated Akt phosphorylation on Ser473 and glucose uptake are significantly reduced (Figure

4HI). Expression levels of very long chain acylcoA dehydrogenase (VLACAD) and medium chain acylcoA dehydrogenase (MACAD) are also significantly reduced in SNRK knockdown adipocytes, suggesting impaired fatty acid oxidation. Furthermore, Atg12 gene was significantly decreased, suggesting deficiency in autophagy.

Effect of SNRK knockdown on protein phosphorylation in cultured adipocytes. To get a broad understanding regarding the function of SNRK in adipocytes and the downstream signaling events, a quantitative phosphoproteomic approach was used to evaluate changes of global phosphorylation in SNRK knockdown adipocytes compared to control adipocytes expressing shGFP. To ensure accurate comparison, the stable isotope labeling with amino acids in cell

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culture (SILAC) method was used. SNRK knockdown adipocytes were labeled with light (12C or

14N) arginine and lysine whereas control adipocytes were labeled with heavy (13C or 15N)

arginine and lysine. All peptide sequence assignments were filtered down to 1% false discovery

rate by a logistic spectral score (36). Results shown in supplemental Tables 2 and 3 are the

statistically significant (q value < 0.05) average peak ratios of light versus heavy amino acids

from four biological replicates. Reduction of SNRK expression in adipocytes significantly

reduced signals of 55 phosphopeptides by 25% or more, which are derived from 49 proteins

involved in various aspects of cell function (Table 1), including transcription, mRNA processing,

translation, glucose and lipid metabolism, and cytoskeleton. Most of the phosphosites have not

been functionally annotated but reduced phosphorylation occurs in factors normally required for

transcription initiation, RNA processing and protein synthesis. Interestingly, several components

of mTORC1 signaling pathway have reduced phosphorylation, including regulatoryassociated

protein of mTOR (raptor) on Ser863, programmed cell death protein 4 (PDCD4) on Thr93 and

Ser94, insulin receptor substrate 1 (IRS1) on Ser1097 and prolinerich Akt1 substrate 1

(PRAS40) on Thr247. Phosphorylation on Ser863 of raptor activates mTORC1 signaling (37).

Ser1097 of IRS1 is reported to be a site for S6K phosphorylation (38). PRAS40 inhibits mTOR

signaling and Akt phosphorylates PRAS 40 on Thr247 to relieve the inhibition. Decreased

phosphorylation on raptor Ser863, IRS1 Ser1097 and PRAS40 Thr247 indicates attenuated

mTOR signaling. Phosphorylation of acetyl CoA carboxylase 1 (ACC1), a well characterized

AMPK substrate, is decreased on Ser29 which is an uncharacterized site. In addition, SNRK

knockdown also decreased phosphorylation of several enzymes involved in glucose and lipid

metabolism, including mitochondrial phosphoenolpyruvate carboxykinase, mitochondrial

pyruvate carboxylase, patatinlike phospholipase domaincontaining protein 2, ATP citrate lyase,

oxysterolbinding protein and oxysterolbinding protein related protein 11.

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Reduction of SNRK expression in adipocytes also significantly increased signals of 55 phospho peptides by one fold or more, which are derived from 43 proteins (Table 2). These proteins also affect various aspects of adipocyte function. Distinct from the dataset of decreased phosphorylation, several proteins involved in inflammatory pathways have increased phosphorylation. Among these proteins, caspase recruitment domain family member 6 (Card6), interferoninduced helicase C domaincontaining protein 1 (IFIH1), ZDNA binding protein 1

(ZBP1) and receptorinteracting serine/threonineprotein kinase 2 (RIPK2) are known to activate

NFκB transcription factors, the substrate of IKKβ. Interferoninduced doublestranded RNA activated protein kinase (PRKRA) has been characterized as a critical component of an inflammatory complex that activates JNK and IKKβ pathways and induces insulin resistance

(39). Phosphorylation levels of multiple sites of protein PML, a potent growth suppressor and proapoptotic factor, are significantly increased. In addition, increased phosphorylation occurs in proteins normally involved in repression of transcription (Trim 28, Ifi204 and HDGF), promotion of mRNA degradation (IFIH1, Patl1) and inhibition of protein synthesis (PRKRA).

Phosphorylation also increases in proteins involved in hydrolysis of glycerophospholipids

(phospholipase A2 on Ser437) and triglycerides (perilipin on Ser81, a PKA phosphorylation site), consistent with observed increase of basal lipolysis. Phosphorylation on Ser358 of SIK2 increased 15 fold, a site that has been reported to be phosphorylated by PKA in response to forskolin and CL316,243 in adipocytes (40).

Effect of SNRK over-expression in hepatocytes. Despite successful SNRK knock down in 3T3

L1 CAR adipocytes, SNRK protein can not be overexpressed at a high level in this cell type despite hugely overexpressed SNRK mRNA but SNRKGFP fusion protein could be expressed at a low level that is observable under fluorescence microscope. One possibility is that the C terminal of SNRK contains two regions of PESTrich sequences, which are motifs indicative of

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rapid protein turn over (23). In addition, there may be a mechanism in adipocytes to limit SNRK

overload due to abundantly expressed endogenous SNRK protein in this cell type. We therefore

used a liver cell line to examine whether SNRK overexpression can increase phosphorylation of

raptor and ACC. As shown in figure 5A, SNRK protein was overexpressed in Fao hepatoma

cells and significantly increased phosphorylation of ACC on serine 79 (an AMPK

phosphorylation site) and raptor on serine 863. SNRK kinase assay confirmed that overexpressed

SNRK is active in hepatoma cells (Figure 5B). To determine whether raptor and SNRK exist in

the same protein complex, raptor and SNRK were coexpressed in 293A cells.

Immunoprecipitation of SNRK brought down raptor as evidenced by immunoblot analysis

(Figure 5C). SNRK overexpression also suppressed Chop gene expression (Figure 5D),

consistent with increased chop gene expression in SNRK knockdown adipocytes. Interestingly,

SNRK overexpression significantly increased LC3II/LC3I ratio under fed condition when treated

with chloroquine and rapamycin and under fasted condition when treated with rapamycin,

indicating activation of autophagy (Figure 5E).

mTOR pathway and adipocyte inflammation. The effects of SNRK on autophagy and

ACC/raptor phosphorylation were further confirmed in adipocytes. In SNRK knock down

adipocytes, both LC3I and LC3II have been significantly reduced after normalization to tubulin

control but LC3II/LC3I ratio was not affected (Figure 6A). Reduction of SNRK also significantly

reduced phosphorylation levels of raptor S863 and ACC S79. Defective autophagy has been

linked to induction of inflammation and may be partially responsible for the inflammatory

phenotype in adipocytes with reduced SNRK expression. In addition, phosphoproteomic study

revealed many potential downstream targets of SNRK. The mTORC1 pathway stood out due to

decreased phosphorylation of several components. To explore whether defective mTOR signaling

pathway contributes to adipocyte inflammation, 3T3L1 adipocytes were treated with rapamycin

and examined for activations of JNK and IKKβ pathways, lipolysis and expression of

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inflammatory cytokines. Treatment with rapamycin increased phosphorylation of IKKβ but not

JNK and stimulated lipolysis (Figure 6BC). Gene expression levels of proinflammatory factors

IL6, MCP1 and MCP3 are also significantly upregulated (Figure 6D). Consistent with these

results, activation of mTOR signaling by overexpressing the constitutively active Akt1 (myr

Akt) repressed lipolysis and decreased expression of proinflammatory factors (figure 6EF).

These data indicate that defective mTOR signaling in SNRK knockdown adipocytes maybe partially responsible for the inflammatory phenotype and other pathways are likely involved since

JNK is not activated by rapamycin treatment.

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DISCUSSION

The underlying molecular mechanism responsible for origination of inflammation in adipocyte

upon overnutrition is still not fully understood. In this study, we identified SNRK as a potential

suppressor of adipocyte inflammation and hypothesize that decreased SNRK expression in

adipose tissue may contribute to the development of adipose inflammation commonly observed in

obesity. AMPKα has been reported to repress inflammation in macrophages and polarize

macrophages to an antiinflammatory phenotype (13; 14; 41). AMPKα1 deficient marrow

macrophages are proinflammatory and are sufficient to induce insulin resistance when

transplanted to irradiated wild type mice upon high fat diet feeding (22). In addition, AMPKα

activity is decreased in adipose tissue of obese and insulin resistant humans (42), suggesting that

AMPKα is potentially another candidate for suppressing obesityinduced adipose tissue

inflammation. However, further experiments are necessary to elucidate the antiinflammatory role

of AMPKα in adipose tissue to determine the site of action since literature data are mostly done

in macrophages. Despite the fact that AMPKα1 is the major isoform in adipocytes, contradictory

phenotypes of AMPKα1 global knock out mice have been reported. Zhang et al showed that

deficiency of AMPKα1 increases adipocyte size and adipose mass in vivo and AMPKα1

knockdown adipocytes are proinflammatory but accumulate more lipids (22). In contrast, Daval

et al reported that absence of AMPKα1 reduces adipocyte size and adipose mass, possibly

attributed to increased lipolysis (18). Interestingly, both laboratories obtained AMPKα1 knock

out mice from the same source.

It will be interesting to determine whether SNRK and AMPKα have redundant roles in

suppressing inflammatory responses in adipocytes. In our study, AMPKα expression levels were

not changed in SNRK knockdown adipocytes and SNRK antibody does not crossreact with

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AMPKα even under the condition of overexpression (data not shown), indicating that SNRK likely functions independent of AMPKα. This is the first study to elucidate the role of SNRK in adipocyte biology, which is a protein with very little available literature information regarding its function. Phosphoproteomic analysis revealed increased phosphorylation levels of several additional inflammatory proteins in SNRK knockdown adipocytes, many of them are known to activate the NFκB pathway. These results suggest that the presence of SNRK in adipocytes is necessary to inhibit inflammatory responses. When SNRK expression is reduced, activation of inflammatory pathways leads to increased lipolysis, impairs insulin signaling, and reduces insulinstimulated glucose uptake.

Interestingly, phosphoproteomic analysis reveals attenuation of mTOR signaling pathway in

SNRK knockdown adipocytes. Phosphorylation of raptor ser863 is critical to activate mTOR

(37). We demonstrated that SNRK interacts with raptor and phosphorylates raptor on Ser863, suggesting that raptor maybe a target of SNRK. In adipocytes, treatment with rapamycin elicited weak inflammatory responses as reflected by IKKβ activation, increased expression of proinflammatory factors and elevated lipolysis. However, the extent of IKKβ activation and fold of increase in proinflammatory gene expression are milder than those observed in SNRK knockdown adipocytes, indicating that impairment in mTOR signaling pathway is most likely partially responsible for the effects elicited by reduced SNRK expression. The role of mTOR in linking nutrient sensing and obesity is complex depending on the tissue examined. In adipocytes, acute inhibition of mTOR signaling by rapamycin increases insulin stimulated glucose uptake but chronic rapamycin treatment impairs insulin stimulated glucose uptake by reducing Akt2 activation despite improved PI3K activation (43). Mice with adipose tissue specific raptor deficiency are protected from dietinduced obesity and have increased energy expenditure (44).

However, it is unclear whether adipose inflammation has been examined. Several transgenic

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models with overexpression of components in the inflammatory pathway prior to obesity

development also display reduced adiposity (4547). However, it is wellestablished that adipose

inflammation and impairment of energy homeostasis coexist in obesity.

Another potential mechanism to explain increased inflammation in SNRK knockdown adipocytes

is defective autophagy. Autophagy has been demonstrated to play a role in repressing adipocyte

inflammation (48). Our data indicate that SNRK is localized to lysosomes in adipocyte, an

important site for degradation of large intracellular organelles or protein aggregates through

autophagy. In addition, our results support a role of SNRK in promoting autophagy. The potential

role of SNRK in linking overnutrition and activation of inflammatory pathways as well as

impairment of energy metabolism in adipocytes requires further investigation. Loss of function in

vivo study in the near future will provide more useful information regarding the role of SNRK in

obesityinduced adipose inflammation. In addition to the inflammatory pathway, the global

phosphoproteomic study also provided evidence to show that SNRK has profound effects on

adipocyte biology and impacts multiple pathways that are common to most cell types, such as

transcription, translation and mRNA processing. The overall changes in protein phosphorylation

patterns suggest a role for SNRK in maintaining normal cell growth and function.

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ACKNOWLEDGMENTS

We want to thank Dr. Diane Finger (University of Michigan Medical School) for providing expression constructs of raptor and raptor S863A, as well as phosphoraptor and raptor antibodies. This work was supported by the scientist development grant from American Heart Association 0830190N and NIDDK R01 DK 080746 awarded to HX. The authors declare that no conflict of interest exists. YL, YN,YH and BF performed experiments, analyzed data and contributed to the writing of the manuscript; GD, GX and AS were involved in experimental design, data analysis and manuscript writing H.X. designed and supervised experiments, drafted and finalized the manuscript. Dr. Haiyan Xu is the guarantor of this work, had full access to all the data, and takes full responsibility for the integrity of data and the accuracy of data analysis.

REFERENCES

1. Hotamisligil GS: Inflammation and metabolic disorders. Nature 444:860867, 2006 2. Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM: Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci U S A 91:48544858, 1994 3. Rotter V, Nagaev I, Smith U: Interleukin6 (IL6) induces insulin resistance in 3T3L1 adipocytes and is, like IL8 and tumor necrosis factoralpha, overexpressed in human fat cells from insulinresistant subjects. J Biol Chem 278:4577745784, 2003 4. Tack CJ, Stienstra R, Joosten LA, Netea MG: Inflammation links excess fat to insulin resistance: the role of the interleukin1 family. Immunol Rev 249:239252, 2012 5. Sartipy P, Loskutoff DJ: Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci U S A 100:72657270, 2003 6. Schipper HS, Prakken B, Kalkhoven E, Boes M: Adipose tissueresident immune cells: key players in immunometabolism. Trends Endocrinol Metab 23:407415, 2012 7. Sun S, Ji Y, Kersten S, Qi L: Mechanisms of inflammatory responses in obese adipose tissue. Annu Rev Nutr 32:261286, 2012 8. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK: The peroxisome proliferator activated receptorgamma is a negative regulator of macrophage activation. Nature 391:7982, 1998 9. Li AC, Brown KK, Silvestre MJ, Willson TM, Palinski W, Glass CK: Peroxisome proliferatoractivated receptor gamma ligands inhibit development of atherosclerosis in LDL receptordeficient mice. J Clin Invest 106:523531, 2000 10. Ghanim H, Garg R, Aljada A, Mohanty P, Kumbkarni Y, Assian E, Hamouda W, Dandona P: Suppression of nuclear factorkappaB and stimulation of inhibitor kappaB by troglitazone: evidence for an antiinflammatory effect and a potential antiatherosclerotic effect in the obese. J Clin Endocrinol Metab 86:13061312, 2001 11. Mohanty P, Aljada A, Ghanim H, Hofmeyer D, Tripathy D, Syed T, AlHaddad W, Dhindsa S, Dandona P: Evidence for a potent antiinflammatory effect of rosiglitazone. J Clin Endocrinol Metab 89:27282735, 2004 12. Goldfine AB, Fonseca V, Jablonski KA, Pyle L, Staten MA, Shoelson SE: The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann Intern Med 152:346357, 2010

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13. Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, Brickey WJ, Ting JP: Fatty acid induced NLRP3ASC inflammasome activation interferes with insulin signaling. Nat Immunol 12:408415, 2011 14. Yang Z, Kahn BB, Shi H, Xue BZ: Macrophage alpha1 AMPactivated protein kinase (alpha1AMPK) antagonizes fatty acidinduced inflammation through SIRT1. J Biol Chem 285:1905119059, 2010 15. Garton AJ, Campbell DG, Carling D, Hardie DG, Colbran RJ, Yeaman SJ: Phosphorylation of bovine hormonesensitive lipase by the AMPactivated protein kinase. A possible antilipolytic mechanism. Eur J Biochem 179:249254, 1989 16. Anthonsen MW, Ronnstrand L, Wernstedt C, Degerman E, Holm C: Identification of novel phosphorylation sites in hormonesensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro. J Biol Chem 273:215 221, 1998 17. Yin W, Mu J, Birnbaum MJ: Role of AMPactivated protein kinase in cyclic AMP dependent lipolysis In 3T3L1 adipocytes. J Biol Chem 278:4307443080, 2003 18. Daval M, DiotDupuy F, Bazin R, Hainault I, Viollet B, Vaulont S, Hajduch E, Ferre P, Foufelle F: Antilipolytic action of AMPactivated protein kinase in rodent adipocytes. J Biol Chem 280:2525025257, 2005 19. Sakoda H, Ogihara T, Anai M, Fujishiro M, Ono H, Onishi Y, Katagiri H, Abe M, Fukushima Y, Shojima N, Inukai K, Kikuchi M, Oka Y, Asano T: Activation of AMPK is essential for AICARinduced glucose uptake by skeletal muscle but not adipocytes. Am J Physiol Endocrinol Metab 282:E12391244, 2002 20. Viollet B, Andreelli F, Jorgensen SB, Perrin C, Geloen A, Flamez D, Mu J, Lenzner C, Baud O, Bennoun M, Gomas E, Nicolas G, Wojtaszewski JF, Kahn A, Carling D, Schuit FC, Birnbaum MJ, Richter EA, Burcelin R, Vaulont S: The AMPactivated protein kinase alpha2 catalytic subunit controls wholebody insulin sensitivity. J Clin Invest 111:9198, 2003 21. Villena JA, Viollet B, Andreelli F, Kahn A, Vaulont S, Sul HS: Induced adiposity and adipocyte hypertrophy in mice lacking the AMPactivated protein kinasealpha2 subunit. Diabetes 53:22422249, 2004 22. Zhang W, Zhang X, Wang H, Guo X, Li H, Wang Y, Xu X, Tan L, Mashek MT, Zhang C, Chen Y, Mashek DG, Foretz M, Zhu C, Zhou H, Liu X, Viollet B, Wu C, Huo Y: AMPActivated Protein Kinase alpha1 Protects Against DietInduced Insulin Resistance and Obesity. Diabetes 61:31143125, 2012 23. Becker W, Heukelbach J, Kentrup H, Joost HG: Molecular cloning and characterization of a novel mammalian protein kinase harboring a homology domain that defines a subfamily of serine/threonine kinases. Eur J Biochem 235:736743, 1996 24. Jaleel M, McBride A, Lizcano JM, Deak M, Toth R, Morrice NA, Alessi DR: Identification of the sucrose nonfermenting related kinase SNRK, as a novel LKB1 substrate. FEBS Lett 579:14171423, 2005 25. Chun CZ, Kaur S, Samant GV, Wang L, Pramanik K, Garnaas MK, Li K, Field L, Mukhopadhyay D, Ramchandran R: Snrk1 is involved in multiple steps of angioblast development and acts via notch signaling pathway in arteryvein specification in vertebrates. Blood 113:11921199, 2009

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26. Pramanik K, Chun CZ, Garnaas MK, Samant GV, Li K, Horswill MA, North PE, Ramchandran R: Dusp5 and Snrk1 coordinately function during vascular development and disease. Blood 113:11841191, 2009 27. Rines AK, Burke MA, Fernandez RP, Volpert OV, Ardehali H: Snf1related kinase inhibits colon cancer cell proliferation through calcyclinbinding proteindependent reduction of betacatenin. Faseb J, 2012 28. Koh HJ, Toyoda T, Fujii N, Jung MM, Rathod A, Middelbeek RJ, Lessard SJ, Treebak JT, Tsuchihara K, Esumi H, Richter EA, Wojtaszewski JF, Hirshman MF, Goodyear LJ: Sucrose nonfermenting AMPKrelated kinase (SNARK) mediates contractionstimulated glucose transport in mouse skeletal muscle. Proc Natl Acad Sci U S A 107:1554115546, 2010 29. Rune A, Osler ME, Fritz T, Zierath JR: Regulation of skeletal muscle sucrose, non fermenting 1/AMPactivated protein kinaserelated kinase (SNARK) by metabolic stress and diabetes. Diabetologia 52:21822189, 2009 30. Orlicky DJ, DeGregori J, Schaack J: Construction of stable coxsackievirus and adenovirus receptorexpressing 3T3L1 cells. J Lipid Res 42:910915, 2001 31. Jiao P, Chen Q, Shah S, Du J, Tao B, Tzameli I, Yan W, Xu H: Obesityrelated upregulation of monocyte chemotactic factors in adipocytes: involvement of nuclear factorkappaB and cJun NH2terminal kinase pathways. Diabetes 58:104115, 2009 32. Feng B, Jiao P, Nie Y, Kim T, Jun D, van Rooijen N, Yang Z, Xu H: Clodronate liposomes improve metabolic profile and reduce visceral adipose macrophage content in dietinduced obese mice. PLoS One 6:e24358, 2011 33. Xu H, Wilcox D, Nguyen P, Voorbach M, Suhar T, Morgan SJ, An WF, Ge L, Green J, Wu Z, Gimeno RE, Reilly R, Jacobson PB, Collins CA, Landschulz K, Surowy T: Hepatic knockdown of mitochondrial GPAT1 in ob/ob mice improves metabolic profile. Biochem Biophys Res Commun 349:439448, 2006 34. Storey JD, Tibshirani R: Statistical significance for genomewide studies. Proc Natl Acad Sci U S A 100:94409445, 2003 35. Yoshida K, Yamada M, Nishio C, Konishi A, Hatanaka H: SNRK, a member of the SNF1 family, is related to low K(+)induced apoptosis of cultured rat cerebellar granule neurons. Brain Res 873:274282, 2000 36. Yu K, Sabelli A, DeKeukelaere L, Park R, Sindi S, Gatsonis CA, Salomon A: Integrated platform for manual and highthroughput statistical validation of tandem mass spectra. Proteomics 9:31153125, 2009 37. Foster KG, AcostaJaquez HA, Romeo Y, Ekim B, Soliman GA, Carriere A, Roux PP, Ballif BA, Fingar DC: Regulation of mTOR complex 1 (mTORC1) by raptor Ser863 and multisite phosphorylation. J Biol Chem 285:8094, 2010 38. Zhang J, Gao Z, Yin J, Quon MJ, Ye J: S6K directly phosphorylates IRS1 on Ser 270 to promote insulin resistance in response to TNF(alpha) signaling through IKK2. J Biol Chem 283:3537535382, 2008 39. Nakamura T, Furuhashi M, Li P, Cao H, Tuncman G, Sonenberg N, Gorgun CZ, Hotamisligil GS: Doublestranded RNAdependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell 140:338348, 2010 40. Henriksson E, Jones HA, Patel K, Peggie M, Morrice N, Sakamoto K, Goransson O: The AMPKrelated kinase SIK2 is regulated by cAMP via phosphorylation at Ser358 in adipocytes. Biochem J 444:503514, 2012

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41. Sag D, Carling D, Stout RD, Suttles J: Adenosine 5'monophosphateactivated protein kinase promotes macrophage polarization to an antiinflammatory functional phenotype. J Immunol 181:86338641, 2008 42. Xu XJ, Gauthier MS, Hess DT, Apovian CM, Cacicedo JM, Gokce N, Farb M, Valentine RJ, Ruderman NB: Insulin sensitive and resistant obesity in humans: AMPK activity, , and depotspecific changes in gene expression in adipose tissue. J Lipid Res 53:792801, 2012 43. Veilleux A, Houde VP, Bellmann K, Marette A: Chronic inhibition of the mTORC1/S6K1 pathway increases insulininduced PI3K activity but inhibits Akt2 and glucose transport stimulation in 3T3L1 adipocytes. Mol Endocrinol 24:766778, 2010 44. Polak P, Cybulski N, Feige JN, Auwerx J, Ruegg MA, Hall MN: Adiposespecific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell Metab 8:399410, 2008 45. Xu H, Hirosumi J, Uysal KT, Guler AD, Hotamisligil GS: Exclusive action of transmembrane TNF alpha in adipose tissue leads to reduced adipose mass and local but not systemic insulin resistance. Endocrinology 143:15021511, 2002 46. Tang T, Zhang J, Yin J, Staszkiewicz J, GawronskaKozak B, Jung DY, Ko HJ, Ong H, Kim JK, Mynatt R, Martin RJ, Keenan M, Gao Z, Ye J: Uncoupling of inflammation and insulin resistance by NFkappaB in transgenic mice through elevated energy expenditure. J Biol Chem 285:46374644, 2010 47. Jiao P, Feng B, Ma J, Nie Y, Paul E, Li Y, Xu H: Constitutive activation of IKKbeta in adipose tissue prevents dietinduced obesity in mice. Endocrinology 153:154165, 2012 48. Jansen HJ, van Essen P, Koenen T, Joosten LA, Netea MG, Tack CJ, Stienstra R: Autophagy activity is upregulated in adipose tissue of obese individuals and modulates proinflammatory cytokine expression. Endocrinology 153:58665874, 2012

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FIGURE LEGENDS

Figure 1. Tissue distribution of SNRK and AMPKααα. A. Relative mRNA expression levels of SNRK, AMPKα1 and AMPKα2 in human tissues. RNA samples from pooled human tissues were purchased from Clonetech (stomach #636126, small intestine #636125, pancreas #636119, WAT #636162, lung #636105, heart #636113, testis #636115, liver #636101, kidney #636118, brain #636102, spleen #636121, skeletal muscle #636120). B. Relative mRNA expression levels of SNRK, AMPKα1 and AMPKα2 in mouse tissues. Tissues from four male C57BL/6 mice were pooled for RNA preparation. C. SNRK protein levels in mouse tissues. Tissues from four male C57BL/6 mice were pooled for protein preparation. SNRK was immunoprecipitated from 1mg of protein lysates. D. SNRK localization. The SNRKGFP fusion protein was expressed in 3T3L1 CAR adipocytes via adenovirus mediated gene transfer. Fortyeight hours after infection, adipocytes were stained with Lyso tracker (red, Invitrogen 10,000x stock #L7528) for presence of lysosomes and DAPI (blue, final concentration at 1g/ml)) for presence of nucleus during a 2h incubation. The images were overlayed and the orange color indicates overlapping of SNRKGFP and Lyso tracker. . Figure 2. Regulation of SNRK expression in adipose tissue. A. Regulation of SNRK gene expression in adipose tissue of ob/ob mice (top panel, n=5 per group) and high fat diet induced obese (DIO) mice (bottom panel, n=4 per group). B. Regulation of SNRK protein expression in adipose tissue of ob/ob mice (n=3 per group). C. Regulation of SNRK protein expression in adipose tissue of DIO mice (n=4 per group). D. Regulation of SNRK gene expression in adipocytes and stromal vascular cells isolated from chow fed and DIO mice (fat pads were pooled from 68 mice in each group). HF. High fat; SV, stromal vascular cells; Adi, adipocytes. * P<0.05. Error bars stand for mean± standard error.

Figure 3. Effect of proinflammatory signals on SNRK expression. A. Effect of FFA on SNRK gene expression in cultured adipocytes. FFA mixture (Sigma #F7050) was used at a final concentration of 0.25M for 6h. B. Effect of TNFα on SNRK gene expression in cultured adipocytes. TNFα was used at a final concentration of 25ng/ml for 6h. C. Effect of over expressing the constitutively active IKKβ (IKKβ SE) on SNRK gene expression in L1CAR adipocytes. D. Effect of intravenous lipid injection in lean mice on SNRK gene expression in isolated adipocytes. Epididymal fat pads were pooled from 3 mice in each group for adipocyte isolation 30 minutes after injection with liposyn II at 3ml/kg/h. E. Effect of rosiglitazone (Rosi) treatment on SNRK gene expression in cultured adipocytes. Rosiglitazone was used at a final concentration of 10M for 6h. F. Effect of adipose tissue macrophage depletion on SNRK gene expression in lean and diet induced obese mice (n=4 each group). Mice were 23 weeks old and on HFD for 19 weeks. Clodronate or PBS liposomes were injected into peritoneal cavity at the dose of 110mg/kg. G. Effect of FFA on SNRK protein expression in cultured adipocytes. H. Effect of TNFα on SNRK protein expression in cultured adipocytes. I. Effect of overexpressing IKKβ SE on SNRK protein expression in L1CAR adipocytes. J. Effect of rosiglitazone treatment on SNRK protein expression in cultured adipocytes. * P<0.05. FFA, free fatty acid; Veh, vehicle; Lipid, liposyn II; PBS, PBS liposomes; Clod, clodronate liposomes; HFD, high fat diet; V, vehicle; F, FFA; T, TNFα; R, rosiglitazone. For cellbased experiments, triplicate samples were used in gene expression and duplicate samples were used in protein expression. Results shown were representative from three independent experiments. Error bars stand for mean± standard error.

Figure 4. Effect of SNRK knockdown on adipocyte biology. A. SNRK knockdown by adenovirusmediated shRNA on mRNA (top panel) and protein (bottom panel) levels. B. Effect

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of SNRK knockdown on phosphorylation of IKKβ and JNK. C. Effect of SNRK knockdown on lipolysis. D. Effect of SNRK knockdown on expression of TNFα, IL6, MCP1, MCP2, MCP3 and Chop genes. E. Effect of SNRK knockdown on TNFα secretion. F. Effect of SNRK knockdown on IL6 secretion. G. Effect of SNRK knockdown on expression of Glut4, adiponectin (Adipo), very long chain acyl CoA dehydrogenase (VLACAD), medium chain acyl CoA dehydrogenase (MACAD) and Atg12 genes. H. Effect of SNRK knockdown on insulin stimulated Akt phosphorylation. I. Effect of SNRK knockdown on insulinstimulated glucose uptake. * P<0.05. Triplicate samples were used in each experiment. Results shown were representative from three independent experiments. Error bars stand for mean± standard error.

Figure 5. SNRK over-expression in hepatoma cells. A. SNRK overexpression and phosphorylation on ACC and raptor. B. SNRK activity in hepatoma cells overexpressing GFP or mouse SNRK. For kinase assay, SNRK was immunoprecipitated and incubated with the reaction mixture (200M AMARA peptide, 1mM ATP, 10ci γ32PATP, 10mM magnesium acetate, 50mM Tris.Cl, pH7.5, 0.1mM EGTA, and 0.1% v/v 2mercaptoethanol) for 30 minutes at 30ºC in a shaking water bath. Reactions were then loaded on p81 filters. Radioactivities were counted after four washes with 0.5% phosphoric acid and once with water. Background activities were determined using IgG immunoprecipitated samples and subtracted from SNRK antibody immunoprecipitated samples. C. SNRK and raptor coIP in 293A cells. D. SNRK overexpression and Chop gene expression. E. Effect of SNRK overexpression on authophagy. * P<0.05, Ad SNRK infected hepatoma cells vs. AdGFP infected hepatoma cells. Duplicate samples were used in western blots and triplicate samples were used in gene expression and kinase activity experiments. Results shown were representative from three independent experiments. Error bars stand for mean± standard error.

Figure 6. mTOR pathway and adipocyte inflammation A. SNRK knock down in 3T3L1 CAR adipocyte and the effect on raptor and ACC phosphorylation. B. Rapamycin activates IKKβ in 3T3L1 adipocytes. C. Rapamycin induces lipolysis in 3T3L1 adipocytes. D. Rapamycin increases expression of proinflammatory factors. *P<0.05, shSNRK infected adipocytes vs. shGFP infected adipocytes, or rapamycin (Rapa) treated adipocytes vs vehicle (Veh) treated adipocytes. Duplicate samples were used in western blots and triplicate samples were used in gene expression and lipolysis experiments. E. Overexpression of the constitutively active Akt1 (myrAkt) activates mTOR signaling. tTA, the tetracycline controlled transactivator. F. Over expression of myrAkt suppresses lipolysis. G. Overexpression of myrAkt decreases expression of inflammatory genes. *P<0.05, cells expressing tTA plus myrAkt vs. cells expressing tTA alone. Error bars stand for mean± standard error.

Table 1. Phosphoproteins decreased by 25% or more in SNRK knockdown adipocytes. Experiments were done with four independent replicates and data was analyzed with ratio of mean.

Table 2. Phosphoproteins increased by one fold or more in SNRK knockdown adipocytes. Experiments were done with four independent replicates and data was analyzed with ratio of mean.

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Table 1.

Symbol Name Phosphorylation KD/Control Q Value sites ratio for SILAC Insulin signaling/ protein synthesis/ amino acid metabolism RPTOR Regulatoryassociated protein of mTOR S863 0.25 0.031 PDCD4 Programmed cell death protein 4 T93, S94 0.26 0.010

IRS1 Insulin receptor substrate 1 S1097 0.29 0.030 PI4K2A Phosphatidylinositol 4kinase type 2alpha S47 0.45 0.025 PEA15 Astrocytic phosphoprotein PEA15 S116 0.51 0.025

BCKDK 3methyl2oxobutanoate dehydrogenase kinase, S33 0.67 0.029 mitochondrial AKT1S1 Prolinerich AKT1 substrate 1 (PRAS40) T247 0.75 0.025 Transcription HDAC1 Histone deacetylase 1 S393 0.18 0.023 TCOF1 S1191 0.23 0.006 NF1 Nuclear factor 1 S265 0.66 0.040 PTRF Polymerase I and transcript release factor T198, S218 0.74 0.046 Messenger RNA processing SNRNP70 Snrnp 70 protein S81 0.11 0.026 SF1 Splicing factor 1 S80, S82 0.39 0.029 SCAF1 Splicing factor, arginine/serinerich 19 S676, S682 0.41 0.044 Smg9 Protein SMG9 S32 0.47 0.026 SRRM1 Serine/arginine repetitive matrix 1 S3 87, S391 0.47 0.011 CSTF3 Cleavage stimulation factor subunit 3 S691 0.56 0.039 G3BP2 Ras GTPaseactivating proteinbinding protein 2 T227 0.61 0.027 FIP1L1 PremRNA 3’endprocessing factor FIP1 S479 0.66 0.031 Translation EEF1D Eef1d protein S128 0.38 0.022 Glucose and lipid metabolism Pck2 Phosphoenolpyruvate carboxykinase [GTP], S2 0.11 0.010 mitochondrial PC Pyruvate carboxylase, mitochondrial S19, S20 0.42 0.007 ACC1 AcetylCoA carboxylase 1 S29 0.52 0.025 ATGL Patatinlike phospholipase domaincontaining protein 2 S406 0.67 0.026 ATGL Patatinlike phospholipase domaincontaining protein 2 S409 0.70 0.037 OSBP Oxysterolbinding protein S188, S191 0.70 0.026 ACLY ATP citrate lyase S455 0.71 0.023 OSBPL11 Oxysterolbinding proteinrelated protein 11 S186 0.72 0.025 Cytoskeleton VCL Vinculin S290 0.00035 0.009 Sdccag8 Serologically defined colon cancer antigen 8 homolog T430, S438 0.0013 0.023 Mylk Myosin, light polypeptide kinase S611 0.013 0.023 Ppfia1 Ppfia1 protein T770 0.16 0.025 RABGAP1 Rab GTPaseactivating protein 1 S42 0.44 0.023 PXN Paxillin S321, S328 0.63 0.022 SH3PXD2A SH3 and PX domaincontaining protein 2A S420 0.67 0.025 Tpr complexassociated intranuclear coiledcoil S2067 0.74 0.031 protein TPR Membrane trafficking PLVAP Plasmalemma vesicleassociated protein S4 0.40 0.040 Tgoln1 TransGolgi network integral 1 S266, S267 0.56 0.035 Tgoln2 TransGolgi network integral membrane protein 2 S277 0.63 0.016 TRAM1 Translocating chainassociated membrane protein 1 S365 0.73 0.028 CANX Calnexin S563 0.75 0.037 Miscellaneous SSFA2 Sperm specific antigen 2 S90 0.11 0.022 SASH1 SAM and SH3 domaincontaining protein 1 S805 0.13 0.009 CLASP2 Clasp2 protein S376 0.45 0.042

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SDPR Serum deprivationresponse protein S363 0.49 0.029 THUMPD1 THUMP domaincontaining protein 1 S86, S88 0.50 0.030 HMOX1 Heme oxygenase 1 S174 0.57 0.047 FAM73B Protein FAM73B T208 0.68 0.011 BAG3 BAG family molecular chaperone regulator 3 S270, S274 0.69 0.034 LUC7I3 Luc7like protein 3 S425, S431 0.71 0.044

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Table 2 Symbol Name Phosphorylation KD/Control Q value for sites ratio SILAC Inflammatory pathways/ apoptosis Card 6 Caspase recruitment domain family, member S870, T873 687.5 0.0065 6 IFIH1 Inteferoninduced helicase C domain S289 11.2 0.0397 containing protein 1 ZBP1 ZDNAbinding protein 1 S384 7.5 0.0334 PML protein PML S515, T527, S528 4.8 0.0270 PML protein PML S514 4.5 0.0440 RIPK2 Receptorinteracting serine/threonineprotein S414 3.7 0.0372 kinase 2 SAMHD1 Sam domain and HD domaincontaining T21, S24, T29 2.6 0.0221 protein 1 H2L H2 class I histocompatibility antigen, LD S353, S356 2.3 0.0293 alpha chain SAMHD1 Sam domain and HD domaincontaining T25 2.2 0.0397 protein 1 Insulin signaling/ protein synthesis Sik2 Serine/threonineprotein Kinase SIK2 S358 16.2 0.0095 PI4KB Phosphatidylinositol 4kinase beta S511 7.2 0.0230 PRKRA Interferoninduced doublestranded RNA S32 4.7 0.0264 activated protein kinase Transcription/ messenger RNA processing /translation RBM 15 RNA binding motif protein 15 S655 6.8 0.0497 Trim28 Transcription intermediary factor 1beta S473 3.5 0.0308 EIF4G3 Eukaryotic translation initiation factor 4 S267 2.9 0.0095 gamma 3 EIF4G1 Eukaryotic translation initiation factor 4 S1189 2.7 0.0434 gamma 1 RBM8A RNAbinding protein 8A S56 2.7 0.0317 Ifi204 Interferonactivable protein 204 T106 2.3 0.0331 INTS1 Integrator complex subunit 1 S1320, T1321, S1328, 2.3 0.0246 S1329 Srrm1 Serine/arginine repetitive matrix protein 1 S610, S612 2.3 0.0313 Patl1 Protein PAT1 homolog 1 S179 2.2 0.0120 NFIB Nuclear factor 1Btype S328 2.0 0.0461 Glucose and lipid metabolism PLIN1 perilipin 1 S81 3.0 0.0366 PLA2G4B cytosolic phospholipase A2 S437 2.6 0.0230 Cytoskeleton/ scaffolding protein/ endocytosis/ exocytosis AaK1 AP2 ssociated protein kinase 1 T618, S621 80.6 0.0065 AKAP13 Akap 13 A kinase anchor protein 13 S1910 4.1 0.0340 MAPT Microtubuleassociated protein S761 3.5 0.0289 CLASP1 CLIPassociating protein 1 S600 3.5 0.0246 Sept2 Septin2 S218 2.8 0.0308 ACTB Actin, cytoplasmic 1 S239 2.8 0.0441 Ctnnb1 Catenin beta1 T556 2.4 0.0441 AP3D1 AP3 complex subunit delta1 S755, T758, S760 2.1 0.0230 Cell growth MEK5 Mitogenactivated protein kinase kinase S433 3.5 0.0321 kinase kinase 5 HDGF Hepatomaderived growth factor S165 3.5 0.0332 Miscellaneous Likely ortholog of H. sapiens 9 T311 1030.4 0.0065 ORF 138 TNKS1BP1 182 kDa tankyrase1binding protein S429 5.5 0.0387 TMCC2 Transmembrane and coiledcoil domains S435 5.5 0.0366 protein 2 Testis expressed gene 2 S195 5.5 0.0276 Arhgef17 Rho guanine nucleotide exchange factor 17 S458 3.2 0.0380 Myl12a MCG5400 T19, S20 3.0 0.0343 DCLK1 Dclk1 protein S330, S332, T336 2.9 0.0246 Tjp1 Tjp1 S617 2.9 0.0481

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Rplp2ps1 MCG10050 S105 2.5 0.0246 Marcksl1 MARCKSrelated protein S104 2.2 0.0492 Nop58 NUcleolar protein 58 S509, S521 2.2 0.0366

29 Diabetes Page 30 of 603 Figure 1 A B 4.5 35 4.0 30 3.5 25 3.0 20 2.5 2.0 15 1.5 10

1.0 Mouse SNRK/28S 5 Human Human SNRK/28S 0.5 0 0.0 9 8 7

2.5 1/28S

 6 2.0 5 4 1/28S

 1.5 3 2 1.0 Mouse AMPK 1 0 0.5 20

Human Human AMPK 18 0.0 16 14 2/8S

 12 14 10

12 8 6 10 4 2/28S

Mouse AMPK 2  8 0 6 BAT liver heart WAT WAT

4 brain Testis Testis spleen spleen kidney kidney stomach stomach Human Human AMPK pancreas 2 s. muscle S. intestine S. 0 C Nonspecific

liver SNRK Lung Lung heart WAT WAT brain Testis Testis spleen spleen kidney kidney stomach stomach pancreas s. muscle s. muscle

S. intestine S. Tubulin liver BAT heart WAT WAT brain Testis Testis spleen spleen kidney kidney stomach stomach pancreas s. muscle s. muscle S. intestine S. Page 31 of 603 Diabetes

D SNRK-GFP Lyso tracker

DAPI Merge Diabetes Page 32 of 603 Figure 2

A B 1.2 1.0 Lean Ob/ob 0.8

actin actin SNRK  0.6 * 0.4 Tubulin 0.2 SNRK/ SNRK/ 0.0 lean Ob/ob

2.5 16 14 * * 2.0 12

1.5 10 actin actin *  8 1.0 6 SNRK/ SNRK/ SNRK /Tubulin SNRK 4 0.5 2 * 0.0 0 Fed Fasted Fed Fasted lean Ob/ob Chow HF Page 33 of 603 Diabetes Figure 2

C D

2.5 * * 2.0 1.5 Chow fast Chow fed HFD fast HFD fed 1.0 SNRK SNRK/ 28S SNRK/ 0.5 0.0 Tubulin Chow HF Chow HF SV Adi

3.0 * * 2.5

2.0

1.5 *

1.0 SNRK /Tubulin SNRK 0.5

0.0 Fed Fasted Fed Fasted Chow HF Diabetes Page 34 of 603

Figure 3 A B C 1.2 1.2 1.2 1.0 1.0 1.0 0.8 0.8 0.8 -actin -actin -actin -actin   0.6  0.6 0.6 * 0.4 0.4 0.4 * SNRK/ SNRK/ SNRK/ SNRK / 0.2 * 0.2 0.2 0.0 0.0 0.0 Control FFA control TNF GFP IKKβ SE D E F 1.2 * 1.6 * 1.4 1.2 0.8 1.2 * actin 1.0 * -actin -actin 

 0.8 0.8 0.4 0.6 SNRK SNRK 28S/ 0.4 0.4 SNRK/ SNRK/

SNRK/ SNRK/ 0.2 0.0 0.0 0.0 Veh Lipid veh Rosi PBS Clod PBS Clod Chow HFD Page 35 of 603 Diabetes

Figure 3 G H

SNRK SNRK Tubulin Tubulin

V F V V F F V V T T V V T T

IgG SNRK Ab IgG SNRK Ab

I J

SNRK SNRK Tubulin Tubulin V V R R V V R R GFP IKKSE GFP GFP IKKSE IKKSE IgG SNRK Ab IgG SNRK Ab Diabetes Page 36 of 603 Figure 4 A B C pJNK 90 * 80 70 1.4 tJNK 60 1.2 50 1.0 pIKK g/mg protein)  40 0.8 30 0.6 tIKK 20 SNRK/28S 0.4 * 10 0.2 0 Tubulin Glycerol ( shGFP shSNRK 0.0 shGFP shSNRK shGFP shGFP

shSNRK shSNRK D shGFP E shSNRK

7 SNRK * * 1.2 6 * 1.0 * 5 0.8 Tubulin 4 * * 3 0.6 *

shGFP shSNRK 2 TNF(pg/ml) 0.4 1 0.2 0

Relative gene expression TNF IL-6 MCP-1 MCP-2 MCP-3 Chop 0.0 shGFP shSNRK Page 37 of 603 Diabetes Figure 4 continued

F G

12 1.2 * * * * * * 10 1.0 8 0.8 6 0.6

IL6 (pg/ml) IL6 (pg/ml) 4 0.4 2 0.2 0 0.0 Relative gene expression shGFP shSNRK Glut4 Adipo VLACAD MACAD Atg12

H I

140000 120000 pAkt * * 100000 S473 80000 60000 * Akt 40000 Cpm/mg proteinCpm/mg 20000 Tubulin 0 shGFP shSNRK shGFP shSNRK

shGFP shSNRK shGFP shSNRK Veh Insulin

Veh Insulin Figure 5 Diabetes Page 38 of 603 A B 1.2 * SNRK 1.0 0.8 140000 120000 * pACC 0.6 100000 (S79) 0.4 80000

pAcc/ACC pAcc/ACC 0.2

Cpm Cpm 60000 ACC 0.0 40000 Ad-GFP Ad-SNRK 20000 Tubulin 0 2.0 * -20000 1.8 p-Raptor 1.6 GFP SNRK (S863) 1.4 1.2 1.0 Raptor 0.8 0.6 0.4 Tublin pRaptor/Raptor 0.2 0.0 Ad-GFP Ad-SNRK Ad-GFP + + - - D 1200 * Ad-SNRK - - + + 1000 800 C 600 IP: SNRK; WS, SNRK 400 SNRK/28S IP: SNRK; WS, p-Raptor 200 IP, SNRK; WS, Raptor 0 GFP SNRK Vec + + - + + + + + + + + - - - - SNRK + - + ------+ + + + + + 1.2 Raptor WT - + + - - + + - - - - + + - - 1.0 Raptor S863A ------+ + - - - - + + 0.8 IgG SNRK Ab 0.6 * SNRK 0.4 Chop/28S pRaptor 0.2 Raptor 0.0 GFP SNRK

Input samples Input samples Tubulin Page 39 of 603 Diabetes Figure 5 Continued

E LC3-I 8 LC3-II 7 * 6 SNRK 5 4 * Fed Fed 3 Tubulin 2 1 0 Ratio of LC3II/LC3I GFP SNRK GFP SNRK GFP SNRK LC3-I Veh Chloroquine Rapamycin LC3-II SNRK 4.5 Fast 2hFast Tublin 4.0 3.5 3.0 Ad-GFP + + - - + + - - + + - - 2.5 * - - + + - - + + - - + + 2.0 Ad-SNRK 1.5 Vehicle + + + + ------1.0 0.5

Chloroquine - - - - + + + + - - - - Ratio of LC3II LC3I / 0.0 Rapamycin ------+ + + + GFP SNRK GFP SNRK GFP SNRK Veh Chloroquine Rapamycin Figure 6 Diabetes Page 40 of 603 A LC3-I 0.30 1.2 LC3-II 0.25 1.0 0.20 0.8 * Tublin 0.15 * 0.6 0.4 pRaptor 0.10 LC3I/Tubulin LC3I/Tubulin (S863) LC3II/Tubulin 0.05 0.2 0.00 0.0

Raptor 0.7 18 0.6 16 14 Tublin 0.5 12 0.4 10 0.3 8 * pACC 6 0.2 *

pACC/ACC pACC/ACC 4 (S79) pRaptor/raptor 0.1 2 0.0 0 ACC shGFP shSNRK shGFP shSNRK

Tublin

shGFP + + - - shSNRK - - + + FigurePage 41 of 6 603 conti Diabetes

B C D 2.0 * * pIKK 1.8 tIKK 250 1.6 * * 1.4 pJNK 200 1.2 1.0 150 JNK 0.8 100 0.6

pS6 g/mg protein)  50 0.4 Glycerol release (

Relative gene expression 0.2 Tubulin 0 0.0 Veh Rapa Veh Rapa Veh Rapa Veh Rapa Veh Rapa IL-6 MCP-1 MCP-3

E F G

Myr-Akt 1.4 60 Endogenous 1.2

Akt 50 1.0 pS6 40 0.8 * 30 0.6 * S6 20 0.4 g/mg g/mg protein)

 * 0.2 Glycerol release ( 10

Tubulin 0 Relative gene expression 0.0 tTA tTA+ tTA + + + + + + myr-Akt Myr-Akt + + + IL-6 MCP-1 TNF Diabetes Page 42 of 603

Supplemental table 1. Sequences of real-time PCR primers

Genes Accession Forward primer Reverse primer number hSNRK NM_017719 ATGGCAGGATTTAAGCGAGGG ATGCCTGGCAAGTTTAACCAC hAMPKα1 NM_006251 GCAGTTGCCTACCATCTCATAAT GGGCTTGTCGCCAAATAGAAATC hAMPKα2 NM_006252 GTGAAGATCGGACACTACGTG CTGCCACTTTATGGCCTGTTA mSNRK NM_133741 TTTAGGCGAGGATATGATGGGA GTCCAGCTTCGTCTTGTCAAT mAMPKα1 NM_001013367 TTCGGGAAAGTGAAGGTGGG TTATGTCCGGTCAACTCGTGC mAMPKα2 NM_178143 ACAGGCCATAAAGTGGCAGTT AAAAGTCTGTCGGAGTGCTGA mTNFα NM_013693.2 GACCCTCACACTCAGATCATCTTCT CCACTTGGTGGTTTGCTACGA mIL-6 NM_031168 TAGTCCTTCCTACCCCAATTTCC TTGGTCCTTAGCCACTCCTTC mMCP-1 NM_011333 TTAAAAACCTGGATCGGAACCAA GCATTAGCTTCAGATTTACGGGT mMCP-2 NM_021443 CCCTTCGGGTGCTGAAAAG CCACTTCTGTGTGGGGTCTAC mMCP-3 NM_013654 AGAAACAAAAGATCCCCAAGAGG CCAGGGACACCGACTACTG mChop NM_007837 CACGCACATCCCAAAGCC GGGCACTGACCACTCTGTT mGlut4 NM_009204 ACCGGATTCCATCCCACAAG TCCCAACCATTGAGAAATGATGC mAdiponectin NM_009605 TGTTCCTCTTAATCCTGCCCA CCAACCTGCACAAGTTCCCTT mVLACAD NM_017366 TCAGGTGTTCCCATACCCATC AAGGCGTCGTTCTTGGCAG mMACAD NM_007382 GATCGCAATGGGTGCTTTTGATAGAA AGCTGATTGGCAATGTCTCCAGCAAA mATG12 NM_026217 GGCCTCGGAACAGTTGTTTA CAGCACCGAAATGTCTCTGA 28S NR_003279.1 TTCACCAAGCGTTGGATTGTT TGTCTGAACCTGCGGTTCCT

Page 43 of 603 Diabetes

timecourse manual naming::protein name counter manual all protein name index 1959017 Vinculin Manual Assigned Name:Vinculin SwissPROT>VINC_MOUSE> Vinculin OS=Mus musculus 1959847 Serologically defined colon cancer antigen 8 ManualGN=Vcl Assigned homolog Name:Serologically defined colon cancer antigen 8 homolog 1960283 Myosin, light polypeptide kinase ManualSwissPROT>SDCG8_MOUS Assigned Name:Myosin, light polypeptide kinase SwissPROT>B1B1A8_MOUS 1960202 Uncharacterized protein (Fragment) ManualE>S611>"Myosin, Assigned light Name:Uncharacterized protein (Fragment) 1959753 Sperm specific antigen 2 Manual Assigned Name:Sperm specific antigen 2 SwissPROT>A2AQD4_MOU 1959761 Snrnp70 protein ManualSE>S90>Sperm Assigned specific Name:Snrnp70 protein IPI>Q99LY5>S81>Snrnp70 protein 1959338 SAM and SH3 domain-containing protein 1 ManualIPI>Q62376>S81>U1 Assigned Name:SAM small and SH3 domain-containing protein 1 HPRD>06408_1>S813>SAS 1960221 Ppfia1 protein ManualH1 Assigned Name:Ppfia1 protein SwissPROT>B2RXW8_MOU SE>T770>Ppfia1 protein 1960061 Histone deacetylase ManualOS=Mus Assigned musculus Name:Histone deacetylase SwissPROT>D3YYI8_MOUS E>S393>MCG128529 OS=Mus musculus Diabetes Page 44 of 603

1960329 Treacle protein Manual Assigned Name:Treacle protein SwissPROT>Q7TPZ2_MOUS E>S1227>Tcof1 protein 1959304 Regulatory-associated protein of mTOR Manual(Fragment) Assigned OS=Mus Name:Regulatory-associated protein of mTOR SwissPROT>A2ACM0_MOU 1959669 Programmed cell death protein 4 ManualSE>S863>Novel Assigned protein Name:Programmed cell death protein 4 SwissPROT>PDCD4_MOUS 1959926 Programmed cell death protein 4 ManualE>T93>Programmed Assigned cell Name:Programmed cell death protein 4 SwissPROT>PDCD4_MOUS 1960269 Insulin receptor substrate 1 ManualE>S94>Programmed Assigned cell Name:Insulin receptor substrate 1 SwissPROT>IRS1_MOUSE> 1958881 Eef1d protein ManualS1097>Insulin Assigned receptor Name:Eef1d protein HPRD>00560_1>S499>Eukar yotic translation elongation 1959816 Splicing factor 1 Manualfactor 1, Assigned delta Name:Splicing factor 1 HPRD>03306_1>S80S82>Sp licing factor 1 1959768 Plasmalemma vesicle associated protein ManualHPRD>03306_2>S80S82>Sp Assigned Name:Plasmalemma vesicle associated protein SwissPROT>B8JK32_MOUS 1958819 Splicing factor, arginine/serine-rich 19 ManualE>S527>Heterogeneous Assigned Name:Splicing factor, arginine/serine-rich 19 IPI>Q5U4C3>S676S682>Spli 1959657 Pyruvate carboxylase, mitochondrial Manualcing factor, Assigned arginine/serine- Name:Pyruvate carboxylase, mitochondrial SwissPROT>PYC_MOUSE> S20>"Pyruvate carboxylase, Page 45 of 603 Diabetes

1960267 Pyruvate carboxylase, mitochondrial Manual Assigned Name:Pyruvate carboxylase, mitochondrial SwissPROT>PYC_MOUSE> 1960219 Rab GTPase-activating protein 1 ManualS19>"Pyruvate Assigned carboxylase, Name:Rab GTPase-activating protein 1 SwissPROT>A2AWA7_MOU SE>S42>RAB GTPase 1960239 Phosphatidylinositol 4-kinase type 2-alpha Manualactivating Assigned protein 1 Name:Phosphatidylinositol 4- kinase type 2-alpha SwissPROT>P4K2A_MOUSE 1959918 Clasp2 protein Manual>S47>Phosphatidylinositol Assigned 4- Name:Clasp2 protein HPRD>12054_1>S603>Cytop lasmic linker associated 1959139 Protein SMG9 Manualprotein 2Assigned Name:Protein SMG9 SwissPROT>D3Z719_MOUS E>S32>Uncharacterized 1959641 Serine/arginine repetitive matrix 1 Manualprotein OS=MusAssigned musculus Name:Serine/arginine repetitive matrix 1 HPRD>10441_1>S389S393> 1960064 Serum deprivation-response protein ManualSerine arginine Assigned repetitive Name:Serum deprivation- response protein SwissPROT>SDPR_MOUSE 1959170 THUMP domain-containing protein 1 Manual>S363>Serum Assigned deprivation- Name:THUMP domain- containing protein 1 SwissPROT>THUM1_MOUS 1960361 Astrocytic phosphoprotein PEA-15 ManualE>S86S88>THUMP Assigned domain- Name:Astrocytic phosphoprotein PEA-15 HPRD>04579_1>S116>PEA1 1958617 Acetyl-CoA carboxylase 1 Manual5 Assigned Name:Acetyl-CoA carboxylase 1 HPRD>01938_1>S66>Acetyl- CoA carboxylase alpha Diabetes Page 46 of 603

1959268 Trans-Golgi network integral membrane Manual Assigned protein 1 Name:Trans-Golgi network integral membrane protein 1 SwissPROT>TGON1_MOUS 1960387 Trans-Golgi network integral membrane ManualE>S266>Trans-Golgi Assigned network protein 1 Name:Trans-Golgi network integral membrane protein 1 SwissPROT>TGON1_MOUS 1960008 Cleavage stimulation factor subunit 3 ManualE>S267>Trans-Golgi Assigned network Name:Cleavage stimulation factor subunit 3 HPRD>02651_1>S691>Cleav 1960139 Heme oxygenase 1 Manualage stimulation Assigned factor, 3 Name:Heme oxygenase 1 SwissPROT>HMOX1_MOUS E>S174>Heme oxygenase 1 1959209 Ras GTPase-activating protein-binding ManualOS=Mus Assigned musculus Name:Ras protein 2 GTPase-activating protein- binding protein 2 SwissPROT>G3B2_MOUSE> 1958637 Paxillin ManualT227>Ras-GTPase-activating Assigned Name:Paxillin SwissPROT>PAXI_MOUSE> S287>Isoform Alpha of 1958638 Paxillin ManualPaxillin OS=MusAssigned musculus Name:Paxillin SwissPROT>PAXI_MOUSE> S294>Isoform Alpha of 1959198 Trans-Golgi network integral membrane ManualPaxillin OS=MusAssigned musculus protein 2 Name:Trans-Golgi network integral membrane protein 2 SwissPROT>TGON2_MOUS 1960338 Pre-mRNA 3'-end-processing factor FIP1 ManualE>S277>Trans-Golgi Assigned Name:Pre- network mRNA 3'-end-processing factor FIP1 HPRD>09646_1>S492>FIP1 1959826 Nuclear factor 1 Manuallike 1 Assigned Name:Nuclear factor 1 HPRD>09007_1>S287>Nucle ar factor I/A SwissPROT>B1AUB9_MOUS Page 47 of 603 Diabetes

1959941 SH3 and PX domain-containing protein 2A Manual Assigned Name:SH3 and PX domain-containing protein 2A HPRD>10228_1>S393>SH3 1960110 Patatin-like phospholipase domain-containing Manualmultiple Assigneddomains 1 protein 2 Name:Patatin-like phospholipase domain- containing protein 2 1960253 [3-methyl-2-oxobutanoate dehydrogenase ManualSwissPROT>PLPL2_MOUSE Assigned Name:[3- [lipoamide]] kinase, mitochondrial methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial 1960039 Protein FAM73B ManualSwissPROT>BCKD_MOUSE Assigned Name:Protein FAM73B SwissPROT>FA73B_MOUSE >T208>Isoform 2 of Protein 1959048 BAG family molecular chaperone regulator 3 ManualFAM73B Assigned OS=Mus Name:BAG musculus family molecular chaperone regulator 3 SwissPROT>A6H663_MOUS 1958635 Patatin-like phospholipase domain-containing ManualE>S270S274>BCL2- Assigned protein 2 Name:Patatin-like phospholipase domain- containing protein 2 1960331 Oxysterol-binding protein ManualSwissPROT>PLPL2_MOUSE Assigned Name:Oxysterol-binding protein IPI>E9QPD4>S188S191>Oxy 1960205 ATP citrate lyase Manualsterol-binding Assigned protein Name:ATP citrate lyase HPRD>00155_1>S455>ATP citrate lyase 1959628 Luc7-like protein 3 ManualHPRD>00155_2>S455>ATP Assigned Name:Luc7- like protein 3 HPRD>16759_1>S425S431> Cisplatin resistance 1960229 Luc7-like protein 3 Manualassociated Assigned overexpressed Name:Luc7- like protein 3 HPRD>16759_1>S425T429> Cisplatin resistance associated overexpressed Diabetes Page 48 of 603

1959345 Oxysterol-binding protein-related protein 11 Manual Assigned Name:Oxysterol-binding protein-related protein 11 SwissPROT>OSB11_MOUSE 1959886 Translocating chain-associated membrane Manual>S186>Oxysterol-binding Assigned protein 1 Name:Translocating chain- associated membrane protein 1 1959869 Nuclear pore complex-associated ManualSwissPROT>TRAM1_MOUS Assigned intranuclear coiled-coil protein TPR Name:Nuclear pore complex- associated intranuclear coiled- coil protein TPR 1958680 Polymerase I and transcript release factor ManualSwissPROT>Q7M739_MOUS Assigned Name:Polymerase I and transcript release factor SwissPROT>PTRF_MOUSE> 1958786 Calnexin ManualT198S218>Polymerase Assigned I and Name:Calnexin SwissPROT>CALX_MOUSE> S563>Calnexin OS=Mus 1958949 Proline-rich AKT1 substrate 1 Manualmusculus Assigned GN=Canx Name:Proline-rich AKT1 substrate 1 HPRD>12441_1>T246>AKT1 1959917 High mobility group protein HMG-I/HMG-Y Manualsubstrate Assigned 1 Name:High mobility group protein HMG- I/HMG-Y HPRD>02829_1>S102S103> 1960171 SRA stem-loop-interacting RNA-binding ManualHigh mobility Assigned group Name:SRA AT hook 1 protein, mitochondrial stem-loop-interacting RNA- binding protein, mitochondrial IPI>Q9D8T7>SRA stem-loop- 1959501 Rapamycin-insensitive companion of mTOR Manualinteracting Assigned RNA-binding Name:Rapamycin-insensitive companion of mTOR HPRD>10682_1>S1591>Rict 1960043 Bcl-2-associated 1 Manualor Assigned Name:Bcl-2- associated transcription factor 1 SwissPROT>BCLF1_MOUSE >S654>Isoform 3 of Bcl-2- Page 49 of 603 Diabetes

1959423 Ankyrin repeat domain-containing protein 57 Manual Assigned Name:Ankyrin repeat domain- containing protein 57 SwissPROT>ANR57_MOUSE 1959375 Kif13b kinesin family member 13B Manual>S205>Ankyrin Assigned repeat Name:Kif13b kinesin family member 13B SwissPROT>Q6A029_MOUS 1959325 BCL2/adenovirus E1B 19 kDa protein- ManualE>MKIAA0639 Assigned protein interacting protein 3 Name:BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 1960449 RNA-binding protein 14 ManualSwissPROT>BNIP3_MOUSE Assigned Name:RNA- binding protein 14 HPRD>11485_1>T206>RNA binding motif protein 14 1959010 Translocation protein SEC62 ManualSwissPROT>Q62019_MOUS Assigned Name:Translocation protein SEC62 SwissPROT>SEC62_MOUSE 1960160 Polymerase I and transcript release factor Manual>T375>Translocation Assigned protein Name:Polymerase I and transcript release factor SwissPROT>PTRF_MOUSE> 1958646 Polymerase I and transcript release factor ManualT373S389S391>Polymerase Assigned I Name:Polymerase I and transcript release factor SwissPROT>PTRF_MOUSE> 1959495 Cation-independent mannose-6-phosphate ManualT198S204>Polymerase Assigned I and receptor Name:Cation-independent mannose-6-phosphate receptor 1960092 Protein FAM73B ManualSwissPROT>MPRI_MOUSE> Assigned Name:Protein FAM73B HPRD>12965_1>S276>C9orf 54 protein 1959517 Kif13b kinesin family member 13B ManualSwissPROT>FA73B_MOUSE Assigned Name:Kif13b kinesin family member 13B SwissPROT>Q6A029_MOUS E>MKIAA0639 protein Diabetes Page 50 of 603

1959848 Kif13b kinesin family member 13B Manual Assigned Name:Kif13b kinesin family member 13B SwissPROT>Q6A029_MOUS 1960364 Glycogen [starch] synthase, muscle ManualE>MKIAA0639 Assigned protein Name:Glycogen [starch] synthase, muscle HPRD>00721_1>S641S649> 1960307 ATP citrate lyase ManualGlycogen Assigned synthase Name:ATP 1 citrate lyase HPRD>00155_1>S481>ATP citrate lyase 1960328 Epidermal growth factor receptor substrate 15-ManualSwissPROT>Q3TS02_MOUS Assigned like 1 Name:Epidermal growth factor receptor substrate 15- like 1 1958756 RNA polymerase-associated protein CTR9 ManualHPRD>09445_1>S255>EPS1 Assigned Name:RNA homolog polymerase-associated protein CTR9 homolog SwissPROT>CTR9_MOUSE> 1960190 RNA polymerase-associated protein CTR9 ManualS925>Isoform Assigned 3 of Name:RNA RNA homolog polymerase-associated protein CTR9 homolog SwissPROT>CTR9_MOUSE> 1959992 Ahnak AHNAK isoform 1 ManualT930>Isoform Assigned 3 of RNA Name:Ahnak AHNAK nucleoprotein isoform 1 IPI>IPI00553798.2>Ahnak 1959470 Nuclear factor 1 ManualAHNAK Assignednucleoprotein isoform Name:Nuclear factor 1 SwissPROT>B1AUB9_MOUS E>S278>Nuclear factor 1 1959834 Nuclear factor 1 ManualOS=Mus Assigned musculus GN=Nfia Name:Nuclear factor 1 SwissPROT>B1AUB9_MOUS E>S285>Nuclear factor 1 1959124 cAMP-dependent protein kinase type II-beta ManualOS=Mus Assigned musculus GN=Nfia regulatory subunit Name:cAMP-dependent protein kinase type II-beta regulatory subunit HPRD>01486_1>S114>Protei Page 51 of 603 Diabetes

1959474 Ehd2 protein Manual Assigned Name:Ehd2 protein SwissPROT>EHD2_MOUSE> S438>EH domain-containing 1959105 Sec1 family domain-containing protein 1 Manualprotein 2Assigned OS=Mus Name:Sec1 musculus family domain-containing protein 1 SwissPROT>SCFD1_MOUS 1959486 Kinesin light chain 4 ManualE>S300>Isoform Assigned 3 of Sec1 Name:Kinesin light chain 4 SwissPROT>KLC4_MOUSE> S590>Kinesin light chain 4 1958708 Eukaryotic translation initiation factor 4E- ManualOS=Mus Assigned musculus GN=Klc4 binding protein 1 Name:Eukaryotic translation initiation factor 4E-binding protein 1 1959301 Regulatory-associated protein of mTOR ManualSwissPROT>4EBP1_MOUSE Assigned Name:Regulatory-associated protein of mTOR SwissPROT>A2ACM0_MOU 1958758 Myristoylated alanine-rich C-kinase substrate ManualSE>S859S863>Novel Assigned protein Name:Myristoylated alanine- rich C-kinase substrate SwissPROT>MARCS_MOUS 1959603 Myristoylated alanine-rich C-kinase substrate ManualE>T143>Myristoylated Assigned Name:Myristoylated alanine- rich C-kinase substrate SwissPROT>MARCS_MOUS 1960272 E>S141>Myristoylated

1959250 SH3 domain-binding protein 5-like Manual Assigned Name:SH3 domain-binding protein 5-like SwissPROT>3BP5L_MOUSE >S361>SH3 domain-binding 1960304 Membrane-associated progesterone receptor Manualprotein 5-likeAssigned OS=Mus component 2 Name:Membrane-associated progesterone receptor component 2 SwissPROT>PGRC2_MOUS Diabetes Page 52 of 603

1959606 Calnexin Manual Assigned Name:Calnexin SwissPROT>CALX_MOUSE> S553S563>Calnexin OS=Mus 1958829 Protein Njmu-R1 Manualmusculus Assigned GN=Canx Name:Protein Njmu-R1 HPRD>11392_1>S18>Protein kinase Njmu-R1 1959035 Tyrosine-protein phosphatase non-receptor ManualSwissPROT>NJMU_MOUSE Assigned type 14 Name:Tyrosine-protein phosphatase non-receptor type 14 1958772 Calnexin ManualHPRD>04402_1>S314>Protei Assigned Name:Calnexin SwissPROT>CALX_MOUSE> S553>Calnexin OS=Mus 1960423 Trans-Golgi network integral membrane Manualmusculus Assigned GN=Canx protein 1 Name:Trans-Golgi network integral membrane protein 1 SwissPROT>TGON1_MOUS 1959709 Endoplasmin ManualE>S210>Trans-Golgi Assigned network Name:Endoplasmin HPRD>01860_1>S306>Tumo r rejection antigen 1 1959598 Nuclear ubiquitous casein and cyclin- ManualSwissPROT>ENPL_MOUSE> Assigned dependent kinases substrate Name:Nuclear ubiquitous casein and cyclin-dependent kinases substrate 1959548 Hormone-sensitive lipase ManualSwissPROT>NUCKS_MOUS Assigned Name:Hormone-sensitive lipase SwissPROT>LIPS_MOUSE> 1958664 Enhancer of mRNA-decapping protein 4 ManualS557>Hormone-sensitive Assigned Name:Enhancer of mRNA- decapping protein 4 HPRD>06911_1>T727>Autoa 1960112 Phosphoglycerate kinase 1 Manualntigen RCD8 Assigned Name:Phosphoglycerate kinase 1 HPRD>02412_1>S203>Phos phoglycerate kinase 1 Page 53 of 603 Diabetes

1959153 Ankyrin repeat domain-containing protein 17 Manual Assigned Name:Ankyrin repeat domain- containing protein 17 IPI>Q99NH0>Ankyrin repeat 1958990 Ankyrin repeat and SAM domain containing 1 Manualdomain-containing Assigned protein 17 Name:Ankyrin repeat and SAM domain containing 1 HPRD>10610_1>S647>Odin 1958873 Ubiquitin-associated protein 2-like ManualSwissPROT>ANKS1_MOUS Assigned Name:Ubiquitin-associated protein 2-like SwissPROT>Q8BJ53_MOUS 1960237 Ubiquitin-associated protein 2-like ManualE>S477>Putative Assigned Name:Ubiquitin-associated protein 2-like SwissPROT>Q8BJ53_MOUS 1958887 Serum deprivation-response protein ManualE>S470>Putative Assigned Name:Serum deprivation- response protein SwissPROT>SDPR_MOUSE 1958683 Polymerase I and transcript release factor Manual>S218>Serum Assigned deprivation- Name:Polymerase I and transcript release factor SwissPROT>PTRF_MOUSE> 1958618 ATP-binding cassette sub-family F member 1 ManualS367S389S391>Polymerase Assigned Name:ATP- binding cassette sub-family F member 1 SwissPROT>ABCF1_MOUSE >S138>ATP-binding cassette Diabetes Page 54 of 603

heatmap peakarea assigned phosphosite accession number Final for display sequence annotated for psite labelfree 1 R.DPNAS*PG S290* UNI:Q64727 18339.32376 DAGEQAIR.Q

K.VT*REKTA T430S438 UNI:Q80UF4 160558.4017 AVS*HLEEIQ NHVASQEMD VTK.V R.EHRLS*PA S611 UNI:B1B1A8 20652.6232 R.S

- S2 UNI:Q3UGF0 334172.8891 .PS*PPSLSP R.L R.TPLGAS*L S90 UNI:A2AQD5 5646867.194 DEQSSGTPK. G

R.GGGGS*G S81 UNI:Q99LY5 620715.8396 QDNGLEGLG SDGR.D

R.S*LPVSICR S805 UNI:P59808 10515894.41 .S

K.GAPHT*VS T770 UNI:B2RXW8 476478.7854 HEDIR.D

R.MLPHAPG S393* UNI:D3YYI8 7769107.264 VQMQAIPED AIPEES*GDE DEEDPDKR.I Page 55 of 603 Diabetes

R.KLS*GDLE S1191* UNI:O08784 1269085.56 AGAPK.N

R.ILDTSSLTQ S863 UNI:Q8K4Q0 9143747.43 SAPAS*PTNK .G

R.SGVAVPT* T93* UNI:Q61823 4418378.816 SPK.G

R.SGVAVPTS S94* UNI:Q61823 4418378.816 *PK.G

R.HSS*ETFS S1097* UNI:P35569 445440.3075 APTR.A

R.ATAPQTQH S128* UNI:Q91VK2 615444.2782 VS*PMR.Q

R.TGDLGIPP S80S82* UNI:Q64213 27253795.71 NPEDRS*PS* PEPIYNSEGK .R R.MGLS*MDR S4 UNI:G3X924 1194900.224 .M

R.APS*PAPA S676S682 UNI:Q5U4C3 1861131.011 VS*PK.R

R.SS*SAPVA S20 UNI:Q05920 1441365.245 SPNVR.R Diabetes Page 56 of 603

R.S*SSAPVA S19 UNI:Q05920 1441365.245 SPNVR.R

R.QGDETPST S42 UNI:A2AWA9 509704.4443 NNGS*DDEK TGLK.I

R.VAAAAGS S47* UNI:Q2TBE6 1212713.546 GPS*PPCSP GHDR.E

R.SRS*DIDVN S376* UNI:B9EJA4 860333.1585 AAAGAK.A

R.WKEPGSS S32 UNI:Q9DB90 1041955.799 GPQNLS*GP GGR.E

R.RLS*PSAS* S387S391* UNI:A2A8V8 8594158.087 PPR.R

R.RGNNSAV S363 UNI:Q63918 343005.2364 GS*NADLTIE EDEEEEPVA LQQAQQVR. K.FIDKDQQPY S86S88* UNI:Q99J36 6462276.978 S*GS*EGEDD DAEAALKK.E

R.QPS*EEEII S116* UNI:Q62048 24251065.72 K.L

R.FIIGSVSED S29* UNI:Q5SWU9 8747264.912 NS*EDEISNL VK.L Page 57 of 603 Diabetes

K.VPGPS*SS S266 UNI:Q62313 1806850.158 ENQEGTLTD SMK.N

K.VPGPSS*S S267 UNI:Q62313 1806850.158 ENQEGTLTD SMK.N

K.RPNEDS*D S691* UNI:Q99LI7 2251703.367 EDEEKGAVV PPVHDIYR.A

K.AMALPSSG S174 UNI:P14901 2234828.148 EGLAFFTFPN IDS*PTK.F

K.SAT*PPPA T227* UNI:P97379 11909942.93 EPASLPQEP PK.A

K.TGSS*SPP S321 UNI:Q8VI36 2157246.557 GGLSKPGSQ LDSMLGSLQ SDLNK.L K.TGSSSPPG S328 UNI:Q8VI36 2157246.557 GLS*KPGSQL DSMLGSLQS DLNK.L K.VSGPSS*S S277 UNI:Q62314 2039123.21 ENQEGTLTD SMK.N

R.ERDHS*PT S479* UNI:Q9D824 2452806.243 PSVFNSDEE R.Y

K.SVEDEMD S265* UNI:B1AUB9 2792055.174 S*PGEEPFYT GQGR.S Diabetes Page 58 of 603

R.AQISS*PNL S420 UNI:O89032 852183.8491 R.T

R.AQS*LPSV S406 UNI:Q8BJ56 9564365.316 PLSCATYSE ALPNWVR.N

R.STS*ATDT S33* UNI:O55028 537429.0221 HHVELAR.E

R.GDGGSTP T208 UNI:Q8BK03 2065514.592 T*PGDSLQN PDTASEALS EPESQR.R R.AAS*PFRS* S270S274* UNI:Q9JLV1 3130125.534 PVR.G

R.AQSLPS*V S409 UNI:Q8BJ56 8566361.337 PLSCATYSE ALPNWVR.N

K.MLAES*DD S188S191 UNI:E9QPD4 1089324.864 S*GDEESVS QTDK.T

R.TAS*FSES S455* UNI:Q3TS02 3269192.189 R.A

K.NEVNGTSE S425S431 UNI:Q5SUF2 966551.1649 DIKS*EGDTQ S*N.-

K.NEVNGTSE S425T429 UNI:Q5SUF2 966551.1649 DIKS*EGDT* QSN.- Page 59 of 603 Diabetes

R.SFSLASSG S186* UNI:Q8CI95 11546441.05 NS*PISQR.R

R.KGTENGV S365* UNI:Q91V04 219471.6322 NGTVTSNGA DS*PR.N

R.QTPQAPQ S2067 UNI:Q7M739 949541.2378 S*PR.R

K.EGDELGE T198S218* UNI:O54724 7057654.528 GERPEDDT* AAIELSSDEA VEVEEVIEES K.SDAEEDGV*R.A S563* UNI:P35564 1072678.478 TGS*QDEED SKPK.A

R.LNT*SDFQ T247* UNI:Q9D1F4 4102877.304 K.L

K.KLEKEEEE S102S103 UNI:P17095 5053026.507 GISQES*S*E EEQ.-

K.ALHGAQTS S105 UNI:Q9D8T7 468395.4753 *DEER.F

K.S*TELLLGV S1591 UNI:Q6QI06 1635993.345 K.T

R.RIDIS*PSA S656* UNI:Q8K019 2791974.427 LR.K Diabetes Page 60 of 603

R.DLVLGSS* S205 UNI:Q8C0J6 2838546.043 PQLK.R

R.WES*QQD S1409 UNI:IPI00761751.2 6146753.542 VSQTLVSR.G

K.NSTLS*EE S88 UNI:O55003 13733433.4 DYIER.R

R.QPT*PPFF T206* UNI:Q8C2Q3 19404705.08 GR.D

K.EELEQQT* T375 UNI:Q8BU14 6913848.095 DGDCDEEDD DKDGEVPK.S

R.GSSPDVHT T373S389S391* UNI:O54724 4298702.556 *LLEITEESDA VLVDKS*DS* D.- K.EGDELGE T198S204* UNI:O54724 34060509.99 GERPEDDT* AAIELS*SDE AVEVEEVIEE K.AEALSSLHSR.A S2401 UNI:Q07113 17035843.33 GDDQDS*ED EVLTVPEVK. V R.TLMLPLTE S276 UNI:Q8BK03 6982835.313 GS*LR.L

R.APLLSEPA T1653 UNI:IPI00761751.2 3649247.556 SAVPT*SPFR .I Page 61 of 603 Diabetes

R.APLLSEPA S1654 UNI:IPI00761751.2 3649247.556 SAVPTS*PFR .I

R.YPRPAS*V S641S649* UNI:Q9Z1E4 14048617.38 PPSPSLS*R. H

K.AKPAMPQ S481* UNI:Q3TS02 7869495.416 DSVPS*PR.S

R.STPSHGSV S255* UNI:Q60902 1538036.211 SSLNSTGSL S*PK.H

K.GEEGS*EE S970* UNI:Q62018 579268.7208 EETENGPKP K.K

K.GEEGSEEE T975* UNI:Q62018 579268.7208 ET*ENGPKPK .K

K.FKAEAPLP S4890 UNI:IPI00553798.2 2314522.172 S*PK.L

R.S*PGSGSQ S278* UNI:B1AUB9 11174076.44 SSGWHEVEP GLPSPSTLK. K R.SPGSGSQ S285* UNI:B1AUB9 11174076.44 S*SGWHEVE PGLPSPSTLK .K R.RAS*VCAE S112* UNI:P31324 3079919.042 AYNPDEEED DAESR.I Diabetes Page 62 of 603

R.GPDEAIED S338* UNI:Q8R2X0 104674997.8 GEEGS*EDD AEWVVTK.D

R.VNLEESTG S300* UNI:Q8BRF7 5652643.312 VENS*PAGA RPK.R

R.AAS*LNYL S590 UNI:Q9DBS5 9085439.123 NQPNAAPLQ VSR.G

R.NS*PVAKT* S64T69 UNI:Q60876 1292695.067 PPK.D

R.ILDTSSLTQ S859S863 UNI:Q8K4Q0 4304256.713 S*APAS*PTN K.G

K.AEDGAAPS T143* UNI:P26645 1627171.296 PSSET*PK.K

K.AEDGAAPS S141* UNI:P26645 1627171.296 PSS*ETPK.K

K.KIS*IR.R Phosphorylated on 1320524.853 non-tryptic peptide, or a tryptic peptide with greater than 2 R.GLSDHAS* S361internal cleavage UNI:Q99LH9 7899036.832 LDGQELGAQ SR.G

R.LLKPGEEP S202* UNI:Q80UU9 1837452.939 S*EYTDEEDT KDHSK.Q Page 63 of 603 Diabetes

K.QKS*DAEE S553S563* UNI:P35564 3292854.433 DGVTGS*QD EEDSKPK.A

K.ELES*SEE S18 UNI:Q9CYI0 300181.1027 GGSAEER.R

K.ICTEQSNS* S314 UNI:Q62130 1674308.319 PPPIR.R

K.QKS*DAEE S553* UNI:P35564 1392505.273 DGVTGSQDE EDSKPK.A

K.TES*GETL S210 UNI:Q62313 2485857.19 AGDSDFSLK PEK.G

K.EES*DDEA S306 UNI:P08113 580404.4357 AVEEEEEEK. K

K.EEDEEAES S214* UNI:Q80XU3 497754.5858 *PPEK.K

R.S*VSEAAL S557* UNI:P54310 142436091.9 AQPEGLLGT DTLK.K

R.T*RSPDVIS T731* UNI:Q3UJB9 3617806.619 SASTALSQDI PEIASEALSR. G K.ALES*PER S203* UNI:P09411 11953725.9 PFLAILGGAK. V Diabetes Page 64 of 603

R.APS*PAPS S2401 UNI:Q99NH0 7802174.384 SVPLGSEKP SSVSQDR.K

R.SES*LSNC S663* UNI:Q3UHP6 3219862.029 SIGK.K

K.STSAPQMS S497* UNI:Q80X50 1571660.811 PGSSDNQSS S*PQPAQQK. L K.STSAPQMS S490* UNI:Q80X50 1571660.811 PGS*SDNQS SSPQPAQQK .L R.DEEALEDS S218 UNI:Q63918 27605977.09 *AEEK.M

R.GS*SPDVH S367S389S391* UNI:O54724 35219746.16 TLLEITEESD AVLVDKS*DS *D.- K.GGNVFEAL S138* UNI:Q6P542 5103259.246 IQDDS*EEEE EEEENR.V Page 65 of 603 Diabetes

peakarea manual peakarea manual peakarea manual peakarea manual 1 rep1 1 rep2 1 rep3 1 thresholded thresholded thresholded 18339.32376 24208 21669 8232

160558.4017 136514 240497

20652.6232 27390 47944 1901

334172.8891 241624 262889 419228

5646867.194 3757016 8637979 8265986

620715.8396 908251 387562 898546

10515894.41 8889244 16486756 12203937

476478.7854 874088 467435 231424

7769107.264 4805151 9797309 7286085 Diabetes Page 66 of 603

1269085.56 1732753 1352984 1054076

9143747.43 2379156 13053945 12868848

4418378.816 3851766 5460507 5478363

4418378.816 3851766 5460507 5478363

445440.3075 725072 280341 428212

615444.2782 749760 750019 656143

27253795.71 12474110 50288074 30771452

1194900.224 361560 1627930 2472248

1861131.011 1325729 2230202 1963007

1441365.245 1123787 1954281 1311904 Page 67 of 603 Diabetes

1441365.245 1123787 1954281 1311904

509704.4443 477915 478218 522050

1212713.546 963054 1521391 1290574

860333.1585 937923 1054433 642889

1041955.799 852949 1408472 1501707

8594158.087 5551107 9542065 11988907

343005.2364 41607 55905

6462276.978 2686817 7750201 6946341

24251065.72 29994910 27344460 24232165

8747264.912 9946298 11247682 13744072 Diabetes Page 68 of 603

1806850.158 3011729 1405351 1717932

1806850.158 3011729 1405351 1717932

2251703.367 339587 467759 82068

2234828.148 2724139 2246473 1733873

11909942.93 10555730 12512597 12916858

2157246.557 786121 4071104 1408999

2157246.557 786121 4071104 1408999

2039123.21 1619383 2380279 2394304

2452806.243 3103118 3231598 1730059

2792055.174 1033493 5034883 3239557 Page 69 of 603 Diabetes

852183.8491 585322 857077 1052196

9564365.316 9603978 12998863 6090255

537429.0221 469690 498280 696958

2065514.592 945745 3078198 2338573

3130125.534 2600631 3992287 4340278

8566361.337 9603978 12998863 6090255

1089324.864 794443 2169091 1180185

3269192.189 2900887 4573391 4326784

966551.1649 534918 1161778 1055190

966551.1649 534918 1161778 1055190 Diabetes Page 70 of 603

11546441.05 5624638 14557210 13609109

219471.6322 184690 174342 69083

949541.2378 942875 1098260 894628

7057654.528 5649017 7928173 7595773

1072678.478 288438 1570617 1814713

4102877.304 3699512 4493161 3695950

5053026.507 59764 108938 23212

468395.4753 371733 406635 566473

1635993.345 2452082 2574090 1133354

2791974.427 1891735 1749041 874104 Page 71 of 603 Diabetes

2838546.043 2669569 4311159 2919448

6146753.542 6473896 9648498 6292197

13733433.4 7002082 17499972 11161269

19404705.08 22561635 21887040 21118877

6913848.095 2012751 7337709 6888738

4298702.556 1449593 6324043 5122472

34060509.99 27121386 70113016 38667874

17035843.33 15374960 30037869 13050967

6982835.313 4755868 8767634 7425004

3649247.556 4696042 5660572 2793601 Diabetes Page 72 of 603

3649247.556 4696042 5660572 2793601

14048617.38 5763796 15240579 17687141

7869495.416 9875047 8724464 7991832

1538036.211 849754 1740586 1525098

579268.7208 363613 806013 978078

579268.7208 363613 806013 978078

2314522.172 2377035 2736062 1720315

11174076.44 6897911 16438091 14891947

11174076.44 6897911 16438091 14891947

3079919.042 2680971 4630858 3818018 Page 73 of 603 Diabetes

104674997.8 52353345 176650169 122891485

5652643.312 6591897 6424327 5436426

9085439.123 3939518 16790453 8071906

1292695.067 814613 1273993 2394807

4304256.713 3666625 4753870 4562101

1627171.296 1374239 1447433 1552721

1627171.296 1374239 1447433 1552721

1320524.853 1938999 1358248 1044101

7899036.832 4807707 8155058 8529308

1837452.939 1342850 2192594 1351949 Diabetes Page 74 of 603

3292854.433 1161164 2670914 3125029

300181.1027 264014 378333 494523

1674308.319 1386680 1903903 2205273

1392505.273 738621 717497 730670

2485857.19 2095917 4024774 2766038

580404.4357 478033 1017390 818236

497754.5858 370350 586586 1026674

142436091.9 136521675 175501742 176926416

3617806.619 4022340 5077628 2300493

11953725.9 15184893 13380212 7296072 Page 75 of 603 Diabetes

7802174.384 5854394 11608561 6760789

3219862.029 2121572 3649880 4421481

1571660.811 666138 1983208 1976016

1571660.811 666138 1983208 1976016

27605977.09 16784839 30864323 55960642

35219746.16 24153543 43279395 38226300

5103259.246 3404832 8940332 8063259 Diabetes Page 76 of 603

peakarea manual peakarea manual peakarea manual 1 rep4 peakarea manual 2 rep1 2 rep2 thresholded 2 thresholded thresholded 19248 52902838.05 22125661 69670402

104665 120217215.2 43091732 289175845

5376 1537226.245 1734397 1641439

412951 2997002.9 1725486 3415435

1926487 50490032.11 31508585 56217663

288504 5411673.012 2307598 7322073

4483641 84070362.32 66182044 156303135

332968 3062996.922 2509836 3092226

9187884 43335379.37 16470509 64833267 Page 77 of 603 Diabetes

936528 5483716.664 6987942 5897247

8273041 36224682.11 33713100 45984048

2882880 17208769.45 12369849 21955441

2882880 17208769.45 12369849 21955441

348136 1511731.361 1623420 1918350

305855 1614881.549 1468573 1889856

15481546 70489608.47 67500367 107816063

317863 3016672.768 783391 3722919

1925587 4504209.884 4479282 5150198

1375489 3465730.986 2660517 4359176 Diabetes Page 78 of 603

1375489 3465730.986 2660517 4359176

560635 1171561.611 1134226 1136205

1075836 2705326.55 1704183 2877546

806087 1899932.576 2158174 2478498

404696 2238269.717 2643395 3134658

7294553 18295049.47 11995298 20459640

931503 697355.0543 186619 239660

8465749 12889149.07 5747446 9343100

15432728 47701328.51 42437386 57168570

51008 16916770.39 13462760 15937764 Page 79 of 603 Diabetes

1092389 3244104.386 3891337 3932466

1092389 3244104.386 3891337 3932466

8117400 4029204.416 2688029 1382241

3929419.38 4142017 5306267

11654587 19408726.17 12690834 23483638

2362763 3450568.474 1479623 5853058

2362763 3450568.474 1479623 5853058

1762526 3245717.437 2358284 4252236

1746450 3728935.197 4349551 3897736

1860287 4211088.863 1912225 8362056 Diabetes Page 80 of 603

914141 1275933.545 971619 1490700

14314091.36 15772893 18725389

484788 804138.6086 572782 758285

1899542 3018531.766 1262168 4604359

1587307 4517223.205 3749034 5577754

5572349 12183828.1 15772893 18725389

213581 1546870.738 1052045 2843514

1275707 4613589.073 3685402 7152378

1114319 1353492.908 761979 1889722

1114319 1353492.908 761979 1889722 Page 81 of 603 Diabetes

12394807 16024341.17 9665617 20336306

449772 300464.6012 249717 295115

862401 1291167.447 1273185 1205408

9552472.406 6358997 12132230

616946 1435702.425 571317 2285196

4522887 5463496.281 5212934 5499215

20020192 6639625.753 58140 106269

528740 612089.1334 471079 623342

384448 2120997.118 3150108 3437315

6653017 3605746.419 1994763 2637442 Diabetes Page 82 of 603

1454008 3653365.701 4600133 4906625

2172423 7835479.496 8289104 11386400

19270412 17498285.41 9992965 26527333

12051268 24538923.49 25822150 29456523

11416194 8704323.112 2615118 10239938

5409854.922 1789344 7015904

339764 42818454.85 32795477 91339847

9679578 21355542.26 17864566 39214213

8709692.526 6303591 11355193

1446775 4551570.62 6388380 6481572 Page 83 of 603 Diabetes

1446775 4551570.62 6388380 6481572

17502953 17499884.07 7883949 21414953

4886639 9797603.643 12627454 11563522

2036707 1904707.747 1336303 2032405

169371 714104.295 397824 938959

169371 714104.295 397824 938959

2424676 2850322.698 3426606 3151850

6468358 13513073.38 9253878 17263744

6468358 13513073.38 9253878 17263744

1189830 3694600.712 2899871 5056857 Diabetes Page 84 of 603

66804992 125064470.5 60262090 217636181

4157924 6717622.834 7595008 8104644

7539879 10755734.46 5150160 19448918

687367 1517724.165 993820 1656391

4234432 5024019.973 3723395 5766849

2134291 1895901.135 1886583 1665790

2134291 1895901.135 1886583 1665790

940752 1528842.7 2207371 1568579

10104075 9117916.943 6225811 10551630

2462418 2120050.157 1658755 2789775 Page 85 of 603 Diabetes

6214310 3780423.723 1335810 3519532

63854 343351.0384 335470 402118

1201377 1907695.741 1582431 2371309

3383232 1583659.098 827633 1033066

1056700 2806451.312 2133952 4290742

7959 654696.4814 378942 815399

7408 558848.9724 332479 474227

80794535 158784759.7 142694538 205372152

3070766 4032986.774 4612772 5216388

13288822.13 17082431 14946226 Diabetes Page 86 of 603

6984954 8668501.98 6538057 11643998

2686515 3577213.93 2154693 3952625

1661280 1744434.586 657055 2195428

1661280 1744434.586 657055 2195428

6814104 29815506.6 17760614 34839301

37950015.3 24696830 47787048

4615 5387862.587 2278062 6751943 Page 87 of 603 Diabetes

peakarea manual peakarea manual 2 rep3 2 rep4 thresholded thresholded shSNRK/shGFP qvalues for SILAC 71534833 48280457 0.00034666 0.009488101

89837324 58763961 0.001335569 0.023035228

1169284 1603785 0.013434993 0.022627204

3926110 2920981 0.111502358 0.010406962

65597521 48636359 0.111841228 0.022143962

8562036 3454985 0.114699436 0.026299006

71237233 42559038 0.125084443 0.009488101

3964619 2685306 0.155559668 0.02461838

22959773 69077968 0.179278626 0.023035228 Diabetes Page 88 of 603

4691426 4358251 0.231427996 0.005885893

44584763 20616818 0.252417603 0.031260141

20136684 14373104 0.256751584 0.010406962

20136684 14373104 0.256751584 0.010406962

1852490 652666 0.29465573 0.030427144

2007571 1093527 0.381108001 0.022143962

78279280 28362725 0.386635652 0.029300234

4653659 2906722 0.396098721 0.039652747

6593261 1794099 0.41319811 0.044046738

3557023 3286208 0.415890688 0.006527052 Page 89 of 603 Diabetes

3557023 3286208 0.415890688 0.006527052

863431 1552384 0.43506414 0.022627204

2802997 3436580 0.448268822 0.02461838

2162834 800225 0.452822995 0.041736861

2174392 1000634 0.465518428 0.026008372

22209449 18515811 0.469753203 0.011398117

84277 2278865 0.491865993 0.028508578

15338550 21127501 0.501373438 0.029723372

52857029 38342329 0.508393927 0.02461838

21349787 0.517076529 0.02461838 Diabetes Page 90 of 603

3591707 1560907 0.556964247 0.035154749

3591707 1560907 0.556964247 0.035154749

976184 11070364 0.558845651 0.0388827

2339973 0.568742588 0.047041541

20818837 20641596 0.613638568 0.026963524

2706960 3762632 0.625185842 0.022143962

2706960 3762632 0.625185842 0.022143962

3766874 2605477 0.628250379 0.016086

3373866 3294588 0.65777658 0.031260141

4647663 1922412 0.66302452 0.039652747 Page 91 of 603 Diabetes

1350714 1290701 0.667890465 0.02461838

8443992 0.668178306 0.026441449

969331 916156 0.668328838 0.028508578

3296010 2911591 0.684277905 0.01143977

5377092 3365013 0.692931341 0.033543599

8443992 5793038 0.703092761 0.037014184

2019839 272085 0.704211953 0.026441449

5886331 1730245 0.708600644 0.022627204

1688118 1074153 0.714116165 0.044088092

1688118 1074153 0.714116165 0.044088092 Diabetes Page 92 of 603

17121789 16973653 0.720556367 0.02461838

116946 540080 0.730440895 0.027575892

1417096 1268981 0.735412932 0.031260141

10166190 0.73883014 0.046411288

2013317 872980 0.747145411 0.037074696

4456656 6685180 0.750961855 0.02461838

19754469 0.761040862 0.033543599

701984 651952 0.765240632 0.02461838

1468884 427682 0.771332187 0.02461838

1028426 8762355 0.774312473 0.039652747 Page 93 of 603 Diabetes

3040106 2066599 0.776967398 0.049744307

7941785 3724629 0.784477012 0.033543599

14074977 19397868 0.784844519 0.041736861

22252293 20624728 0.790772468 0.0490369

8324311 13637926 0.794300488 0.023035228

7424317 0.794605885 0.049445582

46767094 371401 0.795463314 0.025487227

14971320 13372070 0.79772469 0.026441449

8470294 0.801731553 0.034548735

3378188 1958143 0.801755671 0.02461838 Diabetes Page 94 of 603

3378188 1958143 0.801755671 0.02461838

19222492 21478142 0.802783454 0.030514486

9924361 5075077 0.803206141 0.033345923

1814984 2435138 0.80749197 0.035113117

1292558 227077 0.811182239 0.029709629

1292558 227077 0.811182239 0.029709629

1874748 2948086 0.8120211 0.036239668

19005364 8529308 0.826908589 0.031747009

19005364 8529308 0.826908589 0.031747009

5267677 1553998 0.833627036 0.0388827 Page 95 of 603 Diabetes

153562658 68796953 0.836968304 0.03461207

5677536 5493303 0.841464823 0.035154749

10933369 7490491 0.844706529 0.045307861

2640725 779960 0.851732546 0.026974997

5653091 4952745 0.856735589 0.036609927

1615445 2415786 0.858257462 0.043529901

1615445 2415786 0.858257462 0.043529901

1107863 1231557 0.863741478 0.034548735

9549752 10144476 0.866320332 0.044910374

1645142 2386529 0.866702579 0.046990182 Diabetes Page 96 of 603

3400506 6865848 0.871027873 0.034548735

562070 73746 0.874268807 0.031381487

2348698 1328344 0.877660039 0.031441733

1017598 3456339 0.879296103 0.046348557

3505526 1295585 0.885765301 0.047041541

769749 0.886524446 0.046953448

869841 0.89067818 0.032656278

204382161 82690189 0.89703881 0.043412508

2487128 3815660 0.897053926 0.041596747

7837809 0.899532388 0.02721905 Page 97 of 603 Diabetes

8435994 8055959 0.900060287 0.043939

5008502 3193036 0.90010329 0.039652747

2259000 1866256 0.900957148 0.045497702

2259000 1866256 0.900957148 0.045497702

59031890 7630221 0.925893276 0.026642592

41366168 0.928056178 0.049937177

7133583 0.947176949 0.044088092 Diabetes Page 98 of 603

isolated mass mass error timepoints timepoints xcorr timepoints ascorr timepoints 794.337095 0.303590126 50.23 100

1118.188228 0.333775769 20.91 9.782928361

355.8419777 0.956348295 24.45 100

514.245235 1.500754468 25.91

838.38702 0.11218745 63.8 70.79450791

890.36169 0.456252543 23.48 52.30935402

506.23904 1.510671379 33.37 31.09144469

466.8767037 0.423990705 23.71 7.87106093

932.1547815 0.246940268 23.06 100 Page 99 of 603 Diabetes

641.323725 1.484035873 30.35 100

637.6420877 0.554185727 22.02 16.83853399

515.75671 0.133914776 22.82 93.04804387

515.756895 0.492961462 31.96 21.21395681

650.27203 0.213922378 46.08 13.3355922

757.346125 0.443949705 37.64 47.79906413

982.0981407 1.048813336 21.21 35.13058657

450.17291 0.5025916 28.67 100

591.253535 0.424883695 30.04 100

626.289855 0.361145697 29.42 Diabetes Page 100 of 603

626.29095 1.388650713 24.18 16.80486599

724.9692937 0.224125129 24.93 12.33468246

627.6047937 0.732135325 36.93 19.69505857

485.5592907 0.104491532 34.6 11.95526977

630.9547707 0.189332863 25.31 24.6363937

624.276425 0.639655989 26.44 18.66287339

1232.901364 0.221008551 51.18 5.14104821

926.3925737 0.746445156 44.16 100

576.76306 0.41474376 25.32 100

1142.030025 0.3801927 25.5 25.44112358 Page 101 of 603 Diabetes

1026.43896 0.585806908 58.39 12.08620484

1022.4317 0.744670811 52.84 6.532125138

712.3209815 0.25647673 21.4 18.26209739

862.7404137 0.391693364 26.7 10.88136089

631.9716137 0.500026322 29.66

1009.145261 0.944661842 44.9 1.191864077

1014.489131 1.99181125 27.09

1021.429745 0.537747047 49.11 8.223549129

694.6230437 0.678721755 28.73 5.624397344

1160.452755 0.190525598 52.51 42.29987946 Diabetes Page 102 of 603

538.262325 0.277075951 23.81 13.89166084

1313.62109 0.830847231 27.29 37.29610889

807.860715 0.335663125 62.12

1030.774168 1.0610593 20.67

423.1882907 0.353437643 29.7 100

1318.62744 0.852727184 52.69 16.94605199

737.5992407 0.935415115 28.86 59.02161579

482.69253 0.661566461 36.34 16.11801956

731.2762407 0.612278182 29.68 20.60548934

731.2756907 1.365080253 25.74 13.69411045 Page 103 of 603 Diabetes

814.370055 1.383519425 61.67 43.44753708

686.9787577 0.499776162 28.1 33.71036904

600.27551 0.526866987 28.68 40.88392291

1028.931149 0.228073861 25.89 17.18856655

734.9561107 0.904281533 38.26 17.86199421

516.723325 0.360311712 36.55 39.91270389

799.6463577 0.826475751 30.04 20.41907798

468.5320107 0.799383584 23.1 14.68618567

524.28253 0.093550925 34.04 13.97940009

604.313475 0.205362669 20.08 27.68094734 Diabetes Page 104 of 603

618.81573 0.532093749 27.47 27.60422483

876.89575 0.820409025 94.75 97.52191314

773.32025 0.725916071 89.84 38.16970038

568.761715 0.21293142 25.32 100

964.3670007 1.332371085 51.78 100

1033.418941 0.241427214 21 16.34807418

1371.573848 1.254404946 47.36 46.03392095

921.7462737 0.048132177 23.9 28.13595755

710.86224 1.927195634 26.25 9.120448296

910.45428 1.273695456 45.75 57.22701588 Page 105 of 603 Diabetes

910.45471 1.746247733 55.91 20.09597766

597.6098607 0.534951952 28.58 8.368586662

526.9200407 0.558671399 20.5 33.43996719

673.3151807 0.377614498 27.99 13.09984838

647.9358477 0.08291306 25.51 18.35551185

647.9360937 0.297147935 23.85 14.23968294

427.5588337 0.103852542 20.79 100

866.0656707 0.696407137 50.66 24.33188829

866.0648777 0.219938518 25.46 3.521825181

623.9936485 0.825527069 27.68 13.00153518 Diabetes Page 106 of 603

1279.012815 1.806009717 63.45 63.34850278

684.9956637 0.397959554 24.68 17.65338202

706.3527807 1.127988 22.08 6.575773192

607.781005 0.429787134 23.4 100

999.949155 0.07103939 43.5 18.22821645

766.32342 0.477919228 45.84 13.4324443

766.32324 0.712961639 40.54 6.766936096

348.693785 0.103391782 20.1 100

640.9522677 1.276002748 28.01 19.7008109

884.3989207 0.006789424 26.2 10.92545208 Page 107 of 603 Diabetes

855.0097607 1.374162992 37.67 19.06660739

794.80383 0.372655077 83.67 19.08485019

794.85638 0.592935574 58.68 42.42791361

621.5176355 1.294376533 23.23 30.59621724

1045.9624 0.477302422 26.5

973.848445 0.689375434 58.15 100

738.778255 0.827605317 46.83 100

1040.51501 0.874028903 43.39 103.093026

1001.159238 0.119608331 25.99 6.777807053

616.9929177 1.259624166 33.99 100 Diabetes Page 108 of 603

793.3828707 0.568512944 33.91 39.24026127

635.2666 0.99407186 65.82 25.42179704

874.0402807 0.35189412 23.21 10.18885344

871.3687707 0.475480998 22.49 4.58637849

726.778685 0.249216877 62.96 100

1036.089231 0.831226522 31.15 53.55126562

1374.045775 0.137600438 72.5 100 Page 109 of 603 Diabetes

spectral score charge state delta cn drosophila CG timepoints timepoints timepoints accession number 0.839308022 2 0

0.163441795 3 0

0.82904404 3 0

0.170265301 2 0

0.886232417 2 0

0.036569372 2 0

0.885815982 2 0

0.408155294 3 0

0.873407817 4 0 Diabetes Page 110 of 603

0.131338908 2 0

0.671118855 3 0

0.279916258 2 0

0.529475962 2 0

0.96230606 2 0

0.893170789 2 0

0.692095648 3 0

0.489963992 2 0

0.892814274 2 0

0.789363175 2 0 Page 111 of 603 Diabetes

0.509021253 2 0

0.710332007 3 0

0.524301405 3 0

0.585660678 3 0

0.676538399 3 0

0.737585232 2 0

0.858185602 3 0

0.833952626 3 0

0.837612638 2 0

0.716008431 2 0 Diabetes Page 112 of 603

0.859201215 2 0

0.784245014 2 0

0.769222797 4 0

0.631844025 3 0

0.78148677 3 0

0.394064622 3 0

0.145689352 3 0

0.761039435 2 0

0.85760058 3 0

0.854169817 2 0 Page 113 of 603 Diabetes

0.731066548 2 0

0.707875755 2 0

0.93169221 2 0

0.173989194 3 0

0.924968819 3 0

0.868256374 2 0

0.766994268 3 0

0.921666608 2 0

0.867700402 3 0

0.941869077 3 0 Diabetes Page 114 of 603

0.887926545 2 0

0.593481211 3 0

0.713377661 2 0

0.59111672 4 0

0.696867785 3 0

0.957346403 2 0

0.963441941 3 0

0.862405608 3 0

0.77350172 2 0

0.687963568 2 0 Page 115 of 603 Diabetes

0.753416787 2 0

0.982451095 2 0

0.982023417 2 0

0.841218318 2 0

0.932193724 3 0

0.862111087 3 0

0.756407978 3 0

0.681503539 3 0

0.686659829 2 0

0.790521826 2 0 Diabetes Page 116 of 603

0.790141074 2 0

0.442444301 3 0

0.645254227 3 0

0.343257923 3 0

0.837781341 3 0

0.786978284 3 0

0.271835029 3 0

0.630009758 3 0

0.548409959 3 0

0.912716885 4 0 Page 117 of 603 Diabetes

0.899739225 2 0

0.431952483 3 0

0.922613475 3 0

0.588226645 2 0

0.82523021 2 0

0.65470437 2 0

0.815744978 2 0

0.16628827 2 0

0.752950205 3 0

0.774886498 3 0 Diabetes Page 118 of 603

0.667957335 3 0

0.945276372 2 0

0.944162175 2 0

0.751444042 4 0

0.369874908 2 0

0.399102685 2 0

0.933150201 2 0

0.64783811 2 0

0.54556238 3 0

0.624499688 3 0 Page 119 of 603 Diabetes

0.550880576 3 0

0.949929746 2 0

0.769680547 3 0

0.285209129 3 0

0.977002589 2 0

0.950363538 3 0

0.94757577 2 0 Diabetes Page 120 of 603

gi name species IPI accession swissprot gi species adjust adjust number accession 50403784 Vinculin Q64727 VINC_MOUSE (Metavinculin) [MASS=116717]

81865757 Serologically Q80UF4 SDCG8_MOUSE defined colon cancer antigen 8 homolog 94717658 Myosin(Centrosomal light chain colon B1B1A8 B1B1A8_MOUSE kinase, smooth muscle (MLCK) (Telokin) (Kinase- 74190979 unnamedrelated protein) protein Q3UGF0 Q3UGF0_MOUSE product [Mus musculus] 341942107 RecName: A2AQD5 A2AQD6_MOUSE Full=Sperm-specific antigen 2 homolog; AltName: Full=Ki- 83305641 U1ras-induced small nuclear actin- Q99LY5 Q99LY5_MOUSE ribonucleoprotein 70 kDa (U1 SNRNP 70 kDa) (snRNP70) 34098397 SAM and SH3 P59808 SASH1_MOUSE domains containing protein 1

187957400 Ppfia1 protein [Mus B2RXW8 B8QI33_MOUSE musculus] [MASS=140134]

2498444 Histone D3YYI8 HDAC1_MOUSE deacetylase 1 (HD1) Page 121 of 603 Diabetes

41688745 Treacle protein O08784 TCOF_MOUSE (Treacher Collins syndrome protein homolog) 46577497 Regulatory Q8K4Q0 A2ACM0_MOUSE associated protein of mTOR (Raptor) (P150 target of 81883938 Programmedrapamycin (TOR)- cell Q61823 PDCD4_MOUSE death protein 4 (Topoisomerase- inhibitor 81883938 Programmedsuppressed cell Q61823 PDCD4_MOUSE death protein 4 (Topoisomerase- inhibitor 547739 INSULINsuppressed P35569 Q543V3_MOUSE RECEPTOR SUBSTRATE-1

13124192 Elongation factor 1- Q91VK2 Q91VK2_MOUSE delta (EF-1-delta)

341942283 RecName: Q64213 SF01_MOUSE Full=Splicing factor 1; AltName: Full=CW17; 73921754 PlasmalemmaAltName: G3X924 PLVAP_MOUSE vesicle-associated protein (Plasmalemma 81883604 Splicingvesicle protein factor, 1) Q5U4C3 SFR19_MOUSE arginine/serine-rich 19

464506 Pyruvate Q05920 Q3T9S7_MOUSE carboxylase, mitochondrial precursor (Pyruvic carboxylase) (PCB) Diabetes Page 122 of 603

464506 Pyruvate Q05920 Q3T9S7_MOUSE carboxylase, mitochondrial precursor (Pyruvic 156633606 Rabcarboxylase) GTPase- (PCB) A2AWA9 A2AWA7_MOUSE activating protein 1 (Rab6 GTPase- activating protein 123779669 PhosphatidylinositolGAPCenA) (GAP Q2TBE6 P4K2A_MOUSE 4-kinase type 2- alpha (Phosphatidylinosit 77416393 CLIP-associatingol 4-kinase type II- B9EJA4 Q08EB6_MOUSE protein 2 (Cytoplasmic linker- associated protein 81906074 Uncharacterized2) Q9DB90 SMG9_MOUSE protein C19orf61 homolog

347595715 RecName: A2A8V8 SRRM1_MOUSE Full=Serine/arginin e repetitive matrix protein 1; AltName: 81884028 SerumFull=Plenty-of- deprivation- Q63918 SDPR_MOUSE response protein (Phosphatidylserine- binding protein) 61248556 THUMP domain Q99J36 THUM1_MOUSE containing protein 1

2498751 Astrocytic Q62048 PEA15_MOUSE phosphoprotein PEA-15

81862571 Acetyl-CoA Q5SWU9 ACACA_MOUSE carboxylase 1 (ACC-alpha) (Acetyl-CoA carboxylase 265) Page 123 of 603 Diabetes

38372553 Trans-Golgi Q62313 TGON1_MOUSE network integral membrane protein 1 precursor 38372553 Trans-Golgi(TGN38A) Q62313 TGON1_MOUSE network integral membrane protein 1 precursor 71153232 Cleavage(TGN38A) Q99LI7 CSTF3_MOUSE stimulation factor 77 kDa subunit (CSTF 77 kDa 123447 Hemesubunit) oxygenase (CstF-77) 1 P14901 HMOX1_MOUSE (HO-1) (P32 protein)

14916570 Ras-GTPase- P97379 G3BP2_MOUSE activating protein binding protein 2 (GAP SH3-domain 81902126 Paxillinbinding protein 2) Q8VI36 PAXI_MOUSE

81902126 Paxillin Q8VI36 PAXI_MOUSE

38372554 Trans-Golgi Q62314 TGON2_MOUSE network integral membrane protein 2 precursor 81881579 Pre-mRNA(TGN38B) 3'-end- Q9D824 D3Z619_MOUSE processing factor FIP1 (FIP1-like 1)

14194972 Nuclear factor 1 A- B1AUB9 NFIA_MOUSE type (Nuclear factor 1/A) (NF1-A) (NFI- A) (NF-I/A) (CCAAT- box binding Diabetes Page 124 of 603

341942061 RecName: O89032 SPD2A_MOUSE Full=SH3 and PX domain-containing protein 2A; 81896337 Patatin-likeAltName: Full=Five Q8BJ56 PLPL2_MOUSE phospholipase domain-containing protein 2 (Adipose 6685240 [3-methyl-2-triglyceride lipase) O55028 D3Z7R0_MOUSE oxobutanoate dehydrogenase [lipoamide]] kinase, 81896427 Proteinmitochondrial FAM73B Q8BK03 FA73B_MOUSE

341940275 RecName: Q9JLV1 BAG3_MOUSE Full=BAG family molecular chaperone 81896337 Patatin-likeregulator 3; Q8BJ56 PLPL2_MOUSE phospholipase domain-containing protein 2 (Adipose 205829307 RecName:triglyceride lipase) E9QPD4 E9QPD4_MOUSE Full=Oxysterol- binding protein 1 [MASS=84689] 14193672 ATP citrate lyase Q3TS02 Q3V117_MOUSE [Mus musculus]

81862464 Cisplatin resistance- Q5SUF2 LC7L3_MOUSE associated overexpressed protein 81862464 Cisplatin resistance- Q5SUF2 LC7L3_MOUSE associated overexpressed protein Page 125 of 603 Diabetes

46396418 Oxysterol binding Q8CI95 OSR11_MOUSE protein-related protein 11 (OSBP- related protein 11) 50401639 Translocation(ORP-11) Q91V04 TRAM1_MOUSE associated membrane protein 1 19909186 translocated Q7M739 Q7M739_MOUSE promoter region protein [Mus musculus] 56749456 Polymerase I and O54724 PTRF_MOUSE transcript release factor [MASS=43953] 543921 Calnexin precursor P35564 CALX_MOUSE

81881209 Proline-rich AKT1 Q9D1F4 AKTS1_MOUSE substrate 1 (Proline- rich AKT substrate)

57015348 High mobility group P17095 HMGIY_MOUSE protein HMG- I/HMG-Y (HMG- I(Y)) (High mobility 110816418 SRAgroup stem-loop- AT-hook 1) Q9D8T7 SLIRP_MOUSE interacting RNA- binding protein, mitochondrial 341941975 RecName:precursor Q6QI06 RICTR_MOUSE Full=Rapamycin- insensitive companion of 47605501 Bcl-2-associatedmTOR; AltName: Q8K019 Q3UR37_MOUSE transcription factor 1 (Btf) [MASS=106001] Diabetes Page 126 of 603

125987710 Ankyrin repeat Q8C0J6 ANR57_MOUSE domain-containing protein 57 [MASS=54938] 148704095 mCG2476 [Mus IPI00761751.2 Q6A029_MOUSE musculus] [MASS=212836]

6093508 BCL2/adenovirus O55003 BNIP3_MOUSE E1B 19-kDa protein- interacting protein 3

73621447 RNA-binding Q8C2Q3 RBM14_MOUSE protein 14 (RNA- binding motif protein 14) 81875212 Translocation Q8BU14 SEC62_MOUSE protein SEC62 (Translocation protein 1) (TP-1) 56749456 Polymerase I and O54724 PTRF_MOUSE transcript release factor [MASS=43953] 56749456 Polymerase I and O54724 PTRF_MOUSE transcript release factor [MASS=43953] 1709091 Cation-independent Q07113 MPRI_MOUSE mannose-6- phosphate receptor precursor (CI Man- 81896427 Protein6-P receptor) FAM73B (CI- Q8BK03 FA73B_MOUSE

148704095 mCG2476 [Mus IPI00761751.2 Q6A029_MOUSE musculus] [MASS=212836] Page 127 of 603 Diabetes

148704095 mCG2476 [Mus IPI00761751.2 Q6A029_MOUSE musculus] [MASS=212836]

218512063 RecName: Q9Z1E4 GYS3_MOUSE Full=Glycogen [starch] synthase, muscle 123231522 ATP citrate lyase Q3TS02 Q3V117_MOUSE [Mus musculus] [MASS=53705]

341941109 RecName: Q60902 Q3UIS9_MOUSE Full=Epidermal growth factor receptor substrate 91208163 RNA15-like polymerase- 1; AltName: Q62018 CTR9_MOUSE associated protein CTR9 homolog (SH2 domain- 91208163 RNAbinding polymerase- protein 1) Q62018 CTR9_MOUSE associated protein CTR9 homolog (SH2 domain- 37675525 AHNAKbinding protein[Mus 1) IPI00553798.2 musculus] [MASS=224129]

14194972 Nuclear factor 1 A- B1AUB9 NFIA_MOUSE type (Nuclear factor 1/A) (NF1-A) (NFI- A) (NF-I/A) (CCAAT- 14194972 Nuclearbox binding factor 1 A- B1AUB9 NFIA_MOUSE type (Nuclear factor 1/A) (NF1-A) (NFI- A) (NF-I/A) (CCAAT- 54041237 cAMP-dependentbox binding P31324 KAP3_MOUSE protein kinase type II-beta regulatory subunit Diabetes Page 128 of 603

81913131 EH domain- Q8R2X0 EHD2_MOUSE containing protein 2

51316833 Sec1 family domain Q8BRF7 SCFD1_MOUSE containing protein 1 (Syntaxin binding protein 1-like 2) 13878552 Probable kinesin Q9DBS5 KLC8_MOUSE light chain 3 (KLC 3)

34921544 Eukaryotic Q60876 4EBP1_MOUSE translation initiation factor 4E binding protein 1 (4E-BP1) 46577497 Regulatory(eIF4E-binding Q8K4Q0 A2ACM0_MOUSE associated protein of mTOR (Raptor) (P150 target of 126752 Myristoylatedrapamycin (TOR)- P26645 MARCS_MOUSE alanine-rich C- kinase substrate (MARCKS) 126752 Myristoylated P26645 MARCS_MOUSE alanine-rich C- kinase substrate (MARCKS)

81880234 SH3 domain- Q99LH9 Q80TA2_MOUSE binding protein 5- like

122065842 Membrane- Q80UU9 PGRC2_MOUSE associated progesterone receptor component 2 Page 129 of 603 Diabetes

543921 Calnexin precursor P35564 CALX_MOUSE

114152851 Protein Njmu-R1 Q9CYI0 NJMU_MOUSE

2493259 Protein tyrosine Q62130 PTN14_MOUSE phosphatase, non- receptor type 14 (Protein-tyrosine 543921 Calnexinphosphatase precursor P35564 CALX_MOUSE

38372554 Trans-Golgi Q62313 TGON2_MOUSE network integral membrane protein 2 precursor 119362 Endoplasmin(TGN38B) P08113 Q3TUD6_MOUSE precursor (Endoplasmic reticulum protein 50400986 Nuclear99) (94 kDaubiquitous Q80XU3 NUCKS_MOUSE casein and cyclin- dependent kinases substrate (JC7) 85690846 Hormone-sensitive P54310 Q8CDI9_MOUSE lipase (HSL)

145566774 Enhancer of mRNA- Q3UJB9 EDC4_MOUSE decapping protein 4 [MASS=152483]

146345481 Phosphoglycerate P09411 PGK1_MOUSE kinase 1 Diabetes Page 130 of 603

160017861 Ankyrin repeat Q99NH0 ANR17_MOUSE domain-containing protein 17 (Gene trap ankyrin repeat 30580337 Ankyrinprotein) repeat(Ankyrin and Q3UHP6 Q3UHP6_MOUSE SAM domain containing protein 1 [MASS=125241] 81895299 Ubiquitin- Q80X50 UBP2L_MOUSE associated protein 2-like

81895299 Ubiquitin- Q80X50 UBP2L_MOUSE associated protein 2-like

81884028 Serum deprivation- Q63918 SDPR_MOUSE response protein (Phosphatidylserine- binding protein) 56749456 Polymerase I and O54724 PTRF_MOUSE transcript release factor [MASS=43953] 56417892 ATP-binding Q6P542 Q5RL55_MOUSE cassette, sub- family F, member 1 [MASS=94945] Page 131 of 603 Diabetes

mass error minimum across reversed databse hprd accession string accession timepoints direction 372509 0.303590126 F

374312 0.333775769 F

372961 0.956348295 F

1.500754468 F

374553 0.11218745 F

0.456252543 F

06408_1 371036 1.510671379 F

380301 0.423990705 F

388438 0.246940268 F Diabetes Page 132 of 603

388032 1.484035873 F

373935 0.554185727 F

373669 0.133914776 F

373669 0.492961462 F

384184 0.213922378 F

00560_2 386762 0.278789799 F

03306_4 387518 1.048813336 F

369928 0.5025916 F

390221 0.213288184 F

384196 0.361145697 F Page 133 of 603 Diabetes

384196 1.388650713 F

377490 0.224125129 F

373759 0.732135325 F

12054_1 389923 0.104491532 F

369913 0.189332863 F

10441_1 375402 0.434453532 F

382219 0.221008551 F

376371 0.746445156 F

04579_1 370921 0.41474376 F

01938_7 371924 0.3801927 F Diabetes Page 134 of 603

385289 0.585806908 F

385289 0.744670811 F

02651_1 374602 0.25647673 F

370331 0.391693364 F

375703 0.500026322 F

390839 0.944661842 F

390839 1.99181125 F

0.537747047 F

09646_1 388692 0.678721755 F

09007_1 387260 0.190525598 F Page 135 of 603 Diabetes

10228_1 389158 0.277075951 F

373907 0.830847231 F

385760 0.335663125 F

388009 1.0610593 F

376328 0.150684428 F

373907 0.816313151 F

391674 0.935415115 F

00155_2 370550 0.661566461 F

16759_2 0.612278182 F

16759_2 1.365080253 F Diabetes Page 136 of 603

378244 0.339121636 F

374054 0.499776162 F

370415 0.526866987 F

382871 0.128869072 F

371849 0.904281533 F

12441_3 380756 0.011622954 F

02829_7 383821 0.826475751 F

387847 0.799383584 F

10682_1 381260 0.093550925 F

379214 0.205362669 F Page 137 of 603 Diabetes

394572 0.532093749 F

377998 0.32976123 F

376404 0.218680392 F

11485_1 370479 0.21293142 F

374856 0.447236316 F

382871 0.241427214 F

382871 0.009239668 F

373169 0.048132177 F

12965_1 388009 1.927195634 F

377998 0.19891218 F Diabetes Page 138 of 603

377998 1.746247733 F

00721_1 370159 0.534951952 F

00155_1 0.558671399 F

09445_1 370451 0.377614498 F

370357 0.08291306 F

370357 0.297147935 F

391797 0.103852542 F

387260 0.696407137 F

387260 0.219938518 F

01486_1 370027 0.825527069 F Page 139 of 603 Diabetes

0.102463285 F

372116 0.397959554 F

370111 1.127988 F

376603 0.171256073 F

373935 0.07103939 F

394614 0.158000569 F

394614 0.712961639 F

0.103391782 F

386565 1.276002748 F

382466 0.006789424 F Diabetes Page 140 of 603

371849 1.374162992 F

11392_1 386755 0.139745621 F

04402_1 374357 0.284508277 F

371849 1.294376533 F

385289 0.477302422 F

01860_1 371684 0.689375434 F

383895 0.827605317 F

370042 0.874028903 F

06911_1 378130 0.119608331 F

02412_1 390412 1.259624166 F Page 141 of 603 Diabetes

391130 0.125308239 F

10610_1 373326 0.033083184 F

384755 0.35189412 F

384755 0.475480998 F

382219 0.166603534 F

382871 0.347041493 F

377554 0.131776116 F Diabetes Page 142 of 603

xcorr max across Go location Go bio process Go mol process timepoints unique index unqiue index unique index 50.23 membrane cell adhesion protein binding

20.91 centrosome Ras protein signal protein binding transduction

24.45 cytoplasm protein amino acid ATP binding intracellular phosphorylation

25.91

63.8 cytoplasm oxidation reduction oxidoreductase activity

23.48 nucleus nuclear mRNA protein binding splicing, via spliceosome regulation of RNA 33.37 centrosome cellsplicing cycle protein binding

23.71 Golgi cisterna transmembrane protein binding membrane transport nucleus regulation of transcription, DNA- 23.06 nucleus regulationdependent of protein binding transcription Page 143 of 603 Diabetes

30.35 nucleus transport cobalt ion binding transcription of zinc ion binding nuclear rRNA large RNA polymerase I 22.02 TORC1 complex regulationtranscript of cell protein binding size

22.82 nucleus apoptosis protein binding cell aging

31.96 nucleus apoptosis protein binding cell aging

46.08 nucleus signal transduction protein binding response to peptide hormone stimulus

37.64 eukaryotic translation protein binding translation translation elongation factor 1 elongation factor complex activity 21.21 nucleus regulation of protein binding clathrin coat transcription zinc ion binding mitochondrion male sex determination 28.67 nucleus mRNA processing nucleotide binding integral to transport protein membrane actin filament homodimerization organization activity 30.04 nucleus mRNA processing RNA binding

29.42 cytoplasm metabolic process ATP binding Diabetes Page 144 of 603

24.18 cytoplasm metabolic process ATP binding

24.93 cytoplasm cell cycle GTPase activator activity

36.93 membrane phosphatidylinositol ATP binding biosynthetic process

34.6 cytoplasm cell cycle protein binding intracellular translational binding Golgi apparatus termination modification- 25.31 intracellular nuclear-transcribeddependent protein protein binding mRNA catabolic process, nonsense- mediated decay 26.44 nucleus mRNA processing DNA binding spliceosomal protein binding complex lysophospholipase activity 51.18 membrane cell adhesion proteinzinc ion binding binding

44.16

25.32 cytoplasm transport protein binding mitochondrion regulation of apoptosis

25.5 cytoplasm metabolic process protein binding Page 145 of 603 Diabetes

58.39 integral to peptide cross- protein binding membrane linking

52.84 integral to peptide cross- protein binding membrane linking

21.4 nucleus mRNA processing protein binding

26.7 nucleus oxidation reduction metal ion binding

29.66 intracellular transport protein binding

44.9 cytoplasm cell adhesion protein binding

27.09 cytoplasm cell adhesion protein binding

49.11 integral to peptide cross- protein binding membrane linking

28.73 nucleus mRNA processing RNA binding

52.51 nucleus regulation of protein binding transcription, DNA- DNA binding dependent Diabetes Page 146 of 603

23.81 cytoplasm cell communication protein binding integral to membrane dynein complex 27.29 integral to metabolic process hydrolase activity membrane

62.12 mitochondrion signal transduction protein binding

20.67 integral to oxidation reduction protein binding membrane

29.7 cytosol apoptosis protein binding

52.69 integral to metabolic process hydrolase activity membrane

28.86 membrane transport protein binding

36.34 cytoplasm metabolic process ATP binding intracellular acetyl-CoA protein binding integral to biosynthetic binding membrane process 29.68 nucleusintrinsic to apoptosis protein binding

25.74 nucleus apoptosis protein binding Page 147 of 603 Diabetes

61.67 endoplasmic transport protein binding reticulum lumen GTP binding nucleus

28.1 integral to transport protein binding membrane

28.68 cytoplasm translation protein binding nuclear pore mitotic cell cycle spindle assembly checkpoint 25.89 nucleus regulation of protein binding transcription

38.26 integral to protein folding protein binding membrane

36.55 cytoplasm negative regulation protein binding of protein kinase activity

30.04 nucleus regulation of protein binding transcription, DNA- DNA binding dependent

23.1 nucleus regulation of nucleotide binding transcription

34.04 intracellular multicellular binding organismal protein binding development

20.08 nucleus regulation of protein binding membrane transcription integral to negative regulation membrane of transcription Diabetes Page 148 of 603

27.47

94.75 cytoplasm steroid metabolic protein binding process

89.84 integral to apoptosis protein membrane response to homodimerization hypoxia activity

25.32 nucleus regulation of nucleotide binding intracellular transcription transcription factor oxidation reduction complex positive regulation 51.78 integral to transportof transcription protein transporter membrane activity

21 nucleus regulation of protein binding transcription

47.36 nucleus regulation of protein binding transcription

23.9 integral to transport protein binding membrane

26.25 integral to multicellular protein binding membrane organismal development oxidation reduction 45.75 cytoplasm steroid metabolic protein binding process Page 149 of 603 Diabetes

55.91 cytoplasm steroid metabolic protein binding process

28.58 cytoplasm heart development protein binding ribonucleoprotein glycogen glycogen (starch) complex biosynthetic synthase activity process 20.5 cytoplasm metabolic process ATP binding intracellular acetyl-CoA protein binding biosynthetic process 27.99 nucleus endocytosis protein binding integral to proteasomal calcium ion binding membrane ubiquitin-dependent receptor activity myofibril protein catabolic 25.51 nucleustranscription factor histoneprocess H2B protein binding ubiquitination

23.85 nucleus histone H2B protein binding ubiquitination

20.79 nucleus nervous system protein binding development

50.66 nucleus regulation of protein binding transcription, DNA- dependent

25.46 nucleus regulation of protein binding transcription, DNA- dependent

27.68 cytoplasm signal transduction nucleotide binding cytosol protein amino acid cAMP-dependent phosphorylation protein kinase complex Diabetes Page 150 of 603

63.45 membrane endocytosis protein binding

24.68 membrane transport protein binding

22.08 microtubule intraflagellar protein binding transport

23.4 nucleus regulation of protein binding translation

43.5 TORC1 complex regulation of cell protein binding size

45.84 membrane protein amino acid actin binding phosphorylation

40.54 membrane protein amino acid actin binding phosphorylation

20.1

28.01

26.2 integral to axon guidance protein binding membrane metabolic process Page 151 of 603 Diabetes

37.67 integral to protein folding protein binding membrane

83.67 cellular_component spermatogenesis molecular_function

58.68 cytoplasm protein amino acid binding dephosphorylation

23.23 integral to protein folding protein binding membrane

26.5 integral to peptide cross- protein binding membrane linking

58.15 endoplasmic protein folding ATP binding reticulum protein transport protein binding peroxisome

46.83 nucleus in utero embryonic metal ion binding development double-stranded regulation of cell DNA binding cycle 43.39 nucleus metabolic process protein binding cytosol

25.99 nucleus immune response protein binding biological_process transport

33.99 cytoplasm glycolysis ATP binding integral to carbohydrate transferase activity membrane metabolic process Diabetes Page 152 of 603

33.91 nucleus mismatch repair ATP binding

65.82 cytoplasm cell cycle protein binding synapse biological_process embryo implantation 23.21 cellular_component modification- protein binding nucleus dependent protein endosome catabolic process blood coagulation 22.49 cellular_component modification- protein binding nucleus dependent protein endosome catabolic process blood coagulation 62.96 membrane cell adhesion protein binding

31.15 nucleus regulation of protein binding transcription

72.5 transport ATP binding metabolic process Page 153 of 603 Diabetes

Kegg unique index Regulation of actin cytoskeleton Focal adhesion Leukocyte transendothelial

Calcium signaling pathway Regulation of actin cytoskeleton Vascular smooth

Spliceosome

Pathways in cancer Huntington's disease Chronic myeloid leukemia Diabetes Page 154 of 603

Insulin signaling pathway mTOR signaling pathway

Aldosterone- regulated sodium reabsorption Insulin signaling pathway

Spliceosome

Pyruvate metabolism Citrate cycle (TCA cycle) Page 155 of 603 Diabetes

Pyruvate metabolism Citrate cycle (TCA cycle)

Pyruvate metabolism Propanoate metabolism Fatty acid Diabetes Page 156 of 603

Porphyrin and chlorophyll metabolism

Regulation of actin cytoskeleton Focal adhesion Chemokine Regulationsignaling pathway of actin cytoskeleton Focal adhesion Chemokine signaling pathway Page 157 of 603 Diabetes

Citrate cycle (TCA cycle) Reductive carboxylate cycle (CO2 fixation) Diabetes Page 158 of 603

Pathways in cancer MAPK signaling pathway - yeast Thyroid cancer

Antigen processing and presentation

mTOR signaling pathway Page 159 of 603 Diabetes

Protein export

Lysosome Diabetes Page 160 of 603

Starch and sucrose metabolism Insulin signaling pathway Citrate cycle (TCA cycle) Reductive carboxylate cycle (CO2 fixation)

Insulin signaling pathway Apoptosis Page 161 of 603 Diabetes

Endocytosis

Insulin signaling pathway ErbB signaling pathway InsulinmTOR signaling pathway mTOR signaling pathway Fc gamma R- mediated phagocytosis

Fc gamma R- mediated phagocytosis

Glycolysis / Gluconeogenesis Glycerolipid metabolism Glycerophospholipi Diabetes Page 162 of 603

Antigen processing and presentation

Antigen processing and presentation

Pathways in cancer Plant-pathogen interaction Prostate cancer NOD-like receptor

Insulin signaling pathway

RNA degradation

Glycolysis / Gluconeogenesis Carbon fixation in photosynthetic organisms Page 163 of 603 Diabetes Diabetes Page 164 of 603

timecourse manual naming::protein name counter manual all protein name index 1960025 Likely ortholog of H. sapiens chromosome 9 Manual Assigned open reading frame 138 (C9orf138) Name:Likely ortholog of H. sapiens chromosome 9 open reading frame 138 (C9orf138) 1959390 Card6 caspase recruitment domain family, ManualSwissPROT>B1AXP3_MOUS Assigned member 6 Name:Card6 caspase recruitment domain family, member 6 1960315 AP2-associated protein kinase 1 ManualSwissPROT>Q8BWE0_MOU Assigned Name:AP2- associated protein kinase 1 HPRD>10620_1>T620S623> AP2 associated kinase 1 1960292 Serine/threonine-protein kinase SIK2 ManualSwissPROT>AAK1_MOUSE> Assigned Name:Serine/threonine- protein kinase SIK2 HPRD>12348_1>S358>Salt 1959732 Interferon-induced helicase C domain- Manualinducible Assigned kinase 2 containing protein 1 Name:Interferon-induced helicase C domain-containing protein 1 1960434 Z-DNA-binding protein 1 ManualSwissPROT>IFIH1_MOUSE> Assigned Name:Z- DNA-binding protein 1 SwissPROT>A2APF7_MOUS E>Z-DNA binding protein 1 1960406 Phosphatidylinositol 4-kinase beta ManualOS=Mus Assigned musculus GN=Zbp1 Name:Phosphatidylinositol 4- kinase beta HPRD>11805_1>S523>Phos 1960193 RNA binding motif protein 15 Manualphatidylinositol Assigned 4 kinaseName:RNA binding motif protein 15 SwissPROT>Q0VBL3_MOUS E>S655>RNA binding motif 1959318 182 kDa tankyrase-1-binding protein Manualprotein 15Assigned OS=Mus Name:182 musculus kDa tankyrase-1-binding protein SwissPROT>TB182_MOUSE >S429>182 kDa tankyrase-1- Page 165 of 603 Diabetes

1959993 Transmembrane and coiled-coil domains Manual Assigned protein 2 Name:Transmembrane and coiled-coil domains protein 2 HPRD>11040_1>S438>Cere 1960336 Testis expressed gene 2 Manualbral protein Assigned 11 Name:Testis expressed gene 2 HPRD>13716_1>S196>HT00 1959476 Protein PML Manual8 protein Assigned Name:Protein PML SwissPROT>D3YXR5_MOUS E>S515>Uncharacterized 1959737 Protein PML Manualprotein OS=MusAssigned musculus Name:Protein PML SwissPROT>D3YXR5_MOUS E>T527>Uncharacterized 1960353 Protein PML Manualprotein OS=MusAssigned musculus Name:Protein PML SwissPROT>D3YXR5_MOUS E>S528>Uncharacterized 1960213 Interferon-induced, double-stranded RNA- Manualprotein OS=MusAssigned musculus activated protein kinase Name:Interferon-induced, double-stranded RNA- activated protein kinase 1960068 Protein PML ManualSwissPROT>E2AK2_MOUSE Assigned Name:Protein PML SwissPROT>D3YXR5_MOUS E>S514S515>Uncharacterize 1960312 Akap13 A kinase (PRKA) anchor protein 13 Manuald protein Assigned OS=Mus musculus Name:Akap13 A kinase (PRKA) anchor protein 13 HPRD>05253_1>S1933>A 1959855 Receptor-interacting serine/threonine-protein Manualkinase anchoring Assigned protein 13 kinase 2 Name:Receptor-interacting serine/threonine-protein kinase 2 1959998 Mitogen-activated protein kinase kinase ManualSwissPROT>RIPK2_MOUSE Assigned kinase kinase 5 Name:Mitogen-activated protein kinase kinase kinase kinase 5 SwissPROT>M4K5_MOUSE> Diabetes Page 166 of 603

1960018 Transcription intermediary factor 1-beta Manual Assigned Name:Transcription intermediary factor 1-beta SwissPROT>TIF1B_MOUSE 1959872 Microtubule-associated protein Manual>S473>Isoform Assigned 2 of Name:Microtubule-associated protein HPRD>01141_1>S941>Micro 1960235 Hepatoma-derived growth factor Manualtubule associated Assigned protein 4 Name:Hepatoma-derived growth factor IPI>P51859>Hepatoma- 1958938 CLIP-associating protein 1 Manualderived Assignedgrowth factor Name:CLIP- associating protein 1 HPRD>09322_1>S600>CLIP associated protein 1 1960156 Rho guanine nucleotide exchange factor 17 ManualSwissPROT>CLAP1_MOUSE Assigned Name:Rho guanine nucleotide exchange factor 17 HPRD>10658_1>S463>Rho 1958660 MCG5400 Manualguanine Assigned nucleotide exchange Name:MCG5400 HPRD>10095_1>T19S20>My osin regulatory light chain 1959396 Perilipin-1 ManualMRLC2 Assigned Name:Perilipin-1 HPRD>01364_1>S81>Perilipi n 1959339 Eukaryotic translation initiation factor 4 ManualSwissPROT>PLIN_MOUSE> Assigned gamma 3 Name:Eukaryotic translation initiation factor 4 gamma 3 SwissPROT>A2AMI2_MOUS 1959692 Dclk1 protein ManualE>S267>"Eukaryotic Assigned Name:Dclk1 protein HPRD>09202_1>S332T336> Doublecortin and CaM kinase 1959954 Dclk1 protein Manuallike 1 Assigned Name:Dclk1 protein HPRD>09202_1>S330T336> Doublecortin and CaM kinase like 1 Page 167 of 603 Diabetes

1960247 Tjp1 protein Manual Assigned Name:Tjp1 protein HPRD>03002_1>S617>Tight junction protein 1 1959407 Septin-2 ManualHPRD>03002_2>S617>Tight Assigned Name:Septin-2 HPRD>03297_1>S218>Septi n 2 1959537 Actin, cytoplasmic 1 ManualHPRD>03297_2>S218>Septi Assigned Name:Actin, cytoplasmic 1 HPRD>00015_1>S241>Actin alpha, cardiac muscle 1960324 Protein PML ManualHPRD>00016_1>S240>Actin Assigned Name:Protein PML SwissPROT>D3YXR5_MOUS E>T535>Uncharacterized 1959097 Eukaryotic translation initiation factor 4 Manualprotein OS=MusAssigned musculus gamma 1 Name:Eukaryotic translation initiation factor 4 gamma 1 HPRD>06774_1>S1187>eIF 1959090 RNA-binding protein 8A Manual4G1 Assigned Name:RNA- binding protein 8A HPRD>05609_1>S56>RNA binding motif protein 8A 1958781 Cytosolic phospholipase A2 ManualSwissPROT>RBM8A_MOUS Assigned Name:Cytosolic phospholipase A2 SwissPROT>PA24A_MOUSE 1959485 SAM domain and HD domain-containing Manual>S437>Cytosolic Assigned Name:SAM protein 1 domain and HD domain- containing protein 1 SwissPROT>E0CXZ5_MOUS 1959843 SAM domain and HD domain-containing ManualE>T21T29>Uncharacterized Assigned Name:SAM protein 1 domain and HD domain- containing protein 1 SwissPROT>E0CXZ5_MOUS 1958626 MCG10050 ManualE>T21S24>Uncharacterized Assigned Name:MCG10050 HPRD>01611_1>S104>Ribos omal protein, large, P1 HPRD>01611_2>S79>Riboso Diabetes Page 168 of 603

1960000 Catenin beta-1 Manual Assigned Name:Catenin beta-1 HPRD>00286_1>T556>Cate nin beta 1960005 Interferon-activable protein 204 ManualHPRD>00286_2>T556>Cate Assigned Name:Interferon-activable protein 204 SwissPROT>IFI4_MOUSE>Is 1958844 Integrator complex subunit 1 Manualoform 2 Assignedof Interferon-activable Name:Integrator complex subunit 1 SwissPROT>INT1_MOUSE> 1959621 Integrator complex subunit 1 ManualT1321S1328>Integrator Assigned Name:Integrator complex subunit 1 SwissPROT>INT1_MOUSE> 1959623 Integrator complex subunit 1 ManualS1320S1328>Integrator Assigned Name:Integrator complex subunit 1 SwissPROT>INT1_MOUSE> 1958776 Serine/arginine repetitive matrix 1 ManualT1321S1329>Integrator Assigned Name:Serine/arginine repetitive matrix 1 HPRD>10441_1>S605S607> 1960051 H-2 class I histocompatibility antigen, L-D ManualSerine arginine Assigned repetitive Name:H-2 alpha chain class I histocompatibility antigen, L-D alpha chain SwissPROT>HA11_MOUSE> 1959777 Protein PAT1 homolog 1 Manual"H-2 class Assigned I histocompatibility Name:Protein PAT1 homolog 1 HPRD>08214_1>S36>FLJ36 1959415 MARCKS-related protein Manual874 protein Assigned Name:MARCKS-related protein HPRD>04247_1>S104>MAR 1959845 SAM domain and HD domain-containing ManualCKS like Assigned protein Name:SAM protein 1 domain and HD domain- containing protein 1 SwissPROT>E0CXZ5_MOUS E>S24T25>Uncharacterized Page 169 of 603 Diabetes

1959246 Nucleolar protein 58 Manual Assigned Name:Nucleolar protein 58 SwissPROT>NOP58_MOUS E>S509S521>Nucleolar 1959129 AP-3 complex subunit delta-1 Manualprotein 58Assigned OS=Mus Name:AP-3 musculus complex subunit delta-1 SwissPROT>AP3D1_MOUSE >T758S760>AP-3 complex 1959727 AP-3 complex subunit delta-1 Manualsubunit delta-1Assigned OS=Mus Name:AP-3 complex subunit delta-1 SwissPROT>AP3D1_MOUSE >S755S760>AP-3 complex 1960334 Nuclear factor 1 B-type Manualsubunit delta-1Assigned OS=Mus Name:Nuclear factor 1 B-type SwissPROT>NFIB_MOUSE> S328>Isoform 3 of Nuclear 1958916 Drebrin-like protein Manualfactor 1 AssignedB-type OS=Mus Name:Drebrin-like protein SwissPROT>DBNL_MOUSE> S273>Isoform 3 of Drebrin- 1959230 Tight junction-associated protein 1 Manuallike protein Assigned OS=Mus Name:Tight junction-associated protein 1 SwissPROT>TJAP1_MOUSE >S527>Tight junction- 1960224 Microtubule-associated protein Manualassociated Assigned protein 1 OS=Mus Name:Microtubule-associated protein IPI>E9PWC0>S609>Microtub 1959109 Cap-specific mRNA (nucleoside-2'-O-)- Manualule-associated Assigned protein Name:Cap- methyltransferase 1 specific mRNA (nucleoside-2'- O-)-methyltransferase 1 SwissPROT>D3Z491_MOUS 1958984 Cobl-like 1 ManualE>S28>Uncharacterized Assigned Name:Cobl- like 1 SwissPROT>B1AZ14_MOUS E>S864>Cobl-like 1 OS=Mus 1958932 Na(+)/H(+) exchange regulatory cofactor NHE-Manualmusculus Assigned GN=Cobll1 RF1 Name:Na(+)/H(+) exchange regulatory cofactor NHE-RF1 SwissPROT>NHERF_MOUS E>T287>Ezrin-radixin-moesin Diabetes Page 170 of 603

1958934 Na(+)/H(+) exchange regulatory cofactor NHE-Manual Assigned RF1 Name:Na(+)/H(+) exchange regulatory cofactor NHE-RF1 SwissPROT>NHERF_MOUS 1960142 Autophagy-related protein 16-1 ManualE>S282>Ezrin-radixin-moesin Assigned Name:Autophagy-related protein 16-1 HPRD>16498_2>S269>APG 1960209 Cobl-like 1 Manual16L Assigned Name:Cobl- like 1 SwissPROT>B1AZ14_MOUS E>S281>Cobl-like 1 OS=Mus 1958685 Protein PRRC2C Manualmusculus Assigned GN=Cobll1 Name:Protein PRRC2C SwissPROT>BA2L2_MOUSE >S902>Isoform 5 of Protein 1959567 Protein PRRC2C ManualBAT2-like Assigned 2 OS=Mus Name:Protein PRRC2C SwissPROT>BA2L2_MOUSE >S897>Isoform 5 of Protein 1958850 DNA-binding protein A ManualBAT2-like Assigned 2 OS=Mus Name:DNA- binding protein A SwissPROT>DBPA_MOUSE >S259>Isoform 2 of DNA- 1960470 ADP-ribosylation factor GTPase-activating Manualbinding proteinAssigned A OS=MusName:ADP- protein 2 ribosylation factor GTPase- activating protein 2 HPRD>06069_1>Zinc finger 1959418 Tumor necrosis factor receptor superfamily Manualprotein 289,Assigned ID1 regulated member 6 Name:Tumor necrosis factor receptor superfamily member 6 1959306 Isoform 2 of ATP-dependent RNA helicase A ManualSwissPROT>D3Z6E5_MOUS Assigned Name:Isoform 2 of ATP- dependent RNA helicase A IPI>O70133-2>Isoform 2 of 1959115 Serine/threonine-protein kinase TAO3 ManualATP-dependent Assigned RNA helicase Name:Serine/threonine- protein kinase TAO3 SwissPROT>TAOK3_MOUS E>S324>Serine/threonine- Page 171 of 603 Diabetes

1960337 Bcl-2-associated transcription factor 1 Manual Assigned Name:Bcl-2- associated transcription factor 1 HPRD>16544_1>S285S290> 1960396 Thrap3 protein ManualBCL2 associated Assigned transcription Name:Thrap3 protein HPRD>07543_1>S928>TRA P150 1959218 A230067G21Rik protein ManualSwissPROT>Q80VM0_MOU Assigned Name:A230067G21Rik protein HPRD>11135_2>S375S376> 1959991 A230067G21Rik protein ManualChromosome Assigned 20 open Name:A230067G21Rik protein HPRD>11135_2>S373S375> 1959545 Dclk1 protein ManualChromosome Assigned 20 open Name:Dclk1 protein SwissPROT>A8IP62_MOUS E>S45>Activity and 1959130 Ahnak AHNAK nucleoprotein isoform 1 Manualneurotransmitter-induced Assigned Name:Ahnak AHNAK nucleoprotein isoform 1 SwissPROT>Q8BRB8_MOU 1960066 Hematological and neurological expressed 1 ManualSE>Putative Assigned uncharacterized protein Name:Hematological and neurological expressed 1 protein 1958671 Pinin ManualSwissPROT>HN1_MOUSE>S Assigned Name:Pinin SwissPROT>PININ_MOUSE> S380>Pinin OS=Mus musculus GN=Pnn 1959215 Synaptosomal-associated protein ManualSwissPROT>Q3TUQ5_MOU Assigned Name:Synaptosomal- associated protein SwissPROT>B0R030_MOUS 1959277 Acetyl-coenzyme A synthetase, cytoplasmic ManualE>S110>Synaptosomal- Assigned Name:Acetyl-coenzyme A synthetase, cytoplasmic SwissPROT>A2AQN4_MOU SE>S263S267>Acyl-CoA Diabetes Page 172 of 603

1959005 Pericentriolar material 1 protein Manual Assigned Name:Pericentriolar material 1 protein SwissPROT>PCM1_MOUSE 1960225 Ankyrin repeat and IBR domain-containing Manual>S1805S1808>Isoform Assigned 2 of protein 1 Name:Ankyrin repeat and IBR domain-containing protein 1 SwissPROT>AKIB1_MOUSE 1958927 La-related protein 1 Manual>S740>Ankyrin Assigned repeat Name:La- and related protein 1 IPI>Q6ZQ58>S81>La-related protein 1 1960063 Vesicle-trafficking protein SEC22b ManualIPI>IPI00344088.6>S81>Larp Assigned Name:Vesicle-trafficking protein SEC22b HPRD>04939_1>S137>SEC2 1958667 Receptor-interacting serine/threonine-protein Manual2B Assigned kinase 3 Name:Receptor-interacting serine/threonine-protein kinase 3 1959504 E3 ubiquitin-protein ligase NEDD4-like ManualSwissPROT>Q3U3Z9_MOUS Assigned Name:E3 ubiquitin-protein ligase NEDD4-like HPRD>05903_1>S428>Ubiqu 1960300 Drebrin-like protein Manualitin protein Assigned ligase NEDD4 like Name:Drebrin-like protein SwissPROT>DBNL_MOUSE> T295>Isoform 3 of Drebrin- 1959284 Nuclear autoantigen Sp-100 Manuallike protein Assigned OS=Mus Name:Nuclear autoantigen Sp- 100 SwissPROT>Q3UKD8_MOU 1960097 60S acidic ribosomal protein P1 ManualSE>T313>Putative Assigned Name:60S acidic ribosomal protein P1 SwissPROT>RLA1_MOUSE> S101S104>60S acidic 1959210 Microtubule-associated protein Manualribosomal Assigned protein P1 OS=Mus Name:Microtubule-associated protein IPI>E9QPW8>S517>Microtub ule-associated protein Page 173 of 603 Diabetes

1958632 E3 ubiquitin-protein ligase Mdm2 Manual Assigned Name:E3 ubiquitin-protein ligase Mdm2 SwissPROT>MDM2_MOUSE >S134>Isoform Mdm2-p76 of 1958668 Receptor-interacting serine/threonine-protein ManualE3 ubiquitin-protein Assigned ligase kinase 3 Name:Receptor-interacting serine/threonine-protein kinase 3 1959009 MCG126099, isoform CRA_b ManualSwissPROT>Q3U3Z9_MOUS Assigned Name:MCG126099, isoform CRA_b SwissPROT>D3Z3A0_MOUS 1958971 E3 ubiquitin-protein ligase NEDD4 ManualE>S122S123>"MCG126099, Assigned Name:E3 ubiquitin-protein ligase NEDD4 SwissPROT>NEDD4_MOUS 1959133 Myeloid leukemia factor 2 ManualE>S309>E3 Assigned ubiquitin-protein Name:Myeloid leukemia factor 2 HPRD>03238_1>S238>MLF2 1959730 Myeloid leukemia factor 2 ManualSwissPROT>MLF2_MOUSE> Assigned Name:Myeloid leukemia factor 2 HPRD>03238_1>S240>MLF2 1960123 Vimentin ManualSwissPROT>MLF2_MOUSE> Assigned Name:Vimentin SwissPROT>VIME_MOUSE> Vimentin OS=Mus musculus 1960345 Ahnak AHNAK nucleoprotein isoform 1 ManualGN=Vim Assigned Name:Ahnak AHNAK nucleoprotein isoform 1 SwissPROT>Q8BRB8_MOU 1959716 98 ManualSE>Putative Assigned uncharacterized Name:Nucleoporin 98 SwissPROT>Q68G59_MOUS E>S281>Nup98 protein 1959387 Tyrosine-protein kinase JAK2 Manual(Fragment) Assigned OS=Mus Name:Tyrosine-protein kinase JAK2 SwissPROT>JAK2_MOUSE> S523>Tyrosine-protein kinase Diabetes Page 174 of 603

1958831 PHD and RING finger domain-containing Manual Assigned Name:PHD protein 1 and RING finger domain- containing protein 1 SwissPROT>PHRF1_MOUS 1959069 Polymerase I and transcript release factor ManualE>S884S886>Isoform Assigned 2 of Name:Polymerase I and transcript release factor SwissPROT>PTRF_MOUSE> 1959079 Polymerase I and transcript release factor ManualS171>Polymerase Assigned I and Name:Polymerase I and transcript release factor SwissPROT>PTRF_MOUSE> 1959032 Tripartite motif-containing protein 47 ManualS169>Polymerase Assigned I and Name:Tripartite motif- containing protein 47 SwissPROT>Q7TMQ8_MOU 1958852 Serine/arginine repetitive matrix 1 ManualSE>S164>Trim47 Assigned protein Name:Serine/arginine repetitive matrix 1 HPRD>10441_1>S389S391S 1960059 6-phosphofructokinase, liver type Manual393>Serine Assigned arginine Name:6- repetitive phosphofructokinase, liver type SwissPROT>K6PL_MOUSE> 1958966 Isoform 3 of Peripheral plasma membrane ManualS775>"6- Assigned protein CASK Name:Isoform 3 of Peripheral plasma membrane protein CASK 1959670 Isoform 3 of Peripheral plasma membrane ManualIPI>O70589-3>S571>Isoform Assigned protein CASK Name:Isoform 3 of Peripheral plasma membrane protein CASK 1960098 Cyclin-dependent kinase 11 ManualIPI>O70589-3>S570>Isoform Assigned Name:Cyclin-dependent kinase 11 HPRD>00308_1>S271>Cell 1959464 Glycogen [starch] synthase, muscle Manualdivision Assignedcycle 2 like 2 Name:Glycogen [starch] synthase, muscle SwissPROT>D3Z0Q6_MOUS E>S645>Uncharacterized Page 175 of 603 Diabetes

1960446 Glycogen [starch] synthase, muscle Manual Assigned Name:Glycogen [starch] synthase, muscle SwissPROT>D3Z0Q6_MOUS 1959769 Zinc finger -binding domain-containing ManualE>S647>Uncharacterized Assigned Name:Zinc protein 2 finger Ran-binding domain- containing protein 2 HPRD>09185_1>Zinc finger 1959999 Paralemmin-1 Manualprotein 265Assigned Name:Paralemmin-1 SwissPROT>PALM_MOUSE >T141T145>Isoform 2 of 1958603 Ahnak AHNAK nucleoprotein isoform 1 ManualParalemmin Assigned OS=Mus Name:Ahnak AHNAK nucleoprotein isoform 1 IPI>IPI00553798.2>Ahnak 1960147 Dual specificity protein phosphatase ManualAHNAK Assignednucleoprotein Name:Dual isoform specificity protein phosphatase HPRD>02136_1>S325>Dual 1959472 SH2B adapter protein 2 Manualspecificity Assigned phosphatase 9 Name:SH2B adapter protein 2 SwissPROT>APS_MOUSE>S 588>SH2 and PH domain- 1960122 Vimentin Manualcontaining Assigned adapter protein Name:Vimentin SwissPROT>VIME_MOUSE> Vimentin OS=Mus musculus 1958748 Protein DEK ManualGN=Vim Assigned Name:Protein DEK SwissPROT>DEK_MOUSE> S247S248S255>Protein DEK 1959077 Thyroid hormone receptor-associated protein ManualOS=Mus Assigned musculus GN=Dek 3 Name:Thyroid hormone receptor-associated protein 3 SwissPROT>Q8BZN7_MOUS 1960148 Dual specificity protein phosphatase ManualE>S379>Putative Assigned Name:Dual specificity protein phosphatase HPRD>02136_1>S328>Dual specificity phosphatase 9 Diabetes Page 176 of 603

1959446 Patatin-like phospholipase domain-containing Manual Assigned protein 2 Name:Patatin-like phospholipase domain- containing protein 2 1959920 Guanine nucleotide-binding protein ManualHPRD>11443_1>S428>Patati Assigned G(I)/G(S)/G(O) subunit gamma-12 Name:Guanine nucleotide- binding protein G(I)/G(S)/G(O) subunit 1959224 Perilipin-1 Manualgamma-12 Assigned Name:Perilipin-1 HPRD>01364_1>S382>Perili pin 1958974 Protein phosphatase 1 regulatory subunit ManualSwissPROT>PLIN_MOUSE> Assigned 12A Name:Protein phosphatase 1 regulatory subunit 12A HPRD>03606_1>S507>Myosi 1959936 Protein phosphatase 1 regulatory subunit Manualn phosphatase Assigned target subunit 12A Name:Protein phosphatase 1 regulatory subunit 12A HPRD>03606_1>S509>Myosi 1960103 Isoform PLEC-1A of Plectin Manualn phosphatase Assigned target subunit Name:Isoform PLEC-1A of Plectin HPRD>03180_4>S20>Plectin 1959254 Protein phosphatase 1 regulatory subunit Manual1 Assigned 12A Name:Protein phosphatase 1 regulatory subunit 12A SwissPROT>MYPT1_MOUS 1959007 Eukaryotic translation initiation factor 4B ManualE>S299>Isoform Assigned 2 of Protein Name:Eukaryotic translation initiation factor 4B HPRD>04892_1>S445>Eukar 1959292 Microtubule-associated protein Manualyotic translation Assigned initiation Name:Microtubule-associated protein SwissPROT>MAP4_MOUSE 1959060 Vasodilator-stimulated phosphoprotein Manual>S748>Isoform Assigned 4 of Name:Vasodilator-stimulated phosphoprotein SwissPROT>VASP_MOUSE> Vasodilator-stimulated Page 177 of 603 Diabetes

1959695 Vasodilator-stimulated phosphoprotein Manual Assigned Name:Vasodilator-stimulated phosphoprotein SwissPROT>VASP_MOUSE> 1959478 Tyrosine-protein phosphatase non-receptor ManualVasodilator-stimulated Assigned type 12 Name:Tyrosine-protein phosphatase non-receptor type 12 1960163 Serine/arginine repetitive matrix 1 ManualHPRD>02513_1>S435>Protei Assigned Name:Serine/arginine repetitive matrix 1 SwissPROT>A2A8V8_MOUS 1959245 Perilipin-1 ManualE>S577T579>Serine/arginine Assigned Name:Perilipin-1 SwissPROT>PLIN_MOUSE> S460>Perilipin (PERI) (Lipid 1959767 Perilipin-1 Manualdroplet-associated Assigned protein) Name:Perilipin-1 SwissPROT>PLIN_MOUSE> S463>Perilipin (PERI) (Lipid 1959660 Calcium/calmodulin-dependent protein kinase Manualdroplet-associated Assigned protein) type II subunit delta Name:Calcium/calmodulin- dependent protein kinase type II subunit delta 1959702 Dclk1 protein ManualHPRD>09653_1>T337>CaM Assigned Name:Dclk1 protein HPRD>09202_1>T336>Doubl ecortin and CaM kinase like 1 1960317 Dclk1 protein ManualSwissPROT>A8IP62_MOUS Assigned Name:Dclk1 protein HPRD>09202_1>S337>Doubl ecortin and CaM kinase like 1 1959650 Na(+)/H(+) exchange regulatory cofactor NHE-ManualSwissPROT>A8IP62_MOUS Assigned RF1 Name:Na(+)/H(+) exchange regulatory cofactor NHE-RF1 SwissPROT>NHERF_MOUS 1959960 Charged multivesicular body protein 2b ManualE>S284>Ezrin-radixin-moesin Assigned Name:Charged multivesicular body protein 2b HPRD>13174_1>S199>DKFZ P564O123 protein Diabetes Page 178 of 603

1958837 Palladin Manual Assigned Name:Palladin HPRD>09731_1>S892S894S 897>Palladin 1958866 5'-3' exoribonuclease 2 ManualSwissPROT>PALLD_MOUSE Assigned Name:5'-3' exoribonuclease 2 HPRD>10309_1>S499S501> 5`-3` exoribonuclease 2 1960367 Cobl-like 1 ManualSwissPROT>XRN2_MOUSE> Assigned Name:Cobl- like 1 SwissPROT>B1AZ14_MOUS E>S1183>Cobl-like 1 1958848 PC4 and SFRS1-interacting protein ManualOS=Mus Assigned musculus Name:PC4 and SFRS1-interacting protein HPRD>04688_1>S106>PC4 1959895 PC4 and SFRS1-interacting protein Manualand SFRS1 Assigned interacting Name:PC4 protein and SFRS1-interacting protein HPRD>04688_1>S105>PC4 1959384 FACT complex subunit SSRP1 Manualand SFRS1 Assigned interacting protein Name:FACT complex subunit SSRP1 SwissPROT>A2AW05_MOU 1960179 Acin1 protein ManualSE>S444>Structure Assigned Name:Acin1 specific protein HPRD>05191_1>S898>ACIN US 1959026 Ahnak AHNAK nucleoprotein isoform 1 ManualSwissPROT>B8JJ87_MOUS Assigned Name:Ahnak AHNAK nucleoprotein isoform 1 HPRD>14684_2>S5731>AH 1958629 DnaJ homolog subfamily C member 5 ManualNAK nucleoprotein Assigned Name:DnaJ homolog subfamily C member 5 HPRD>08539_1>S10>Cystei 1960107 DnaJ homolog subfamily C member 5 Manualne string Assigned protein Name:DnaJ homolog subfamily C member 5 HPRD>08539_1>S8>Cystein e string protein Page 179 of 603 Diabetes

1960228 Ras GTPase-activating protein 3 Manual Assigned Name:Ras GTPase-activating protein 3 HPRD>05537_1>S809>Ras p21 protein activator 3 1959672 NEDD9-interacting protein with calponin ManualSwissPROT>Q3UGJ5_MOUS Assigned homology and LIM domains Name:NEDD9-interacting protein with calponin homology and LIM domains 1959570 Serine/arginine repetitive matrix 1 ManualSwissPROT>MICA1_MOUSE Assigned Name:Serine/arginine repetitive matrix 1 SwissPROT>A2A8V8_MOUS 1959571 Serine/arginine repetitive matrix 1 ManualE>S401T404>Serine/arginine Assigned Name:Serine/arginine repetitive matrix 1 SwissPROT>A2A8V8_MOUS 1958957 PC4 and SFRS1-interacting protein ManualE>S400T404>Serine/arginine Assigned Name:PC4 and SFRS1-interacting protein SwissPROT>A2BI12_MOUS 1959666 PC4 and SFRS1-interacting protein ManualE>S272S274>PC4 Assigned Name:PC4 and and SFRS1-interacting protein SwissPROT>A2BI12_MOUS 1959922 PC4 and SFRS1-interacting protein ManualE>T271S274>PC4 Assigned Name:PC4 and and SFRS1-interacting protein SwissPROT>A2BI12_MOUS 1959923 PC4 and SFRS1-interacting protein ManualE>T269S274>PC4 Assigned Name:PC4 and and SFRS1-interacting protein SwissPROT>A2BI12_MOUS 1960441 Oxysterol-binding protein-related protein 11 ManualE>S270T271>PC4 Assigned and Name:Oxysterol-binding protein-related protein 11 SwissPROT>OSB11_MOUSE 1960405 Dclk1 protein Manual>S194>Oxysterol-binding Assigned Name:Dclk1 protein HPRD>09202_1>S32T34>Do ublecortin and CaM kinase like 1 Diabetes Page 180 of 603

1959707 Serine/arginine repetitive matrix 1 Manual Assigned Name:Serine/arginine repetitive matrix 1 SwissPROT>A2A8V8_MOUS 1959368 1-phosphatidylinositol-3-phosphate 5-kinase ManualE>S558S560>Serine/arginine Assigned Name:1- phosphatidylinositol-3- phosphate 5-kinase HPRD>17852_1>S307>Phos 1958742 Hmga2 protein Manualphatidylinositol-3- Assigned Name:Hmga2 protein SwissPROT>HMGA2_MOUS E>S44>High mobility group 1959463 Thyroid hormone receptor-associated protein Manualprotein HMGI-CAssigned OS=Mus 3 Name:Thyroid hormone receptor-associated protein 3 HPRD>07543_1>S682>TRA 1960214 RNA-binding protein 25 ManualP150 Assigned Name:RNA- binding protein 25 HPRD>15229_1>S677>RNA binding motif protein 25 1958892 Caspase-8 ManualIPI>B2RY56>S675>RNA- Assigned Name:Caspase-8 SwissPROT>CASP8_MOUS E>S188>Caspase-8 OS=Mus 1959385 Serine/arginine repetitive matrix protein 2 Manualmusculus Assigned GN=Casp8 Name:Serine/arginine repetitive matrix protein 2 SwissPROT>SRRM2_MOUS 1959558 Prelamin-A/C ManualE>S1305>Isoform Assigned 3 of Name:Prelamin-A/C SwissPROT>LAMA_MOUSE >S403>Lamin A 1960141 Prelamin-A/C ManualSwissPROT>LAMC_MOUSE Assigned Name:Prelamin-A/C SwissPROT>LAMA_MOUSE >S404>Lamin A 1958723 Serine/threonine-protein kinase PRP4 ManualSwissPROT>LAMC_MOUSE Assigned homolog Name:Serine/threonine- protein kinase PRP4 homolog SwissPROT>B2RUN6_MOU SE>S278>PRP4 pre-mRNA Page 181 of 603 Diabetes

1960275 Sister chromatid cohesion protein PDS5 Manual Assigned homolog B Name:Sister chromatid cohesion protein PDS5 homolog B 1960138 Vimentin ManualSwissPROT>PDS5B_MOUS Assigned Name:Vimentin SwissPROT>VIME_MOUSE> Vimentin OS=Mus musculus 1959687 Rab GTPase-binding effector protein 1 ManualGN=Vim Assigned Name:Rab GTPase-binding effector protein 1 SwissPROT>Q5QNU3_MOU 1959460 Perilipin-1 ManualSE>S407>"Rabaptin, Assigned RAB Name:Perilipin-1 HPRD>01364_1>S408>Perili pin 1960461 Perilipin-1 ManualSwissPROT>PLIN_MOUSE> Assigned Name:Perilipin-1 HPRD>01364_1>S408>Perili pin 1958975 Kif13b kinesin family member 13B ManualSwissPROT>PLIN_MOUSE> Assigned Name:Kif13b kinesin family member 13B SwissPROT>Q6A029_MOUS 1958921 Kif13b kinesin family member 13B ManualE>MKIAA0639 Assigned protein Name:Kif13b kinesin family member 13B SwissPROT>Q6A029_MOUS 1959466 Rab-3A-interacting protein ManualE>MKIAA0639 Assigned protein Name:Rab- 3A-interacting protein SwissPROT>RAB3I_MOUSE >S240>Rab-3A-interacting 1960173 DNA-(apurinic or apyrimidinic site) lyase Manualprotein OS=MusAssigned musculus Name:DNA- (apurinic or apyrimidinic site) lyase SwissPROT>APEX1_MOUSE 1959502 Pleckstrin homology domain-containing family Manual>S18>DNA-(apurinic Assigned or O member 2 Name:Pleckstrin homology domain-containing family O member 2 SwissPROT>PKHO2_MOUS Diabetes Page 182 of 603

1959503 Pleckstrin homology domain-containing family Manual Assigned O member 2 Name:Pleckstrin homology domain-containing family O member 2 1959635 Rho guanine nucleotide exchange factor 2 ManualSwissPROT>PKHO2_MOUS Assigned Name:Rho guanine nucleotide exchange factor 2 HPRD>10458_1>S955S959> 1959340 WASH complex subunit FAM21 ManualRho guanine Assigned nucleotide Name:WASH complex subunit FAM21 SwissPROT>FAM21_MOUSE 1960319 Guanine nucleotide-binding protein-like 3 Manual>Isoform Assigned 2 of WASH complex Name:Guanine nucleotide- binding protein-like 3 SwissPROT>GNL3_MOUSE> 1960007 Protein phosphatase 1 regulatory subunit ManualS472>Isoform Assigned 2 of Guanine 12A Name:Protein phosphatase 1 regulatory subunit 12A SwissPROT>MYPT1_MOUS 1959724 Ubiquitin-conjugating enzyme E2 J1 ManualE>S909>Isoform Assigned 2 of Protein Name:Ubiquitin-conjugating enzyme E2 J1 SwissPROT>A3KG52_MOUS 1959116 mRNA cap guanine-N7 methyltransferase ManualE>S209>Ubiquitin- Assigned Name:mRNA cap guanine-N7 methyltransferase SwissPROT>D3YYS7_MOUS 1958935 MCG14935, isoform CRA_a ManualE>S100>Uncharacterized Assigned Name:MCG14935, isoform CRA_a SwissPROT>Q3UWE6_MOU 1959499 Glucosamine--fructose-6-phosphate ManualSE>"MCG14935, Assigned isoform aminotransferase [isomerizing] 1 Name:Glucosamine--fructose- 6-phosphate aminotransferase 1959618 Nardilysin Manual[isomerizing] Assigned 1 Name:Nardilysin HPRD>04036_1>S86>Nardily sin SwissPROT>A2A9Q2_MOUS Page 183 of 603 Diabetes

1959363 Sipa1l1 protein Manual Assigned Name:Sipa1l1 protein HPRD>11559_1>S1549>E6 targeted protein 1 1959262 Heterogeneous nuclear ribonucleoprotein L- ManualSwissPROT>SI1L1_MOUSE> Assigned like Name:Heterogeneous nuclear ribonucleoprotein L-like SwissPROT>Q3UXJ3_MOUS 1960359 Bin1 protein ManualE>S129>Putative Assigned Name:Bin1 protein SwissPROT>BIN1_MOUSE> S265>Isoform 2 of Myc box- 1959108 Bin1 protein Manualdependent-interacting Assigned Name:Bin1 protein protein SwissPROT>BIN1_MOUSE> S265S267>Isoform 2 of Myc 1959061 Dclk1 protein Manualbox-dependent-interacting Assigned Name:Dclk1 protein HPRD>09202_1>S307>Doubl ecortin and CaM kinase like 1 1959694 Dclk1 protein ManualSwissPROT>DCAK1_MOUS Assigned Name:Dclk1 protein HPRD>09202_1>S312>Doubl ecortin and CaM kinase like 1 1959951 Dclk1 protein ManualSwissPROT>DCAK1_MOUS Assigned Name:Dclk1 protein HPRD>09202_1>S310>Doubl ecortin and CaM kinase like 1 1959968 RNA-binding protein Raly ManualSwissPROT>DCAK1_MOUS Assigned Name:RNA- binding protein Raly SwissPROT>A2AU62_MOUS E>T268>HnRNP-associated 1960347 RNA-binding protein Raly Manualwith lethal Assigned yellow (Fragment)Name:RNA- binding protein Raly SwissPROT>A2AU62_MOUS E>S270>HnRNP-associated 1960376 SAFB-like transcription modulator Manualwith lethal Assigned yellow (Fragment) Name:SAFB-like transcription modulator SwissPROT>SLTM_MOUSE> S534>Isoform 2 of SAFB-like Diabetes Page 184 of 603

1959995 Calmodulin-regulated spectrin-associated Manual Assigned protein 2 Name:Calmodulin-regulated spectrin-associated protein 2 SwissPROT>B2RRE3_MOUS 1959160 Vigilin ManualE>S1131>Camsap1l1 Assigned protein Name:Vigilin SwissPROT>Q8BX68_MOUS E>Putative uncharacterized 1959668 Zinc finger Ran-binding domain-containing Manualprotein OS=MusAssigned musculus Name:Zinc protein 2 finger Ran-binding domain- containing protein 2 HPRD>09185_1>Zinc finger 1959294 Ahnak AHNAK nucleoprotein isoform 1 Manualprotein 265Assigned Name:Ahnak AHNAK nucleoprotein isoform 1 SwissPROT>Q8BRB8_MOU 1960017 Ahnak AHNAK nucleoprotein isoform 1 ManualSE>Putative Assigned uncharacterized Name:Ahnak AHNAK nucleoprotein isoform 1 SwissPROT>Q8BRB8_MOU 1959740 Ubiquinone biosynthesis protein COQ9, ManualSE>Putative Assigned uncharacterized mitochondrial Name:Ubiquinone biosynthesis protein COQ9, mitochondrial 1960170 Heterogeneous nuclear ribonucleoprotein G ManualSwissPROT>COQ9_MOUSE Assigned Name:Heterogeneous nuclear ribonucleoprotein G SwissPROT>D3Z613_MOUS 1959483 Small acidic protein ManualE>T163>Uncharacterized Assigned Name:Small acidic protein HPRD>18069_1>S15>SMAP SwissPROT>D6RI64_MOUS 1959789 Eukaryotic translation initiation factor 3 ManualE>S15>Uncharacterized Assigned subunit C Name:Eukaryotic translation initiation factor 3 subunit C HPRD>04889_1>S39>EIF3S 1958825 Small glutamine-rich tetratricopeptide repeat- Manual8 Assigned Name:Small containing protein alpha glutamine-rich tetratricopeptide repeat- containing protein alpha SwissPROT>SGTA_MOUSE Page 185 of 603 Diabetes

1958677 Yorkie homolog Manual Assigned Name:Yorkie homolog HPRD>09424_1>Yes associated protein 1959788 Nucleolar protein 58 ManualSwissPROT>Q3U046_MOUS Assigned Name:Nucleolar protein 58 SwissPROT>NOP58_MOUS E>S509>Nucleolar protein 58 1959389 Cyclin-dependent kinase 11 ManualOS=Mus Assigned musculus Name:Cyclin-dependent kinase 11 HPRD>00308_1>T736S737> 1960424 Cyclin-dependent kinase 11 ManualCell division Assigned cycle 2 like 2 Name:Cyclin-dependent kinase 11 HPRD>00308_1>T736S737> 1959648 Microtubule-associated protein 1A ManualCell division Assigned cycle 2 like 2 Name:Microtubule-associated protein 1A HPRD>02549_1>S986>Micro 1958666 Vimentin Manualtubule associated Assigned protein 1A Name:Vimentin SwissPROT>VIME_MOUSE> Vimentin OS=Mus musculus 1958904 Cyclin-dependent kinase 12 ManualGN=Vim Assigned Name:Cyclin-dependent kinase 12 SwissPROT>B1AQH7_MOU 1958997 E3 ubiquitin-protein ligase UBR4 ManualSE>S807>"Cdc2-related Assigned Name:E3 ubiquitin-protein ligase UBR4 HPRD>10184_1>S2719>Reti noblastoma associated factor 1959673 E3 ubiquitin-protein ligase UBR4 Manual600 Assigned Name:E3 ubiquitin-protein ligase UBR4 HPRD>10184_1>S2718>Reti noblastoma associated factor 1960168 Heterogeneous nuclear ribonucleoprotein D0 Manual600 Assigned Name:Heterogeneous nuclear ribonucleoprotein D0 HPRD>03206_1>S83>Hetero geneous nuclear Diabetes Page 186 of 603

1959297 Ahnak AHNAK nucleoprotein isoform 1 Manual Assigned Name:Ahnak AHNAK nucleoprotein isoform 1 SwissPROT>Q8BRB8_MOU 1960342 KN motif and ankyrin repeat domain- ManualSE>Putative Assigned uncharacterized Name:KN containing protein 2 motif and ankyrin repeat domain-containing protein 2 HPRD>13865_1>S137>Immu 1959179 SEC16 homolog A (S. cerevisiae) Manualnoglobulin Assigned superfamily Name:SEC16 homolog A (S. cerevisiae) SwissPROT>A2AIX1_MOUS 1959072 Prelamin-A/C ManualE>S1028>SEC16 Assigned homolog A Name:Prelamin-A/C HPRD>01035_1>S390S392> Lamin A/C 1959091 Prelamin-A/C ManualHPRD>01035_2>S390S392> Assigned Name:Prelamin-A/C HPRD>01035_1>S390S395> Lamin A/C 1959685 Archvillin ManualHPRD>01035_2>S390S395> Assigned Name:Archvillin SwissPROT>Q8K4L2_MOUS E>S857>Archvillin OS=Mus 1958754 Transcription elongation factor A protein 1 Manualmusculus Assigned GN=Svil Name:Transcription elongation factor A protein 1 SwissPROT>TCEA1_MOUSE 1960145 Zc3h13 Zinc finger CCCH type containing 13 Manual>S65>Isoform Assigned 1 of Name:Zc3h13 Zinc finger CCCH type containing 13 SwissPROT>B9EHN9_MOUS 1959807 Ubiquitin carboxyl-terminal hydrolase ManualE>Zinc fingerAssigned CCCH type Name:Ubiquitin carboxyl- terminal hydrolase HPRD>03950_1>Ubiquitin 1959252 Protein phosphatase 1 regulatory subunit Manualspecific Assignedprotease 7 12A Name:Protein phosphatase 1 regulatory subunit 12A SwissPROT>MYPT1_MOUS E>S299>Isoform 2 of Protein Page 187 of 603 Diabetes

1959276 N(2),N(2)-dimethylguanosine tRNA Manual Assigned methyltransferase Name:N(2),N(2)- dimethylguanosine tRNA methyltransferase 1959756 Cobl-like 1 ManualSwissPROT>D3Z1P5_MOUS Assigned Name:Cobl- like 1 SwissPROT>B1AZ14_MOUS E>S1183>Cobl-like 1 1959425 Apoptotic condensation inducer 1 ManualOS=Mus Assigned musculus (Fragment) Name:Apoptotic chromatin condensation inducer 1 (Fragment) 1960045 Hormone-sensitive lipase ManualSwissPROT>ACINU_MOUSE Assigned Name:Hormone-sensitive lipase SwissPROT>LIPS_MOUSE> 1958869 RNA-binding protein 10 ManualS650>Hormone-sensitive Assigned Name:RNA- binding protein 10 HPRD>02095_1>S723>RNA binding motif protein 10 1959977 Serine/arginine repetitive matrix 1 ManualHPRD>02095_2>S645>RNA Assigned Name:Serine/arginine repetitive matrix 1 SwissPROT>A2A8V8_MOUS 1959065 Prelamin-A/C ManualE>S220>Serine/arginine Assigned Name:Prelamin-A/C HPRD>01035_1>S390>Lami n A/C 1959370 Insulin-like growth factor 2 mRNA-binding ManualHPRD>01035_2>S390>Lami Assigned protein 3 Name:Insulin-like growth factor 2 mRNA-binding protein 3 1960166 RNA-binding protein 26 ManualSwissPROT>IF2B3_MOUSE> Assigned Name:RNA- binding protein 26 HPRD>12611_1>S127>Cuta neous T cell lymphoma tumor 1959897 D(1B) dopamine receptor Manualantigen Assignedse70-2 Name:D(1B) dopamine receptor HPRD>00542_1>S261>Dopa mine receptor, D5 Diabetes Page 188 of 603

1958818 Eukaryotic translation initiation factor 3 Manual Assigned subunit B Name:Eukaryotic translation initiation factor 3 subunit B SwissPROT>Q8CIJ3_MOUS 1958862 Apolipoprotein A-I-binding protein ManualE>Eif3b Assignedprotein OS=Mus Name:Apolipoprotein A-I- binding protein SwissPROT>AIBP_MOUSE> 1958999 Swi5-dependent recombination DNA repair ManualS43>Apolipoprotein Assigned Name:Swi5- A-I- protein 1 homolog dependent recombination DNA repair protein 1 homolog SwissPROT>CJ078_MOUSE 1959674 Swi5-dependent recombination DNA repair Manual>S67T70>Uncharacterized Assigned Name:Swi5- protein 1 homolog dependent recombination DNA repair protein 1 homolog SwissPROT>CJ078_MOUSE 1958925 Formin-like protein 2 Manual>S67S71>Uncharacterized Assigned Name:Formin-like protein 2 HPRD>13545_1>S171>Formi n like 2 1958716 High mobility group protein HMGI-C ManualHPRD>13545_2>S171>Formi Assigned Name:High mobility group protein HMGI- C SwissPROT>HMGA2_MOUS 1958769 Prelamin-A/C ManualE>S104>High Assigned mobility group Name:Prelamin-A/C HPRD>01035_1>S390>Lami n A/C 1959871 Prelamin-A/C ManualHPRD>01035_2>S390>Lami Assigned Name:Prelamin-A/C HPRD>01035_1>S392>Lami n A/C 1958840 Transformer-2 protein homolog beta ManualHPRD>01035_2>S392>Lami Assigned Name:Transformer-2 protein homolog beta HPRD>04096_1>S260S262> 1960177 Serine/arginine repetitive matrix protein 2 ManualTRA2A Assigned Name:Serine/arginine repetitive matrix protein 2 IPI>Q8BTI8>Serine/arginine repetitive matrix protein 2 Page 189 of 603 Diabetes

1958834 Glycylpeptide N-tetradecanoyltransferase 1 Manual Assigned Name:Glycylpeptide N- tetradecanoyltransferase 1 SwissPROT>NMT1_MOUSE 1959082 Zinc finger CCCH domain-containing protein Manual>S47>Glycylpeptide Assigned Name:Zinc N- 18 finger CCCH domain- containing protein 18 HPRD>11232_1>S534>Cons 1959591 Acin1 protein Manualerved nuclear Assigned protein Name:Acin1 NHN1 protein SwissPROT>ACINU_MOUSE >S798>Isoform 4 of Apoptotic 1959705 Polymerase I and transcript release factor Manualchromatin Assigned condensation Name:Polymerase I and transcript release factor SwissPROT>PTRF_MOUSE> 1959471 Glycogen [starch] synthase, muscle ManualS171>Polymerase Assigned I and Name:Glycogen [starch] synthase, muscle SwissPROT>D3Z0Q6_MOUS 1960447 Glycogen [starch] synthase, muscle ManualE>T650>Uncharacterized Assigned Name:Glycogen [starch] synthase, muscle SwissPROT>D3Z0Q6_MOUS 1959289 Novel protein (1200015F23Rik) (Fragment) ManualE>S655>Uncharacterized Assigned Name:Novel protein (1200015F23Rik) (Fragment) SwissPROT>A3KGH5_MOU 1958612 Eukaryotic translation initiation factor 3 ManualSE>S46>Novel Assigned protein subunit G Name:Eukaryotic translation initiation factor 3 subunit G SwissPROT>EIF3G_MOUSE 1960102 Eukaryotic translation initiation factor 3 Manual>T41>Eukaryotic Assigned translation subunit G Name:Eukaryotic translation initiation factor 3 subunit G SwissPROT>EIF3G_MOUSE 1960012 Disintegrin and metalloproteinase domain- Manual>S42>Eukaryotic Assigned translation containing protein 17 Name:Disintegrin and metalloproteinase domain- containing protein 17 HPRD>04703_1>S791>ADA Diabetes Page 190 of 603

1959719 Bcl-2-associated transcription factor 1 Manual Assigned Name:Bcl-2- associated transcription factor 1 HPRD>16544_1>Y284S297> 1959335 Serine/arginine repetitive matrix protein 2 ManualBCL2 associated Assigned transcription Name:Serine/arginine repetitive matrix protein 2 SwissPROT>SRRM2_MOUS 1959627 Tyrosine-protein kinase BAZ1B ManualE>T955>Isoform Assigned 3 of Name:Tyrosine-protein kinase BAZ1B HPRD>10416_1>S283>Brom 1958692 Bcl-2-like protein 13 Manualodomain Assigned adjacent Name:Bcl-2-to zinc like protein 13 SwissPROT>B2L13_MOUSE >S387>Bcl-2-like protein 13 1958823 MCG123425, isoform CRA_e ManualOS=Mus Assigned musculus Name:MCG123425, isoform CRA_e HPRD>10139_1>S1834>Pec 1958969 MCG127409 Manualanex homolog Assigned Name:MCG127409 SwissPROT>D3YXK2_MOUS E>S345>Uncharacterized 1959433 Bcl-2-associated transcription factor 1 Manualprotein OS=MusAssigned musculus Name:Bcl-2- associated transcription factor 1 SwissPROT>BCLF1_MOUSE 1958725 Serine/arginine repetitive matrix 1 Manual>S654>Isoform Assigned 3 of Bcl-2- Name:Serine/arginine repetitive matrix 1 HPRD>10441_1>S616>Serin 1958846 Heat shock protein 84b Manuale arginine Assigned repetitive Name:Heat matrix shock protein 84b HPRD>06763_1>S255>HSP9 0B 1959778 Perilipin-1 ManualHPRD>11811_1>S218>Heat Assigned Name:Perilipin-1 SwissPROT>PLIN_MOUSE> S222>Perilipin (PERI) (Lipid droplet-associated protein) Page 191 of 603 Diabetes

1958889 Sntb2 protein Manual Assigned Name:Sntb2 protein SwissPROT>B7ZNU9_MOUS E>S90>Sntb2 protein 1959508 Elongation factor 1-beta ManualOS=Mus Assigned musculus GN=Sntb2 Name:Elongation factor 1- beta HPRD>02804_1>S106>Eukar 1959319 Manualyotic translation Assigned elongation Name:Aladin HPRD>05646_1>S495>Aladi n 1958807 Transformer-2 protein homolog beta ManualSwissPROT>AAAS_MOUSE> Assigned Name:Transformer-2 protein homolog beta HPRD>04096_1>S260Y264> 1959772 Kinesin light chain 2 ManualTRA2A Assigned Name:Kinesin light chain 2 HPRD>13917_1>S610>FLJ1 2387 1958620 ATP-binding cassette sub-family F member 1 ManualSwissPROT>D3YXZ3_MOUS Assigned Name:ATP- binding cassette sub-family F member 1 SwissPROT>ABCF1_MOUSE 1959637 Nuclease-sensitive element-binding protein 1 Manual>S138>ATP-binding Assigned cassette Name:Nuclease-sensitive element-binding protein 1 HPRD>01095_1>YB-1 1959580 High mobility group protein HMGI-C ManualSwissPROT>A2BGG7_MOU Assigned Name:High mobility group protein HMGI- C SwissPROT>HMGA2_MOUS 1959864 High mobility group protein HMGI-C ManualE>S101S104>High Assigned Name:High mobility mobility group protein HMGI- C SwissPROT>HMGA2_MOUS 1960188 Serrate RNA effector molecule homolog ManualE>S100S104>High Assigned mobility Name:Serrate RNA effector molecule homolog HPRD>10665_1>S74>Arsenit e resistance protein 2 Diabetes Page 192 of 603

1958910 Pinin Manual Assigned Name:Pinin SwissPROT>PININ_MOUSE> S346>Pinin OS=Mus musculus GN=Pnn 1958791 Heat shock protein 84b ManualSwissPROT>Q3TUQ5_MOU Assigned Name:Heat shock protein 84b HPRD>06763_1>S226>HSP9 0B 1959188 SAM and SH3 domain-containing protein 1 ManualSwissPROT>HS90B_MOUSE Assigned Name:SAM and SH3 domain-containing protein 1 SwissPROT>SASH1_MOUS 1959747 SAM and SH3 domain-containing protein 1 ManualE>S831>SAM Assigned and Name:SAM SH3 and SH3 domain-containing protein 1 SwissPROT>SASH1_MOUS 1959234 Serine/arginine repetitive matrix protein 2 ManualE>S829>SAM Assigned and SH3 Name:Serine/arginine repetitive matrix protein 2 SwissPROT>SRRM2_MOUS 1959831 ATP-binding cassette sub-family F member 1 ManualE>S1360>Isoform Assigned Name:ATP- 3 of binding cassette sub-family F member 1 SwissPROT>ABCF1_MOUSE 1959861 Serine/arginine-rich splicing factor 2 Manual>S107>ATP-binding Assigned cassette Name:Serine/arginine-rich splicing factor 2 HPRD>02888_1>S189S191> 1958688 Serine/arginine repetitive matrix 1 ManualSplicing Assignedfactor, arginine/serine Name:Serine/arginine repetitive matrix 1 HPRD>10441_1>S450>Serin 1960184 Pinin Manuale arginine Assigned repetitive Name:Pinin matrix HPRD>04401_1>S99>Pinin HPRD>04401_2>S100>Pinin SwissPROT>PININ_MOUSE> 1960011 Nuclear ubiquitous casein and cyclin- ManualS100>Pinin Assigned OS=Mus dependent kinases substrate Name:Nuclear ubiquitous casein and cyclin-dependent kinases substrate HPRD>11406_1>S19>Nuclea Page 193 of 603 Diabetes

1959362 Heterogeneous nuclear ribonucleoproteins Manual Assigned C1/C2 Name:Heterogeneous nuclear ribonucleoproteins C1/C2 SwissPROT>HNRPC_MOUS 1959799 Heterogeneous nuclear ribonucleoproteins ManualE>S261>Isoform Assigned 5 of C1/C2 Name:Heterogeneous nuclear ribonucleoproteins C1/C2 SwissPROT>HNRPC_MOUS 1958883 Melanoma inhibitory activity protein 3 ManualE>S254>Isoform Assigned 5 of Name:Melanoma inhibitory activity protein 3 SwissPROT>MIA3_MOUSE> 1959905 Melanoma inhibitory activity protein 3 ManualS617>Isoform Assigned 3 of Melanoma Name:Melanoma inhibitory activity protein 3 SwissPROT>MIA3_MOUSE> 1960246 Melanoma inhibitory activity protein 3 ManualS616>Isoform Assigned 3 of Melanoma Name:Melanoma inhibitory activity protein 3 SwissPROT>MIA3_MOUSE> 1959488 A3 subunit of vacuolar-adenosine ManualS615>Isoform Assigned 3 of Name:A3 Melanoma triphosphatase subunit of vacuolar-adenosine triphosphatase SwissPROT>Q91W06_MOU 1960266 EH domain-binding protein 1-like protein 1 ManualSE>S693>"T-cell, Assigned Name:EHimmune domain-binding protein 1-like protein 1 SwissPROT>EH1L1_MOUSE 1959119 Cobl-like 1 Manual>S499>Isoform Assigned 5 Name:Cobl-of EH like 1 SwissPROT>B1AZ14_MOUS E>S268>Cobl-like 1 OS=Mus 1959123 Cobl-like 1 Manualmusculus Assigned GN=Cobll1 Name:Cobl- like 1 SwissPROT>B1AZ14_MOUS E>S268>Cobl-like 1 OS=Mus 1959639 Serine/arginine-rich splicing factor 7 Manualmusculus Assigned GN=Cobll1 Name:Serine/arginine-rich splicing factor 7 SwissPROT>SFRS7_MOUSE >S208S210S212>Splicing Diabetes Page 194 of 603

1958812 Eukaryotic translation initiation factor 3 Manual Assigned subunit B Name:Eukaryotic translation initiation factor 3 subunit B SwissPROT>Q8CIJ3_MOUS 1960176 Bcl-2-associated transcription factor 1 ManualE>Eif3b Assignedprotein OS=Mus Name:Bcl-2- associated transcription factor 1 SwissPROT>BCLF1_MOUSE 1958918 Tensin-like C1 domain-containing Manual>S492>Isoform Assigned 3 of Bcl-2- phosphatase Name:Tensin-like C1 domain- containing phosphatase SwissPROT>TENC1_MOUS 1958697 Myosin-9 ManualE>S1087>Isoform Assigned 4 of Tensin- Name:Myosin-9 SwissPROT>MYH9_MOUSE >S1943>Myosin-9 OS=Mus 1958847 Ahnak AHNAK nucleoprotein isoform 1 Manualmusculus Assigned GN=Myh9 Name:Ahnak AHNAK nucleoprotein isoform 1 IPI>IPI00553798.2>Ahnak 1959192 Pre-mRNA 3'-end-processing factor FIP1 ManualAHNAK Assignednucleoprotein Name:Pre- isoform mRNA 3'-end-processing factor FIP1 HPRD>09646_1>S492>FIP1 1959748 Pre-mRNA 3'-end-processing factor FIP1 Manuallike 1 Assigned Name:Pre- mRNA 3'-end-processing factor FIP1 HPRD>09646_1>S496>FIP1 1959984 Pre-mRNA 3'-end-processing factor FIP1 Manuallike 1 Assigned Name:Pre- mRNA 3'-end-processing factor FIP1 HPRD>09646_1>T494>FIP1 1959560 Heterogeneous nuclear ribonucleoprotein D0 Manuallike 1 Assigned Name:Heterogeneous nuclear ribonucleoprotein D0 HPRD>03206_1>S82>Hetero 1959671 Isoform 3 of Peripheral plasma membrane Manualgeneous Assigned CASK Name:Isoform 3 of Peripheral plasma membrane protein CASK IPI>O70589-3>S569>Isoform Page 195 of 603 Diabetes

1959217 Ankyrin repeat domain-containing protein 57 Manual Assigned Name:Ankyrin repeat domain- containing protein 57 SwissPROT>ANR57_MOUSE 1959411 subunit alpha-3 Manual>S82>Ankyrin Assigned repeat domain- Name:Importin subunit alpha- 3 HPRD>03536_1>S60>Karyop 1958842 Protein KRI1 homolog Manualherin alpha3 Assigned Name:Protein KRI1 homolog SwissPROT>KRI1_MOUSE> S148>Protein KRI1 homolog 1959427 Kinesin light chain 2 ManualOS=Mus Assigned musculus GN=Kri1 Name:Kinesin light chain 2 HPRD>13917_1>S582>FLJ1 2387 1958615 Eukaryotic translation initiation factor 3 ManualSwissPROT>D3YXZ3_MOUS Assigned subunit G Name:Eukaryotic translation initiation factor 3 subunit G SwissPROT>EIF3G_MOUSE 1958710 Serine/arginine repetitive matrix protein 2 Manual>T41>Eukaryotic Assigned translation Name:Serine/arginine repetitive matrix protein 2 HPRD>06913_1>S1925T192 1960062 Ras-related GTP-binding protein C Manual7>SRRM2 Assigned Name:Ras- related GTP-binding protein C HPRD>12198_1>S95>Ras related GTP binding C 1959632 Bcl-2-associated transcription factor 1 ManualHPRD>12199_1>S96>Ras Assigned Name:Bcl-2- associated transcription factor 1 HPRD>16544_1>S177>BCL2 1958902 Tln2 talin-2 Manualassociated Assigned transcription Name:Tln2 factor talin-2 HPRD>09555_1>T1843>Tali n 2 1958729 Serine/arginine-rich splicing factor 2 ManualSwissPROT>B2RY15_MOUS Assigned Name:Serine/arginine-rich splicing factor 2 HPRD>02888_1>S206S208S 212S220>Splicing factor, Diabetes Page 196 of 603

1958655 40S ribosomal protein S17 Manual Assigned Name:40S ribosomal protein S17 HPRD>01600_1>S113>Ribos omal protein S17 1959365 Acetyl-coenzyme A synthetase, cytoplasmic ManualHPRD>18936_1>S113>Simil Assigned Name:Acetyl-coenzyme A synthetase, cytoplasmic SwissPROT>A2AQN4_MOU 1960180 Ahnak AHNAK nucleoprotein isoform 1 ManualSE>S30>Acyl-CoA Assigned Name:Ahnak AHNAK nucleoprotein isoform 1 IPI>IPI00553798.2>Ahnak 1959380 Prelamin-A/C ManualAHNAK Assignednucleoprotein isoform Name:Prelamin-A/C HPRD>01035_2>S628>Lami n A/C 1959381 Prelamin-A/C ManualHPRD>01035_3>S598>Lami Assigned Name:Prelamin-A/C HPRD>01035_2>S632>Lami n A/C 1959568 Bcl-2-associated transcription factor 1 ManualHPRD>01035_3>S602>Lami Assigned Name:Bcl-2- associated transcription factor 1 HPRD>16544_1>S648>BCL2 1958998 Swi5-dependent recombination DNA repair Manualassociated Assigned transcription Name:Swi5- factor protein 1 homolog dependent recombination DNA repair protein 1 homolog SwissPROT>CJ078_MOUSE 1960262 Serine/arginine repetitive matrix protein 2 Manual>S67T70>Uncharacterized Assigned Name:Serine/arginine repetitive matrix protein 2 IPI>Q8BTI8>Serine/arginine 1959435 Protein phosphatase 1 regulatory subunit Manualrepetitive Assigned matrix protein 2 12A Name:Protein phosphatase 1 regulatory subunit 12A SwissPROT>MYPT1_MOUS 1959441 Protein phosphatase 1 regulatory subunit ManualE>T443>Isoform Assigned 2 of Protein 12A Name:Protein phosphatase 1 regulatory subunit 12A SwissPROT>MYPT1_MOUS E>S445>Isoform 2 of Protein Page 197 of 603 Diabetes

1959099 Protein FAM54B Manual Assigned Name:Protein FAM54B HPRD>14248_1>S103>Famil y with sequence similarity 54, 1959034 E3 ubiquitin-protein ligase UBR4 Manualmember Assigned B Name:E3 ubiquitin-protein ligase UBR4 HPRD>10184_1>T2715S271 9>Retinoblastoma associated 1960174 Serine/arginine repetitive matrix 1 Manualfactor 600 Assigned Name:Serine/arginine repetitive matrix 1 HPRD>10441_1>T581S583> 1959751 Sodium/hydrogen exchanger ManualSerine arginine Assigned repetitive Name:Sodium/hydrogen exchanger SwissPROT>Q7TSV2_MOUS 1958700 High mobility group protein HMGI-C ManualE>S790>Sodium/hydrogen Assigned Name:High mobility group protein HMGI- C SwissPROT>HMGA2_MOUS 1958634 Protein FAM54B ManualE>S100S104>High Assigned mobility Name:Protein FAM54B HPRD>14248_1>S238>Famil y with sequence similarity 54, 1958720 Heat shock protein HSP 90-alpha Manualmember Assigned B Name:Heat shock protein HSP 90-alpha SwissPROT>HS90A_MOUSE >S231>Heat shock protein 1960149 Tuberin ManualHSP 90-alpha Assigned OS=Mus Name:Tuberin SwissPROT>Q3TCQ7_MOU SE>S1323>Putative 1959585 Vacuolar protein sorting-associated protein Manualuncharacterized Assigned protein 4B Name:Vacuolar protein sorting-associated protein 4B SwissPROT>VPS4B_MOUSE 1959664 Serine/arginine repetitive matrix protein 2 Manual>Vacuolar Assigned protein sorting- Name:Serine/arginine repetitive matrix protein 2 IPI>Q8BTI8>Serine/arginine repetitive matrix protein 2 Diabetes Page 198 of 603

1960420 Transcription intermediary factor 1-beta Manual Assigned Name:Transcription intermediary factor 1-beta SwissPROT>TIF1B_MOUSE 1959178 Eukaryotic translation initiation factor 5B Manual>S51>Isoform Assigned 2 of Name:Eukaryotic translation initiation factor 5B SwissPROT>IF2P_MOUSE> 1959083 Heterogeneous nuclear ribonucleoprotein H ManualS215>Eukaryotic Assigned translation Name:Heterogeneous nuclear ribonucleoprotein H HPRD>03021_1>T107>Heter 1959713 Heterogeneous nuclear ribonucleoprotein H Manualogeneous Assigned nuclear Name:Heterogeneous nuclear ribonucleoprotein H HPRD>03021_1>S104>Heter 1958728 Heterogeneous nuclear ribonucleoprotein U- Manualogeneous Assigned nuclear like protein 2 Name:Heterogeneous nuclear ribonucleoprotein U-like protein 2 1959309 Serine/arginine repetitive matrix protein 2 ManualSwissPROT>HNRL2_MOUS Assigned Name:Serine/arginine repetitive matrix protein 2 SwissPROT>SRRM2_MOUS 1959074 Brain-specific angiogenesis inhibitor 1- ManualE>S2351>Isoform Assigned Name:Brain- 3 of associated protein 2 specific angiogenesis inhibitor 1-associated protein 2 HPRD>05686_1>S366>BAI1 1959075 Brain-specific angiogenesis inhibitor 1- Manualassociated Assigned protein Name:Brain- 2 associated protein 2 specific angiogenesis inhibitor 1-associated protein 2 HPRD>05686_1>S365>BAI1 1959149 Papillary renal cell carcinoma (Translocation- Manualassociated Assigned protein 2 associated) Name:Papillary renal cell carcinoma (Translocation- associated) 1959588 Microtubule-associated protein 1A ManualSwissPROT>Q05CA9_MOUS Assigned Name:Microtubule-associated protein 1A SwissPROT>A2ARP8_MOUS E>S2841T2843>Microtubule- Page 199 of 603 Diabetes

1958676 Yorkie homolog Manual Assigned Name:Yorkie homolog HPRD>09424_1>Yes associated protein 1958806 Exocyst complex component 1 ManualSwissPROT>Q3U046_MOUS Assigned Name:Exocyst complex component 1 HPRD>07615_1>S470>Exoc 1960394 Serine/arginine repetitive matrix 1 Manualyst complex Assigned component 1 Name:Serine/arginine repetitive matrix 1 SwissPROT>A2A8V8_MOUS 1958950 Rho GTPase activating protein 1 ManualE>S878>Serine/arginine Assigned Name:Rho GTPase activating protein 1 SwissPROT>A2AGT9_MOUS E>S91>Rho GTPase 1958653 CLIP-associating protein 1 Manualactivating Assigned protein 1Name:CLIP- OS=Mus associating protein 1 HPRD>09322_1>T796>CLIP associated protein 1 1959236 Serine/arginine repetitive matrix protein 2 ManualIPI>Q80TV8>T793>CLIP- Assigned Name:Serine/arginine repetitive matrix protein 2 SwissPROT>SRRM2_MOUS 1958985 28 kDa heat- and acid-stable phosphoprotein ManualE>S1360>Isoform Assigned Name:28 3 of kDa heat- and acid-stable phosphoprotein SwissPROT>HAP28_MOUSE 1959675 28 kDa heat- and acid-stable phosphoprotein Manual>S57S63>28 Assigned kDa Name:28heat- and kDa heat- and acid-stable phosphoprotein SwissPROT>HAP28_MOUSE 1959165 Glycogen synthase kinase-3 beta Manual>S60S63>28 Assigned kDa heat- and Name:Glycogen synthase kinase-3 beta HPRD>05418_1>Y216>Glyco 1958917 Pleckstrin homology-like domain family B Manualgen synthase Assigned kinase 3 beta member 1 Name:Pleckstrin homology- like domain family B member 1 HPRD>15128_1>S563>Pleck Diabetes Page 200 of 603

1958875 Transcriptional regulator ATRX Manual Assigned Name:Transcriptional regulator ATRX SwissPROT>A2ADH4_MOUS 1959731 182 kDa tankyrase-1-binding protein ManualE>Alpha Assigned thalassemia/mental Name:182 kDa tankyrase-1-binding protein HPRD>06164_1>S1620S162 1960065 Serine/threonine-protein kinase PRP4 Manual1>Tankyrase Assigned 1 binding homolog Name:Serine/threonine- protein kinase PRP4 homolog HPRD>09087_1>T847>PRP4 1959491 Ras-related GTP-binding protein C Manualpre-mRNA Assigned processing Name:Ras- factor related GTP-binding protein C HPRD>12198_1>T96>Ras related GTP binding C 1958867 Serine/arginine repetitive matrix protein 2 ManualHPRD>12199_1>T97>Ras Assigned Name:Serine/arginine repetitive matrix protein 2 SwissPROT>SRRM2_MOUS 1959027 Choline-phosphate cytidylyltransferase A ManualE>S1972T1974>Isoform Assigned 3 of Name:Choline-phosphate cytidylyltransferase A HPRD>00438_1>S315>Phos 1959302 Hepatoma-derived growth factor Manualphate cytidylyltransferase Assigned 1 Name:Hepatoma-derived growth factor SwissPROT>E0CXA0_MOUS 1959305 Hepatoma-derived growth factor ManualE>S96S101>Uncharacterized Assigned Name:Hepatoma-derived growth factor SwissPROT>E0CXA0_MOUS 1960013 Hepatoma-derived growth factor ManualE>S100S101>Uncharacterize Assigned Name:Hepatoma-derived growth factor SwissPROT>E0CXA0_MOUS 1959820 Protein transport protein Sec31A ManualE>S96S100>Uncharacterized Assigned Name:Protein transport protein Sec31A IPI>Q3UPL0>S526>Protein transport protein Sec31A Page 201 of 603 Diabetes

1960054 Protein transport protein Sec31A Manual Assigned Name:Protein transport protein Sec31A IPI>Q3UPL0>S531>Protein 1959801 Ragulator complex protein LAMTOR1 Manualtransport Assigned protein Sec31A Name:Ragulator complex protein LAMTOR1 SwissPROT>CK059_MOUSE 1960035 Ragulator complex protein LAMTOR1 Manual>S26>RhoA Assigned activator Name:Ragulator complex protein LAMTOR1 SwissPROT>CK059_MOUSE 1960411 Ragulator complex protein LAMTOR1 Manual>S27>RhoA Assigned activator Name:Ragulator complex protein LAMTOR1 SwissPROT>CK059_MOUSE 1959352 Intersectin-1 Manual>T28>RhoA Assigned activator Name:Intersectin-1 HPRD>03898_1>S904>Inters ectin 1 1959798 Intersectin-1 ManualHPRD>03898_2>S904>Inters Assigned Name:Intersectin-1 HPRD>03898_1>S901>Inters ectin 1 1959132 Heat shock protein HSP 90-alpha ManualHPRD>03898_2>S901>Inters Assigned Name:Heat shock protein HSP 90-alpha SwissPROT>HS90A_MOUSE >S263>Heat shock protein 1960454 Serine/threonine-protein kinase PRP4 ManualHSP 90-alpha Assigned OS=Mus homolog Name:Serine/threonine- protein kinase PRP4 homolog HPRD>09087_1>Y849>PRP4 1958991 mRNA cap guanine-N7 methyltransferase Manualpre-mRNA Assigned processing factor Name:mRNA cap guanine-N7 methyltransferase SwissPROT>D3YYS7_MOUS 1958607 Utrn utrophin ManualE>S15>Uncharacterized Assigned Name:Utrn utrophin SwissPROT>O08614_MOUS E>Cytoskeletal protein OS=Mus musculus GN=Utrn Diabetes Page 202 of 603

1958815 Nolc1 nucleolar and coiled-body Manual Assigned phosphoprotein 1 isoform D Name:Nolc1 nucleolar and coiled-body phosphoprotein 1 isoform D 1959261 Sntb2 protein ManualSwissPROT>Q3TKZ9_MOUS Assigned Name:Sntb2 protein HPRD>02491_1>S95>Syntro phin beta 2 1959282 Protein bicaudal D homolog 2 ManualHPRD>02491_2>S95>Syntro Assigned Name:Protein bicaudal D homolog 2 SwissPROT>D3Z390_MOUS 1959283 Serine/arginine-rich splicing factor 10 ManualE>S503>Uncharacterized Assigned Name:Serine/arginine-rich splicing factor 10 HPRD>05562_1>S133>FUS 1958951 Itsn1 protein Manualinteracting Assigned protein Name:Itsn1 1 protein SwissPROT>D3Z6P4_MOUS E>S274>Uncharacterized 1959661 Itsn1 protein Manualprotein OS=MusAssigned musculus Name:Itsn1 protein SwissPROT>D3Z6P4_MOUS E>S273>Uncharacterized 1958956 Thyroid hormone receptor-associated protein Manualprotein OS=MusAssigned musculus 3 Name:Thyroid hormone receptor-associated protein 3 SwissPROT>Q8BZN7_MOUS 1959379 Rho guanine nucleotide exchange factor 7 ManualE>S243>Putative Assigned Name:Rho guanine nucleotide exchange factor 7 HPRD>02226_1>S488>Rho 1958771 Ahnak AHNAK nucleoprotein isoform 1 Manualguanine Assigned nucleotide exchange Name:Ahnak AHNAK nucleoprotein isoform 1 HPRD>14684_2>S5782>AH 1959452 Ahnak AHNAK nucleoprotein isoform 1 ManualNAK nucleoprotein Assigned Name:Ahnak AHNAK nucleoprotein isoform 1 HPRD>14684_2>T5824>AHN AK nucleoprotein Page 203 of 603 Diabetes

1959825 Ahnak AHNAK nucleoprotein isoform 1 Manual Assigned Name:Ahnak AHNAK nucleoprotein isoform 1 HPRD>14684_2>S5830>AH 1959128 HIV Tat-specific factor 1 homolog ManualNAK nucleoprotein Assigned Name:HIV Tat-specific factor 1 homolog HPRD>02282_1>S721>TATS F1 1959723 Synapse-associated protein 1 ManualIPI>Q8BGC0>S724>HIV Assigned Tat- Name:Synapse-associated protein 1 HPRD>06733_1>T248>Syna 1958828 Serine/threonine-protein kinase B-raf Manualpse associated Assigned protein 1 Name:Serine/threonine- protein kinase B-raf HPRD>01264_1>S729>B-Raf 1959701 Cad protein ManualSwissPROT>BRAF_MOUSE> Assigned Name:Cad protein HPRD>06437_1>S1859>Glut amine dependent carbamoyl 1959015 Serine/arginine repetitive matrix 1 Manualphosphate Assigned synthase Name:Serine/arginine repetitive matrix 1 SwissPROT>A2A8V8_MOUS 1959166 Activating signal cointegrator 1 complex ManualE>S558S560>Serine/arginine Assigned subunit 3-like 1 Name:Activating signal cointegrator 1 complex subunit 3-like 1 1959038 Rab GTPase-binding effector protein 1 ManualHPRD>03391_1>S225>U5 Assigned Name:Rab GTPase-binding effector protein 1 SwissPROT>Q5QNU3_MOU 1959445 Protein phosphatase 1 regulatory subunit ManualSE>S407S410>"Rabaptin, Assigned 12A Name:Protein phosphatase 1 regulatory subunit 12A SwissPROT>MYPT1_MOUS 1959341 General vesicular transport factor p115 ManualE>Y446>Isoform Assigned 2 of Protein Name:General vesicular transport factor p115 SwissPROT>USO1_MOUSE >Isoform 4 of General Diabetes Page 204 of 603

1959290 Protein SON Manual Assigned Name:Protein SON SwissPROT>Q811G3_MOUS E>S1723>Son protein 1959084 Yorkie homolog Manual(Fragment) Assigned OS=Mus Name:Yorkie homolog HPRD>09424_1>Yes associated protein 1960322 Yorkie homolog ManualSwissPROT>Q3U046_MOUS Assigned Name:Yorkie homolog HPRD>09424_1>Yes associated protein 1959351 Acetyl-coenzyme A synthetase, cytoplasmic ManualSwissPROT>Q3U046_MOUS Assigned Name:Acetyl-coenzyme A synthetase, cytoplasmic SwissPROT>A2AQN4_MOU 1958928 Secreted frizzled-related protein 2 ManualSE>S30>Acyl-CoA Assigned Name:Secreted frizzled- related protein 2 HPRD>16041_1>S289>Secre 1959912 DNA polymerase eta Manualted frizzled Assigned related Name:DNA protein 2 polymerase eta HPRD>01592_1>S235>Ribos omal protein S6 1960264 DNA polymerase eta ManualHPRD>04913_1>S379>DNA Assigned Name:DNA polymerase eta HPRD>01592_1>S236>Ribos omal protein S6 1958650 Ubiquitin carboxyl-terminal hydrolase ManualHPRD>04913_1>S380>DNA Assigned Name:Ubiquitin carboxyl- terminal hydrolase HPRD>11664_1>Ubiquitin 1958651 Ubiquitin carboxyl-terminal hydrolase Manualspecific Assignedprotease 24 Name:Ubiquitin carboxyl- terminal hydrolase HPRD>11664_1>Ubiquitin 1959256 RNA-binding protein 39 Manualspecific Assignedprotease 24Name:RNA- binding protein 39 HPRD>09201_2>S136>Splici ng factor HCC1 HPRD>09201_3>S136>Splici Page 205 of 603 Diabetes

1960240 Itsn1 protein Manual Assigned Name:Itsn1 protein SwissPROT>D3Z6P4_MOUS E>S273>Uncharacterized 1959453 Prostaglandin E synthase 3 Manualprotein OS=MusAssigned musculus Name:Prostaglandin E synthase 3 HPRD>06138_1>Unactive 1960125 Microtubule-associated protein 1A Manualprogesterone Assigned receptor 23KD Name:Microtubule-associated protein 1A SwissPROT>A2ARP8_MOUS 1960217 40S ribosomal protein S6 ManualE>S764S765>Microtubule- Assigned Name:40S ribosomal protein S6 HPRD>01592_1>S236S240> Ribosomal protein S6 1959711 Heat shock protein HSP 90-alpha ManualSwissPROT>D3YX41_MOUS Assigned Name:Heat shock protein HSP 90-alpha SwissPROT>HS90A_MOUSE >S263>Heat shock protein 1960301 Ubiquitin carboxyl-terminal hydrolase ManualHSP 90-alpha Assigned OS=Mus Name:Ubiquitin carboxyl- terminal hydrolase HPRD>11664_2>Ubiquitin 1959553 Proline-rich AKT1 substrate 1 Manualspecific Assignedprotease 24 Name:Proline-rich AKT1 substrate 1 SwissPROT>AKTS1_MOUSE 1959947 Histone deacetylase Manual>Proline-rich Assigned AKT1 substrate Name:Histone deacetylase SwissPROT>D3YYI8_MOUS E>S421S423>MCG128529 1959214 Ras GTPase-activating protein-binding ManualOS=Mus Assigned musculus Name:Ras protein 1 GTPase-activating protein- binding protein 1 SwissPROT>G3BP_MOUSE> 1958901 Protein SET ManualS231>Ras-GTPase-activating Assigned Name:Protein SET SwissPROT>A2BE92_MOUS E>S30>SET translocation (Fragment) OS=Mus Diabetes Page 206 of 603

1959874 Proteasome subunit alpha type-3 Manual Assigned Name:Proteasome subunit alpha type-3 HPRD>01463_1>S243>Prote 1960189 Proteasome subunit alpha type-3 Manualasome subunit,Assigned alpha type 3 Name:Proteasome subunit alpha type-3 HPRD>01463_1>S250>Prote 1959815 Apoptotic chromatin condensation inducer 1 Manualasome subunit,Assigned alpha type 3 (Fragment) Name:Apoptotic chromatin condensation inducer 1 (Fragment) 1960398 Novel protein (1200015F23Rik) (Fragment) ManualSwissPROT>ACINU_MOUSE Assigned Name:Novel protein (1200015F23Rik) (Fragment) SwissPROT>A3KGH5_MOU 1958930 Torsin-1A-interacting protein 1 ManualSE>S44>Novel Assigned protein Name:Torsin-1A-interacting protein 1 SwissPROT>Q1EQW1_MOU 1959646 Retrotransposon-derived protein PEG10 ManualSE>S140>Lamina-associated Assigned Name:Retrotransposon- derived protein PEG10 SwissPROT>PEG10_MOUSE 1959171 A-kinase anchor protein 1, mitochondrial Manual>S30>Isoform Assigned RF1 Name:A- of kinase anchor protein 1, mitochondrial SwissPROT>AKAP1_MOUSE 1959120 Superkiller viralicidic activity 2-like (S. Manual>S101>"Isoform Assigned 6 of A-kinase cerevisiae) Name:Superkiller viralicidic activity 2-like (S. cerevisiae) SwissPROT>Q3TW36_MOU 1959041 Pyruvate dehydrogenase E1 component ManualSE>S240>Putative Assigned subunit alpha, somatic form, mitochondrial Name:Pyruvate dehydrogenase E1 component subunit alpha, 1958905 Uncharacterized protein Manualsomatic Assignedform, mitochondrial Name:Uncharacterized protein SwissPROT>CF203_MOUSE >S106>Uncharacterized Page 207 of 603 Diabetes

1960295 Pyruvate dehydrogenase E1 component Manual Assigned subunit alpha, somatic form, mitochondrial Name:Pyruvate dehydrogenase E1 component subunit alpha, 1960030 Protein phosphatase 1 regulatory subunit Manualsomatic Assignedform, mitochondrial 12A Name:Protein phosphatase 1 regulatory subunit 12A SwissPROT>MYPT1_MOUS 1958731 Heterogeneous nuclear ribonucleoproteins ManualE>S445>Isoform Assigned 2 of Protein C1/C2 Name:Heterogeneous nuclear ribonucleoproteins C1/C2 SwissPROT>HNRPC_MOUS 1958601 Microfibrillar-associated protein 1 ManualE>S299>Isoform Assigned 5 of Name:Microfibrillar- associated protein 1 HPRD>02569_1>S52S53>Mi 1959222 Translation initiation factor eIF-2B subunit Manualcrofibrillar Assigned associated protein epsilon Name:Translation initiation factor eIF-2B subunit epsilon SwissPROT>EI2BE_MOUSE 1958826 La-related protein 7 Manual>S540>Translation Assigned Name:La- initiation related protein 7 IPI>Q05CL8>S253S256>La- related protein 7 1959681 STIP1 homology and U box-containing ManualIPI>IPI00340860.5>S253S25 Assigned protein 1 Name:STIP1 homology and U box-containing protein 1 SwissPROT>CHIP_MOUSE> 1959270 Calcium-regulated heat stable protein 1 ManualS20>STIP1 Assigned homology and U Name:Calcium-regulated heat stable protein 1 HPRD>08515_1>S41>Calciu 1959265 Protein kinase, cAMP dependent regulatory, Manualm regulated Assigned heat stable type I, alpha Name:Protein kinase, cAMP dependent regulatory, type I, alpha 1959067 Programmed cell death protein 5 ManualHPRD>01786_1>S83>Protein Assigned Name:Programmed cell death protein 5 SwissPROT>D3YVV5_MOUS E>S121>Uncharacterized Diabetes Page 208 of 603

accession assigned phosphosite number for sequence annotated psite shSNRK/shGFP qvalues for SILAC K.MDLLTTVQ T311 UNI:B1AXP3 1030.367211 0.006527052 T*HYK.Y

K.S*IRT*LPHI S870T873 UNI:IPI00351 687.5857302 0.006527052 K.Y 041.1

K.VGSLT*PP T618S621* UNI:Q3UHJ0 80.62611954 0.006527052 S*SPK.T

R.RPS*TIAEQ S358 UNI:Q8CFH6 16.17843572 0.009488101 TVAK.A

R.DSGTMGS* S289 UNI:Q8R5F7 11.21476787 0.039652747 DSDESVIQTK .R

R.AMALGDS S384 UNI:Q9QY24 7.510311874 0.033424285 S*PQTTEPVL R.E

R.RLS*EQLA S511* UNI:Q8BKC8 7.186401515 0.023035228 HTPTAFK.R

R.HLDRS*PE S655 UNI:Q0VBL3 6.791986233 0.04972369 SERPR.K

R.RFS*EGVL S429* UNI:P58871 5.516680661 0.038676564 QPPSQDQEK .L Page 209 of 603 Diabetes

R.NKFGS*AD S435 UNI:Q80W04 5.494552692 0.036609927 NIAHLK.D

K.SLS*TEVEP S195 UNI:B1ATR2 5.461699349 0.027575892 K.E

R.LATSS*PE S515 UNI:Q60953 4.868743253 0.026974997 QSWPSTFK. A

K.AT*SPPHL T527 UNI:Q60953 4.833140109 0.028508578 DGTSNPEST VPEK.K

K.ATS*PPHL S528 UNI:Q60953 4.833140109 0.028508578 DGTSNPEST VPEK.K

K.ELSTS*GP S32 UNI:Q03963 4.737904532 0.026441449 PHDR.R

R.LATS*S*PE S514S515 UNI:Q60953 4.486470131 0.044088092 QSWPSTFK. A

K.FLSHS*TD S1910* UNI:IPI00126 4.146197509 0.033977346 SLNK.I 181.9

R.ASSCS*LA S414 UNI:P58801 3.723166758 0.037260875 VISPFLVEK.G

R.RQS*SPSC S433 UNI:Q8BPM 3.527083918 0.032065908 VPVAETSSSI 2 GNGDGISK.L Diabetes Page 210 of 603

R.SRS*GEGE S473* UNI:Q62318 3.507745161 0.030830229 VSGLLR.K

R.SKVGS*TE S761* UNI:E9PWC 3.482284266 0.028919489 NIK.H 0

R.RAGDVLED S165 UNI:P51859 3.458883758 0.033163515 S*PKRPK.E

R.SRS*DIDVN S600* UNI:Q80TV8 3.457942251 0.02461838 AAASAK.S

K.SLS*NPDIA S458 UNI:Q80U35 3.167637163 0.037972079 SETLTLLSFL R.S

R.AT*S*NVFA T19S20 UNI:Q6ZWQ 3.044362225 0.034250636 MFDQSQIQE 9 FK.E

R.RLS*TQFT S81* UNI:Q8CGN 3.023249444 0.036609927 AANELACR.G 5

R.TSS*PTSLP S267 UNI:Q80XI3 2.904965445 0.009488101 PLAR.S

K.SPS*PSPT* S332T336 UNI:Q80VB6 2.895648188 0.02461838 SPGSLR.K

K.S*PSPSPT* S330T336 UNI:Q80VB6 2.895648188 0.02461838 SPGSLR.K Page 211 of 603 Diabetes

K.S*REDLSA S617* UNI:B9EHJ3 2.862407711 0.048092894 QPVQTK.F

K.IYHLPDAE S218* UNI:P42208 2.84493259 0.030830229 S*DEDEDFK. E

K.S*YELPDG S239 UNI:P60710 2.79460464 0.044088092 QVITIGNER.F

K.ATSPPHLD T535 UNI:Q60953 2.715230621 0.032869467 GT*SNPESTV PEKK.I

R.SFS*KEVE S1189* UNI:Q6NZJ6 2.692839154 0.043412508 ER.S

R.MREDYDS* S56 UNI:Q9CWZ 2.680331377 0.031719238 VEQDGDEPG 3 PQR.S

K.HIVSNDSS S437* UNI:P47713 2.590381322 0.023035228 DS*DDEAQG PK.G

R.T*PPSTPP T21T29 UNI:Q60710 2.58444013 0.022143962 AT*ANLSADD DFQNTDLR.T

R.T*PPS*TPP T21S24 UNI:Q60710 2.58444013 0.022143962 ATANLSADD DFQNTDLR.T

K.KEESEES* S105 UNI:G3UW6 2.462061548 0.02461838 DDDMGFGLF 9 D.- Diabetes Page 212 of 603

R.RTSMGGT* T556* UNI:Q02248 2.432719976 0.044088092 QQQFVEGVR .M

K.NGQEAGP T106 UNI:P15092 2.346603429 0.033163515 AT*PTSTTSH MLASER.G

R.RDST*EAP T1321S1328 UNI:Q6P4S8 2.346094034 0.02461838 KPES*SPEPP PGQGR.T

R.RDS*TEAP S1320S1328 UNI:Q6P4S8 2.346094034 0.02461838 KPES*SPEPP PGQGR.T

R.RDST*EAP T1321S1329 UNI:Q6P4S8 2.346094034 0.02461838 KPESS*PEPP PGQGR.T

R.RYS*PS*PP S610S612* UNI:A2A8V8 2.279917374 0.031260141 PK.R

K.GGDYALAP S353S356 UNI:P01897 2.259740506 0.02925192 GSQSS*EMS* LR.D

R.STS*PIIGS S179* UNI:Q3TC46 2.248154776 0.012029028 PPVR.A

K.LSGLS*FK. S104* UNI:P28667 2.243378641 0.049236616 R

R.TPPS*T*PP S24T25 UNI:Q60710 2.22358103 0.039740525 ATANLSADD DFQNTDLR.T Page 213 of 603 Diabetes

K.HIKEEPLS* S509S521* UNI:Q6DFW 2.17332402 0.036609927 EEEPCTSTA 4 VPS*PEK.K

R.RHSSLPT* T758S760* UNI:O54774 2.092782528 0.023035228 ES*DEDIAPA QR.V

R.RHSS*LPT S755S760* UNI:O54774 2.092782528 0.023035228 ES*DEDIAPA QR.V

K.KPEKPLFS S328 UNI:P97863 2.034584622 0.046134291 STS*PQDSSP R.L

R.AMS*TTSV S277 UNI:Q62418 1.983585439 0.023035228 TSSQPGK.L

R.KDS*LTQA S527 UNI:Q9DCD 1.981460652 0.023035228 QEQGTVLS.- 5

K.RTSPS*KP S609 UNI:E9PWC 1.972946035 0.044382609 SSAPALKPG 0 PK.T

R.HLSS*TSD S28 UNI:Q9DBC3 1.946710849 0.034250636 DEPLSSVNH AAK.A

R.TLS*SPTG S864 UNI:B1AZ14 1.916074199 0.023035228 TETNPPK.A

R.SASSDT*S T288* UNI:P70441 1.913017392 0.020146265 EELNSQDSP K.R Diabetes Page 214 of 603

R.S*ASSDTS S283* UNI:P70441 1.913017392 0.020146265 EELNSQDSP K.R

K.RLS*QPAG S269 UNI:Q8C0J2 1.912680833 0.034250636 GLLDSITNIF GR.R

K.HRPS*FTR. S281 UNI:B1AZ14 1.885574555 0.038735827 S

R.SVSHGS*N S902* UNI:Q3TLH4 1.869229993 0.028508578 HAQNAEEQR .N

R.S*VSHGSN S897* UNI:Q3TLH4 1.869229993 0.028508578 HAQNAEEQR .N

R.S*RPLNAV S328 UNI:Q9JKB3 1.867937489 0.034250636 SQDGK.E

K.AIS*SDMFF S431 UNI:Q99K28 1.867812251 0.036609927 GR.E

R.ETIPMNAS S220 UNI:P25446 1.860315338 0.018494698 NLS*LSK.Y

K.AEAENNSG S137 UNI:O70133- 1.858217199 0.026441449 VESSGYGS* 2 PGPTWDR.G

R.NGPLNES* S324* UNI:Q8BYC6 1.857986821 0.027903064 QEEEEDGEQ GSNLNR.E Page 215 of 603 Diabetes

R.YS*PSQNS S284S289* UNI:Q8K019 1.850863069 0.044088092 *PIHHIPSR.R

K.WAHDKFS* S34* UNI:Q80VM0 1.846695764 0.037972079 GEEGEIEDD ESGTENR.E

R.RLSNS*S*L S375S376 UNI:B2RX86 1.837821631 0.02461838 CSIEEEHR.T

R.RLS*NS*SL S373S375 UNI:B2RX86 1.837821631 0.02461838 CSIEEEHR.T

R.DLYRPLS* S352 UNI:Q80VB6 1.831289336 0.047923383 SDDLDSVGD SV.-

R.LRS*EDGV S136 UNI:IPI00553 1.827206088 0.02461838 EGDLGETQS 798.2 R.T

R.SNS*SEAS S87* UNI:P97825 1.826814176 0.02461838 SGDFLDLK.G

K.QQDS*QPE S380* UNI:O35691 1.809456489 0.023035228 EVMDVLEMV ESVK.H

K.ATWGDGG S121 UNI:Q9D3L3 1.807430692 0.02461838 DNS*PSNVV SK.Q

R.AELGMND S263S267* UNI:Q9QXG 1.805175222 0.026441449 S*PSQS*PPV 4 K.R Diabetes Page 216 of 603

K.NVRS*DVS S1766S1769* UNI:Q9R0L6 1.800967205 0.023035228 *DQEEDEES ER.C

R.GVAPADS* S738* UNI:Q6ZPS6 1.793389489 0.034339712 PDAPR.R

R.ESPRPPAA S81 UNI:Q6ZQ58 1.787033178 0.02461838 AEAPAGS*D GEDGGR.R

R.NLGS*INTE S137 UNI:O08547 1.784445139 0.042445681 LQDVQR.I

R.DS*GGTLA S184 UNI:Q9QZL0 1.782303538 0.028508578 YLDPELLFK. V

R.SLS*SPTVT S477* UNI:Q8CFI0 1.778058028 0.032869467 LSAPLEGAK. D

K.QLT*QPET T299* UNI:Q62418 1.777704319 0.018653912 SYGR.E

R.DRGGDT*S T313 UNI:O35892 1.766445226 0.034458466 DTESSIIIR.R

K.KEES*EES* S101S104 UNI:P47955 1.748758643 0.032333852 EDDMGFGLF D.-

K.DMS*PSAE S517 UNI:E9QPW 1.746091572 0.010595587 TEAPLAK.N 8 Page 217 of 603 Diabetes

R.S*LSFDPSL S183* UNI:P23804 1.739577844 0.022067974 GLCELR.E

R.DSGGT*LA T187 UNI:Q9QZL0 1.738093379 0.022173871 YLDPELLFK. V

R.EQES*S*G S122S123* UNI:D3Z3A0 1.732356121 0.033345923 EEDNDLSPE ER.E

R.QIS*EDVD S309 UNI:P46935 1.721334508 0.031181888 GPDNR.E

R.LAIQGPED S237* UNI:Q99KX1 1.703508357 0.023035228 S*PSR.Q

R.LAIQGPED S239* UNI:Q99KX1 1.703508357 0.023035228 SPS*R.Q

R.ISLPLPTFS S420* UNI:P20152 1.69542697 0.033977346 S*LNLR.E

R.LRS*EDGV S136 UNI:IPI00553 1.694508221 0.018138037 EGDLGETQS 798.2 R.T

K.YGLQDS*D S888* UNI:Q6PFD9 1.694181488 0.031441733 EEEEEHPPK. T

R.TNGISDVQI S523 UNI:Q62120 1.673153393 0.043529901 S*PTLQR.H Diabetes Page 218 of 603

R.S*VS*PVAE S1043S1045 UNI:A6H619 1.672232254 0.028508578 EHTR.R

K.LPAKLSVS* S171* UNI:O54724 1.665277371 0.02461838 K.S

K.LPAKLS*VS S169* UNI:O54724 1.665277371 0.02461838 K.S

R.GLGS*NED S393 UNI:Q8C0E3 1.662188757 0.02461838 GLQK.L

R.RLS*PS*AS S387S389S391* UNI:A2A8V8 1.66118578 0.025258451 *PPR.R

R.TLS*IDKGF S775 UNI:P12382 1.66108809 0.02461838 .-

R.TQSSS*CE S571 UNI:O70589- 1.658730791 0.036609927 DLPSTTQPK. 3 G

R.TQSS*SCE S570 UNI:O70589- 1.658730791 0.036609927 DLPSTTQPK. 3 G

R.DLLSDLQD S270* UNI:P24788 1.658476204 0.031260141 IS*DSER.K

R.S*NSVDTG S709* UNI:Q9Z1E4 1.652170775 0.035949602 PSSSLSTPTE PLSPTSSLGE ER.N Page 219 of 603 Diabetes

R.SNS*VDTG S711* UNI:Q9Z1E4 1.652170775 0.035949602 PSSSLSTPTE PLSPTSSLGE ER.N R.EES*DGEY S120* UNI:Q9R020 1.648868901 0.046001469 DEFGR.K

K.SETLVNAQ T141T145 UNI:Q9Z0P4 1.648171607 0.02461838 QT*PLGT*PK. E

K.ASLGS*LE S5525 UNI:IPI00553 1.64730001 0.023035228 GEVEAEASS 798.2 PK.G

K.S*NISPNFN S328 UNI:E9Q3P6 1.64474176 0.043586433 FMGQLLDFE R.T

R.SNS*TEHL S588 UNI:Q9JID9 1.642516967 0.028508578 LDAASGATE EPTEATLGR. A R.ISLPLPTFS S420* UNI:P20152 1.640260405 0.020146265 S*LNLR.E

K.NKEES*S*E S247S248S255* UNI:Q7TNV0 1.639143449 0.023035228 DEEKES*EEE QPPK.K

K.GGFS*DAD S379 UNI:Q569Z6 1.638930717 0.02461838 VK.M

K.SNIS*PNFN S331 UNI:E9Q3P6 1.625048815 0.043529901 FMGQLLDFE R.T Diabetes Page 220 of 603

R.NNLS*LGD S430 UNI:Q8BJ56 1.624564203 0.010595587 ALAK.W

R.LEAS*IER.I S26* UNI:Q9DAS9 1.616372588 0.028508578

R.AMS*LSDA S384 UNI:Q8CGN 1.611886008 0.026441449 LK.G 5

R.LAS*TSDIE S507 UNI:Q9DBR7 1.608325752 0.02461838 EK.E

R.LASTS*DIE S509 UNI:Q9DBR7 1.608325752 0.02461838 EK.E

R.TS*SEDNL S20 UNI:Q9QXS1- 1.607599616 0.02461838 YLAVLR.A 3

K.S*PLIESTA S299 UNI:Q9DBR7 1.603331838 0.03577241 NMENNQPQK .A

K.S*LENETLN S445* UNI:Q8BGD 1.600652371 0.034548735 K.E 9

R.LATTVS*AP S748* UNI:E9PWC 1.590243507 0.006527052 DLK.S 0

K.S*SSSVTT S317 UNI:P70460 1.581743576 0.043529901 SEAHPSTPC SSDDSDLER. V Page 221 of 603 Diabetes

K.SSS*SVTT S319 UNI:P70460 1.581743576 0.043529901 SEAHPSTPC SSDDSDLER. V R.NLS*FEIK.K S434* UNI:P35831 1.577085947 0.023035228

R.RRS*PT*PP S577T579 UNI:A2A8V8 1.569251883 0.023035228 PR.R

R.GLS*APSC S460 UNI:Q8CGN 1.557414097 0.0388827 PGLDDK.T 5

R.GLSAPS*C S463 UNI:Q8CGN 1.557414097 0.0388827 PGLDDK.T 5

K.ESTESSNT T337* UNI:Q6PHZ2 1.550852103 0.031132282 T*IEDEDVK.A

K.SPSPSPT* T336 UNI:Q80VB6 1.547173489 0.028508578 SPGSLR.K

K.SPSPSPTS S337 UNI:Q80VB6 1.547173489 0.028508578 *PGSLR.K

R.SAS*SDTS S285* UNI:P70441 1.546559055 0.026974997 EELNSQDSP K.R

K.ATIS*DEEI S199* UNI:Q8BJF9 1.539216882 0.027575892 ER.Q Diabetes Page 222 of 603

R.S*RS*RDS* S1141S1143S114 UNI:Q9ET54 1.539006346 0.026730019 GDENEPIQE 6* R.F

R.KAEDS*DS S499S501* UNI:Q9DBR1 1.538960225 0.031441733 *EPEPEDNV R.L

R.QSS*LTFQ S1183 UNI:B1AZ14 1.537458494 0.033543599 SSDPEHVR. Q

K.QSNASS*D S106* UNI:Q99JF8 1.532255554 0.018653912 VEVEEK.E

K.QSNAS*SD S105* UNI:Q99JF8 1.532255554 0.018653912 VEVEEK.E

K.EGINPGYD S444* UNI:Q08943 1.526535721 0.025258451 DYADS*DED QHDAYLER. M R.IS*EDETER S112 UNI:Q52KR6 1.521532722 0.035499969 .N

K.GGVTGS*P S5504 UNI:IPI00553 1.514696472 0.011048245 EASISGSK.G 798.2

R.SLS*TSGE S10* UNI:P60904 1.514310896 0.047305429 SLYHVLGLD K.N

R.S*LSTSGE S8* UNI:P60904 1.514310896 0.047305429 SLYHVLGLD K.N Page 223 of 603 Diabetes

R.YGS*QEHP S809 UNI:Q60790 1.513040337 0.02461838 IGDK.S

R.VS*PVPSP S777 UNI:Q8VDP3 1.508647518 0.02461838 SQPAR.R

R.HRPSS*PA S401T404* UNI:A2A8V8 1.508416289 0.027575892 T*PPPK.T

R.HRPS*SPA S400T404* UNI:A2A8V8 1.508416289 0.027575892 T*PPPK.T

K.NLAKPGVT S272S274* UNI:Q99JF8 1.505903125 0.010406962 STS*DS*EDE DDQEGEK.K

K.NLAKPGVT T271S274* UNI:Q99JF8 1.505903125 0.010406962 ST*SDS*EDE DDQEGEK.K

K.NLAKPGVT T269S274* UNI:Q99JF8 1.505903125 0.010406962 *STSDS*EDE DDQEGEK.K

K.NLAKPGVT S270T271* UNI:Q99JF8 1.505903125 0.010406962 S*T*SDSEDE DDQEGEK.K

R.RPS*QNAM S194* UNI:Q8CI95 1.502099031 0.037972079 SFFNVGHSK. L

R.VNGLPS*P S32T34 UNI:Q80VB6 1.496783223 0.034250636 T*HSAHCSFY R.T Diabetes Page 224 of 603

R.S*PS*PAPP S558S560* UNI:A2A8V8 1.495818924 0.046134291 PPPPPPPPR. R

R.SAS*ITNLS S307 UNI:Q9Z1T6 1.493433679 0.02461838 LDR.S

K.QQQEPTC S44* UNI:Q6NSP9 1.492803929 0.023035228 EPS*PK.R

R.IDIS*PSTF S679* UNI:Q569Z6 1.48857383 0.005885893 R.K

K.LGASNS*P S675* UNI:B2RY56 1.487448678 0.02721905 GQPNSVK.R

R.RMS*LEGR S188 UNI:O89110 1.485715271 0.026441449 .E

K.NSGPVSEV S1305 UNI:Q8BTI8 1.48158489 0.012029028 NTGFS*PEVK .E

R.AS*SHSSQ S403* UNI:P48678 1.478609713 0.032869467 SQGGGSVTK .K

R.ASS*HSSQ S404* UNI:P48678 1.478609713 0.032869467 SQGGGSVTK .K

R.KKS*PIVNE S278* UNI:Q61136 1.473136457 0.02461838 R.S Page 225 of 603 Diabetes

R.AES*PETS S1356* UNI:Q4VA53 1.466310875 0.027575892 AVESTQSTP QK.G

R.ISLPLPTFS S419* UNI:P20152 1.461662503 0.02461838 *SLNLR.E

R.AQS*TDSL S407* UNI:O35551 1.458931272 0.03461207 GTSSSLQSK. A

R.LS*LMEPE S410 UNI:Q8CGN 1.458232843 0.039652747 SEFR.D 5

R.LS*LMEPE S410 UNI:Q8CGN 1.458232843 0.039652747 SEFR.D 5

R.RRS*S*GL S1794S1795 UNI:IPI00761 1.456566669 0.030536122 QPQGAPEVR 751.2 .R

R.SIS*SPSM S1380 UNI:IPI00761 1.455309865 0.044769447 NR.L 751.2

K.S*TSSAMG S240 UNI:Q68EF0 1.453791107 0.012029028 GSHQDLSVI QPIVK.D

K.AAADDGEE S18 UNI:P28352 1.449665035 0.049439966 PKS*EPETK. K

R.SS*SLGDL S394 UNI:Q8K124 1.446931743 0.039652747 LR.E Diabetes Page 226 of 603

R.SSS*LGDL S395 UNI:Q8K124 1.446931743 0.039652747 LR.E

R.LS*PPHS*P S955S959 UNI:Q60875 1.444512803 0.011650196 R.D

R.VS*PEVGS S747 UNI:Q6PGL7 1.43736064 0.023035228 ADVASIAQK. E

R.ELS*PEQS S505 UNI:Q8CI11 1.433364785 0.041596747 TAGKPSDGS SALDR.A

R.SAS*YSYL S909* UNI:Q9DBR7 1.431451475 0.042013979 EDR.K

R.RPS*TSPD S266 UNI:Q9JJZ4 1.42604215 0.024170293 VLQGQPPR. A

R.GDVS*EDE S100 UNI:Q9D0L8 1.422807805 0.048711205 PSLGR.L

R.SNS*LPHS S434 UNI:Q3UWE 1.422009044 0.032333852 AVSNAASK.G 6

R.VDS*TTCL S259* UNI:P47856 1.419646368 0.039652747 FPVEEK.A

R.LGADES*E S85 UNI:Q8BHG 1.419130072 0.03461207 EEGR.S 1 Page 227 of 603 Diabetes

K.LIDLES*PT S1528* UNI:Q4VBF8 1.408639338 0.023035228 PESQK.N

R.LKTEEGEI S37 UNI:Q921F4 1.403853594 0.033345923 VYS*AEESEN R.Q

K.S*PSPPPD S265* UNI:Q6P1B9 1.398066809 0.010406962 GSPAATPEIR .V

K.GNKS*PS* S265S267* UNI:Q6P1B9 1.391840445 0.03854909 PPPDGSPAA TPEIR.V

R.SKS*PAST S307 UNI:Q80VB6 1.387821942 0.039652747 SSVNGTPGS QLSTPR.S

R.SKSPASTS S312 UNI:Q80VB6 1.387821942 0.039652747 *SVNGTPGS QLSTPR.S

R.SKSPAS*T S310 UNI:Q80VB6 1.387821942 0.039652747 SSVNGTPGS QLSTPR.S

R.LPAPQEDT T268 UNI:Q64012 1.386587308 0.040625492 *ASEAGTPQ GEVQTR.D

R.LPAPQEDT S270 UNI:Q64012 1.386587308 0.040625492 AS*EAGTPQ GEVQTR.D

K.S*PGHMVIL S552* UNI:Q8CH25 1.383510534 0.032869467 NQTK.G Diabetes Page 228 of 603

K.ADVSVEKL S1120 UNI:Q8C1B1 1.381093408 0.024913634 DGES*DKEQ FDDDQK.V

K.VATLNS*E S31* UNI:Q8VDJ3 1.38029287 0.043865778 EENDPPTYK. D

K.YNLDAS*E S188* UNI:Q9R020 1.375744805 0.030901956 EEDSNKK.K

R.LPSGS*GP S213S217 UNI:IPI00553 1.375631671 0.039652747 AS*PTTGSAV 798.2 DIR.A

R.LPS*GSGP S211S217 UNI:IPI00553 1.375631671 0.039652747 AS*PTTGSAV 798.2 DIR.A

R.YTDQS*GE S81 UNI:Q8K1Z0 1.374809674 0.02461838 EEEDYESEE QLQHR.I

K.RST*PSGP T163 UNI:O35479 1.373219393 0.046655501 VR.S

R.S*ASPDDD S15* UNI:Q9R0P4 1.369739358 0.046134291 LGSSNWEAA DLGNEER.K

K.QPLLLS*ED S39* UNI:Q8R1B4 1.360180049 0.03854909 EEDTKR.V

R.APDRT*PP T82* UNI:Q8BJU0 1.359439024 0.02461838 SEEDSAEAE R.L Page 229 of 603 Diabetes

R.GDS*ETDL S46 UNI:P46938 1.357241222 0.035949602 EALFNAVMN PK.T

K.EEPLS*EE S509* UNI:Q6DFW 1.357123392 0.036238122 EPCTSTAVP 4 SPEK.K

K.RGT*S*PR T740S741* UNI:P24788 1.357089895 0.04069897 PPEGGLGYS QLGDDDLK.E

K.RGT*S*PR T740S741* UNI:P24788 1.357089895 0.04069897 PPEGGLGYS QLGDDDLK.E

R.CLS*PDDS S981 UNI:Q9QYR 1.354478809 0.044382609 TVK.M 6

R.ISLPLPT*F T417* UNI:P20152 1.354359101 0.030901956 SSLNLR.E

K.NNS*PAPP S1079* UNI:Q14AX6 1.353928784 0.02461838 QPAPVK.A

R.HVTLPSS* S2716* UNI:A2AN08 1.353619484 0.02461838 PR.S

R.HVTLPS*S S2715* UNI:A2AN08 1.353619484 0.02461838 PR.S

K.IDASKNEE S83* UNI:Q60668 1.352892569 0.046134291 DEGHSNSS* PR.H Diabetes Page 230 of 603

R.LPSGS*GP S213S217 UNI:IPI00553 1.351894538 0.031747009 AS*PTTGSAV 798.2 DIR.A

R.LGS*LPR.D S72 UNI:Q8BX02 1.349009679 0.039652747

R.MYS*PSPS S1028 UNI:A2AIX1 1.345686476 0.03461207 DGPASQQPL PNHPR.Q

R.LRLS*PS*P S390S392* UNI:P48678 1.344837222 0.036609927 TSQR.S

R.LRLS*PSPT S390S395* UNI:P48678 1.344837222 0.036609927 S*QR.S

R.KLS*VDNN S857 UNI:Q8K4L2 1.343305074 0.044088092 TSATDYK.S

K.KKEPAISS S100* UNI:P10711 1.34274994 0.031381487 QNS*PEAR.E

R.T*PS*PPPP T263S265 UNI:IPI00515 1.342318767 0.028964788 ILEDIILGK.K 528.3

K.AGEQQLS* S19* UNI:E9QLK0 1.335951337 0.0490369 EPEDMEMEA GDTDDPPR.I

K.S*PLIESTA S299 UNI:Q9DBR7 1.333626849 0.028508578 NMENNQPQK .A Page 231 of 603 Diabetes

K.IAVDLS*DQ S121 UNI:Q3TX08 1.333363929 0.02435676 EEETAGK.N

R.QSS*LTFQ S1183 UNI:B1AZ14 1.332451842 0.039652747 SSDPEHVR. Q

K.SQS*PS*PP S243S245 UNI:B8JJ89 1.331690458 0.039652747 PLPEDLEK.A

R.RS*SQGVL S650* UNI:P54310 1.3313273 0.028508578 HMPLYTSPIV K.N

K.LASDDRPS S723* UNI:Q99KG3 1.328817873 0.028312977 *PPR.G

K.EKS*PELP S220* UNI:A2A8V8 1.328741142 0.010595587 EPSVR.M

R.LRLS*PSPT S390* UNI:P48678 1.328305987 0.038676564 SQR.S

K.VAYIPDET S165 UNI:Q9CPN8 1.327894113 0.018441724 AAQQNPS*P QLR.G

R.LNHS*PPQ S127* UNI:Q6NZN0 1.327583003 0.037940786 SSSR.Y

R.ISS*LER.S S255 UNI:Q8BLD9 1.32556176 0.040485407 Diabetes Page 232 of 603

R.GHPSAGA S120S123 UNI:Q8JZQ9 1.323809946 0.02461838 EEEGGS*DG S*AAEAEPR. A R.RGS*ETMA S43 UNI:Q8K4Z3 1.323215203 0.023035228 GAAVK.Y

R.ENPPS*PP S67T70 UNI:Q8BP27 1.321531455 0.02461838 T*SPAAPQPR .E

R.ENPPS*PP S67S71 UNI:Q8BP27 1.321531455 0.02461838 TS*PAAPQPR .E

R.S*IEDLHR. S171* UNI:A2APV2 1.320922284 0.0388827 G

K.KPAQETEE S104 UNI:P52927 1.318347756 0.03292067 TSSQES*AEE D.-

R.LS*PSPTS S390* UNI:P48678 1.315671756 0.026974997 QR.S

R.LSPS*PTS S392* UNI:P48678 1.315671756 0.026974997 QR.S

R.RS*PS*PYY S264S266* UNI:P62996 1.313439533 0.026441449 SR.Y

R.S*RT*PPSA S2360T2362 UNI:Q8BTI8 1.312567771 0.026441449 PSQSR.M Page 233 of 603 Diabetes

R.SGLS*PAN S47* UNI:O70310 1.309997347 0.035936682 DTGAK.K

K.LGVSVS*P S530* UNI:Q0P678 1.309312234 0.034250636 SR.A

K.GVQAGNS* S64 UNI:Q52KR6 1.308024285 0.040485407 DTEGGQPGR .K

K.LPAKLSVS* S171* UNI:O54724 1.307988791 0.041736861 K.S

R.SNSVDT*G T714* UNI:Q9Z1E4 1.30755911 0.031260141 PSSSLSTPTE PLSPTSSLGE ER.N R.SNSVDTGP S719* UNI:Q9Z1E4 1.30755911 0.031260141 SSS*LSTPTE PLSPTSSLGE ER.N R.SHS*LPNS S46 UNI:A3KGH5 1.307200209 0.043529901 LDYAQASER. G

K.GIPLPTGD T41* UNI:Q9Z1D1 1.30639995 0.02461838 T*SPEPELLP GDPLPPPK.E

K.GIPLPTGD S42* UNI:Q9Z1D1 1.30639995 0.02461838 TS*PEPELLP GDPLPPPK.E

K.S*FEDLTD S794* UNI:Q9Z0F8 1.304380939 0.043412508 HPVTR.S Diabetes Page 234 of 603

R.Y*SPSQNS Y283S296* UNI:Q8K019 1.304046112 0.026974997 PIHHIPS*R.R

K.MELGT*PL T955 UNI:Q8BTI8 1.303599997 0.02461838 R.H

K.YS*LPSK.F S283 UNI:Q9Z277 1.303298404 0.01143977

K.S*HTGEAA S387 UNI:P59017 1.302910906 0.039652747 AVR.G

R.ISS*IR.E S134 UNI:A6H6N9 1.300038734 0.006402985

R.APTAALS* S366 UNI:D3YXK2 1.299251705 0.029772069 PEPQDSK.E

R.IDIS*PSAL S656* UNI:Q8K019 1.298281706 0.034250636 R.K

R.TAS*PPPP S621* UNI:A2A8V8 1.297065955 0.028508578 PKR.R

K.IEDVGS*DE S255* UNI:Q71LX8 1.294530206 0.032656278 EDDSGK.D

R.RVS*TLAN S222 UNI:Q8CGN 1.294481779 0.045399155 TLSR.H 5 Page 235 of 603 Diabetes

R.GPAGEAS S90* UNI:B7ZNU9 1.290342975 0.03854909 AS*PPVR.R

K.DDDDIDLF S106* UNI:O70251 1.288460557 0.02461838 GS*DDEEES EEAK.K

R.FS*PVLGR. S495 UNI:P58742 1.288458848 0.02461838 A

R.RRS*PSPY* S264Y268* UNI:P62996 1.288331108 0.030344453 YSR.Y

R.TLSSS*SM S607* UNI:Q91YS4 1.284158337 0.042411267 DLSR.R

K.GGNVFEAL S138* UNI:Q6P542 1.283815988 0.039652747 IQDDS*EEEE EEEENR.V

R.NYQQNYQ S163* UNI:P62960 1.282931326 0.043168007 NS*ESGEKN EGSESAPEG QAQQR.R K.KPAQETEE S101S104 UNI:P52927 1.280342022 0.02461838 TSS*QES*AE ED.-

K.KPAQETEE S100S104 UNI:P52927 1.280342022 0.02461838 TS*SQES*AE ED.-

R.HELS*PPQ S74* UNI:Q99MR6 1.276686796 0.04497445 KR.M Diabetes Page 236 of 603

K.EAGIVHS*D S346* UNI:O35691 1.275339779 0.02461838 AEKEQEEEE QK.Q

R.EKEIS*DDE S226* UNI:Q71LX8 1.274954909 0.020146265 AEEEK.G

R.SHS*LDDL S831 UNI:P59808 1.274155533 0.043529901 QGDADVGK. N

R.S*HSLDDL S829 UNI:P59808 1.274155533 0.043529901 QGDADVGK. N

K.VSS*PVLET S1360 UNI:Q8BTI8 1.273571832 0.02461838 VQQR.T

K.QLSVPAS* S107* UNI:Q6P542 1.272821049 0.036609927 DEEDEVPAPI PR.G

R.S*RS*PPPV S189S191* UNI:Q62093 1.268468469 0.029723372 SK.R

K.RES*PSPA S448 UNI:A2A8V8 1.267824984 0.044088092 PKPR.K

R.QES*DPED S100* UNI:O35691 1.26740847 0.047447802 DDVK.K

R.KVVDYSQF S19* UNI:Q80XU3 1.267402056 0.023035228 QES*DDADE DYGR.D Page 237 of 603 Diabetes

K.MESEAGA S268* UNI:Q9Z204 1.266165059 0.010595587 DDS*AEEGD LLDDDDNED R.G K.MES*EAGA S261* UNI:Q9Z204 1.266165059 0.010595587 DDSAEEGDL LDDDDNEDR. G K.HSASDPGP S1766 UNI:Q8BI84 1.265678006 0.034250636 APVVNSSS*R .S

K.HSASDPGP S1765 UNI:Q8BI84 1.265678006 0.034250636 APVVNSS*SR .S

K.HSASDPGP S1764 UNI:Q8BI84 1.265678006 0.034250636 APVVNS*SSR .S

K.LLASPDAS S693 UNI:Q9JHF5 1.264686596 0.039740525 TLENS*WSP DEEK.A

R.RSS*VNGE S1444* UNI:Q99MS7 1.264224025 0.047767606 AGPVPPPR.A

R.EQTAS*AP S268 UNI:B1AZ14 1.263559329 0.039652747 ATPLVSK.H

R.EQTAS*AP S268 UNI:B1AZ14 1.263559329 0.039652747 ATPLVSK.H

R.S*RS*GS*II S208S210S212 UNI:Q8BL97 1.26147089 0.042928021 GSR.Y Diabetes Page 238 of 603

R.GHPSAGA S120S123 UNI:Q8JZQ9 1.260020213 0.032333852 EEEGGS*DG S*AAEAEPR. A K.KEVQS*PE S494* UNI:Q8K019 1.259834185 0.032869467 QVK.S

R.HLPGSGQ S1087 UNI:Q8CGB 1.258542724 0.026441449 QPS*PPAR.S 6

R.KGTGDCS* S1943* UNI:Q8VDD5 1.258383136 0.048092894 DEEVDGK.A

K.GHYEVTGS S5607 UNI:IPI00553 1.257344397 0.016086 *DDEAGK.L 798.2

R.DHS*PTPS S479* UNI:Q9D824 1.25535656 0.0490369 VFNSDEER.Y

R.DHSPTPS* S483* UNI:Q9D824 1.25535656 0.0490369 VFNSDEER.Y

R.DHSPT*PS T481* UNI:Q9D824 1.25535656 0.0490369 VFNSDEER.Y

K.NEEDEGH S82* UNI:Q60668 1.252431128 0.02461838 SNS*SPR.H

R.TQS*SSCE S569 UNI:O70589- 1.251752259 0.030830229 DLPSTTQPK. 3 G Page 239 of 603 Diabetes

R.FCTGDS*P S82 UNI:Q8C0J6 1.25105153 0.043529901 PLEAK.L

R.NVPQEESL S60* UNI:O35344 1.249710999 0.02461838 EDS*DVDADF K.A

K.YVDEDNS* S148* UNI:Q8VDQ 1.249671799 0.021014369 DGETVDHR.L 9

R.ASS*LNFL S575* UNI:O88448 1.249201467 0.028508578 NK.S

K.GIPLPTGD T41* UNI:Q9Z1D1 1.24861558 0.027926853 T*SPEPELLP GDPLPPPK.E

R.S*RT*PPVT S1878T1880 UNI:Q8BTI8 1.248014626 0.028508578 R.R

K.MSPNETLF S94* UNI:Q99K70 1.247766568 0.04692638 LES*TNK.I

K.KAEGEPQE S177* UNI:Q8K019 1.24533987 0.02461838 ES*PLK.S

K.LDEGT*PP T1844* UNI:IPI00229 1.244064683 0.031441733 EPK.G 647.5

R.S*KS*PPKS S206S208S212S2 UNI:Q62093 1.243982285 0.023035228 *PEEEGAVS* 20 S.- Diabetes Page 240 of 603

K.LLDFGS*LS S113* UNI:P63276 1.2426966 0.037100195 NLQVTQPTV GMNFK.T

R.GWS*PPPE S30* UNI:Q9QXG 1.241969833 0.023035228 VR.R 4

R.HRS*NS*FS S5553S5555 UNI:IPI00553 1.239927976 0.025540115 DER.E 798.2

R.S*VGGSGG S629 UNI:P48678 1.239367373 0.029723372 GSFGDNLVT R.S

R.SVGGS*GG S633 UNI:P48678 1.239367373 0.029723372 GSFGDNLVT R.S

R.QKS*PEIH S646* UNI:Q8K019 1.237761463 0.02461838 R.R

R.ENPPS*PP S67T70 UNI:Q8BP27 1.235598567 0.044088092 T*SPAAPQPR .E

K.RVPS*PTP S2535 UNI:Q8BTI8 1.233710269 0.043586433 VPK.E

K.T*GSYGAL T443* UNI:Q9DBR7 1.232507411 0.032869467 AEISASK.E

K.TGS*YGAL S445* UNI:Q9DBR7 1.232507411 0.032869467 AEISASK.E Page 241 of 603 Diabetes

R.NAS*VPNL S100 UNI:Q9CWE 1.231305977 0.009488101 R.G 0

R.HVT*LPSS* T2712S2716* UNI:A2AN08 1.22837412 0.039652747 PR.S

R.RRT*PS*PP T586S588 UNI:A2A8V8 1.228129997 0.041312983 PR.R

R.SKEPSSPG S790* UNI:Q7TSV2 1.22777835 0.039652747 TDDVFTPGS SDS*PSSQR.I

K.KPAQETEE S100S104 UNI:P52927 1.2265018 0.019815842 TS*SQES*AE ED.-

K.ASS*FADM S235 UNI:Q9CWE 1.225748465 0.020758727 MGILK.D 0

R.DKEVS*DD S231* UNI:P07901 1.223617148 0.031713029 EAEEKEEK.E

K.SSS*SPEL S1388* UNI:Q61037 1.221515309 0.03461207 QTLQDILGDL GDK.I

K.GNDS*DGE S102 UNI:P46467 1.220182339 0.035154749 AESDDPEK.K

R.S*RS*RT*P S1832S1834T183 UNI:Q8BTI8 1.219281444 0.041596747 LISR.R 6 Diabetes Page 242 of 603

K.RPAASSAA S51* UNI:Q62318 1.218892839 0.036609927 AASAAASS*P AGGGGEAQ ELLEHCGVC K.SVPTVDS*R.E S215* UNI:Q05D44 1.216586845 0.043586433 GNEDDDSSF K.I

K.HTGPNSPD T107* UNI:O35737 1.215205043 0.037869211 T*ANDGFVR. L

K.HTGPNS*P S104* UNI:O35737 1.215205043 0.037869211 DTANDGFVR. L

R.S*GDETPG S159 UNI:Q00PI9 1.21517713 0.034548735 SEAPGDK.A

R.TS*PLMLD S2351 UNI:Q8BTI8 1.214119195 0.029272654 R.A

R.SSS*MAAG S367 UNI:B1AZ46 1.214017769 0.02461838 LER.N

R.SS*SMAAG S366 UNI:B1AZ46 1.214017769 0.02461838 LER.N

R.IAAPELQK S157S159 UNI:Q9EQC 1.213572283 0.026441449 GDS*DS*EED 8 EPAK.K

K.RS*PT*PGK S2603T2605 UNI:Q9QYR 1.212917246 0.026883818 GPVDR.T 6 Page 243 of 603 Diabetes

R.GDSET*DL T48 UNI:P46938 1.211260524 0.02461838 EALFNAVMN PK.T

K.LTGS*TSSL S455 UNI:Q5PPR2 1.20909741 0.038676564 NK.L

R.KETES*EA S878 UNI:A2A8V8 1.208630523 0.04653522 EDDNLDDLE R.H

K.SSS*PEPV S91 UNI:A2AH25 1.20699461 0.011398117 THLK.W

R.VLST*STDL T793* UNI:Q80TV8 1.206357744 0.028508578 EAAVADALK. K

K.VSS*PVLET S1360 UNI:Q8BTI8 1.20517565 0.035154749 VQQR.T

K.S*LDSDES* S57S63* UNI:Q3UHX2 1.204827819 0.026441449 EDEDDDYQQ K.R

K.SLDS*DES* S60S63* UNI:Q3UHX2 1.204827819 0.026441449 EDEDDDYQQ K.R

R.GEPNVSY*I Y216* UNI:Q9WV6 1.204673176 0.033163515 CSR.Y 0

R.KLS*SGDL S565 UNI:Q6PDH0 1.204039741 0.02461838 R.V Diabetes Page 244 of 603

K.YVES*DDE S92* UNI:Q61687 1.202881238 0.031181888 KPTDENVNE K.A

R.VPS*S*DEE S1611S1612* UNI:P58871 1.202853148 0.043412508 VVEEPQSR.R

K.LCDFGSAS T847* UNI:Q61136 1.202195727 0.028508578 HVADNDIT*P YLVSR.F

K.MSPNETLF T95* UNI:Q99K70 1.200861328 0.042061773 LEST*NK.I

R.S*RT*PPAI S1972T1974 UNI:Q8BTI8 1.199887164 0.043381208 R.R

R.MLQAIS*PK S315* UNI:P49586 1.199397296 0.040625492 .Q

K.GS*AEGSS S128S133* UNI:P51859 1.19910738 0.043529901 *DEEGKLVID EPAK.E

K.GSAEGS*S S132S133* UNI:P51859 1.19910738 0.043529901 *DEEGKLVID EPAK.E

K.GS*AEGS* S128S132* UNI:P51859 1.19910738 0.043529901 SDEEGKLVID EPAK.E

K.DSDQVAQ S526 UNI:Q3UPL0 1.198015626 0.039652747 S*DGEESPA AEEQLLGER. I Page 245 of 603 Diabetes

K.DSDQVAQ S531 UNI:Q3UPL0 1.198015626 0.039652747 SDGEES*PA AEEQLLGER. I K.LLLDPS*ST S26 UNI:Q9CQ22 1.197794473 0.012029028 PTK.A

K.LLLDPSS*T S27 UNI:Q9CQ22 1.197794473 0.012029028 PTK.A

K.LLLDPSST* T28 UNI:Q9CQ22 1.197794473 0.012029028 PTK.A

R.SAFTPATA S897* UNI:Q9Z0R4 1.197259362 0.027003469 TGSSPS*PVL GQGEK.V

R.SAFTPATA S894* UNI:Q9Z0R4 1.197259362 0.027003469 TGS*SPSPVL GQGEK.V

K.ESDDKPEI S263* UNI:P07901 1.196409362 0.010406962 EDVGS*DEE EEEK.K

K.LCDFGSAS Y849* UNI:Q61136 1.185885196 0.026730019 HVADNDITPY *LVSR.F

K.ASVASDPE S15 UNI:Q9D0L8 1.18566609 0.039740525 S*PPGGNEP AAASGQR.L

K.AAQAS*LN S933 UNI:IPI00353 1.18508029 0.010406962 ALNDPIAVEQ 420.7 ALQEK.K Diabetes Page 246 of 603

K.AAKES*EE S562 UNI:IPI00719 1.183397384 0.039652747 EEEEEETEE 871.1 K.K

R.GLGPPS*P S75* UNI:B7ZNU9 1.183039063 0.034339712 PAPPR.G

R.S*PVLLPK. S578 UNI:Q921C5 1.181715079 0.02461838 G

R.S*FDYNYR. S133* UNI:Q9R0U0 1.179481336 0.043412508 R

R.LPEEPSS* S335 UNI:Q6NZJ5 1.179155531 0.044088092 EDEQQPEK. K

R.LPEEPS*S S334 UNI:Q6NZJ5 1.179155531 0.044088092 EDEQQPEK. K

R.ASVSDLS* S243 UNI:Q569Z6 1.177281142 0.038676564 PR.E

R.MS*GFIYQ S497* UNI:Q9ES28 1.175684801 0.035154749 GK.L

R.SNS*FSDE S5555 UNI:IPI00553 1.171046126 0.029723372 R.E 798.2

K.FGT*FGGL T5590 UNI:IPI00553 1.168496252 0.03292067 GSK.S 798.2 Page 247 of 603 Diabetes

K.FGTFGGLG S5596 UNI:IPI00553 1.168496252 0.03292067 S*K.S 798.2

K.LFDDS*DE S724* UNI:Q8BGC 1.167576478 0.035154749 R.G 0

K.T*PPVVIK.S T262* UNI:Q9D5V6 1.16691471 0.02461838

R.SAS*EPSL S766* UNI:P28028 1.166801608 0.026441449 NR.A

R.AS*DPGLP S1859* UNI:B7ZN27 1.166660411 0.033345923 AEEPK.E

R.RRS*PS*P S558S560* UNI:A2A8V8 1.163053437 0.049439966 APPPPPPPP PPR.R

R.EEAS*DDD S225* UNI:Q6P4T2 1.160817815 0.04042083 MEGDEAVVR .C

R.AQS*TDS*L S407S410* UNI:O35551 1.159713296 0.043412508 GTSSSLQSK. A

K.TGSY*GAL Y446* UNI:Q9DBR7 1.158597227 0.033345923 AEISASK.E

K.DLGHPVEE S940* UNI:Q9Z1Z0 1.157898905 0.028508578 EDES*GDQE DDDDEIDDG DKDQDI.- Diabetes Page 248 of 603

K.ESAQAVAV S1723 UNI:Q9QX47 1.153430139 0.033345923 ALS*PK.E

R.QAST*DAG T95* UNI:P46938 1.15007245 0.036609927 TAGALTPQH VR.A

R.QAS*TDAG S94* UNI:P46938 1.15007245 0.036609927 TAGALTPQH VR.A

R.GWS*PPPE S30* UNI:Q9QXG 1.149999218 0.028508578 VR.R 4

R.ISRS*IR.K S289* UNI:P97299 1.147237448 0.028508578

R.RLS*SLR.R S378* UNI:Q9JJN0 1.147237448 0.028508578

R.RLSS*LR.R S379* UNI:Q9JJN0 1.147237448 0.028508578

R.TIS*AQDTL S2559* UNI:E9PV45 1.146141355 0.026974997 AYATALLNEK .E

R.TISAQDT*L T2563* UNI:E9PV45 1.146141355 0.026974997 AYATALLNEK .E

K.DKS*PVRE S136 UNI:Q8VH51 1.145063025 0.040625492 PIDNLTPEER .D Page 249 of 603 Diabetes

R.LPEEPS*S S334 UNI:Q6NZJ5 1.143202411 0.031381487 EDEQQPEKK .L

K.DWEDDS*D S113* UNI:Q9R0Q7 1.141728543 0.04195003 EDMSNFDR.F

R.ELALS*S*P S526S527* UNI:Q9QYR 1.135887329 0.049463094 EDLTQDFEE 6 LK.R

R.LSS*LRAS* S236S240* UNI:D3Z6N6 1.135728973 0.025258451 TSK.S

K.ESDDKPEI S263* UNI:P07901 1.135575714 0.044382609 EDVGS*DEE EEEKK.D

R.VSDQNS*P S2045 UNI:E9PV45 1.130055681 0.047260617 VLPK.K

K.S*LPVSVP S184 UNI:Q9D1F4 1.129673555 0.026974997 VWAFK.E

R.IACEEEFS* S421S423* UNI:D3YYI8 1.126321992 0.035409265 DS*DEEGEG GRK.N

K.STS*PAPA S231* UNI:P97855 1.123545951 0.04497445 DVAPAQEDL R.T

K.SAS*PGLP S30 UNI:Q9EQU 1.120443063 0.035440905 K.G 5 Diabetes Page 250 of 603

K.ES*LKEED S243 UNI:O70435 1.118533554 0.038735827 ESDDDNM.-

K.ESLKEEDE S250 UNI:O70435 1.118533554 0.038735827 S*DDDNM.-

K.SQS*PSPP S243 UNI:B8JJ89 1.115959354 0.041661807 PLPEDLEK.A

R.S*HSLPNS S44 UNI:A3KGH5 1.110580276 0.043412508 LDYAQASER. G

R.LEQHSQQ S140 UNI:Q921T2 1.109930849 0.044950659 PQLS*PATSG R.G

K.S*PGVPDA S30 UNI:Q7TN75 1.106030911 0.034548735 EDDDER.R

R.S*ESSGNL S101 UNI:O08715 1.102747106 0.044088092 PSVADTR.S

R.GDNAS*PS S240 UNI:Q6NZR5 1.101229304 0.03461207 PSGTPLVR.A

R.YGMGTS*V S232* UNI:P35486 1.099674541 0.039740525 ER.A

K.EADEEDS* S106 UNI:D3Z316 1.096919394 0.023035228 DEETSYPER. S Page 251 of 603 Diabetes

R.YHGHS*MS S293* UNI:P35486 1.096512771 0.040362963 DPGVSYR.T

R.KTGS*YGA S445* UNI:Q9DBR7 1.087833141 0.038676564 LAEISASK.E

K.DDEKEPEE S306 UNI:Q9Z204 1.087739104 0.04972369 GEDDRDS*A NGEDDS.-

K.RPDYAPME S52S53* UNI:Q9CQU 1.087613553 0.047449869 S*S*DEEDEE 1 FQFIK.K

R.AGS*PQLD S540 UNI:Q8CHW 1.080193162 0.046134291 DIR.V 4

R.TAS*EGS*E S253S256 UNI:Q05CL8 1.071901333 0.029723372 AETPEAPK.Q

R.LGTGGGG S20* UNI:Q9WUD 1.062188797 0.03461207 S*PDKSPSA 1 QELK.E

R.GNVVPS*P S42* UNI:Q9CR86 1.061943602 0.044382609 LPTR.R

R.EDEIS*PPP S83* UNI:A2AI69 1.053446788 0.044934857 PNPVVK.G

R.KVMDS*DE S119 UNI:P56812 1.023464661 0.049236616 DDADY.- Diabetes Page 252 of 603

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5265060 2303707 1363264.859 478678 Page 299 of 603 Diabetes

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3831761 2457494 2194587.131 1682496

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15352110 12086654.98 12501324 Page 311 of 603 Diabetes

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201768 116466 137698.4905 99680

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9534904 2976377 4693305.957 4422137

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18747242 14369439 13695197.55 16815221

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8130812 6204890 5042695.164 3135156

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30593878 5673973 13632484.61 6394651

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33642543 13900987 27744429.13 20294584 Page 329 of 603 Diabetes

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4144260 4182274 3746240.178 2815539

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5099181 4390851 3001842.484 808204

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13567132 8777319 9795231.607 6511736

13567132 8777319 9795231.607 6511736

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14258203 10128407 11553984.95 9341868

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9702287 3717364 5893856.736 3950350

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9909529 9821801 11345911.06 15781987

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peakarea manual peakarea manual peakarea manual 2 rep2 2 rep3 2 rep4 isolated mass thresholded thresholded thresholded timepoints 203172 335808 201136 510.5743677

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136818 152201 1072825 571.775265

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mass error spectral score timepoints xcorr timepoints ascorr timepoints timepoints 1.051834345 20.19 10.92545208 0.637972451

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0.571011578 31.9 22.46769817 0.667321909

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1.18521963 29.19 28.84721822 0.677521724

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0.01873273 26.79 100 0.259272481

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0.382637238 35.04 16.94605199 0.846280352

0.546187306 34.71 6.777807053 0.861328967

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1.994805894 31.38 21.19358778 0.884140928

0.653324654 23.01 7.781512504 0.929670076

1.855841491 31.61 0.638871241

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0.105840991 24.13 6.641110557 0.479836601

1.760983653 24.2 13.89166084 0.271319029

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0.305041362 21.19 0.695840146

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0.443934146 51 11.26142116 0.946154487

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0.874273977 43.63 71.75200994 0.981501074

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1.860316962 36.37 3.055304969 0.743211633

0.988805743 23.97 36.75746927 0.774394477

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1.400454924 21.61 0.336198363 Page 389 of 603 Diabetes

0.959861017 31.51 27.43807012 0.862976868

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0.159603611 59.07 91.10113085 0.968901871 Page 391 of 603 Diabetes

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1.266275328 30.51 0.837974799 Diabetes Page 406 of 603

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0.063190555 40.19 16.94605199 0.717474061 Page 411 of 603 Diabetes

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0.881100365 24.83 100 0.283536726 Page 419 of 603 Diabetes

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0.263747151 20.18 10.79181246 0.511535365 Diabetes Page 420 of 603

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1.078070265 34.25 28.6378447 0.94802511 Page 421 of 603 Diabetes

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0.563559943 48.79 55.52255219 0.857982382 Page 423 of 603 Diabetes

1.302277979 21.26 22.04119983 0.084369914

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0.377078495 42.76 75.59209119 0.811502517 Page 425 of 603 Diabetes

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0.085815068 23.11 0.640715625

0.749602515 25.22 5.915068189 0.913769279

0.912524481 41.62 16.90240394 0.801371745

0.219969552 34.94 10.6694679 0.915939736

0.664130252 38.43 29.13527486 0.926992229

1.227097721 49.24 100 0.915073869

0.524626714 67.44 16.44274426 0.9497554

0.011728755 49.45 26.0224091 0.754834337

0.609584717 60.72 30.19300959 0.929255124

0.980469067 49.35 61.37442738 0.976434335 Page 427 of 603 Diabetes

1.344297398 40.57 19.82271233 0.901224396

0.235482849 93.11 16.94605199 0.868631439

1.462630835 28.15 81.53078279 0.935614429

0.675230823 38.45 16.92285552 0.94957646

1.367175121 55.1 100 0.89618705

0.64438084 51.05 24.19997279 0.883607696

0.218397223 26.03 13.80807391 0.370343024

0.723941932 34.98 42.38717557 0.674232559

0.299170449 73.35 100 0.935025314

0.032377787 37.07 101.7626802 0.371846899 Diabetes Page 428 of 603

charge state delta cn drosophila CG timepoints timepoints accession number gi species adjust 3 0 148699061

2 0 253314487

2 0 115503759

3 0 59798961

2 0 62510931

2 0 25453361

3 0 229462734

3 0 223459828

2 0 150387848 Page 429 of 603 Diabetes

3 0 158518639

2 0 109895137

2 0 9313029

3 0 9313029

3 0 9313029

2 0 2507204

2 0 9313029

3 0 189181672

2 0 20455219

3 0 30315995 Diabetes Page 430 of 603

3 0 3183181

2 0 148887397

3 0

3 0 124007127

2 0 147742931

3 0 38605043

3 0 261260072

2 0 48428375

2 0 20137987

2 0 20137987 Page 431 of 603 Diabetes

3 0 342187308

3 0 1346679

2 0 6425087

4 0 9313029

2 0 67461015

3 0 251757447

3 0 1352708

2 0 22261823

2 0 22261823

2 0 46397855 Diabetes Page 432 of 603

3 0 399310

3 0 166214952

3 0 166214944

3 0 166214944

3 0 166214944

2 0 347595715

2 0 122183

2 0 187608835

2 0 114930

3 0 22261823 Page 433 of 603 Diabetes

3 0 49901389

3 0 81882150

3 0 81882150

3 0 14195676

2 0 51315842

2 0 78099268

4 0

3 0 81906080

2 0 118568015

3 0 41688568 Diabetes Page 434 of 603

3 0 41688568

3 0 62510494

3 0 118568015

3 0 205688689

3 0 205688689

3 0 61212920

2 0 81880083

2 0 342187056

2 0 116283679

3 0 78098987 Page 435 of 603 Diabetes

2 0 47605501

3 0 81882407

3 0 147742933

3 0 147742933

2 0 158148935

3 0 61743961

2 0 81882232

3 0 73921751

2 0 41017844

2 0 6691151 Diabetes Page 436 of 603

3 0 341941235

2 0 158518599

3 0 147744571

3 0 48474741

2 0 20455238

2 0 73921205

2 0 51315842

3 0 341942058

2 0 1350781

2 0 148887397 Page 437 of 603 Diabetes

2 0 341940995

2 0 20455238

3 0 51316524

2 0 32172436

2 0 17368615

2 0 17368615

3 0 138536

2 0 61743961

3 0 51258091

2 0 189047109 Diabetes Page 438 of 603

2 0 215275613

2 0 56749456

2 0 56749456

2 0 55976729

2 0 347595715

2 0 341941131

2 0 123213541

2 0 123213541

3 0 57015295

3 0 218512063 Page 439 of 603 Diabetes

3 0 218512063

2 0 146291107

2 0 22653923

2 0 34766351

3 0 338817907

3 0 341942026

2 0 138536

3 0 73620776

2 0 81882407

2 0 338817907 Diabetes Page 440 of 603

2 0 81896337

2 0 20138335

2 0 261260072

2 0 281185473

2 0 281185473

3 0 6578739

2 0 281185473

2 0 55976513

2 0 148887397

3 0 90110086 Page 441 of 603 Diabetes

3 0 90110086

2 0 1346902

3 0 347595715

2 0 261260072

2 0 261260072

2 0 81911483

2 0 20137987

2 0 20137987

2 0 41688568

2 0 73917747 Diabetes Page 442 of 603

3 0 158564030

2 0 30173483

2 0 118568015

2 0 68565928

2 0 68565928

3 0 110283006

2 0 341940614

2 0 34766351

2 0 46397410

2 0 46397410 Page 443 of 603 Diabetes

3 0 13959565

2 0 46396473

2 0 347595715

2 0 347595715

3 0 68565928

3 0 68565928

3 0 68565928

3 0 68565928

3 0 46396418

3 0 20137987 Diabetes Page 444 of 603

3 0 347595715

2 0 341941090

2 0 1708264

2 0 81882407

3 0 226736666

2 0 25090576

2 0 341942108

3 0 85700428

3 0 85700428

3 0 341942183 Page 445 of 603 Diabetes

3 0 81908799

2 0 138536

2 0 47605961

2 0 261260072

2 0 261260072

3 0 148704095

2 0 148704095

3 0 71152026

3 0 113985

2 0 81900897 Diabetes Page 446 of 603

2 0 81900897

2 0 341940631

2 0 81885787

3 0 62510642

2 0 281185473

3 0 52000879

2 0 81881162

3 0 28380207

2 0 30923239

2 0 29839513 Page 447 of 603 Diabetes

2 0 50401562

3 0 62286942

2 0 14916536

3 0 14916536

3 0 20137987

3 0 20137987

3 0 20137987

3 0 341942168

3 0 341942168

2 0 81914411 Diabetes Page 448 of 603

3 0 166991454

2 0 46396970

2 0 146291107

2 0 61743961

2 0 61743961

3 0 81900953

2 0 3914804

2 0 81907185

2 0 81878875

3 0 41018011 Page 449 of 603 Diabetes

2 0 294862480

2 0 49901389

3 0 57015295

3 0 57015295

2 0 122065442

2 0 138536

2 0 166234056

2 0 147742910

2 0 147742910

3 0 33516945 Diabetes Page 450 of 603

3 0 61743961

2 0 81897880

3 0 123228045

2 0 85700428

2 0 85700428

2 0 57013084

3 0 28380825

2 0 223461012

3 0 81891295

3 0 281185473 Page 451 of 603 Diabetes

2 0 84029593

3 0 118568015

2 0 9622185

3 0 85690846

3 0 81880120

2 0 347595715

2 0 85700428

3 0 81916748

3 0 124021003

2 0 47115791 Diabetes Page 452 of 603

2 0 81914516

2 0 81878684

2 0 19353460

2 0 19353460

2 0 148886616

2 0 1708264

2 0 85700428

2 0 85700428

2 0 51703331

3 0 341942108 Page 453 of 603 Diabetes

2 0 6225769

2 0 123785957

2 0 9622185

3 0 56749456

2 0 218512063

2 0 218512063

2 0 147643261

2 0 23503073

2 0 23503073

2 0 341940611 Diabetes Page 454 of 603

4 0 47605501

2 0 341942108

2 0 239938603

2 0 23396700

2 0 122066548

2 0 38372440

2 0 47605501

3 0 347595715

2 0 123681

2 0 261260072 Page 455 of 603 Diabetes

2 0 23822163

2 0 46397804

2 0 20137304

2 0 51703331

2 0 148701159

3 0 56417892

4 0 51704189

3 0 1708264

3 0 1708264

3 0 20137436 Diabetes Page 456 of 603

3 0 73921751

2 0 123681

3 0 34098397

3 0 34098397

2 0 341942108

2 0 56417892

2 0 18280933

3 0 347595715

2 0 73921751

3 0 50400986 Page 457 of 603 Diabetes

2 0 20455216

2 0 20455216

3 0 152040391

3 0 152040391

3 0 152040391

2 0 7329158

3 0 81903237

2 0 118568015

2 0 118568015

2 0 71162370 Diabetes Page 458 of 603

3 0 81914516

2 0 47605501

3 0 81878080

3 0 205371802

2 0 34766351

3 0 81881579

3 0 81881579

3 0 81881579

2 0 33516945

3 0 123213541 Page 459 of 603 Diabetes

2 0 125987710

2 0 3122277

3 0 156630946

2 0 13878547

2 0 23503073

3 0 341942108

3 0 81880094

2 0 47605501

2 0 51261360

2 0 18280933 Diabetes Page 460 of 603

2 0 54039390

3 0 6691151

3 0 34766351

2 0 85700428

2 0 85700428

3 0 47605501

3 0 19353460

2 0 341942108

2 0 281185473

2 0 281185473 Page 461 of 603 Diabetes

2 0 81904209

2 0 147742910

3 0 347595715

3 0 2498048

2 0 1708264

2 0 81904209

3 0 1170384

3 0 9297076

2 0 41019534

3 0 341942108 Diabetes Page 462 of 603

4 0 3183181

2 0 215275645

2 0 46577330

2 0 46577330

2 0 123778087

2 0 341942108

2 0 73917637

2 0 73917637

3 0 11527239

3 0 122065442 Page 463 of 603 Diabetes

3 0 294862480

2 0 24418669

2 0 347595715

3 0 81882902

3 0 124007127

3 0 341942108

2 0 84029300

2 0 84029300

2 0 11133187

2 0 81892500 Diabetes Page 464 of 603

3 0 341940583

3 0 150387848

3 0 341942183

2 0 81880094

3 0 341942108

2 0 1345856

2 0 22261803

2 0 22261803

2 0 22261803

3 0 152112288 Page 465 of 603 Diabetes

3 0 152112288

2 0 81903514

2 0 81903514

2 0 81903514

2 0 20138800

2 0 20138800

2 0 1170384

3 0 341942183

3 0 81881162

3 0 1934963 Diabetes Page 466 of 603

3 0 148710033

2 0 23822163

2 0 34098661

2 0 47605750

2 0 20138800

2 0 20138800

2 0 81882407

2 0 125987791

2 0 34766351

2 0 34766351 Page 467 of 603 Diabetes

2 0 34766351

2 0 81913100

2 0 30580527

2 0 122065141

2 0 219518475

3 0 347595715

2 0 123232173

2 0 47605961

3 0 281185473

3 0 85681904 Diabetes Page 468 of 603

2 0 338817942

3 0 294862480

3 0 294862480

2 0 6691151

2 0 61216765

2 0 51338633

2 0 51338633

2 0 212288549

2 0 212288549

3 0 28201882 Page 469 of 603 Diabetes

3 0 20138800

2 0 8928249

2 0 122065442

2 0 51338633

3 0 1170384

2 0 212288549

2 0 81881209

3 0 2498444

2 0 14916571

2 0 46396655 Diabetes Page 470 of 603

3 0 3914438

3 0 3914438

2 0 9622185

3 0 147643261

3 0 342187057

2 0 172045711

2 0 14194433

2 0 148694805

2 0 548409

2 0 71152389 Page 471 of 603 Diabetes

2 0 548409

2 0 281185473

3 0 20455216

3 0 59798469

2 0 81878145

2 0 134034152

3 0 78099174

2 0 41016923

2 0 54036156

2 0 6686019 Diabetes Page 472 of 603

gi name species IPI accession swissprot adjust number accession hprd accession mCG1697, isoform B1AXP3 B1AXP3_MOUSE CRA_a [Mus musculus] [MASS=54784] caspase IPI00351041.1 Q8BWE0_MOUSE recruitment domain family, member 6 [Mus musculus] [MASS=131468]AP2-associated Q3UHJ0 AAK1_MOUSE 10620_1 protein kinase 1 (Adaptor- associated kinase 1)Serine/threonine- [MASS=103345] Q8CFH6 SN1L2_MOUSE 12348_1 protein kinase SNF1-like kinase 2 (Salt inducible kinaseInterferon 2) induced Q8R5F7 IFIH1_MOUSE with helicase C domain protein 1 (Helicase with 2 CARDZ-DNA domains)binding Q9QY24 ZBP1_MOUSE protein 1 (Tumor stroma and activated macrophageRecName: Q8BKC8 PI4KB_MOUSE 11805_1 Full=Phosphatidylin ositol 4-kinase beta; Short=PtdIns 4-kinaseRNA binding beta; motif Q0VBL3 Q0VBL3_MOUSE protein 15 [Mus musculus] [MASS=105721] 182 kDa tankyrase P58871 TB182_MOUSE 1-binding protein [MASS=181824] Page 473 of 603 Diabetes

Transmembrane Q80W04 TMCC3_MOUSE 15519_1 and coiled-coil domains protein 3

Testis-expressed B1ATR2 TEX2_MOUSE 13716_1 sequence 2 protein

PML isoform 1 Q60953 PML_MOUSE [Mus musculus]

PML isoform 1 Q60953 PML_MOUSE [Mus musculus]

PML isoform 1 Q60953 PML_MOUSE [Mus musculus]

Interferon-induced, Q03963 E2AK2_MOUSE double-stranded RNA-activated protein kinase (Interferon-PML isoform 1 Q60953 PML_MOUSE [Mus musculus]

A kinase (PRKA) IPI00126181.9 Q3UZK5_MOUSE 05253_3 anchor protein 13 [Mus musculus] [MASS=303974] Receptor- P58801 RIPK2_MOUSE interacting serine/threonine protein kinase 2 Mitogen-activated Q8BPM2 M4K5_MOUSE protein kinase kinase kinase kinase 5 (MAPK/ERK kinase Diabetes Page 474 of 603

Transcription Q62318 TIF1B_MOUSE intermediary factor 1-beta (TIF1-beta) (Tripartite motif proteinMicrotubule- 28) (KRAB- E9PWC0 MAP4_MOUSE 01141_3 associated protein 4 (MAP 4)

P51859 HDGF_MOUSE

CLIP-associating Q80TV8 CLAP1_MOUSE 09322_1 protein 1 (Cytoplasmic linker- associated protein 1)Rho [MASS=169226] guanine Q80U35 ARHGH_MOUSE 10658_1 nucleotide exchange factor 17 [MASS=221670] Myosin regulatory Q6ZWQ9 Q9D6E6_MOUSE 17619_2 light chain 2, smooth muscle isoform (Myosin RLC)RecName: Q8CGN5 PLIN1_MOUSE 01364_1 Full=Perilipin-1; AltName: Full=Lipid droplet-associated protein;Eukaryotic AltName: Q80XI3 IF4G3_MOUSE translation initiation factor 4 gamma 3 (eIF-4-gamma 3) (eIF-4GSerine/threonine- 3) (eIF4G Q80VB6 Q9JLM7_MOUSE 09202_1 protein kinase DCAMKL1 (Doublecortin-like andSerine/threonine- CAM kinase- Q80VB6 Q9JLM7_MOUSE 09202_1 protein kinase DCAMKL1 (Doublecortin-like and CAM kinase- Page 475 of 603 Diabetes

RecName: B9EHJ3 ZO1_MOUSE 03002_2 Full=Tight junction protein ZO-1; AltName: Full=Tight junctionSeptin 2 protein(NEDD5 1; P42208 SEPT2_MOUSE 03297_4 protein)

gamma actin-like P60710 Q9QZ83_MOUSE 18642_1 protein [Mus musculus]

PML isoform 1 Q60953 PML_MOUSE [Mus musculus]

Eukaryotic Q6NZJ6 Q8K0J8_MOUSE 06774_5 translation initiation factor 4 gamma 1 (eIF-4-gamma 1) (eIF-4GRecName: 1) (eIF- Q9CWZ3 RBM8A_MOUSE 05609_1 Full=RNA-binding protein 8A; AltName: Full=RNA- bindingCytosolic motif P47713 Q9DBX5_MOUSE phospholipase A2 (CPLA2) [Includes: Phospholipase A2 (PhosphatidylcholinSAM domain and Q60710 SAMH1_MOUSE HD domain- containing protein 1 (Interferon-gamma inducibleSAM domain protein and Q60710 SAMH1_MOUSE HD domain- containing protein 1 (Interferon-gamma inducible60S acidic protein G3UW69 RLA2_MOUSE 01612_1 ribosomal protein P2 Diabetes Page 476 of 603

Beta-catenin Q02248 CTNB1_MOUSE 00286_3

Interferon-activable P15092 IFI4_MOUSE protein 205-B (Interferon- inducible protein p205-B)Integrator (Ifi-205-B) complex Q6P4S8 INT1_MOUSE subunit 1 (Int1) [MASS=245166]

Integrator complex Q6P4S8 INT1_MOUSE subunit 1 (Int1) [MASS=245166]

Integrator complex Q6P4S8 INT1_MOUSE subunit 1 (Int1) [MASS=245166]

RecName: A2A8V8 SRRM1_MOUSE 10441_1 Full=Serine/arginin e repetitive matrix protein 1; AltName: Full=Plenty-of-H-2 CLASS I P01897 HA1L_MOUSE HISTOCOMPATIBI LITY ANTIGEN, ALPHA CHAIN (CLONEProtein PAT1 PH-2D-2) Q3TC46 PATL1_MOUSE 08214_1 homolog 1 (PAT1- like protein 1)

MARCKS-related P28667 MRP_MOUSE 04247_1 protein (Macrophage myristoylated alanine-richSAM domain C and Q60710 SAMH1_MOUSE HD domain- containing protein 1 (Interferon-gamma inducible protein Page 477 of 603 Diabetes

Nol5 protein [Mus Q6DFW4 NOP58_MOUSE musculus] [MASS=60343]

AP-3 complex O54774 AP3D1_MOUSE subunit delta-1 (Adapter-related protein complex 3 subunitAP-3 complex delta-1) O54774 AP3D1_MOUSE subunit delta-1 (Adapter-related protein complex 3 subunitNuclear delta-1)factor 1 B- P97863 Q8BN68_MOUSE type (Nuclear factor 1/B) (NF1-B) (NFI- B) (NF-I/B) (CCAAT- boxDrebrin-like binding protein Q62418 DBNL_MOUSE (SH3 domain- containing protein 7) (Actin-binding proteinTight junction- 1) Q9DCD5 TJAP1_MOUSE associated protein 1 (Tight junction protein 4) (Protein incorporated later E9PWC0 E9PWC0_MOUSE

Uncharacterized Q9DBC3 MTR1_MOUSE protein KIAA0082

Cordon-bleu B1AZ14 COBL1_MOUSE protein-like 1 (Cobl- related protein 1) [MASS=137381] Ezrin-radixin- P70441 NHERF_MOUSE moesin binding phosphoprotein 50 (EBP50) (Na(+)/H(+) Diabetes Page 478 of 603

Ezrin-radixin- P70441 NHERF_MOUSE moesin binding phosphoprotein 50 (EBP50) (Na(+)/H(+)Autophagy protein Q8C0J2 APG16_MOUSE 16498_2 16-like (APG16- like)

Cordon-bleu B1AZ14 COBL1_MOUSE protein-like 1 (Cobl- related protein 1) [MASS=137381] RecName: Q3TLH4 D3Z3U3_MOUSE Full=BAT2 domain- containing protein 1 [MASS=308902] RecName: Q3TLH4 D3Z3U3_MOUSE Full=BAT2 domain- containing protein 1 [MASS=308902] DNA-binding Q9JKB3 Q68G78_MOUSE protein A (Cold shock domain protein A) (Y-box proteinADP-ribosylation 3) Q99K28 ARFG2_MOUSE 6069 factor GTPase- activating protein 2 (ARF GAP 2) (GTPase-activatingRecName: P25446 TNR6_MOUSE Full=Tumor necrosis factor receptor superfamilyDhx9 protein [Mus O70133-2 DHX9_MOUSE musculus] [MASS=21770]

Serine/threonine- Q8BYC6 TAOK3_MOUSE protein kinase TAO3 (Thousand and one amino acid protein 3) Page 479 of 603 Diabetes

Bcl-2-associated Q8K019 Q3UR37_MOUSE 16544_3 transcription factor 1 (Btf) [MASS=106001] Thyroid hormone Q80VM0 TR150_MOUSE 07543_1 receptor-associated protein 3 (Thyroid hormone receptor- associated250 kDa substrate protein B2RX86 RGPA2_MOUSE 11135_2 of Akt (AS250) [MASS=210287]

250 kDa substrate B2RX86 RGPA2_MOUSE 11135_2 of Akt (AS250) [MASS=210287]

activity and Q80VB6 DCLK1_MOUSE neurotransmitter- induced early gene protein 4 [Mus musculus]AHNAK IPI00553798.2 Q8BRB8_MOUSE nucleoprotein isoform 1 [Mus musculus] [MASS=604249]Hematological and P97825 HN1_MOUSE neurological expressed 1 protein

Pinin O35691 Q3TUQ5_MOUSE [MASS=82435]

Synaptosomal- Q9D3L3 SNP23_MOUSE associated protein 23 (SNAP-23) (Vesicle-membrane fusionacetyl-CoA protein Q9QXG4 Q8BK97_MOUSE synthetase [Mus musculus] Diabetes Page 480 of 603

RecName: Q9R0L6 PCM1_MOUSE Full=Pericentriolar material 1 protein; Short=PCM-1; Short=mPCM-1Ankyrin repeat and Q6ZPS6 B2RX15_MOUSE IBR domain- containing protein 1 [MASS=121875] La-related protein 1 Q6ZQ58 LARP1_MOUSE (La ribonucleoprotein domain family memberVesicle trafficking 1) O08547 SC22B_MOUSE 04939_1 protein SEC22b (SEC22 vesicle trafficking protein- likeReceptor- 1) Q9QZL0 RIPK3_MOUSE interacting serine/threonine protein kinase 3 (RIP-likeE3 ubiquitin-protein protein Q8CFI0 NED4L_MOUSE 05903_1 ligase NEDD4-like protein (Nedd4-2) (NEDD4.2) [MASS=115418]Drebrin-like protein Q62418 DBNL_MOUSE (SH3 domain- containing protein 7) (Actin-binding proteinRecName: 1) O35892 SP100_MOUSE Full=Nuclear autoantigen Sp- 100; AltName: Full=Nuclear60S acidic dot- P47955 RLA1_MOUSE ribosomal protein P1

Microtubule- E9QPW8 E9QPW8_MOUSE associated protein 4 (MAP 4) Page 481 of 603 Diabetes

RecName: Full=E3 P23804 Q3TVL4_MOUSE ubiquitin-protein ligase Mdm2; AltName: Full=DoubleReceptor- minute Q9QZL0 RIPK3_MOUSE interacting serine/threonine protein kinase 3 (RIP-likeProtein protein D3Z3A0 IPP2_MOUSE phosphatase inhibitor 2 (IPP-2)

E3 ubiquitin-protein P46935 NEDD4_MOUSE ligase Nedd-4

Myeloid leukemia Q99KX1 MLF2_MOUSE 03238_1 factor 2 (Myelodysplasia- myeloid leukemia factorMyeloid 2) leukemia Q99KX1 MLF2_MOUSE 03238_1 factor 2 (Myelodysplasia- myeloid leukemia factorVimentin 2) P20152 VIME_MOUSE

AHNAK IPI00553798.2 Q8BRB8_MOUSE nucleoprotein isoform 1 [Mus musculus] [MASS=604249]AI849286 protein Q6PFD9 Q6PFD9_MOUSE [Mus musculus] [MASS=136359]

Tyrosine-protein Q62120 JAK2_MOUSE kinase JAK2 (Janus kinase 2) (JAK-2) [MASS=130234] Diabetes Page 482 of 603

RecName: A6H619 Q3TPE7_MOUSE Full=PHD and RING finger domain-containing proteinPolymerase 1 I and O54724 PTRF_MOUSE transcript release factor [MASS=43953] Polymerase I and O54724 PTRF_MOUSE transcript release factor [MASS=43953] Tripartite motif Q8C0E3 TRI47_MOUSE protein 47 [MASS=69912]

RecName: A2A8V8 SRRM1_MOUSE 10441_1 Full=Serine/arginin e repetitive matrix protein 1; AltName: Full=Plenty-of-RecName: Full=6- P12382 Q8VDX7_MOUSE phosphofructokinas e, liver type; AltName: Full=Phosphofructo-calcium/calmodulin- O70589-3 CSKP_MOUSE dependent serine protein kinase (MAGUK family) [Muscalcium/calmodulin- musculus] O70589-3 CSKP_MOUSE dependent serine protein kinase (MAGUK family) [MusPITSLRE musculus] P24788 CD2L1_MOUSE 08909_8 serine/threonine- protein kinase CDC2L1 (GalactosyltransferRecName: Q9Z1E4 GYS3_MOUSE Full=Glycogen [starch] synthase, muscle Page 483 of 603 Diabetes

RecName: Q9Z1E4 GYS3_MOUSE Full=Glycogen [starch] synthase, muscle Zinc finger Ran- Q9R020 ZRAB2_MOUSE 9185 binding domain- containing protein 2 (Zinc finger protein 265)Paralemmin (Zinc finger, Q9Z0P4 PALM_MOUSE

AHNAK [Mus IPI00553798.2 musculus] [MASS=68761]

RecName: E9Q3P6 Q7TNL7_MOUSE 04125_1 Full=Dual specificity protein phosphatase 7 RecName: Q9JID9 SH2B2_MOUSE Full=SH2B adapter protein 2; AltName: Full=Adapter proteinVimentin with P20152 VIME_MOUSE

Protein DEK Q7TNV0 Q3UR53_MOUSE

Thyroid hormone Q569Z6 TR150_MOUSE receptor-associated protein 3 (Thyroid hormone receptor- associatedRecName: protein E9Q3P6 Q7TNL7_MOUSE 04125_1 Full=Dual specificity protein phosphatase 7 Diabetes Page 484 of 603

Patatin-like Q8BJ56 PLPL2_MOUSE 11443_1 phospholipase domain-containing protein 2 (Adipose Guaninetriglyceride nucleotide- lipase) Q9DAS9 GBG12_MOUSE 13592_1 binding protein G(I)/G(S)/G(O) gamma-12 subunit RecName: Q8CGN5 PLIN_MOUSE 01364_1 Full=Perilipin-1; AltName: Full=Lipid droplet-associated protein;RecName: AltName: Q9DBR7 MYPT1_MOUSE 03606_1 Full=Protein phosphatase 1 regulatory subunit 12A;RecName: AltName: Q9DBR7 MYPT1_MOUSE 03606_1 Full=Protein phosphatase 1 regulatory subunit 12A;plectin AltName: isoform plec Q9QXS1-3 PLEC_MOUSE 03180_4 1a [Mus musculus]

RecName: Q9DBR7 MYPT1_MOUSE Full=Protein phosphatase 1 regulatory subunit 12A;Eukaryotic AltName: Q8BGD9 IF4B_MOUSE 04892_1 translation initiation factor 4B (eIF-4B)

Microtubule- E9PWC0 MAP4_MOUSE associated protein 4 (MAP 4)

Vasodilator- P70460 VASP_MOUSE stimulated phosphoprotein (VASP) Page 485 of 603 Diabetes

Vasodilator- P70460 VASP_MOUSE stimulated phosphoprotein (VASP) Protein-tyrosine P35831 Q80UM4_MOUSE 02513_1 phosphatase, non- receptor type 12 (Protein-tyrosine phosphataseRecName: P19) A2A8V8 SRRM1_MOUSE Full=Serine/arginin e repetitive matrix protein 1; AltName: Full=Plenty-of-RecName: Q8CGN5 PLIN_MOUSE Full=Perilipin-1; AltName: Full=Lipid droplet-associated protein;RecName: AltName: Q8CGN5 PLIN_MOUSE Full=Perilipin-1; AltName: Full=Lipid droplet-associated Calcium/calmodulin-protein; AltName: Q6PHZ2 Q8CCM0_MOUSE 09653_4 dependent protein kinase type II delta chain (CaM-kinase IISerine/threonine- delta chain) (CaM Q80VB6 Q9JLM7_MOUSE 09202_1 protein kinase DCAMKL1 (Doublecortin-like andSerine/threonine- CAM kinase- Q80VB6 Q9JLM7_MOUSE 09202_1 protein kinase DCAMKL1 (Doublecortin-like andEzrin-radixin- CAM kinase- P70441 NHERF_MOUSE moesin binding phosphoprotein 50 (EBP50) (Na(+)/H(+)Charged Q8BJF9 CHM2B_MOUSE 13174_1 multivesicular body protein 2b (Chromatin- modifying protein Diabetes Page 486 of 603

Palladin Q9ET54 Q8C306_MOUSE 09731_1 [MASS=152130]

5'-3' Q9DBR1 XRN2_MOUSE 10309_1 exoribonuclease 2 (Dhm1 protein)

Cordon-bleu B1AZ14 COBL1_MOUSE protein-like 1 (Cobl- related protein 1) [MASS=137381] PC4 and SFRS1- Q99JF8 PSIP1_MOUSE 04688_2 interacting protein (Lens epithelium- derived growth factor)PC4 and (mLEDGF) SFRS1- Q99JF8 PSIP1_MOUSE 04688_2 interacting protein (Lens epithelium- derived growth factor)FACT complex(mLEDGF) Q08943 SSRP1_MOUSE subunit SSRP1 (Facilitates chromatin transcriptionRecName: Q52KR6 Q52KR6_MOUSE 05191_1 Full=Apoptotic chromatin condensation inducerAHNAK in[Mus the IPI00553798.2 14684_2 musculus] [MASS=68761]

DnaJ homolog P60904 DNJC5_MOUSE 08539_1 subfamily C member 5 (Cysteine string protein)DnaJ homolog (CSP) P60904 DNJC5_MOUSE 08539_1 subfamily C member 5 (Cysteine string protein) (CSP) Page 487 of 603 Diabetes

Ras GTPase- Q60790 RASA3_MOUSE 05537_1 activating protein 3 (GAP1(IP4BP)) (Ins P4-binding protein) (GapIII)NEDD9 interacting Q8VDP3 Q3TX89_MOUSE protein with calponin homology and LIM domains (MoleculeRecName: A2A8V8 SRRM1_MOUSE Full=Serine/arginin e repetitive matrix protein 1; AltName: Full=Plenty-of-RecName: A2A8V8 SRRM1_MOUSE Full=Serine/arginin e repetitive matrix protein 1; AltName: Full=Plenty-of-PC4 and SFRS1- Q99JF8 PSIP1_MOUSE interacting protein (Lens epithelium- derived growth factor)PC4 and (mLEDGF) SFRS1- Q99JF8 PSIP1_MOUSE interacting protein (Lens epithelium- derived growth factor)PC4 and (mLEDGF) SFRS1- Q99JF8 PSIP1_MOUSE interacting protein (Lens epithelium- derived growth factor)PC4 and (mLEDGF) SFRS1- Q99JF8 PSIP1_MOUSE interacting protein (Lens epithelium- derived growth factor)Oxysterol (mLEDGF) binding Q8CI95 OSR11_MOUSE protein-related protein 11 (OSBP- related protein 11) (ORP-11)Serine/threonine- Q80VB6 Q9JLM7_MOUSE 09202_1 protein kinase DCAMKL1 (Doublecortin-like and CAM kinase- Diabetes Page 488 of 603

RecName: A2A8V8 SRRM1_MOUSE Full=Serine/arginin e repetitive matrix protein 1; AltName: Full=Plenty-of-RecName: Full=1- Q9Z1T6 FYV1_MOUSE 17852_3 phosphatidylinositol- 3-phosphate 5- kinase; Short=PhosphatidylHigh mobility group Q6NSP9 Q6NSP9_MOUSE protein HMGI-C (High mobility group AT-hook 2) Thyroid hormone Q569Z6 TR150_MOUSE 07543_1 receptor-associated protein 3 (Thyroid hormone receptor- associatedRecName: protein B2RY56 RBM25_MOUSE 15229_1 Full=RNA-binding protein 25; AltName: Full=RNA- bindingCaspase-8 motif O89110 CASP8_MOUSE precursor

RecName: Q8BTI8 SRRM2_MOUSE Full=Serine/arginin e repetitive matrix protein 2 Lamin-A/C P48678 LMNA_MOUSE

Lamin-A/C P48678 LMNA_MOUSE

RecName: Q61136 PRP4B_MOUSE Full=Serine/threoni ne-protein kinase PRP4 homolog; AltName: Page 489 of 603 Diabetes

Sister chromatid Q4VA53 PDS5B_MOUSE cohesion protein PDS5 homolog B (Androgen-induced proliferationVimentin P20152 VIME_MOUSE

Rab GTPase O35551 RABE1_MOUSE binding effector protein 1 (Rabaptin- 5) (Rabaptin- 5alpha)RecName: Q8CGN5 PLIN_MOUSE 01364_1 Full=Perilipin-1; AltName: Full=Lipid droplet-associated protein;RecName: AltName: Q8CGN5 PLIN_MOUSE 01364_1 Full=Perilipin-1; AltName: Full=Lipid droplet-associated protein;mCG2476 AltName: [Mus IPI00761751.2 Q6A029_MOUSE musculus] [MASS=212836]

mCG2476 [Mus IPI00761751.2 Q6A029_MOUSE musculus] [MASS=212836]

RAB3A-interacting Q68EF0 RAB3I_MOUSE protein (Rabin-3) (SSX2-interacting protein) DNA-(apurinic or P28352 D3Z6R9_MOUSE apyrimidinic site) lyase (AP endonuclease 1) (APEXPleckstrin nuclease) Q8K124 PKHO2_MOUSE homology domain- containing family O member 2 (Pleckstrin Diabetes Page 490 of 603

Pleckstrin Q8K124 PKHO2_MOUSE homology domain- containing family O member 2 (PleckstrinRecName: Q60875 ARHG2_MOUSE 10458_2 Full=Rho guanine nucleotide exchange factor 2; AltName:Protein FAM21 Q6PGL7 FAM21_MOUSE

Guanine nucleotide Q8CI11 GNL3_MOUSE binding protein-like 3 (Nucleolar GTP- binding protein 3) (Nucleostemin)RecName: Q9DBR7 MYPT1_MOUSE Full=Protein phosphatase 1 regulatory subunit 12A;Ubiquitin- AltName: Q9JJZ4 UB2J1_MOUSE conjugating enzyme E2 J1 (Non- canonical ubiquitin mRNAconjugating cap guanine- Q9D0L8 MCES_MOUSE N7 methyltransferase (mRNA (guanine- N(7)-)-WD-repeat protein Q3UWE6 Q3UWE6_MOUSE 20

Glucosamine-- P47856 GFPT1_MOUSE 00702_1 fructose-6- phosphate aminotransferase [isomerizing]Nardilysin 1 Q8BHG1 NRDC_MOUSE 04036_1 precursor (N- arginine dibasic convertase) (NRD convertase) (NRD- Page 491 of 603 Diabetes

Signal-induced Q4VBF8 SI1L1_MOUSE 11559_1 proliferation- associated 1 like protein 1 [MASS=197030]Heterogeneous Q921F4 Q3UXJ3_MOUSE nuclear ribonucleoprotein L- like [MASS=64124] Myc box dependent Q6P1B9 Q6P1B9_MOUSE interacting protein 1 (Bridging integrator 1) (Amphiphysin- Myclike protein) box dependent Q6P1B9 Q6P1B9_MOUSE interacting protein 1 (Bridging integrator 1) (Amphiphysin- likeSerine/threonine- protein) Q80VB6 Q9JLM7_MOUSE 09202_1 protein kinase DCAMKL1 (Doublecortin-like andSerine/threonine- CAM kinase- Q80VB6 Q9JLM7_MOUSE 09202_1 protein kinase DCAMKL1 (Doublecortin-like andSerine/threonine- CAM kinase- Q80VB6 Q9JLM7_MOUSE 09202_1 protein kinase DCAMKL1 (Doublecortin-like andRecName: CAM kinase- Q64012 RALY_MOUSE Full=RNA-binding protein Raly; AltName: Full=Maternally-RecName: Q64012 RALY_MOUSE Full=RNA-binding protein Raly; AltName: Full=Maternally-SAFB-like Q8CH25 SLTM_MOUSE transcription modulator (SAF-like transcription modulator) Diabetes Page 492 of 603

Calmodulin- Q8C1B1 CAMP2_MOUSE regulated spectrin- associated protein 1-like protein 1 Vigilin[MASS=164331] (High density Q8VDJ3 VIGLN_MOUSE lipoprotein-binding protein) (HDL- binding protein) [MASS=141742]Zinc finger Ran- Q9R020 ZRAB2_MOUSE 9185 binding domain- containing protein 2 (Zinc finger protein 265)AHNAK (Zinc finger, IPI00553798.2 Q8BRB8_MOUSE nucleoprotein isoform 1 [Mus musculus] [MASS=604249]AHNAK IPI00553798.2 Q8BRB8_MOUSE nucleoprotein isoform 1 [Mus musculus] [MASS=604249]Ubiquinone Q8K1Z0 COQ9_MOUSE biosynthesis protein COQ9, mitochondrial precursorHeterogeneous O35479 Q91VM5_MOUSE nuclear ribonucleoprotein G (hnRNP G) (RNA bindingSmall acidic motif protein Q9R0P4 SMAP_MOUSE 18069_1 (Sid 2057)

Eukaryotic Q8R1B4 EIF3C_MOUSE 04889_2 translation initiation factor 3 subunit C (eIF3c) (Eukaryotic translationSmall glutamine- initiation Q8BJU0 SGTA_MOUSE rich tetratricopeptide repeat-containing protein A Page 493 of 603 Diabetes

RecName: P46938 YAP1_MOUSE 9424 Full=Yorkie homolog; AltName: Full=65 kDa Yes- associatedNol5 protein protein; [Mus Q6DFW4 NOP58_MOUSE musculus] [MASS=60343]

PITSLRE P24788 CDK11_MOUSE 08909_8 serine/threonine- protein kinase CDC2L1 (GalactosyltransferPITSLRE P24788 CDK11_MOUSE 08909_8 serine/threonine- protein kinase CDC2L1 (GalactosyltransferMicrotubule- Q9QYR6 MAP1A_MOUSE 02549_1 associated protein 1A (MAP 1A)

Vimentin P20152 VIME_MOUSE

Cell division cycle 2- Q14AX6 CDK12_MOUSE related protein kinase 7 (CDC2- related protein kinaseE3 ubiquitin-protein 7) (Cdc2- A2AN08 UBR4_MOUSE 10184_1 ligase UBR4 (N- recognin-4) (Zinc finger UBR1-type proteinE3 ubiquitin-protein 1) (p600) A2AN08 UBR4_MOUSE 10184_1 ligase UBR4 (N- recognin-4) (Zinc finger UBR1-type proteinHeterogeneous 1) (p600) Q60668 HNRPD_MOUSE 03206_3 nuclear ribonucleoprotein D0 (hnRNP D0) (AU-rich element Diabetes Page 494 of 603

AHNAK IPI00553798.2 Q8BRB8_MOUSE nucleoprotein isoform 1 [Mus musculus] [MASS=604249]KN motif and Q8BX02 KANK2_MOUSE 13865_1 ankyrin repeat domain-containing protein 2 (Ankyrin repeatSEC16 domain- homolog A A2AIX1 A2AIX1_MOUSE (S. cerevisiae) [Mus musculus] [MASS=256471] Lamin-A/C P48678 LMNA_MOUSE 01035_4

Lamin-A/C P48678 LMNA_MOUSE 01035_4

Supervillin Q8K4L2 SVIL_MOUSE (Archvillin) (p205/p250) [MASS=243160] Transcription P10711 TCEA1_MOUSE elongation factor A protein 1 (Transcription elongationZinc finger factorCCCH S- IPI00515528.3 B9EHN9_MOUSE type containing 13 [Mus musculus] [MASS=203825] Ubiquitin carboxyl- E9QLK0 E9QLK0_MOUSE 3950 terminal hydrolase 7 (Ubiquitin thioesterase 7) (Ubiquitin-specific-RecName: Q9DBR7 MYPT1_MOUSE Full=Protein phosphatase 1 regulatory subunit 12A; AltName: Page 495 of 603 Diabetes

N(2),N(2)- Q3TX08 TRM1_MOUSE dimethylguanosine tRNA methyltransferase (tRNA(guanine-Cordon-bleu B1AZ14 COBL1_MOUSE protein-like 1 (Cobl- related protein 1) [MASS=137381] acinusL protein B8JJ89 B8JJ89_MOUSE [Mus musculus]

Hormone-sensitive P54310 Q8CDI9_MOUSE lipase (HSL)

RecName: Q99KG3 RBM10_MOUSE 02095_2 Full=RNA-binding protein 10; AltName: Full=RNA- bindingRecName: motif A2A8V8 SRRM1_MOUSE Full=Serine/arginin e repetitive matrix protein 1; AltName: Full=Plenty-of-Lamin-A/C P48678 LMNA_MOUSE 01035_4

Insulin-like growth Q9CPN8 IF2B3_MOUSE factor 2 mRNA- binding protein 3 (IGF2 mRNA- bindingRNA-binding protein 3) Q6NZN0 RBM26_MOUSE 12611_1 protein 26 (RNA- binding motif protein 26) [MASS=114142]D(1B) dopamine Q8BLD9 DRD5_MOUSE 00542_1 receptor (D(5) dopamine receptor) Diabetes Page 496 of 603

Eukaryotic Q8JZQ9 EIF3B_MOUSE translation initiation factor 3 subunit B (Eukaryotic translationApolipoprotein initiation A-I- Q8K4Z3 AIBP_MOUSE binding protein precursor (AI-BP)

6330577E15Rik Q8BP27 Q3TH62_MOUSE protein [Mus musculus]

6330577E15Rik Q8BP27 Q3TH62_MOUSE protein [Mus musculus]

Formin-like protein A2APV2 FMNL2_MOUSE 13545_4 2 (Protein Man) [MASS=123100]

High mobility group P52927 HMGIC_MOUSE protein HMGI-C (High mobility group AT-hook 2) Lamin-A/C P48678 LMNA_MOUSE 01035_4

Lamin-A/C P48678 LMNA_MOUSE 01035_4

Arginine/serine-rich P62996 TRA2A_MOUSE 04097_1 splicing factor 10 (Transformer-2- beta) (HTRA2-beta) (TransformerRecName: 2 Q8BTI8 SRRM2_MOUSE Full=Serine/arginin e repetitive matrix protein 2 Page 497 of 603 Diabetes

Glycylpeptide N- O70310 NMT1_MOUSE tetradecanoyltransf erase 1 (Peptide N- myristoyltransferas eZinc 1) (Myristoyl-finger CCCH Q0P678 ZCH18_MOUSE 11232_1 domain-containing protein 18 (Nuclear protein NHN1) acinusL protein Q52KR6 Q52KR6_MOUSE [Mus musculus]

Polymerase I and O54724 PTRF_MOUSE transcript release factor [MASS=43953] RecName: Q9Z1E4 GYS3_MOUSE Full=Glycogen [starch] synthase, muscle RecName: Q9Z1E4 GYS3_MOUSE Full=Glycogen [starch] synthase, muscle Protein FAM82C A3KGH5 RMD3_MOUSE

Eukaryotic Q9Z1D1 IF34_MOUSE translation initiation factor 3 subunit 4 (eIF-3 delta) (eIF3 p44)Eukaryotic (eIF-3 RNA- Q9Z1D1 IF34_MOUSE translation initiation factor 3 subunit 4 (eIF-3 delta) (eIF3 p44)RecName: (eIF-3 RNA- Q9Z0F8 Q3UNK7_MOUSE 04703_1 Full=Disintegrin and metalloproteinase domain-containing Diabetes Page 498 of 603

Bcl-2-associated Q8K019 Q3UR37_MOUSE 16544_3 transcription factor 1 (Btf) [MASS=106001] RecName: Q8BTI8 SRRM2_MOUSE Full=Serine/arginin e repetitive matrix protein 2 RecName: Q9Z277 BAZ1B_MOUSE 10416_3 Full=Tyrosine- protein kinase BAZ1B; AltName: Full=BromodomainBCL2-like protein P59017 Q3TNR7_MOUSE 13 (Mil1 protein) (Bcl-rambo)

Tetratricopeptide A6H6N9 TTC14_MOUSE 15579_2 repeat protein 14 (TPR repeat protein 14) [MASS=86792] Scaffold D3YXK2 SAFB2_MOUSE attachment factor B2 [MASS=111838]

Bcl-2-associated Q8K019 Q3UR37_MOUSE transcription factor 1 (Btf) [MASS=106001] RecName: A2A8V8 SRRM1_MOUSE 10441_1 Full=Serine/arginin e repetitive matrix protein 1; AltName: Full=Plenty-of-Heat shock protein Q71LX8 Q71LX8_MOUSE 11811_1 HSP 90-beta (HSP 84) (Tumor specific transplantation 84 kDaRecName: antigen) Q8CGN5 PLIN_MOUSE Full=Perilipin-1; AltName: Full=Lipid droplet-associated protein; AltName: Page 499 of 603 Diabetes

Beta-2-syntrophin B7ZNU9 SNTB2_MOUSE (59 kDa dystrophin- associated protein A1, basic componentElongation factor2) 1- O70251 EF1B_MOUSE 19235_1 beta (EF-1-beta)

Aladin (Adracalin) P58742 AAAS_MOUSE 05646_1

Arginine/serine-rich P62996 TRA2A_MOUSE 04097_1 splicing factor 10 (Transformer-2- beta) (HTRA2-beta) kinesin(Transformer light chain 2 2 Q91YS4 Q91YS4_MOUSE 13917_1 [Mus musculus] [MASS=68419]

ATP-binding Q6P542 Q5RL55_MOUSE cassette, sub- family F, member 1 [MASS=94945] Nuclease sensitive P62960 YBOX1_MOUSE 1095 element binding protein 1 (Y box binding protein-1) (Y-boxHigh mobility transcription group P52927 HMGIC_MOUSE protein HMGI-C (High mobility group AT-hook 2) High mobility group P52927 HMGIC_MOUSE protein HMGI-C (High mobility group AT-hook 2) Arsenite-resistance Q99MR6 SRRT_MOUSE 10665_1 protein 2 Diabetes Page 500 of 603

Pinin O35691 Q3TUQ5_MOUSE [MASS=82435]

Heat shock protein Q71LX8 Q71LX8_MOUSE 06763_1 HSP 90-beta (HSP 84) (Tumor specific transplantation 84 kDaSAM antigen) and SH3 P59808 SASH1_MOUSE domains containing protein 1

SAM and SH3 P59808 SASH1_MOUSE domains containing protein 1

RecName: Q8BTI8 SRRM2_MOUSE Full=Serine/arginin e repetitive matrix protein 2 ATP-binding Q6P542 Q5RL55_MOUSE cassette, sub- family F, member 1 [MASS=94945] Splicing factor, Q62093 SRSF2_MOUSE 02888_1 arginine/serine-rich 2 (Splicing factor SC35) (SC-35) (SplicingRecName: A2A8V8 SRRM1_MOUSE 10441_1 Full=Serine/arginin e repetitive matrix protein 1; AltName: Full=Plenty-of-Pinin O35691 Q3TUQ5_MOUSE 04401_2 [MASS=82435]

Nuclear ubiquitous Q80XU3 NUCKS_MOUSE 11406_1 casein and cyclin- dependent kinases substrate (JC7) Page 501 of 603 Diabetes

Heterogeneous Q9Z204 Q3U6P5_MOUSE nuclear ribonucleoproteins C1/C2 (hnRNP C1 / hnRNPHeterogeneous C2) Q9Z204 Q3U6P5_MOUSE nuclear ribonucleoproteins C1/C2 (hnRNP C1 / hnRNPMelanoma C2) Q8BI84 MIA3_MOUSE inhibitory activity protein 3 precursor (Protein TANGO) [MASS=213673]Melanoma Q8BI84 MIA3_MOUSE inhibitory activity protein 3 precursor (Protein TANGO) [MASS=213673]Melanoma Q8BI84 MIA3_MOUSE inhibitory activity protein 3 precursor (Protein TANGO) [MASS=213673]vacuolar proton- Q9JHF5 Q91W06_MOUSE translocating ATPase 100 kDa subunit isoform a3 [MusEH domain-binding musculus] Q99MS7 EH1L1_MOUSE protein 1-like protein 1 (Tangerin)

Cordon-bleu B1AZ14 COBL1_MOUSE protein-like 1 (Cobl- related protein 1) [MASS=137381] Cordon-bleu B1AZ14 COBL1_MOUSE protein-like 1 (Cobl- related protein 1) [MASS=137381] Splicing factor, Q8BL97 SRSF7_MOUSE arginine/serine-rich 7 Diabetes Page 502 of 603

Eukaryotic Q8JZQ9 EIF3B_MOUSE translation initiation factor 3 subunit B (Eukaryotic translationBcl-2-associated initiation Q8K019 Q3UR37_MOUSE transcription factor 1 (Btf) [MASS=106001] Tensin-like C1 Q8CGB6 TENC1_MOUSE domain-containing phosphatase (C1 domain-containing phosphataseRecName: and Q8VDD5 MYH9_MOUSE Full=Myosin-9; AltName: Full=Myosin heavy chainAHNAK 9; [MusAltName: IPI00553798.2 musculus] [MASS=68761]

Pre-mRNA 3'-end- Q9D824 D3Z619_MOUSE 09646_1 processing factor FIP1 (FIP1-like 1)

Pre-mRNA 3'-end- Q9D824 D3Z619_MOUSE 09646_1 processing factor FIP1 (FIP1-like 1)

Pre-mRNA 3'-end- Q9D824 D3Z619_MOUSE 09646_1 processing factor FIP1 (FIP1-like 1)

Heterogeneous Q60668 HNRPD_MOUSE 03206_3 nuclear ribonucleoprotein D0 (hnRNP D0) (AU-richcalcium/calmodulin- element O70589-3 CSKP_MOUSE dependent serine protein kinase (MAGUK family) [Mus musculus] Page 503 of 603 Diabetes

Ankyrin repeat Q8C0J6 ANR57_MOUSE domain-containing protein 57 [MASS=54938] Importin alpha-3 O35344 Q9CT07_MOUSE 03536_1 subunit (Karyopherin alpha- 3 subunit) (Importin alphaProtein Q2) KRI1 Q8VDQ9 KRI1_MOUSE homolog [MASS=82601]

Kinesin light chain O88448 Q91YS4_MOUSE 13917_1 2 (KLC 2)

Eukaryotic Q9Z1D1 IF34_MOUSE translation initiation factor 3 subunit 4 (eIF-3 delta) (eIF3 p44)RecName: (eIF-3 RNA- Q8BTI8 SRRM2_MOUSE 06913_1 Full=Serine/arginin e repetitive matrix protein 2 Ras-related GTP- Q99K70 RRAGC_MOUSE 12199_1 binding protein C (Rag C) (GTPase- interacting protein 2)Bcl-2-associated (TIB929) Q8K019 Q3UR37_MOUSE 16544_3 transcription factor 1 (Btf) [MASS=106001] Tln2 protein [Mus IPI00229647.5 Q8CHG4_MOUSE 09555_1 musculus] [MASS=186688]

Splicing factor, Q62093 SRSF2_MOUSE 02888_1 arginine/serine-rich 2 (Splicing factor SC35) (SC-35) (Splicing Diabetes Page 504 of 603

40S ribosomal P63276 RS17_MOUSE 18936_1 protein S17 acetyl-CoA Q9QXG4 Q8BK97_MOUSE synthetase [Mus musculus]

AHNAK [Mus IPI00553798.2 musculus] [MASS=68761]

Lamin-A/C P48678 LAMA_MOUSE 01035_3

Lamin-A/C P48678 LAMA_MOUSE 01035_3

Bcl-2-associated Q8K019 Q3UR37_MOUSE 16544_3 transcription factor 1 (Btf) [MASS=106001] 6330577E15Rik Q8BP27 Q3TH62_MOUSE protein [Mus musculus]

RecName: Q8BTI8 SRRM2_MOUSE Full=Serine/arginin e repetitive matrix protein 2 RecName: Q9DBR7 MYPT1_MOUSE Full=Protein phosphatase 1 regulatory subunit 12A;RecName: AltName: Q9DBR7 MYPT1_MOUSE Full=Protein phosphatase 1 regulatory subunit 12A; AltName: Page 505 of 603 Diabetes

Protein FAM54B Q9CWE0 D6RCX5_MOUSE 14248_1

E3 ubiquitin-protein A2AN08 UBR4_MOUSE 10184_1 ligase UBR4 (N- recognin-4) (Zinc finger UBR1-type proteinRecName: 1) (p600) A2A8V8 SRRM1_MOUSE 10441_1 Full=Serine/arginin e repetitive matrix protein 1; AltName: Full=Plenty-of-Sodium/hydrogen Q7TSV2 SL9A1_MOUSE exchanger 1 (Na(+)/H(+) exchanger 1) (NHE- 1)High mobility group P52927 HMGIC_MOUSE protein HMGI-C (High mobility group AT-hook 2) Protein FAM54B Q9CWE0 FA54B_MOUSE 14248_1

Heat shock protein P07901 HS90A_MOUSE HSP 90-alpha (HSP 86) (Tumor specific transplantationTuberin (Tuberous 86 Q61037 TSC2_MOUSE sclerosis 2 homolog protein)

SKD1 protein P46467 VPS4B_MOUSE (Vacuolar sorting protein 4b)

RecName: Q8BTI8 SRRM2_MOUSE Full=Serine/arginin e repetitive matrix protein 2 Diabetes Page 506 of 603

Transcription Q62318 TIF1B_MOUSE intermediary factor 1-beta (TIF1-beta) (Tripartite motif proteinRecName: 28) (KRAB- Q05D44 IF2P_MOUSE Full=Eukaryotic translation initiation factor 5B; Short=eIF-5B;Heterogeneous O35737 Q8C2Q7_MOUSE 03022_2 nuclear ribonucleoprotein H' (hnRNP H') Heterogeneous O35737 Q8C2Q7_MOUSE 03022_2 nuclear ribonucleoprotein H' (hnRNP H') Heterogeneous Q00PI9 HNRL2_MOUSE nuclear ribonucleoprotein U- like protein 2 (MLF1- associatedRecName: nuclear Q8BTI8 SRRM2_MOUSE Full=Serine/arginin e repetitive matrix protein 2 Brain-specific B1AZ46 BAIP2_MOUSE 05686_3 angiogenesis inhibitor 1- associated protein 2Brain-specific (BAI1-associated B1AZ46 BAIP2_MOUSE 05686_3 angiogenesis inhibitor 1- associated protein 2papillary (BAI1-associated renal cell Q9EQC8 Q9EQC8_MOUSE carcinoma- associated protein [Mus musculus] Microtubule- Q9QYR6 MAP1A_MOUSE associated protein 1A (MAP 1A) Page 507 of 603 Diabetes

RecName: P46938 YAP1_MOUSE 9424 Full=Yorkie homolog; AltName: Full=65 kDa Yes- associatedExocyst complex protein; Q5PPR2 SEC3_MOUSE 07615_3 component Sec3

RecName: A2A8V8 A2A8V9_MOUSE Full=Serine/arginin e repetitive matrix protein 1; AltName: Full=Plenty-of-Rho GTPase- A2AH25 RHG01_MOUSE activating protein 1 (Rho-type GTPase- activating protein 1) CLIP-associating Q80TV8 CLAP1_MOUSE 09322_1 protein 1 (Cytoplasmic linker- associated protein 1)RecName: [MASS=169226] Q8BTI8 SRRM2_MOUSE Full=Serine/arginin e repetitive matrix protein 2 28 kDa heat- and Q3UHX2 HAP28_MOUSE acid-stable phosphoprotein (PDGF-associated protein)28 kDa heat-(PAP) and Q3UHX2 HAP28_MOUSE acid-stable phosphoprotein (PDGF-associated protein)Glycogen (PAP) synthase Q9WV60 GSK3B_MOUSE 06002_1 kinase-3 beta (GSK- 3 beta)

Pleckstrin Q6PDH0 PHLB1_MOUSE 15128_1 homology-like domain family B member 1 (Protein LL5-alpha) Diabetes Page 508 of 603

RecName: Q61687 ATRX_MOUSE Full=Transcriptional regulator ATRX; AltName: Full=ATP- dependent182 kDa tankyrase helicase P58871 TB182_MOUSE 06164_1 1-binding protein [MASS=181824]

RecName: Q61136 PRP4B_MOUSE 09087_2 Full=Serine/threoni ne-protein kinase PRP4 homolog; AltName:Ras-related GTP- Q99K70 RRAGC_MOUSE 12199_1 binding protein C (Rag C) (GTPase- interacting protein 2)RecName: (TIB929) Q8BTI8 SRRM2_MOUSE Full=Serine/arginin e repetitive matrix protein 2 Cholinephosphate P49586 PCY1A_MOUSE 00438_1 cytidylyltransferase A (Phosphorylcholine transferaseHepatoma-derived A) P51859 HDGF_MOUSE growth factor (HDGF)

Hepatoma-derived P51859 HDGF_MOUSE growth factor (HDGF)

Hepatoma-derived P51859 HDGF_MOUSE growth factor (HDGF)

Protein transport Q3UPL0 SC31A_MOUSE protein Sec31A (SEC31-related protein A) (SEC31- like 1) Page 509 of 603 Diabetes

Protein transport Q3UPL0 SC31A_MOUSE protein Sec31A (SEC31-related protein A) (SEC31- likeUPF0404 1) protein Q9CQ22 CK059_MOUSE C11orf59 homolog

UPF0404 protein Q9CQ22 CK059_MOUSE C11orf59 homolog

UPF0404 protein Q9CQ22 CK059_MOUSE C11orf59 homolog

Intersectin 1 (EH Q9Z0R4 Q3TUF4_MOUSE 03898_2 and SH3 domains protein 1)

Intersectin 1 (EH Q9Z0R4 Q3TUF4_MOUSE 03898_2 and SH3 domains protein 1)

Heat shock protein P07901 HS90A_MOUSE HSP 90-alpha (HSP 86) (Tumor specific transplantationRecName: 86 Q61136 PRP4B_MOUSE 09087_2 Full=Serine/threoni ne-protein kinase PRP4 homolog; mRNAAltName: cap guanine- Q9D0L8 MCES_MOUSE N7 methyltransferase (mRNA (guanine- N(7)-)-cytoskeletal protein IPI00353420.7 O08614_MOUSE [Mus musculus] Diabetes Page 510 of 603

nucleolar and IPI00719871.1 Q3TKZ9_MOUSE coiled-body phosphoprotein 1, isoform CRA_c [MusBeta-2-syntrophin musculus] B7ZNU9 SNTB2_MOUSE 02491_2 (59 kDa dystrophin- associated protein A1, basic componentCytoskeleton-like 2) Q921C5 D3Z390_MOUSE bicaudal D protein homolog 2

FUS interacting Q9R0U0 SRS10_MOUSE 05562_2 serine-arginine rich protein 1 (TLS- associated protein withIntersectin Ser-Arg 1 (EH Q6NZJ5 Q6NZJ5_MOUSE and SH3 domains protein 1)

Intersectin 1 (EH Q6NZJ5 Q6NZJ5_MOUSE and SH3 domains protein 1)

Thyroid hormone Q569Z6 TR150_MOUSE receptor-associated protein 3 (Thyroid hormone receptor- associatedRho guanine protein Q9ES28 ARHG7_MOUSE 05688_2 nucleotide exchange factor 7 (PAK-interacting exchangeAHNAK [Mus factor IPI00553798.2 14684_2 musculus] [MASS=68761]

AHNAK [Mus IPI00553798.2 14684_2 musculus] [MASS=68761] Page 511 of 603 Diabetes

AHNAK [Mus IPI00553798.2 14684_2 musculus] [MASS=68761]

HIV Tat-specific Q8BGC0 HTSF1_MOUSE 02282_1 factor 1 homolog

Synapse Q9D5V6 SYAP1_MOUSE 06733_1 associated protein 1

B-Raf proto- P28028 BRAF1_MOUSE 01264_1 oncogene serine/threonine- protein kinase Cad protein [Mus B7ZN27 Q80VF8_MOUSE 06437_1 musculus] [MASS=235849]

RecName: A2A8V8 SRRM1_MOUSE Full=Serine/arginin e repetitive matrix protein 1; AltName: Full=Plenty-of-activating signal Q6P4T2 Q8BYH6_MOUSE 03391_1 cointegrator 1 complex subunit 3- like 1 [Mus musculus]Rab GTPase O35551 RABE1_MOUSE binding effector protein 1 (Rabaptin- 5) (Rabaptin- 5alpha)RecName: Q9DBR7 MYPT1_MOUSE Full=Protein phosphatase 1 regulatory subunit 12A;General AltName: vesicular Q9Z1Z0 USO1_MOUSE transport factor p115 (Protein USO1 homolog) (Transcytosis- Diabetes Page 512 of 603

RecName: Q9QX47 SON_MOUSE Full=Protein SON; AltName: Full=Negative regulatoryRecName: element- P46938 YAP1_MOUSE 9424 Full=Yorkie homolog; AltName: Full=65 kDa Yes- associatedRecName: protein; P46938 YAP1_MOUSE 9424 Full=Yorkie homolog; AltName: Full=65 kDa Yes- associatedacetyl-CoA protein; Q9QXG4 Q8BK97_MOUSE synthetase [Mus musculus]

Secreted frizzled- P97299 SFRP2_MOUSE 16041_1 related protein 2 precursor (sFRP-2) (Secreted apoptosis40S ribosomal related Q9JJN0 RS6_MOUSE 04913_1 protein S6 (Phosphoprotein NP33) 40S ribosomal Q9JJN0 RS6_MOUSE 04913_1 protein S6 (Phosphoprotein NP33) RecName: E9PV45 E9PV45_MOUSE 11664 Full=Ubiquitin carboxyl-terminal hydrolase 24 RecName: E9PV45 E9PV45_MOUSE 11664 Full=Ubiquitin carboxyl-terminal hydrolase 24 RNA-binding region Q8VH51 RNPC2_MOUSE 09201_3 containing protein 2 (Coactivator of activating protein-1 and estrogen Page 513 of 603 Diabetes

Intersectin 1 (EH Q6NZJ5 Q6NZJ5_MOUSE and SH3 domains protein 1)

Telomerase- Q9R0Q7 TEBP_MOUSE 6138 binding protein p23 (Hsp90 co- chaperone) (ProgesteroneMicrotubule- Q9QYR6 MAP1A_MOUSE associated protein 1A (MAP 1A)

40S ribosomal D3Z6N6 RS6_MOUSE 01592_1 protein S6 (Phosphoprotein NP33) Heat shock protein P07901 HS90A_MOUSE HSP 90-alpha (HSP 86) (Tumor specific transplantationRecName: 86 E9PV45 E9PV45_MOUSE 11664 Full=Ubiquitin carboxyl-terminal hydrolase 24 Proline-rich AKT1 Q9D1F4 AKTS1_MOUSE substrate 1 (Proline- rich AKT substrate)

Histone D3YYI8 HDAC1_MOUSE deacetylase 1 (HD1)

Ras-GTPase- P97855 Q3UR88_MOUSE activating protein binding protein 1 (GAP SH3-domain bindingSET protein protein 1) Q9EQU5 SET_MOUSE (Phosphatase 2A inhibitor I2PP2A) (I- 2PP2A) (Template activating factor I) Diabetes Page 514 of 603

Proteasome O70435 PSA3_MOUSE 01463_2 subunit alpha type 3 (Proteasome component C8) (MacropainProteasome subunit O70435 PSA3_MOUSE 01463_2 subunit alpha type 3 (Proteasome component C8) (MacropainacinusL protein subunit B8JJ89 B8JJ89_MOUSE [Mus musculus]

Protein FAM82C A3KGH5 RMD3_MOUSE

RecName: Q921T2 TOIP1_MOUSE Full=Torsin-1A- interacting protein 1; AltName: Full=Lamina-Retrotransposon- Q7TN75 PEG10_MOUSE derived protein PEG10 (Paternally expressed gene 10 protein)A kinase anchor O08715 B1AR25_MOUSE protein 1, mitochondrial precursor (Protein kinasemCG15924, A anchoring Q6NZR5 Q3TW36_MOUSE isoform CRA_a [Mus musculus] [MASS=136654] Pyruvate P35486 ODPA_MOUSE 02420_1 dehydrogenase E1 component alpha subunit, somatic form,Uncharacterized mitochondrial D3Z316 CF203_MOUSE protein C6orf203 homolog Page 515 of 603 Diabetes

Pyruvate P35486 ODPA_MOUSE 02420_1 dehydrogenase E1 component alpha subunit, somatic form,RecName: mitochondrial Q9DBR7 MYPT1_MOUSE Full=Protein phosphatase 1 regulatory subunit 12A;Heterogeneous AltName: Q9Z204 HNRPC_MOUSE nuclear ribonucleoproteins C1/C2 (hnRNP C1 / hnRNPMicrofibrillar- C2) Q9CQU1 MFAP1_MOUSE 02569_1 associated protein 1

Translation Q8CHW4 EI2BE_MOUSE initiation factor eIF- 2B subunit epsilon (eIF-2B GDP-GTP La-relatedexchange factorprotein 7 Q05CL8 LARP7_MOUSE (La ribonucleoprotein domain family memberSTIP1 homology 7) Q9WUD1 STUB1_MOUSE and U box- containing protein 1 (STIP1 homology andCalcium-regulated U-box- Q9CR86 CHSP1_MOUSE 08515_2 heat stable protein 1 (Calcium- regulated heat- stablecAMP-dependent protein of 24 A2AI69 Q8C3Z4_MOUSE 01786_3 protein kinase type I-alpha regulatory subunit Programmed cell P56812 PDCD5_MOUSE death protein 5 (TFAR19 protein) (TF-1 cell apoptosis related gene-19 Diabetes Page 516 of 603

mass error minimum across reversed databse xcorr max across string accession timepoints direction timepoints 375246 1.051834345 F 20.19

383411 0.475261291 F 22.63

370122 0.559566988 F 35.76

378034 0.080788692 F 34.31

374495 0.265690871 F 51.63

374775 0.571011578 F 31.9

386312 0.100665261 F 20.9

381915 1.18521963 F 29.19

379763 1.128383285 F 71.45 Page 517 of 603 Diabetes

377932 0.01873273 F 26.79

378855 0.0916332 F 26.34

379470 0.382637238 F 35.04

379470 0.546187306 F 34.71

379470 0.479487596 F 29.76

373265 1.216744387 F 22.62

379470 1.994805894 F 31.38

0.653324654 F 23.01

378046 0.258408855 F 31.61

380271 0.374207046 F 25.93 Diabetes Page 518 of 603

370352 0.105840991 F 24.13

377095 1.760983653 F 24.2

370274 0.223325126 F 22.4

374249 0.928148997 F 34.85

0.305041362 F 21.19

392092 0.195031517 F 25.98

390074 0.443934146 F 51

389515 1.91942289 F 21.55

380814 0.700907613 F 43.41

380814 0.015389179 F 21.64 Page 519 of 603 Diabetes

376170 0.294400436 F 29.05

374203 0.21483889 F 43.63

375785 0.442577433 F 58.88

379470 0.243832799 F 26.77

380235 0.267112594 F 30.41

379451 0.308742347 F 27.22

385887 0.006563065 F 70.03

383230 0.165673246 F 34.05

383230 0.435631765 F 37.89

389649 0.481838291 F 42.16 Diabetes Page 520 of 603

370549 1.860316962 F 36.37

370703 0.988805743 F 23.97

386405 0.496427037 F 23.59

386405 0.652795351 F 26.21

386405 0.282921111 F 25.62

375402 0.472871155 F 20.57

386217 1.499165933 F 27.96

383395 1.300123098 F 35.45

382208 0.12990117 F 31.87

383230 1.400454924 F 21.61 Page 521 of 603 Diabetes

374089 0.959861017 F 31.51

371766 0.346289781 F 23.08

371766 0.740549268 F 31.42

387336 0.79159515 F 24.5

371900 0.103993562 F 71.78

391148 0.17094228 F 54.82

377095 0.700958795 F 25.75

373236 0.858834121 F 24.72

386496 0.06093994 F 79.72

372022 0.119780855 F 48.39 Diabetes Page 522 of 603

372022 0.049204503 F 30.78

1.364630632 F 28.72

386496 0.268875514 F 21.1

0.462309328 F 41.89

0.214119771 F 30.3

376036 0.052528917 F 24.79

374639 1.138374823 F 59.41

373569 0.026502874 F 26.51

0.094810821 F 71.05

0.017029663 F 59.07 Page 523 of 603 Diabetes

379214 1.096415238 F 29.85

0.232236072 F 56.83

379158 0.742110445 F 28.04

379158 0.183630771 F 24.62

0.845862721 F 32.84

0.173010721 F 46.14

372026 0.652542563 F 78.3

372133 0.416104694 F 43.83

393033 0.563318121 F 56.87

385364 0.439252389 F 53.36 Diabetes Page 524 of 603

378270 0.26874925 F 38.93

378581 0.212570815 F 28.93

0.264821513 F 47.26

374938 0.323377987 F 21.23

0.548696212 F 64.55

0.136949472 F 75.78

371900 0.611947756 F 38.58

384814 0.278055916 F 30.87

387885 0.010359242 F 26.36

377095 0.778176699 F 74.68 Page 525 of 603 Diabetes

371763 0.450180395 F 91.04

0.923983728 F 57.47

383332 0.066518062 F 26.11

376955 1.534949377 F 39.2

376003 0.060311065 F 41.2

376003 0.994362573 F 33.14

374414 1.66699312 F 37.39

0.514565978 F 49.83

385648 0.08174512 F 27.32

384319 0.697555192 F 55.57 Diabetes Page 526 of 603

389655 0.730569302 F 23.23

382871 0.229156134 F 39.79

382871 1.748541832 F 29.9

372038 0.056406773 F 42.09

375402 0.090248933 F 22.59

371806 0.064019301 F 41.98

0.109440191 F 63.86

0.109440191 F 44.32

389776 1.33354785 F 24.9

370159 1.063903105 F 27.63 Page 527 of 603 Diabetes

370159 0.027672788 F 32.32

392976 1.006271213 F 47.2

378507 0.055080414 F 49.42

0.563878471 F 80.49

371649 1.302410338 F 26.59

370295 0.11408386 F 47.67

374414 0.123331212 F 41.83

372292 0.447855783 F 25.03

388931 0.459307052 F 52.27

371649 0.544392348 F 80.47 Diabetes Page 528 of 603

373907 0.015055557 F 44.93

379958 0.174120778 F 24.97

390074 0.056231632 F 59.34

385473 0.599734126 F 67.73

385473 0.39402725 F 21.43

0.036521358 F 57.71

385473 0.425065248 F 76.21

388213 0.108204198 F 45.4

377095 0.419874104 F 48.44

376133 0.613813051 F 37.31 Page 529 of 603 Diabetes

376133 1.165963955 F 21.81

375381 0.109626368 F 32.61

375402 0.236923408 F 26.93

390074 0.488335534 F 54.99

390074 0.257725489 F 24.71

384960 0.623478615 F 46.52

380814 1.781385951 F 43.15

380814 0.709834357 F 29.53

372022 0.2105565 F 110.75

370263 1.012453526 F 37.08 Diabetes Page 530 of 603

376686 0.099310781 F 55.05

374733 0.941967369 F 36.96

386496 0.212484292 F 22.57

375244 0.141182254 F 61.21

375244 0.424878431 F 32.52

374565 1.370025897 F 25.37

372668 1.853738382 F 22.71

0.033955238 F 73.73

391386 0.608729404 F 49.35

391386 0.326309218 F 75.58 Page 531 of 603 Diabetes

376587 0.115982627 F 20.87

371588 0.267358051 F 21.17

375402 1.391434441 F 36.34

375402 0.291106722 F 37.35

375244 0.217158398 F 44.61

375244 1.210876798 F 46.16

375244 0.625049036 F 29.39

375244 0.86485732 F 34.98

378244 0.242204258 F 36.62

380814 0.632586199 F 21.79 Diabetes Page 532 of 603

375402 0.0837705 F 31.96

391348 0.085947004 F 60.11

394387 0.58814919 F 30.34

388931 0.001776954 F 58.69

370803 0.098212837 F 22.86

374092 0.040930324 F 36.92

392144 0.646673807 F 56.25

375038 0.604543824 F 22.42

375038 0.436685555 F 27.7

372307 0.215540054 F 22.34 Page 533 of 603 Diabetes

371162 0.19010212 F 20.01

374414 0.271865293 F 47.15

381442 0.594746763 F 70.81

390074 0.131138212 F 38.99

390074 1.210408786 F 27.96

377998 0.07397867 F 41.63

377998 0.16659771 F 40.43

371750 0.457834094 F 39.03

378986 0.340990033 F 23.53

384160 0.036983617 F 63.55 Diabetes Page 534 of 603

384160 0.643861076 F 63.53

375035 0.230384768 F 22.73

378088 1.073404276 F 80.7

380083 1.090428687 F 23.68

385473 0.190476422 F 45.53

375146 0.024786094 F 24.93

370726 0.202903868 F 31.04

377503 0.754338693 F 33.45

375935 0.658521129 F 40.38

385255 0.103816143 F 38.17 Page 535 of 603 Diabetes

383532 0.222552085 F 49.58

382867 1.049531269 F 47.29

373396 0.308692187 F 49.33

373396 0.947108733 F 23.81

380814 0.75354472 F 46.21

380814 0.450576156 F 46.01

380814 0.20260199 F 32.23

374809 0.33953485 F 30.68

374809 0.667638304 F 27.81

380593 0.464166011 F 33.3 Diabetes Page 536 of 603

378837 0.508625317 F 34.04

385689 0.104939263 F 56.45

392976 0.361273041 F 31.17

0.037116393 F 84.07

1.384575902 F 41.75

376750 0.224168812 F 26.48

380361 0.310662914 F 25.25

376233 0.702984621 F 69.92

376272 0.075307865 F 50.51

370281 0.030462744 F 59.86 Page 537 of 603 Diabetes

385548 0.466793045 F 81.97

374089 0.244778122 F 40.4

389776 0.779054555 F 21.46

389776 0.018639889 F 20.41

0.189765817 F 33.08

374414 0.192975826 F 20.32

370041 0.438187804 F 43.62

379987 0.147180183 F 37.63

379987 0.057220797 F 33.57

386449 1.266275328 F 30.51 Diabetes Page 538 of 603

0.854476254 F 22.6

376947 0.537128281 F 31.91

0.056097871 F 21.22

375038 0.072772488 F 36.4

375038 0.113952493 F 32.44

373337 0.443165312 F 41.5

379751 0.064466608 F 42.07

372585 0.876061691 F 48.87

1.224034792 F 21.85

385473 0.001009656 F 32.78 Page 539 of 603 Diabetes

369868 0.749081443 F 92.31

386496 0.233987591 F 31.33

372668 0.352661426 F 48.93

370042 0.169716363 F 27.43

385223 0.405243131 F 25.05

375402 0.857923474 F 30.61

375038 0.308702046 F 43.82

375883 0.343889784 F 33.53

372643 0.479231741 F 32.2

378265 0.155540841 F 20.42 Diabetes Page 540 of 603

387347 0.244668977 F 71.82

375041 0.014111137 F 54.18

373715 1.13271457 F 47.96

373715 1.471087197 F 24.07

0.128500352 F 29.32

0.241951419 F 64.71

375038 0.790516562 F 20.45

375038 0.045177086 F 24.28

375886 0.150886368 F 39.24

392144 0.686434159 F 35.16 Page 541 of 603 Diabetes

394602 0.150971102 F 44.97

394886 0.069283367 F 76.8

372668 0.529737749 F 65.52

382871 1.398047262 F 26.56

370159 0.574127311 F 21.43

370159 0.574127311 F 100.82

379058 0.151221861 F 82.89

0.205790776 F 28.76

0.000762684 F 22.5

385169 1.094449116 F 44.52 Diabetes Page 542 of 603

379214 0.100011227 F 20.03

392144 0.720551409 F 32.02

369983 0.061988004 F 23.39

370698 0.350497165 F 28.74

374850 0.117235799 F 30.19

377552 0.410277852 F 74.35

379214 0.150258891 F 56.49

375402 0.744599372 F 33.14

373204 0.026538804 F 65.11

390074 0.063190555 F 40.19 Page 543 of 603 Diabetes

377669 0.123865897 F 43.35

374066 0.005082906 F 63.71

379467 0.494556911 F 27.24

375886 0.498396539 F 25.05

373614 0.750279225 F 24.84

377554 0.000364022 F 29.28

388522 0.008940852 F 24.1

0.239506757 F 33.92

1.535990077 F 23.13

379108 0.010087557 F 28.95 Diabetes Page 544 of 603

372133 1.609395863 F 37.03

373204 0.053966648 F 74.94

371036 0.254783226 F 53.74

371036 0.927483636 F 25.3

392144 0.015355546 F 50.04

377554 0.224520634 F 50.1

0.717003485 F 20.87

375402 0.643036439 F 27.25

372133 1.033555562 F 33.68

383895 1.895766399 F 50.66 Page 545 of 603 Diabetes

387360 0.209775804 F 94.1

387360 0.23702257 F 28.93

385819 0.733997417 F 29.61

385819 0.411449334 F 35.01

385819 0.573716557 F 28.97

369843 0.100131525 F 24.97

377765 0.115447734 F 34.46

386496 0.089206735 F 67.93

386496 0.122334596 F 54.72

390866 0.056273096 F 24.5 Diabetes Page 546 of 603

387347 0.197189498 F 44.83

379214 0.552893474 F 24.57

378617 0.277867692 F 20.79

392678 0.234050379 F 49.38

0.11783063 F 60.1

388692 0.100739566 F 54

388692 0.305001435 F 32.63

388692 1.568036847 F 22.19

386449 0.050401812 F 25.36

0.345657477 F 25.91 Page 547 of 603 Diabetes

394572 0.429516794 F 32.53

372546 0.459170995 F 25.46

378263 0.103765465 F 29.55

373614 0.769290487 F 39.16

1.116567552 F 32.55

392144 0.247834804 F 31.24

375320 0.804707016 F 22.57

379214 0.057830694 F 48.69

378739 0.258005728 F 29.17

0.667477784 F 33.21 Diabetes Page 548 of 603

388896 0.374415428 F 61.11

385364 0.643737964 F 41.37

0.460938809 F 25.35

375038 0.043723361 F 86.82

375038 0.415276878 F 106.89

379214 0.380638773 F 22.99

373715 0.07226553 F 20.75

392144 0.120786284 F 31.16

385473 0.092008437 F 44.3

385473 0.04297601 F 65.76 Page 549 of 603 Diabetes

375410 0.050502631 F 28.93

379987 0.268159142 F 22.66

375402 0.35179557 F 23.44

389531 0.004559089 F 41.27

0.692419856 F 49.52

375410 0.234064852 F 59.67

372250 0.130125527 F 38.9

392004 1.427639813 F 21.38

385650 0.39402754 F 59.91

392144 0.133797262 F 20.15 Diabetes Page 550 of 603

370352 0.353917591 F 37.05

385908 0.041341106 F 89.67

387964 0.735521186 F 22.47

387964 0.457859232 F 70.6

386142 0.127581708 F 60.4

392144 0.442070604 F 46.16

373840 0.225772129 F 61.15

373840 0.540220348 F 56.25

370272 1.507699792 F 35.68

0.881100365 F 24.83 Page 551 of 603 Diabetes

385548 0.010790175 F 26.91

379998 1.138386285 F 40.29

0.30749657 F 100.36

385026 0.088777404 F 29.02

374249 0.550815778 F 29.83

392144 0.167990551 F 40.31

375809 0.06979856 F 68.36

375809 0.155209921 F 43.64

372943 0.158942637 F 28.16

378735 0.263747151 F 20.18 Diabetes Page 552 of 603

376488 0.37591284 F 30.45

379763 1.463141264 F 23.09

372307 0.723748292 F 26.13

375320 0.162884147 F 82.54

392144 0.050120144 F 22.61

388568 0.049614031 F 53.04

370274 0.031222899 F 22.28

370274 0.031222899 F 49.03

370274 0.031222899 F 26.41

0.251688296 F 34.25 Page 553 of 603 Diabetes

0.270066171 F 24.35

376325 0.693498968 F 20.88

376325 1.963845967 F 36.58

376325 1.084989897 F 25.7

373009 0.123501926 F 59.43

373009 0.574834201 F 23.36

372250 0.490028274 F 72.94

372307 0.112430468 F 22.98

370726 1.690930464 F 22.9

387656 1.372270093 F 20.54 Diabetes Page 554 of 603

371023 0.062711453 F 37.56

377669 0.132504734 F 30.45

378193 0.251940893 F 40.05

375335 0.247035931 F 23.93

373009 0.059024235 F 57.36

373009 0.355703261 F 48.68

388931 0.491454171 F 69.43

376615 0.266432195 F 33.36

0.195855943 F 41.25

0.563559943 F 48.79 Page 555 of 603 Diabetes

1.302277979 F 21.26

392170 0.035303083 F 28.67

376540 0.675010816 F 23.71

369950 0.069201444 F 51.13

370917 1.117344532 F 44.44

375402 0.036894834 F 29.1

370129 0.432129362 F 75.73

381442 0.209483196 F 54.71

385473 0.094963106 F 34.48

375704 0.357872981 F 33.79 Diabetes Page 556 of 603

373011 0.13836951 F 74.46

385548 0.178949552 F 35.22

385548 0.473974629 F 22.1

385364 0.689913293 F 28.92

374996 0.108452033 F 22.28

375247 0.182396588 F 30.09

375247 0.093813689 F 31.66

375250 0.928896038 F 22.17

375250 0.140790718 F 32.1

374823 0.377078495 F 42.76 Page 557 of 603 Diabetes

373009 0.774214129 F 22.29

377662 0.166867119 F 96.88

384635 0.01702548 F 56.25

375247 0.254164856 F 20.8

372250 1.240855962 F 58.9

0.761318627 F 41.49

380756 0.54170805 F 35.71

388438 0.463858606 F 31.46

371392 0.045434115 F 66.62

386126 0.333962866 F 39.74 Diabetes Page 558 of 603

385508 0.085815068 F 23.11

385508 0.749602515 F 25.22

372668 0.163454596 F 41.62

379058 0.219969552 F 34.94

374288 0.381707597 F 38.43

383052 0.484629713 F 49.24

371358 0.279535883 F 67.44

377408 0.011728755 F 49.45

376517 0.066702324 F 60.72

371575 0.798713585 F 49.35 Page 559 of 603 Diabetes

376517 1.344297398 F 40.57

385473 0.235482849 F 93.11

387360 1.392066934 F 28.15

380687 0.675230823 F 38.45

393041 0.001721885 F 55.1

374985 0.64438084 F 51.05

378465 0.218397223 F 26.03

370652 0.128809564 F 34.98

371954 0.067595013 F 73.35

376141 0.032377787 F 37.07 Diabetes Page 560 of 603

Go location Go bio process Go mol process Kegg unique unique index unqiue index unique index index

intracellular regulation of protein binding NOD-like receptor apoptosis signaling pathway membrane protein amino acid ATP binding phosphorylation nucleus protein amino acid protein binding phosphorylation nucleus immune response protein binding RIG-I-like receptor signaling pathway intracellular multicellular DNA binding integral to organismal RNA binding membrane development protein amino acid membrane signaldephosphorylation transduction protein binding Inositol phosphate phosphatidylinositol metabolism metabolic process Phosphatidylinositol signaling system nucleus regulation of protein binding transcription nucleus regulation of Rab GTPase activator GTPase activity activity Page 561 of 603 Diabetes

integral to sensory perception protein binding membrane of sound binding carbohydrate zinc ion binding metabolic process integral to protein amino acid ATP binding membrane phosphorylation molecular_function signal transduction

nucleus regulation of protein binding Pathways in cancer transcription Acute myeloid leukemia Ubiquitin mediated nucleus regulation of protein binding Pathwaysproteolysis in cancer transcription Acute myeloid leukemia Ubiquitin mediated nucleus regulation of protein binding Pathwaysproteolysis in cancer transcription Acute myeloid leukemia Ubiquitin mediated intracellular protein amino acid protein binding proteolysis phosphorylation

nucleus regulation of protein binding Pathways in cancer transcription Acute myeloid leukemia Ubiquitin mediated nucleus apoptosis protein binding proteolysis intracellular intracellular zinc ion binding signaling cascade

cytoplasm protein amino acid protein binding Neurotrophin phosphorylation signaling pathway NOD-like receptor signaling pathway cytoplasm protein amino acid protein binding phosphorylation Diabetes Page 562 of 603

nucleus protein amino acid protein binding phosphorylation microtubule negative regulation protein binding of microtubule binding depolymerization metal ion binding

cytoplasm cell cycle protein binding integral to G-protein coupled binding membrane receptor protein signaling pathway intracellular actin cytoskeleton guanyl-nucleotide organization exchange factor apoptosis activity myosin complex signal transduction protein binding Cardiac muscle protein complex multicellular calcium ion binding contraction integral to organismal Regulation of actin membrane development cytoskeleton lipidmembrane particle lipidregulation metabolic of protein binding PPARVascular signaling smooth process pathway cytoplasm translation protein binding Viral myocarditis integral to RNA metabolic membrane process nucleus protein amino acid ATP binding integral to plasma phosphorylation protein binding membrane brain development guanyl-nucleotide integral to transport exchange factor nucleusmembrane proteinintracellular amino acid ATPactivity binding integral to plasma phosphorylation protein binding membrane brain development guanyl-nucleotide integral to transport exchange factor membrane intracellular activity Page 563 of 603 Diabetes

nucleus blastocyst protein binding Tight junction membrane formation Epithelial cell cytoplasm cell-cell junction signaling in assembly Helicobacter pylori nucleus cellregulation cycle of protein binding infection

cytoplasm DNA repair protein binding Cardiac muscle membrane muscle contraction contraction cytoskeleton response to Regulation of actin actin cytoskeleton mechanical cytoskeleton nucleuscytosol regulationstimulus of protein binding PathwaysVascular smooth in cancer transcription Acute myeloid leukemia Ubiquitin mediated cytoplasm translation protein binding Viralproteolysis myocarditis RNA metabolic process

nucleus transport nucleotide binding Spliceosome protein binding

nucleus metabolic process calcium ion binding Glycerophospholipi phospholipase A2 d metabolism activity Arachidonic acid phospholipase metabolism nucleus immune response catalyticactivity activity Linoleic acid extracellular space carbohydrate metabolic process

nucleus immune response catalytic activity extracellular space carbohydrate metabolic process

cytoplasm translation protein binding Ribosome intracellular translational structural elongation constituent of ribosome RNA binding Diabetes Page 564 of 603

nucleus regulation of protein binding Wnt signaling transcription, DNA- binding pathway dependent Melanogenesis intracellular Pathways in cancer nucleus regulationsignaling cascade of protein binding Basal cell transcription integral to negative regulation protein binding membrane of apoptosis integral to negative regulation protein binding membrane of apoptosis integral to negative regulation protein binding membrane of apoptosis nucleus mRNA processing DNA binding spliceosomal protein binding complex lysophospholipase activity integral to immune response proteinzinc ion binding binding Autoimmune membrane peptide antigen thyroid disease binding Endocytosis calcium ion binding Natural killer cell cytoplasm response to calciumreceptor ion activity binding RNAmediated degradation membrane wounding protein binding multicellular isomerase activity organismal plasma membrane vesicle-mediateddevelopment calmodulin binding Fc gamma R- transport mediated phagocytosis Leishmania nucleus immune response catalytic activity infection extracellular space carbohydrate metabolic process Page 565 of 603 Diabetes

nucleus ribosome protein binding biogenesis

membrane transport protein binding Lysosome Golgi apparatus protein transport

membrane transport protein binding Lysosome Golgi apparatus protein transport

nucleus regulation of DNA binding transcription, DNA- dependent

cytoplasm immune response protein binding

Golgi apparatus protein amino acid protein binding Tight junction phosphorylation

nucleus protein binding

membrane Wnt receptor protein binding signaling pathway Diabetes Page 566 of 603

membrane Wnt receptor protein binding signaling pathway membrane transport protein binding

nucleus regulation of protein binding Tight junction integral to transcription, DNA- DNA binding membrane dependent membrane transport zinc ion binding Endocytosis cytoplasm regulation of ARF integral to GTPase activity membrane integral to signal transduction protein binding membrane

cytoplasm protein amino acid ATP binding MAPK signaling phosphorylation pathway Page 567 of 603 Diabetes

nucleus regulation of protein binding membrane transcription integral to negative regulation membrane of transcription nucleus regulation of protein binding transcription ATP binding positive regulation of transcription cytoplasm regulationfrom RNA of small GTPase activator intracellular GTPase mediated activity signal transduction binding

cytoplasm regulation of small GTPase activator intracellular GTPase mediated activity signal transduction binding

integral to brain development guanyl-nucleotide membrane intracellular exchange factor integral to plasma signaling cascade activity membrane kinase activity mitochondrion protein amino acid protein binding phosphorylation

nucleus regulation of DNA binding transcription, DNA- metal ion binding dependent immune response nucleus regulation of protein binding cytoplasm transcription neurotransmitter secretion membrane transport protein binding SNARE interactions nucleus apoptosis in vesicular transport

cytoplasm metabolic process ATP binding Glycolysis / nucleus catalytic activity Gluconeogenesis Pyruvate metabolism Propanoate Diabetes Page 568 of 603

cytoplasm centrosome protein binding centriolar satellite organization membrane porphyrin protein binding biosynthetic process

integral to transport hydrolase activity SNARE interactions membrane protein binding in vesicular transport cytoplasm protein amino acid protein binding intracellular phosphorylation ATP binding cytoplasm modification- protein binding Aldosterone- intracellular dependent protein regulated sodium catabolic process reabsorption Endocytosis cytoplasm immune response protein binding Ubiquitin mediated

nucleus oxidation reduction metal ion binding regulation of DNA binding apoptosis positive regulation intracellular translationalof transcription structural Ribosome cytoplasm elongation constituent of ribosome protein binding microtubule negative regulation protein binding of microtubule depolymerization Page 569 of 603 Diabetes

nucleus modification- protein binding Pathways in cancer dependent protein Bladder cancer catabolic process Endocytosis negative regulation Glioma cytoplasm proteinof transcription amino acid protein binding Prostate cancer intracellular phosphorylation ATP binding

nucleus carbohydrate protein binding metabolic process

cytoplasm modification- protein binding Endocytosis dependent protein Ubiquitin mediated catabolic process proteolysis

nucleus defense response protein binding

nucleus defense response protein binding

cytoplasm intermediate protein binding filament-based process

mitochondrion protein amino acid protein binding phosphorylation

nucleus transport peptide binding protein binding microtubule binding

nucleus protein amino acid protein binding Jak-STAT signaling phosphorylation pathway Chemokine signaling pathway Adipocytokine Diabetes Page 570 of 603

nucleus intracellular protein binding signaling cascade protein domain mRNA processing specific binding nucleus regulation of protein binding transcription nucleus regulation of protein binding transcription nucleus acrosome reaction protein binding

nucleus mRNA processing DNA binding spliceosomal protein binding complex lysophospholipase activity cytoplasm carbohydrate ATPzinc ionbinding binding Glycolysis / metabolic process Gluconeogenesis Fructose and mannose integral to protein amino acid protein binding Tightmetabolism junction membrane phosphorylation integral to protein amino acid protein binding Tight junction membrane phosphorylation nucleus protein amino acid protein binding intracellular phosphorylation ATP binding mitochondrion cell division structural constituent of cytoplasm heart development proteinribosome binding Starch and sucrose metabolism Insulin signaling pathway Page 571 of 603 Diabetes

cytoplasm heart development protein binding Starch and sucrose metabolism Insulin signaling pathway nucleus mRNA processing zinc ion binding protein binding

membrane cytoskeleton D3 dopamine organization receptor binding

cytoplasm cell differentiation protein binding MAPK signaling nucleus protein amino acid hydrolase activity pathway endoplasmic dephosphorylation protein tyrosine reticulum phosphatase membrane intracellular proteinactivity binding Insulin signaling cytoplasm signaling cascade pathway Neurotrophin signaling pathway cytoplasm intermediate protein binding filament-based process

nucleus response to protein DNA binding intracellular stimulus histone binding

nucleus regulation of protein binding mediator complex transcription ATP binding transcription from receptor activity RNA polymerase II cytoplasm cellpromoter differentiation protein binding MAPK signaling nucleus protein amino acid hydrolase activity pathway endoplasmic dephosphorylation protein tyrosine reticulum phosphatase activity Diabetes Page 572 of 603

integral to metabolic process hydrolase activity membrane membrane G-protein coupled signal transducer Regulation of actin receptor protein activity cytoskeleton signaling pathway Chemokine signaling pathway lipid particle lipid metabolic protein binding PPARMAPK signalingsignaling process pathway cytoplasm integrin-mediated protein binding Regulation of actin intracellular signaling pathway cytoskeleton membrane- protein amino acid Vascular smooth bounded organelle dephosphorylation muscle contraction cytoplasm integrin-mediated protein binding RegulationFocal adhesion of actin intracellular signaling pathway cytoskeleton membrane- protein amino acid Vascular smooth bounded organelle dephosphorylation muscle contraction perinuclear region response to actin binding Focal adhesion of cytoplasm nutrient cytoplasm integrin-mediated protein binding Regulation of actin intracellular signaling pathway cytoskeleton membrane- protein amino acid Vascular smooth bounded organelle dephosphorylation muscle contraction nucleus translation nucleotide binding mTORFocal adhesion signaling integral to transport translation initiation pathway membrane phagocytosis factor activity cytoskeleton oxidation reduction microtubulecytoplasm negativenucleosome regulation protein binding of microtubule depolymerization membrane actin cytoskeleton protein binding Fc gamma R- organization mediated phagocytosis Focal adhesion Leukocyte Page 573 of 603 Diabetes

membrane actin cytoskeleton protein binding Fc gamma R- organization mediated phagocytosis Focal adhesion cytoplasm protein amino acid protein binding Leukocyte cytosol dephosphorylation

nucleus mRNA processing DNA binding zinc ion binding

lipid particle lipid metabolic protein binding PPAR signaling process pathway

lipid particle lipid metabolic protein binding PPAR signaling process pathway

nucleus protein amino acid protein binding Wnt signaling membrane phosphorylation ATP binding pathway intracellular Melanogenesis Calcium signaling nucleus protein amino acid ATP binding pathway integral to plasma phosphorylation protein binding membrane brain development guanyl-nucleotide integral to transport exchange factor nucleusmembrane proteinintracellular amino acid ATPactivity binding integral to plasma phosphorylation protein binding membrane brain development guanyl-nucleotide integral to transport exchange factor membrane Wntintracellular receptor proteinactivity binding signaling pathway

membrane transport protein domain Endocytosis microsome protein transport specific binding protein binding metal ion binding Diabetes Page 574 of 603

cytoplasm protein amino acid actin binding nucleus phosphorylation protein binding cytoskeleton organization nucleus regulation of protein binding RNA degradation transcription

nucleus regulation of DNA binding transcription nucleus regulation of DNA binding transcription nucleus regulation of DNA binding transcription protein binding transport nucleus apoptosis nucleotide binding Spliceosome erythrocyte nucleic acid binding intracellular differentiation response to protein nucleus nervousstimulus system protein binding development membrane protein folding unfolded protein plasma membrane binding membrane protein folding unfolded protein plasma membrane binding Page 575 of 603 Diabetes

membrane signal transduction zinc ion binding MAPK signaling intracellular GTPase activator pathway - fly activity

cytoplasm oxidation reduction protein binding extracellular region proteolysis zinc ion binding

nucleus mRNA processing DNA binding zinc ion binding

nucleus mRNA processing DNA binding zinc ion binding

nucleus regulation of DNA binding transcription

nucleus regulation of DNA binding transcription

nucleus regulation of DNA binding transcription

nucleus regulation of DNA binding transcription

endoplasmic transport protein binding reticulum lumen

integral to plasma protein amino acid protein binding membrane phosphorylation ATP binding nucleus intracellular kinase activity intracellular signaling cascade transferase activity Diabetes Page 576 of 603

nucleus mRNA processing DNA binding zinc ion binding membrane intracellular protein binding Inositol phosphate plasma membrane signaling cascade prenylcysteine metabolism integral to oxidase activity Phosphatidylinositol membrane zinc ion binding signaling system nucleus regulation of proteinkinase activitybinding Endocytosis transcription, DNA- DNA binding dependent nucleus regulation of protein binding mediator complex transcription ATP binding transcription from receptor activity RNA polymerase II nucleus mRNApromoter processing nucleotide binding Spliceosome

nucleus proteolysis protein binding Alzheimer's disease Pathways in cancer Huntington's nucleus mRNA processing protein binding disease

nucleus spermatogenesis protein binding Hypertrophic structural molecule cardiomyopathy activity (HCM) Arrhythmogenic nucleus spermatogenesis protein binding Hypertrophicright ventricular structural molecule cardiomyopathy activity (HCM) Arrhythmogenic nucleus protein amino acid protein binding right ventricular chromosome phosphorylation Page 577 of 603 Diabetes

nucleus cell cycle DNA binding

cytoplasm intermediate protein binding filament-based process

cytoplasm transport protein binding Endocytosis endosome growth factor activity

lipid particle lipid metabolic protein binding PPAR signaling process pathway

lipid particle lipid metabolic protein binding PPAR signaling process pathway

cytoplasm steroid metabolic protein binding process

cytoplasm steroid metabolic protein binding microtubule process ATP binding microtubule-based movement nucleus transport protein binding

nucleus DNA repair protein binding Base excision repair Diabetes Page 578 of 603

cytoplasm cell cycle protein binding Pathogenic intracellular apoptosis zinc ion binding Escherichia coli intracellular infection signaling cascade

nucleus regulation of cell protein binding proliferation cytoplasm protein amino acid protein binding Regulation of actin intracellular dephosphorylation cytoskeleton membrane- Vascular smooth bounded organelle muscle contraction integral to modification- ATP binding Parkinson'sFocal adhesion membrane dependent protein small conjugating disease catabolic process protein ligase Ubiquitin mediated regulation of activity proteolysis nucleus mRNAprotein processingmetabolic transferase activity

cytoplasm metabolic process transferase activity Amino sugar and nucleotide sugar metabolism Alanine, aspartate cytosol proteolysis protein binding and glutamate integral to zinc ion binding membrane mitochondrion intracellular Page 579 of 603 Diabetes

intracellular regulation of small protein binding GTPase mediated signal transduction biological_process nucleus mRNA processing protein binding

nucleus multicellular protein binding cytoplasm organismal development regulation of nucleus multicellularendocytosis protein binding cytoplasm organismal development regulation of integral to plasma proteinendocytosis amino acid protein binding membrane phosphorylation ATP binding nucleus intracellular kinase activity intracellular signaling cascade transferase activity integral to plasma protein amino acid protein binding membrane phosphorylation ATP binding nucleus intracellular kinase activity intracellular signaling cascade transferase activity integral to plasma protein amino acid protein binding membrane phosphorylation ATP binding nucleus intracellular kinase activity intracellular signaling cascade transferase activity nucleus mRNA processing nucleotide binding

nucleus mRNA processing nucleotide binding

nucleus regulation of nucleotide binding transcription Diabetes Page 580 of 603

microtubule epidermal growth protein binding factor receptor signaling pathway nucleus transport protein binding cytosol fructose 2,6- bisphosphate metabolic process nucleus mRNA processing zinc ion binding protein binding mitochondrion protein amino acid protein binding phosphorylation mitochondrion protein amino acid protein binding phosphorylation mitochondrion ubiquinone metal ion binding biosynthetic process nucleus mRNA processing nucleotide binding regulation of transcription, DNA- dependent cellular_component biological_process molecular_function

cytoplasm translation translation initiation factor activity protein binding cytoplasm regulation of binding transcription Page 581 of 603 Diabetes

nucleus regulation of protein binding transcription factor transcription complex positive regulation of transcription nucleus ribosomefrom RNA protein binding biogenesis

nucleus protein amino acid protein binding intracellular phosphorylation ATP binding mitochondrion

nucleus protein amino acid protein binding intracellular phosphorylation ATP binding mitochondrion

microtubule negative regulation protein binding cytosol of microtubule microtubule depolymerization associated complex oxidation reduction cytoplasm intermediatesensory perception protein binding filament-based process

nucleus protein amino acid ATP binding mediator complex phosphorylation

integral to modification- zinc ion binding membrane dependent protein protein binding catabolic process

integral to modification- zinc ion binding membrane dependent protein protein binding catabolic process

nucleus regulation of protein binding transcription, DNA- dependent regulation of transcription Diabetes Page 582 of 603

mitochondrion protein amino acid protein binding phosphorylation integral to regulation of protein binding Phenylalanine membrane transcription, DNA- metabolism intracellular dependent Ubiquinone and signal transduction other terpenoid- quinone

nucleus spermatogenesis protein binding Hypertrophic intermediate DNA repair structural molecule cardiomyopathy filament DNA metabolic activity (HCM) process Arrhythmogenic nucleus spermatogenesisG-protein coupled protein binding Hypertrophicright ventricular intermediate DNA repair structural molecule cardiomyopathy filament DNA metabolic activity (HCM) process Arrhythmogenic nucleus cytoskeletonG-protein coupled calcium ion binding right ventricular organization actin binding skeletal muscle tissue development nucleus regulation of protein binding transcription, DNA- dependent nucleus regulation of ARF zinc ion binding integral to GTPase activity membrane transport nucleus modification- hydrolase activity dependent protein protein binding catabolic process cytoplasm integrin-mediated protein binding Regulation of actin intracellular signaling pathway cytoskeleton membrane- protein amino acid Vascular smooth bounded organelle dephosphorylation muscle contraction Focal adhesion Page 583 of 603 Diabetes

intracellular tRNA processing zinc ion binding integral to membrane

nucleus apoptosis nucleotide binding erythrocyte differentiation

nucleus metabolic process protein binding Insulin signaling cytosol pathway

nucleus regulation of zinc ion binding intracellular transcription mRNA processing translation nucleus mRNA processing DNA binding zinc ion binding

nucleus spermatogenesis protein binding Hypertrophic intermediate DNA repair structural molecule cardiomyopathy filament DNA metabolic activity (HCM) process Arrhythmogenic nucleus regulationG-protein coupledof protein binding right ventricular translation

nucleus mRNA processing protein binding zinc ion binding

nucleus cell cycle calmodulin binding Calcium signaling integral to G-protein coupled receptor activity pathway membrane receptor protein protein binding Neuroactive ligand- nuclear pore signaling pathway DNA binding receptor interaction spindle pole proteolysis peptidase activity Gap junction Diabetes Page 584 of 603

cytoplasm translation nucleotide binding

extracellular region protein folding protein binding

cytoplasm actin cytoskeleton actin binding Pyrimidine organization metabolism nucleus regulation of protein binding transcription, DNA- dependent nucleus spermatogenesis protein binding Hypertrophic intermediate DNA repair structural molecule cardiomyopathy filament DNA metabolic activity (HCM) process Arrhythmogenic nucleus spermatogenesisG-protein coupled protein binding Hypertrophicright ventricular intermediate DNA repair structural molecule cardiomyopathy filament DNA metabolic activity (HCM) process Arrhythmogenic nucleus mRNAG-protein processing coupled nucleotide binding Spliceosomeright ventricular plasma membrane angiogenesis protein binding soluble fraction protein amino acid dephosphorylation nucleus mRNAnuclear processing mRNA protein binding membrane ER-associated protein catabolic process Page 585 of 603 Diabetes

cytoplasm in utero embryonic transferase activity development

nucleus cell communication zinc ion binding regulation of transcription

nucleus apoptosis nucleotide binding Spliceosome nucleolus erythrocyte nucleic acid binding differentiation response to protein nucleus regulationstimulus of protein binding transcription

cytoplasm heart development protein binding Starch and sucrose metabolism Insulin signaling pathway cytoplasm heart development protein binding Starch and sucrose metabolism Insulin signaling pathway integral to apoptosis protein binding membrane protein folding Golgi apparatus

cytoplasm translation protein binding

cytoplasm translation protein binding

integral to proteolysis protein binding Alzheimer's membrane zinc ion binding disease cytoplasm Epithelial cell signaling in Helicobacter pylori Diabetes Page 586 of 603

nucleus regulation of protein binding membrane transcription integral to negative regulation membrane of transcription nucleus mRNA processing protein binding

nucleus regulation of protein binding Nucleotide excision transcription repair integral to apoptosis protein binding membrane prolactin receptor activity integral to protein amino acid protein binding Glycerolipid membrane phosphorylation binding metabolism cytoplasm immune response RNA binding Glycine, serine and membrane regulation of threonine nucleus regulationtranscription, of DNA- DNA binding metabolism transcription nucleotide binding inflammatory response nucleus regulation of protein binding membrane transcription integral to negative regulation membrane of transcription nucleus mRNA processing DNA binding spliceosomal protein binding complex lysophospholipase activity cytoplasm protein folding proteinzinc ion binding binding Pathways in cancer ATP binding Plant-pathogen interaction Progesterone- lipid particle lipid metabolic protein binding PPARmediated signaling process pathway Page 587 of 603 Diabetes

membrane neuromuscular protein binding synapse junction development fatty acid metabolic eukaryotic translationprocess protein binding translation elongation factor 1 complex cytosolnuclear pore learning hydrolase activity Nitrogen molecular_function metabolism

nucleus mRNA processing nucleotide binding Spliceosome plasma membrane angiogenesis protein binding soluble fraction protein amino acid dephosphorylation cytoplasm axonnuclear cargo mRNA protein binding kinesin complex transport binding regulation of ARF GTPase activity ribosome transport ATP binding metabolic process

nucleus regulation of protein binding proteasome core transcription, DNA- DNA binding complex dependent

nucleus regulation of protein binding transcription, DNA- dependent

nucleus regulation of protein binding transcription, DNA- dependent

cytoplasm cell proliferation protein binding Diabetes Page 588 of 603

nucleus regulation of protein binding cytoplasm transcription neurotransmitter secretion cytoplasm protein folding protein binding Pathways in cancer Plant-pathogen interaction Progesterone- centrosome cell cycle protein binding mediated oocyte

centrosome cell cycle protein binding

nucleus mRNA processing protein binding

ribosome transport ATP binding metabolic process nucleus mRNA processing protein binding Spliceosome cytoplasm translation nucleotide binding mitochondrion signal transduction skeletal muscle nucleus mRNAfiber development processing DNA binding spliceosomal protein binding complex lysophospholipase activity nucleus regulation of proteinzinc ion binding binding cytoplasm transcription neurotransmitter secretion nucleus in utero embryonic metal ion binding integral to development double-stranded membrane regulation of cell DNA binding cycle kinase activity protein folding Page 589 of 603 Diabetes

nucleus mRNA processing protein binding Spliceosome ribonucleoprotein metabolic process nucleotide binding complex female pregnancy

nucleus mRNA processing protein binding Spliceosome ribonucleoprotein metabolic process nucleotide binding complex female pregnancy

integral to transport protein binding membrane

integral to transport protein binding membrane

integral to transport protein binding membrane

plasma membrane ATP synthesis hydrogen ion Oxidative coupled proton transmembrane phosphorylation transport transporter activity Lysosome Epithelial cell signaling in

nucleus mRNA processing protein binding Spliceosome Diabetes Page 590 of 603

cytoplasm translation nucleotide binding

nucleus regulation of protein binding membrane transcription integral to negative regulation membrane of transcription membrane intracellular protein binding signaling cascade nucleus cell adhesion protein binding Tight junction Viral myocarditis

nucleus mRNA processing RNA binding

nucleus mRNA processing RNA binding

nucleus mRNA processing RNA binding

nucleus regulation of protein binding transcription, DNA- dependent regulation of integral to proteintranscription amino acid protein binding Tight junction membrane phosphorylation Page 591 of 603 Diabetes

nucleus transport protein binding intracellular protein binding transport

cytoplasm microtubule-based protein binding kinesin complex movement binding axon cargo transport cytoplasm translationregulation of ARF protein binding

nucleus mRNA processing protein binding

nucleus apoptosis protein binding transcription immune response

nucleus regulation of protein binding membrane transcription integral to negative regulation membrane of transcription membrane cell adhesion protein binding Focal adhesion cytoskeleton cytoskeletal actin binding synapse anchoring at plasma membrane nucleus mRNAvisual perception processing protein binding Spliceosome cytoplasm translation nucleotide binding mitochondrion signal transduction Diabetes Page 592 of 603

intracellular translation structural Ribosome constituent of ribosome cytoplasm metabolic process ATP binding Glycolysis / membrane catalytic activity Gluconeogenesis nucleus Pyruvate metabolism nucleus nervous system protein binding Propanoate development nucleus spermatogenesis protein binding Hypertrophic intermediate DNA repair structural molecule cardiomyopathy filament activity (HCM) Arrhythmogenic nucleus spermatogenesis protein binding Hypertrophicright ventricular intermediate DNA repair structural molecule cardiomyopathy filament activity (HCM) Arrhythmogenic nucleus regulation of protein binding right ventricular membrane transcription integral to negative regulation membrane of transcription

nucleus mRNA processing protein binding membrane ER-associated protein catabolic process cytoplasm protein amino acid protein binding Regulation of actin intracellular dephosphorylation cytoskeleton membrane- Vascular smooth bounded organelle muscle contraction cytoplasm protein amino acid protein binding RegulationFocal adhesion of actin intracellular dephosphorylation cytoskeleton membrane- Vascular smooth bounded organelle muscle contraction Focal adhesion Page 593 of 603 Diabetes

cytoplasm protein folding isomerase activity

integral to modification- zinc ion binding membrane dependent protein protein binding catabolic process

nucleus mRNA processing DNA binding spliceosomal protein binding complex lysophospholipase activity integral to transport sodiumzinc ion ionbinding binding Cardiac muscle membrane transcription factor contraction binding Regulation of actin cytoskeleton nucleus regulation of protein binding transcription, DNA- dependent

cytoplasm protein folding isomerase activity

cytoplasm protein folding protein binding Pathways in cancer Plant-pathogen interaction Progesterone- nucleus signal transduction protein binding Insulinmediated signaling oocyte cytoplasm negative regulation pathway of cell proliferation mTOR signaling pathway nucleus transport protein binding Endocytosisp53 signaling potassium ion transport

nucleus mRNA processing protein binding Diabetes Page 594 of 603

nucleus protein amino acid protein binding phosphorylation cytoplasm translation protein binding

nucleus mRNA processing protein binding ribonucleoprotein nuclear mRNA nucleotide binding complex splicing, via spliceosome nucleus mRNAregulation processing of protein binding ribonucleoprotein nuclear mRNA nucleotide binding complex splicing, via spliceosome nucleus biological_processregulation of protein binding intracellular signal transduction nucleic acid binding nucleus mRNA processing protein binding

membrane signal transduction protein binding Regulation of actin nuclear pore SH3 domain cytoskeleton cytoskeleton binding Adherens junction nucleus membraneintegral to signal transduction protein binding Regulation of actin nuclear pore SH3 domain cytoskeleton cytoskeleton binding Adherens junction nucleus integral to

microtubule negative regulation protein binding cytosol of microtubule depolymerization sensory perception of sound Page 595 of 603 Diabetes

nucleus regulation of protein binding transcription factor transcription complex positive regulation of transcription secretory granule transportfrom RNA protein binding exocyst molecular_function

nucleus mRNA processing DNA binding zinc ion binding

cytoplasm signal transduction protein binding intracellular zinc ion binding

cytoplasm cell cycle protein binding

nucleus mRNA processing protein binding

cytosol protein amino acid protein binding Alzheimer's cytoplasm phosphorylation ATP binding disease nucleus Wnt signaling intracellular pathway Hedgehog signaling Diabetes Page 596 of 603

nucleus DNA repair protein binding oligosaccharyltransf transmembrane erase complex transport nucleolus proteolysis nucleus regulationforebrain of Rab GTPase activator GTPase activity activity telomere protein binding maintenance via nucleus proteintelomerase amino acid protein binding chromosome phosphorylation nucleus apoptosis protein binding transcription immune response nucleus mRNA processing protein binding

membrane biosynthetic catalytic activity Glycerophospholipi membrane fraction process d metabolism cytoskeleton Phosphonate and phosphinate nucleus regulation of DNA binding metabolism transcription nucleus regulation of DNA binding transcription nucleus regulation of DNA binding transcription membrane transport protein binding Page 597 of 603 Diabetes

membrane transport protein binding

plasma membrane biological_process protein binding

plasma membrane biological_process protein binding

plasma membrane biological_process protein binding

membrane apoptosis protein binding intracellular endocytosis calcium ion binding lamellipodium small GTPase mediated signal membrane apoptosistransduction protein binding intracellular endocytosis calcium ion binding lamellipodium small GTPase mediated signal cytoplasm proteintransduction folding protein binding Pathways in cancer Plant-pathogen interaction Progesterone- nucleus protein amino acid protein binding mediated oocyte chromosome phosphorylation

nucleus mRNA processing transferase activity

plasma membrane neuromuscular protein binding junction development Diabetes Page 598 of 603

nucleolus nucleolus protein binding organization lipid transport membrane muscle contraction protein binding synapse neuromuscular junction development cytoplasm transportfatty acid metabolic protein binding Golgi apparatus nucleus regulation of protein binding Spliceosome mitochondrion transcription nucleotide binding intracellular Ras protein signal transduction membranecytoplasm smallregulation GTPase of Rab protein binding lamellipodium mediated signal transduction membrane small GTPase protein binding lamellipodium mediated signal transduction nucleus regulation of protein binding mediator complex transcription ATP binding transcription from receptor activity RNA polymerase II intracellular apoptosispromoter guanyl-nucleotide Regulation of actin cytoplasm small GTPase exchange factor cytoskeleton mediated signal activity Pancreatic cancer transduction protein binding nucleus nervoussignal transduction system proteinRho guanyl- binding development nucleus nervous system protein binding development Page 599 of 603 Diabetes

nucleus nervous system protein binding development

nucleus regulation of protein binding integral to transcription nucleotide binding membrane cell growth

nucleus translation ATP binding carbohydrate calcium ion binding phosphorylation kinase activity female pregnancy nucleus protein amino acid protein binding Pathways in cancer membrane phosphorylation ATP binding Insulin signaling pathway Bladder cancer nucleus metabolic process ATP binding Alanine,Regulation aspartate of actin cellular amino acid hydrolase activity and glutamate metabolic process metabolism Pyrimidine nucleus mRNA processing DNA binding metabolism zinc ion binding

nucleus mRNA processing protein binding Spliceosome ribonucleoprotein RNA splicing ATP binding complex G-protein coupled integral to receptor protein cytoplasmmembrane transportsignaling pathway protein binding Endocytosis endosome growth factor activity

cytoplasm protein amino acid protein binding Regulation of actin intracellular dephosphorylation cytoskeleton membrane- Vascular smooth bounded organelle muscle contraction membrane transport protein binding Focal adhesion Diabetes Page 600 of 603

nucleus signal transduction protein binding myosin complex anti-apoptosis nucleus regulation of protein binding transcription factor transcription complex positive regulation of transcription nucleus regulationfrom RNA of protein binding transcription factor transcription complex positive regulation of transcription cytoplasm metabolicfrom RNA process ATP binding Glycolysis / membrane catalytic activity Gluconeogenesis nucleus Pyruvate metabolism extracellular region multicellular protein binding WntPropanoate signaling cytoplasm organismal pathway development Nucleotide excision repair nucleus DNA repair DNA binding Lysine degradation cytoplasm translation protein binding Folate biosynthesis intracellular intracellular structural Insulin signaling integral to signaling cascade constituent of pathway nucleusmembrane DNAproteolysis repair DNAribosome binding LysinemTOR degradationsignaling cytoplasm translation protein binding Folate biosynthesis intracellular intracellular structural Insulin signaling integral to signaling cascade constituent of pathway nucleusmembrane modification-proteolysis hydrolaseribosome activity mTOR signaling intracellular dependent protein catabolic process nucleus modification- hydrolase activity intracellular dependent protein catabolic process nucleus regulation of protein binding transcription nucleotide binding mRNA processing transcription Page 601 of 603 Diabetes

membrane small GTPase protein binding lamellipodium mediated signal transduction

cytoplasm lipid biosynthetic unfolded protein process binding signal transduction protein binding cell proliferation microtubule negative regulation protein binding cytosol of microtubule microtubule depolymerization associated complex sensory perception nucleus translationof sound protein binding Insulin signaling cytoplasm structural pathway intracellular constituent of mTOR signaling ribosome pathway cytoplasm protein folding protein binding PathwaysRibosome in cancer Plant-pathogen interaction Progesterone- nucleus modification- hydrolase activity mediated oocyte intracellular dependent protein catabolic process

cytoplasm negative regulation protein binding of protein kinase activity

nucleus regulation of protein binding Pathways in cancer transcription Huntington's disease Chronic myeloid nucleus transport protein binding leukemia intracellular histone binding

cytoplasm transport protein binding nucleus nucleosome zinc ion binding assembly ATP binding lipid binding Diabetes Page 602 of 603

nucleus ubiquitin-dependent protein binding Proteasome protein catabolic hydrolase activity process nucleus ubiquitin-dependent protein binding Proteasome protein catabolic hydrolase activity process nucleus apoptosis nucleotide binding erythrocyte differentiation integral to apoptosis protein binding membrane protein folding Golgi apparatus integral to regulation of gene protein binding membrane expression negative regulation of transcription nucleus proteolysisfrom RNA zinc ion binding

integral to signal transduction protein binding membrane regulation of cytoplasm transcription nucleus negative regulation ATP binding RNA degradation of transcription mitochondrion oxidation reduction oxidoreductase Glycolysis / intracellular activity Gluconeogenesis membrane- oxidoreductase Butanoate bounded organelle activity, acting on metabolism mitochondrion cell communication proteinthe aldehyde binding or oxo Pyruvate Page 603 of 603 Diabetes

mitochondrion oxidation reduction oxidoreductase Glycolysis / intracellular activity Gluconeogenesis membrane- oxidoreductase Butanoate bounded organelle activity, acting on metabolism cytoplasm protein amino acid proteinthe aldehyde binding or oxo RegulationPyruvate of actin intracellular dephosphorylation cytoskeleton membrane- Vascular smooth bounded organelle muscle contraction nucleus mRNA processing protein binding SpliceosomeFocal adhesion ribonucleoprotein female pregnancy nucleotide binding complex

extracellular region biological_process molecular_function protein amino acid protein binding phosphorylation

nucleus translation protein binding

nucleus RNA processing nucleotide binding

cytoplasm modification- protein binding Ubiquitin mediated dependent protein proteolysis catabolic process

cytoplasm regulation of protein binding transcription, DNA- dependent

cytoplasm signal transduction protein binding Insulin signaling cytosol protein amino acid kinase activity pathway integral to phosphorylation cAMP-dependent Apoptosis membrane protein kinase nucleuscAMP-dependent apoptosis DNAregulator binding activity