Insights into the Cellular Response Triggered by

Silver Nanoparticles using Quantitative Proteomics

Thiago Verano-Braga, † Rona Miethling-Graff, ‡ Katarzyna Wojdyla, † Adelina Rogowska-

Wrzesinska, † Jonathan R. Brewer, †† Helmut Erdmann, ‡ Frank Kjeldsen †*

† Research Group and †† MEMPHYS Center for Biomembrane Physics – Department of

Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark

‡Biotechnology, University of Applied Science, Flensburg, Germany

Supplementary Figure S1 – Proteomics reproducibility. In total, 3352 were identified in this study using 3 independent biological replicates and 2524 proteins (75%) were identified in at least 2 replicates.

Supplementary Figure S2 – Data normalization and significance analysis. (A) Boxplots for each of the 5 experimental conditions from the 3 independent biological replicates. Data was normalized by the median. (B) Histogram and (C) Q Q plot depicting the normal distribution of the dataset. (D) Volcano plot representing the p- values versus intensity changes for each experimental condition (20 nm AgNPs, 100 nm AgNPs, Ctrl 20 nm and Ctrl 100 nm). The p-values were corrected for multiple testing with Benjamini-Hochberg. Points above the dashed lines represent the proteins differentially regulated ( p < 0.01).

Supplementary Figure S3 – Protein-protein interacting networks. Stronger interactions are represented by thicker lines. Over-represented biological functions based on ontology annotation are depicted in the figure.

Confocal imaging – Confocal imaging was carried out on a Zeiss LSM 510 META. The samples were imaged using a 63 x 1.4 NA oil immersion objective (Carl Zeiss). For the 100 nm nanoparticles, the excitation laser was a 543 nm HeNe laser, they were imaged by detecting their reflection of the excitation laser. The reflection of the laser from the AgNPs was collected through a 500-550 nm band pass filter. The 20 nm nanoparticles were imaged using a femto second pulsed laser (Mai Tai broad band, Spectra Physics, Mountain View, CA ) operated at 800 nm. The emission was collected through a 685 nm short pass filter. Control measurements were performed to ensure that only the AgNPs were imaged in the channel designated for recording the nanoparticles. The fluorescent emission from the DiI was collected through a 560 nm long pass filter. The images shown are representative of more than 30 cells. The multiphoton excited emission of AgNPs has been previously demonstrated. Figure S4 shows spectrally resolved images of emission from 20 nm AgNPs excited by 800 nm femto second pulsed light. The data for the spectra were collected using a band width of about 43nm, using the Zeiss LSM 510 META.

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1100 Emission [arb. units] [arb. Emission 1000

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800 400 450 500 550 600 650 Wavelength [nm] Supplementary Figure S4 – 20 nm AgNPs imaged using a Zeiss LSM 510 META, excited with 800 nm femto second pulsed light. Supplementary Table 1 - List of all proteins identified in the study

AgNPs Ct rl ID GENE Control 20nm 100nm 20nm 100nm Description Q9NRG9 AAAS 0.1 0.0 -0.1 0.0 -0.1 isoform 1 Q13685 AAMP -0.1 0.3 0.1 -0.1 -0.2 angio -associated migratory cell protein P49588 AARS -0.4 0.3 0.2 -0.1 0.0 alanine--tRNA , cytoplasmic Q5JTZ9 AARS2 0.2 -0.1 -0.1 0.1 -0.1 Alanine--tRNA ligase, mitochondrial Q9NRN7 AASDHPPT -0.2 0.1 0.1 -0.1 0.1 L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl Q9UDR5 AASS 0.3 -0.1 -0.2 0.1 -0.1 alpha-aminoadipic semialdehyde synthase, mitochondrial Q9NY61 AATF 0.1 0.0 -0.1 0.1 0.0 protein AATF P08183 ABCB1 0.3 -0.1 -0.2 0.1 -0.1 multidrug resistance protein 1 Q9NRK6 ABCB10 0.3 0.0 -0.2 0.0 -0.1 ATP-binding cassette sub-family B member 10, mitochondrial O75027 ABCB7 0.1 -0.1 -0.1 0.0 0.0 ATP-binding cassette sub-family B member 7, mitochondrial Q9NUT2 ABCB8 0.1 0.3 -0.5 0.0 0.0 ATP-binding cassette sub-family B member 8, mitochondrial P33527 ABCC1 0.0 -0.1 0.0 0.1 0.0 multidrug resistance-associated protein 1 O15439 ABCC4 0.2 -0.1 -0.2 0.1 0.0 multidrug resistance-associated protein 4 isoform 1 P28288 ABCD3 0.1 -0.1 -0.1 0.0 0.0 ATP -binding cassette sub -family D member 3 isoform a P61221 ABCE1 -0.2 0.1 0.2 -0.2 0.0 ATP-binding cassette sub-family E member 1 Q8NE71 ABCF1 -0.2 0.1 0.0 -0.1 0.2 ATP -binding cassette sub -family F member 1 isoform a Q9UG63 ABCF2 0.2 0.0 0.1 -0.3 0.0 ATP-binding cassette sub-family F member 2 isoform a Q9UNQ0 ABCG2 0.5 -0.1 -0.3 0.1 -0.1 ATP -binding cassette sub -family G member 2 isoform 1 Q9NUJ1 ABHD10 0.0 0.1 -0.1 0.1 0.0 abhydrolase domain-containing protein 10, mitochondrial precursor Q8NFV4 ABHD11 0.1 0.0 -0.1 0.1 -0.1 abhydrolase domain -containing protein 11 isoform 1 Q8N2K0 ABHD12 -0.2 0.0 -0.1 0.1 0.1 monoacylglycerol lipase ABHD12 isoform a O95870 ABHD16A 0.2 0.0 -0.2 0.1 -0.1 abhydrolase domain-containing protein 16A isoform a Q9ULW3 ABT1 0.3 0.1 0.1 -0.4 0.0 activator of basal transcription 1 P09110 ACAA1 0.2 -0.2 -0.1 0.1 -0.1 3-ketoacyl-CoA thiolase, peroxisomal isoform a P42765 ACAA2 -0.1 0.0 0.0 0.1 0.0 3-ketoacyl-CoA thiolase, mitochondrial Q13085 ACACA -0.1 0.1 0.1 -0.1 0.0 acetyl-CoA carboxylase 1 isoform 2 Q6JQN1 ACAD10 -0.3 0.2 -0.1 0.3 -0.1 acyl-CoA dehydrogenase family member 10 isoform b Q9UKU7 ACAD8 0.2 0.1 -0.1 -0.2 -0.1 isobutyryl-CoA dehydrogenase, mitochondrial Q9H845 ACAD9 0.2 0.0 -0.1 -0.1 0.0 acyl-CoA dehydrogenase family member 9, mitochondrial P11310 ACADM 0.3 -0.1 -0.2 0.1 -0.1 medium-chain specific acyl-CoA dehydrogenase, mitochondrial isoform a precursor P16219 ACADS 0.3 0.0 -0.2 0.2 -0.3 short-chain specific acyl-CoA dehydrogenase, mitochondrial precursor P45954 ACADSB 0.2 -0.1 -0.2 0.1 0.0 short/branched chain specific acyl-CoA dehydrogenase, mitochondrial precursor P49748 ACADVL 0.1 0.0 -0.1 0.1 0.0 very long-chain specific acyl-CoA dehydrogenase, mitochondrial isoform 1 precursor P24752 ACAT1 0.1 -0.1 -0.1 0.1 -0.1 acetyl -CoA acetyltransferase, mitochondrial precursor Q9BWD1 ACAT2 -0.1 0.0 0.1 0.0 -0.1 acetyl -CoA acetyltransferase, cytosolic Q9H3P7 ACBD3 -0.2 -0.1 0.1 0.2 0.0 Golgi resident protein GCP60 Q9UKV3 ACIN1 0.0 0.0 0.0 0.1 -0.1 Apoptotic condensation inducer in the nucleus P53396 ACLY -0.2 0.1 0.2 -0.2 0.1 ATP-citrate synthase isoform 1 Q99798 ACO2 0.3 -0.1 -0.1 0.0 0.0 aconitate hydratase, mitochondrial precursor Q86TX2 ACOT1 0.1 0.0 -0.1 0.0 0.0 acyl -coenzyme A thioesterase 1 Q9NPJ3 ACOT13 -0.1 0.1 0.0 0.2 -0.1 acyl-coenzyme A thioesterase 13 isoform 1 O00154 ACOT7 -0.3 0.1 0.2 0.0 0.0 cytosolic acyl coenzyme A thioester isoform hBACHb Q9Y305 ACOT9 0.0 -0.1 -0.1 0.3 0.0 acyl-coenzyme A thioesterase 9, mitochondrial isoform b precursor Q15067 ACOX1 0.1 -0.1 -0.2 0.1 0.0 peroxisomal acyl -coenzyme A oxidase 1 isoform b O15254 ACOX3 0.1 0.1 -0.2 0.1 0.0 peroxisomal acyl-coenzyme A oxidase 3 isoform a P24666 ACP1 -0.3 0.1 0.1 0.1 0.0 low molecular weight phosphotyrosine protein phosphatase isoform c Q96CM8 ACSF2 0.1 -0.1 -0.1 0.0 0.0 acyl-CoA synthetase family member 2, mitochondrial precursor P33121 ACSL1 0.0 -0.1 0.0 0.1 0.0 long -chain -fatty -acid -- CoA ligase 1 O95573 ACSL3 0.1 -0.1 -0.1 0.1 0.0 long-chain-fatty-acid--CoA ligase 3 O60488 ACSL4 0.2 -0.1 -0.2 0.0 0.0 long -chain -fatty -acid -- CoA ligase 4 isoform 2 Q9ULC5 ACSL5 0.2 -0.2 -0.2 0.2 0.0 long-chain-fatty-acid--CoA ligase 5 isoform b Q9NUB1 ACSS1 0.3 -0.2 -0.2 0.1 0.0 acetyl -coenzyme A synthetase 2 -like, mitochondrial isoform 1 precursor P60709 ACTB 0.1 0.0 -0.1 0.0 0.0 , cytoplasmic 1 Q562R1 ACTBL2 -0.2 0.1 0.3 -0.3 0.0 beta -actin -like protein 2 P68032 ACTC1 0.2 0.0 -0.2 0.0 -0.1 actin, alpha cardiac muscle 1 proprotein O96019 ACTL6A 0.0 0.0 0.0 0.0 0.0 actin -like protein 6A isoform 1 P12814 ACTN1 -0.2 0.1 0.1 0.0 0.0 alpha-actinin-1 isoform b Q08043 ACTN3 -0.3 -0.2 0.1 -0.3 0.7 Alpha -actinin -3 O43707 ACTN4 -0.2 0.1 0.0 0.0 0.1 alpha-actinin-4 P61163 ACTR1A 0.0 0.0 0.2 -0.3 0.1 alpha -centractin P61160 ACTR2 -0.1 0.0 0.1 -0.1 0.0 actin-related protein 2 isoform b P61158 ACTR3 0.0 0.0 0.2 -0.2 0.0 actin -related protein 3 O14672 ADAM10 0.1 -0.1 -0.1 0.2 -0.1 disintegrin and metalloproteinase domain-containing protein 10 precursor P55265 ADAR -0.1 0.0 0.0 0.1 0.0 Double-stranded RNA-specific Q8NI60 ADCK3 -0.1 -0.1 0.1 0.4 -0.3 chaperone activity of bc1 complex-like, mitochondrial P35611 ADD1 0.0 0.0 0.0 0.0 -0.1 alpha -adducin isoform a Q9UEY8 ADD3 0.2 0.0 0.0 -0.1 -0.1 gamma-adducin isoform a P11766 ADH5 -0.2 0.1 0.2 -0.1 0.0 alcohol dehydrogenase class -3 P55263 ADK -0.2 0.3 0.3 -0.2 -0.2 adenosine kinase isoform b Q9H2P0 ADNP 0.1 0.0 -0.1 0.0 0.0 activity -dependent neuroprotector homeobox protein Q9BRR6 ADPGK 0.2 -0.1 -0.1 0.1 0.0 ADP-dependent glucokinase Q16186 ADRM1 -0.3 0.2 0.3 -0.2 0.0 proteasomal ubiquitin receptor ADRM1 precursor P30566 ADSL -0.2 0.1 0.3 -0.2 0.1 adenylosuccinate isoform a P30520 ADSS -0.1 0.1 0.0 0.0 0.0 adenylosuccinate synthetase isozyme 2 Q9Y4W6 AFG3L2 0.0 -0.1 -0.1 0.1 0.0 AFG3-like protein 2 P52594 AGFG1 -0.2 0.3 0.4 -0.2 -0.3 arf-GAP domain and FG repeat-containing protein 1 isoform 2 Q53H12 AGK 0.1 -0.1 -0.1 0.1 0.0 acylglycerol kinase, mitochondrial precursor P35573 AGL 0.0 0.1 0.2 -0.5 0.2 glycogen debranching isoform 1 Q9BSE5 AGMAT -0.1 -0.1 -0.1 0.3 0.0 , mitochondrial precursor Q99943 AGPAT1 0.1 -0.1 0.1 0.0 -0.1 1-acyl-sn-glycerol-3- acyltransferase alpha O15120 AGPAT2 0.0 0.1 0.0 -0.1 0.0 1-acyl-sn-glycerol-3-phosphate acyltransferase beta isoform a precursor Q9NRZ7 AGPAT3 -0.1 0.0 -0.1 0.1 0.0 1-acyl-sn-glycerol-3-phosphate acyltransferase gamma Q9NUQ2 AGPAT5 0.0 -0.1 0.0 0.1 0.0 1-acyl -sn -glycerol -3-phosphate acyltransferase epsilon Q86UL3 AGPAT6 0.0 -0.1 0.0 0.0 0.0 glycerol-3-phosphate acyltransferase 6 Q53EU6 AGPAT9 -0.1 -0.1 -0.1 0.2 0.0 glycerol -3-phosphate acyltransferase 3 O00116 AGPS 0.2 -0.1 -0.1 0.1 0.0 alkyldihydroxyacetonephosphate synthase, peroxisomal precursor Q8WYP5 AHCTF1 0.1 -0.1 0.0 0.0 0.0 Protein ELYS P23526 AHCY -0.3 0.2 0.3 -0.2 0.0 adenosylhomocysteinase isoform 1 O43865 AHCYL1 -0.2 0.2 0.2 0.0 -0.1 putative adenosylhomocysteinase 2 isoform a Q09666 AHNAK -0.1 0.0 0.0 0.1 0.0 neuroblast differentiation-associated protein AHNAK isoform 1 Q8IVF2 AHNAK2 -0.5 0.2 0.0 0.3 0.0 protein AHNAK2 P35869 AHR 0.2 -0.1 -0.1 0.0 0.0 aryl hydrocarbon receptor precursor O95433 AHSA1 -0.3 0.3 0.3 -0.3 0.0 activator of 90 kDa heat shock protein ATPase homolog 1 Q9BQI0 AIF1L 0.3 0.0 -0.1 -0.1 -0.1 allograft inflammatory factor 1-like isoform 1 O95831 AIFM1 0.0 -0.1 -0.1 0.1 0.0 apoptosis -inducing factor 1, mitochondrial isoform 1 precursor Q9BRQ8 AIFM2 -0.1 0.0 -0.1 0.3 -0.1 apoptosis-inducing factor 2 Q12904 AIMP1 -0.3 0.1 0.2 0.0 0.1 aminoacyl tRNA synthase complex -interacting multifunctional protein 1 isoform a precursor Q13155 AIMP2 -0.3 0.1 0.2 -0.1 0.1 aminoacyl tRNA synthase complex-interacting multifunctional protein 2 O00170 AIP -0.4 0.2 0.3 -0.2 0.1 AH receptor -interacting protein P00568 AK1 0.0 0.0 0.2 0.0 -0.2 adenylate kinase isoenzyme 1 P54819 AK2 -0.1 -0.1 0.0 0.2 -0.1 adenylate kinase 2, mitochondrial isoform a Q9UIJ7 AK3 -0.1 0.0 0.0 0.1 0.1 GTP:AMP phosphotransferase, mitochondrial isoform a Q92667 AKAP1 0.0 0.0 -0.1 0.1 0.0 A-kinase anchor protein 1, mitochondrial precursor Q02040 AKAP17A 0.4 0.0 -0.3 0.0 -0.1 A-kinase anchor protein 17A isoform 1 Q9Y2D5 AKAP2 -0.1 0.1 0.0 -0.1 0.1 A-kinase anchor protein 2 isoform 2 O43823 AKAP8 -0.1 0.0 -0.1 0.1 0.2 A-kinase anchor protein 8 Q9ULX6 AKAP8L 0.0 0.0 -0.1 0.1 0.0 A-kinase anchor protein 8-like Q99996 AKAP9 0.3 -0.4 0.1 -0.1 0.0 A-kinase anchor protein 9 P14550 AKR1A1 -0.2 0.1 0.2 -0.1 0.0 alcohol dehydrogenase [NADP(+)] O43488 AKR7A2 -0.1 0.0 0.0 0.0 0.0 aflatoxin B1 aldehyde reductase member 2 P13196 ALAS1 0.1 -0.2 0.1 0.1 -0.1 5-aminolevulinate synthase, nonspecific, mitochondrial precursor Q13740 ALCAM 0.3 -0.1 -0.1 0.2 -0.3 CD166 antigen isoform 1 precursor P54886 ALDH18A1 0.3 -0.1 -0.2 0.1 -0.2 delta -1-pyrroline -5-carboxylate synthase isoform 1 P47895 ALDH1A3 -0.2 0.1 0.3 -0.2 0.0 aldehyde dehydrogenase family 1 member A3 P30837 ALDH1B1 0.2 -0.2 -0.1 0.1 -0.1 Aldehyde dehydrogenase X, mitochondrial P05091 ALDH2 0.1 -0.1 -0.1 0.2 0.0 aldehyde dehydrogenase, mitochondrial isoform 1 precursor P51648 ALDH3A2 0.0 -0.1 -0.1 0.2 0.0 fatty aldehyde dehydrogenase isoform 2 P30038 ALDH4A1 0.1 -0.1 0.0 0.1 0.0 delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial isoform a precursor P51649 ALDH5A1 0.0 -0.1 -0.1 0.2 -0.1 succinate-semialdehyde dehydrogenase, mitochondrial isoform 2 precursor Q02252 ALDH6A1 0.0 -0.1 -0.1 0.2 0.0 methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial precursor P49419 ALDH7A1 0.0 0.0 -0.1 0.1 0.0 alpha-aminoadipic semialdehyde dehydrogenase isoform 1 precursor P49189 ALDH9A1 0.0 0.0 0.0 0.0 0.0 4-trimethylaminobutyraldehyde dehydrogenase P04075 ALDOA -0.2 0.1 0.3 -0.2 0.0 fructose-bisphosphate aldolase A isoform 1 P09972 ALDOC -0.2 -0.1 0.2 0.1 0.0 fructose-bisphosphate aldolase C Q9BT22 ALG1 0.3 -0.3 -0.2 0.2 0.0 chitobiosyldiphosphodolichol beta-mannosyltransferase Q9H553 ALG2 0.0 0.0 -0.2 0.2 0.1 alpha -1,3/1,6 -mannosyltransferase ALG2 Q9Y673 ALG5 0.1 -0.1 -0.2 0.2 0.0 dolichyl-phosphate beta-glucosyltransferase isoform 1 Q6P6C2 ALKBH5 -0.3 0.4 0.1 -0.2 0.0 Probable alpha -ketoglutarate -dependent dioxygenase ABH5 P05187 ALPP 0.2 -0.2 -0.1 0.1 -0.1 alkaline phosphatase, placental type preproprotein Q86V81 ALYREF 0.0 -0.1 0.0 0.1 0.0 THO complex subunit 4 Q9UKV5 AMFR 0.3 0.0 -0.3 0.1 0.0 E3 ubiquitin-protein ligase AMFR Q9UJX4 ANAPC5 0.0 0.0 -0.3 0.2 0.1 anaphase -promoting complex subunit 5 isoform a Q9UJX3 ANAPC7 0.0 0.1 0.0 -0.1 -0.1 anaphase-promoting complex subunit 7 isoform a Q9P2R3 ANKFY1 -0.4 0.6 -0.3 0.6 -0.5 Ankyrin repeat and FYVE domain -containing protein 1 Q8IWZ3 ANKHD1 -0.2 0.2 0.2 -0.3 0.2 ankyrin repeat and KH domain-containing protein 1 isoform 1 Q86XL3 ANKLE2 0.2 -0.2 0.0 0.0 0.0 ankyrin repeat and LEM domain -containing protein 2 O75179 ANKRD17 -0.1 0.2 0.3 -0.5 0.2 ankyrin repeat domain-containing protein 17 isoform a Q8N283 ANKRD35 -0.1 0.1 0.0 0.1 -0.1 ankyrin repeat domain -containing protein 35 Q9NQW6 ANLN -0.4 0.2 0.2 -0.1 0.1 actin-binding protein anillin Q4KMQ2 ANO6 0.0 -0.1 0.0 0.0 0.1 anoctamin -6 isoform a P39687 ANP32A -0.1 0.1 0.2 -0.3 0.0 acidic leucine-rich nuclear phosphoprotein 32 family member A Q92688 ANP32B -0.4 0.3 0.4 -0.4 0.1 acidic leucine -rich nuclear phosphoprotein 32 family member B Q9BTT0 ANP32E -0.2 0.2 0.1 -0.1 0.1 acidic leucine-rich nuclear phosphoprotein 32 family member E isoform 1 P04083 ANXA1 -0.3 0.1 0.2 0.0 0.0 annexin A1 P50995 ANXA11 -0.3 0.3 0.2 -0.2 0.1 annexin A11 P07355 ANXA2 0.0 -0.1 0.0 0.1 -0.1 annexin A2 isoform 2 P12429 ANXA3 -0.3 0.2 0.2 -0.2 0.0 annexin A3 P09525 ANXA4 -0.3 0.1 0.1 0.1 0.0 Annexin A4 P08758 ANXA5 -0.2 0.2 0.1 -0.1 0.0 annexin A5 P08133 ANXA6 0.0 -0.1 0.0 0.0 0.0 annexin A6 isoform 1 P20073 ANXA7 -0.5 0.2 0.3 -0.1 0.1 annexin A7 isoform 2 Q10567 AP1B1 0.0 0.0 0.1 0.0 0.0 AP -1 complex subunit beta -1 O43747 AP1G1 0.0 0.0 0.1 -0.1 0.1 AP-1 complex subunit gamma-1 isoform b O75843 AP1G2 0.2 -0.2 0.1 -0.3 0.1 AP -1 complex subunit gamma -like 2 Q9BXS5 AP1M1 0.1 -0.1 0.0 0.0 0.0 AP-1 complex subunit mu-1 isoform 2 P61966 AP1S1 0.2 -0.1 0.1 -0.6 0.3 AP -1 complex subunit sigma -1A P56377 AP1S2 0.0 0.0 0.0 -0.1 0.1 AP-1 complex subunit sigma-2 O95782 AP2A1 0.0 0.0 0.0 -0.1 0.0 AP -2 complex subunit alpha -1 isoform 1 O94973 AP2A2 0.0 0.1 0.0 -0.1 0.0 AP-2 complex subunit alpha-2 isoform 2 P63010 AP2B1 0.0 0.0 0.0 0.0 0.0 AP-2 complex subunit beta isoform b Q96CW1 AP2M1 0.0 0.1 0.0 0.0 0.0 AP-2 complex subunit mu isoform a P53680 AP2S1 0.3 0.1 -0.2 -0.2 0.0 AP-2 complex subunit sigma isoform AP17 O00203 AP3B1 -0.2 0.0 0.2 -0.1 0.1 AP-3 complex subunit beta-1 O14617 AP3D1 -0.3 0.2 0.1 0.0 0.0 AP-3 complex subunit delta-1 isoform 2 Q9Y2T2 AP3M1 -0.3 0.2 0.2 -0.1 0.0 AP-3 complex subunit mu-1 P13798 APEH -0.3 0.2 0.3 -0.3 0.1 acylamino-acid-releasing enzyme P27695 APEX1 -0.1 0.1 0.2 -0.1 0.0 DNA-(apurinic or apyrimidinic site) lyase Q9BZZ5 API5 -0.2 0.0 0.1 0.1 0.0 apoptosis inhibitor 5 isoform a Q06481 APLP2 -0.2 0.0 0.2 0.0 0.0 amyloid -like protein 2 isoform 1 precursor Q9HDC9 APMAP 0.0 -0.1 -0.1 0.1 0.0 adipocyte plasma membrane-associated protein Q8NCW5 APOA1BP 0.0 0.1 0.0 0.1 -0.1 NAD(P)H -hydrate epimerase precursor Q9UH17 APOBEC3B 0.1 -0.1 -0.1 0.1 0.1 Probable DNA dC->dU-editing enzyme APOBEC-3B Q9NRW3 APOBEC3C 0.4 -0.2 -0.2 0.0 0.0 probable DNA dC ->dU -editing enzyme APOBEC -3C Q8IUX4 APOBEC3F -0.1 0.1 0.0 -0.3 0.3 DNA dC->dU-editing enzyme APOBEC-3F isoform a Q9HC16 APOBEC3G -0.1 -0.3 0.2 -0.1 0.2 DNA dC ->dU -editing enzyme APOBEC -3G Q9BUR5 APOO -0.1 0.1 -0.2 0.1 0.0 apolipoprotein O precursor P05067 APP 0.1 -0.1 0.0 0.1 -0.2 amyloid beta A4 a precursor Q9UKG1 APPL1 -0.4 0.2 0.4 0.0 -0.2 DCC-interacting protein 13-alpha P07741 APRT 0.2 0.0 0.1 -0.5 0.2 adenine phosphoribosyltransferase isoform a Q7Z2E3 APTX -0.3 0.0 0.0 0.2 0.1 isoform e O60306 AQR 0.2 0.0 -0.1 0.1 -0.1 intron -binding protein aquarius P48444 ARCN1 -0.3 0.1 0.2 -0.2 0.1 coatomer subunit delta isoform 1 P61204 ARF3 0.1 0.0 0.1 -0.1 -0.1 ADP -ribosylation factor 3 P18085 ARF4 0.1 0.1 0.1 -0.2 -0.1 ADP-ribosylation factor 4 P84085 ARF5 0.0 0.0 0.0 -0.1 0.1 ADP -ribosylation factor 5 P62330 ARF6 0.1 0.0 0.1 -0.1 -0.1 ADP-ribosylation factor 6 Q8N6T3 ARFGAP1 -0.2 0.0 0.1 0.1 0.0 ADP -ribosylation factor GTPase -activating protein 1 isoform a Q8N6H7 ARFGAP2 -0.2 0.1 0.3 -0.1 0.0 ADP-ribosylation factor GTPase-activating protein 2 isoform 1 Q9NWB6 ARGLU1 -0.1 0.0 0.0 0.1 0.0 arginine and glutamate -rich protein 1 Q07960 ARHGAP1 0.1 0.2 0.0 -0.4 0.1 rho GTPase-activating protein 1 Q68EM7 ARHGAP17 -0.4 0.0 1.1 -0.3 -0.4 rho GTPase -activating protein 17 isoform 1 Q8N392 ARHGAP18 -0.2 0.1 0.2 -0.1 0.1 rho GTPase-activating protein 18 P52565 ARHGDIA -0.3 0.1 0.2 -0.1 0.0 rho GDP-dissociation inhibitor 1 isoform a Q92888 ARHGEF1 -0.3 0.1 0.0 -0.2 0.3 rho guanine nucleotide exchange factor 1 isoform 2 Q92974 ARHGEF2 -0.4 0.2 0.2 0.1 -0.1 rho guanine nucleotide exchange factor 2 isoform 1 O14497 ARID1A -0.1 0.1 0.0 -0.1 0.1 AT-rich interactive domain-containing protein 1A isoform a Q8NFD5 ARID1B 0.0 0.1 0.1 -0.2 0.0 AT -rich interactive domain -containing protein 1B isoform 1 P40616 ARL1 -0.3 0.0 0.1 0.1 0.1 ADP-ribosylation factor-like protein 1 P56559 ARL4C -0.1 0.0 -0.1 0.2 0.0 ADP -ribosylation factor -like protein 4C Q15041 ARL6IP1 0.2 -0.4 -0.1 0.3 0.0 ADP-ribosylation factor-like protein 6-interacting protein 1 O75915 ARL6IP5 0.1 -0.1 -0.1 0.1 -0.1 PRA1 family protein 3 Q96BM9 ARL8A -0.3 -0.1 0.0 0.3 0.1 ADP-ribosylation factor-like protein 8A isoform 1 Q9NVJ2 ARL8B 0.0 0.1 0.0 0.2 -0.3 ADP-ribosylation factor-like protein 8B Q9NVT9 ARMC1 0.1 -0.1 -0.2 0.1 0.1 -containing protein 1 Q8N2F6 ARMC10 0.0 -0.1 -0.1 0.2 0.0 armadillo repeat-containing protein 10 isoform a Q92747 ARPC1A -0.3 0.3 0.4 -0.2 -0.2 actin-related protein 2/3 complex subunit 1A isoform 1 O15143 ARPC1B 0.0 0.0 0.1 0.0 0.0 actin-related protein 2/3 complex subunit 1B O15144 ARPC2 -0.1 0.0 0.2 -0.1 0.0 actin-related protein 2/3 complex subunit 2 O15145 ARPC3 0.0 0.0 0.1 -0.2 0.1 actin-related protein 2/3 complex subunit 3 P59998 ARPC4 0.0 0.0 0.2 -0.2 0.1 actin-related protein 2/3 complex subunit 4 isoform a O15511 ARPC5 -0.1 -0.1 0.2 -0.1 0.1 actin-related protein 2/3 complex subunit 5 isoform 1 Q9BPX5 ARPC