Integrated proteomic and miRNA transcriptional analysis reveals the hepatotoxicity mechanism of PFNA exposure in mice

Jianshe Wang, Shengmin Yan, Wei Zhang, Jiayin Dai *

Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology,

Chinese Academy of Sciences, Beijing, 100101, P.R. China

*Corresponding author: Dai JY; Tel. +861064807185; Email: [email protected]

Supplementary materials and methods PFNA concentration detection in the serum and liver

PFNA in liver and serum samples were quantified using HPLCMS/MS. Briefly, samples with internal standard were extracted with 5 mL of acetonitrile in 15 mL polypropylene (PP) tubes, and all tubes were placed on a mechanical shaker for 20 min followed by centrifugation at 3,000 × g for 10 min. The top layers, which contained PFNA (analytes and internal standard), were transferred into new PP tubes.

The extraction procedure was repeated and a final solution of 10 mL of acetonitrile was combined and concentrated to 0.5 mL under nitrogen gas at 40°C. After the addition of 0.5 mL methanol, the final solution was diluted into 10 mL MilliQ water for SPE cleanup. All samples were then extracted using an Oasis WAX cartridge

(Oasis1 HLB; 150 mg, 6 cc; Waters). The cartridge was preequilibrated by the addition of a sequence of 4 mL of 0.1% NH 4OH in methanol, 4 mL methanol, and 4 mL water at a rate of 1 drop per second. Samples (11 mL) were then passed through these cartridges at a rate of 1 drop per second. After loading all samples, cartridges were rinsed with 5 mL MilliQ water and then washed with 4 mL of 25 mM acetate buffer solution (pH 4). Any water remaining in the cartridges was removed by centrifugation at 3,000 rpm for 2 min, and PFNA were eluted by 4 mL of 0.1%

NH 4OH in methanol and then concentrated to 1 mL under a stream of nitrogen.

The instrumental chromatographic setup consisted of a P680 binary gradient pump, an UltiMate 3000 autosampler, and a Chromeleon 6.70 chromatography workstation (Dionex, USA). Mass spectra were collected using an API 3200 triple quadrupole tandem mass spectrometer, fitted with an electrospray ionization source

and operated in negative ionization mode. Quantification using these transitions was performed using Analyst 1.4.1 software. Chromatographic separations were carried out on an Acclaim 120 C18 column (4.6 × 150 mm, 3 m) (Dionex, USA), with a binary gradient. Methanol (A) and 50 mM ammonium acetate (NH 4Ac) (B) were employed as mobile phases. The flow rate was 1 mL/min and the injection volume was 10 L. The elution gradient was: 0 to 4 min, from 28 to 5% B linearly; 4 to 7 min,

5% B; 7 to 10 min, 28% B.

A calibration curve was prepared from a series of concentrations (0, 10, 50, 100,

500, 1000, 5000, 20000, and 50000 pg/mL), and standard deviations were less than

20%. Blanks and recoveries were assessed following the same procedure as described above with each group of extractions. The blanks were all below the limit of quantifications (LOQs). Quality control is given in the Supplementary Table S1. The concentrations of PFNA in the experimental samples were not corrected for their corresponding recoveries.

Supplementary Fig. S1. The PFNA content in mouse liver (A) and serum (B) after treatment.

Supplementary Fig. S2. Volcano plots of miRNAs expression in PFNA treatment mice liver tissues. (A) miRNA expression in 1 mg/kg/d dose of PFNA treatment groups compared with control. (B) miRNA expression in 5 mg/kg/d dose of PFNA treatment groups compared with control. On all plots, the X axis represents the log2 ratio of the normalized miRNA signal (mean of the three replicates) of the treatment condition compared with the appropriate control, and the Y axis represents the log10

P value obtained from the student’s ttest comparing the mean normalized miRNA signal in treatment to that in control. Differentially expressed miRNAs were selected based on fold change at least 2 and student’s ttest ( P < 0.05).

Supplementary Fig. S3. Potential binding sites of target . (A) Lactate dehydrogenase A (Ldha); (B) fucosyltransferase 8 (Fut8).

Supplementary Table S1. Quality control for PFNA concentration detection.

Analyte LOQ Instrument Cartridge Procedural Procedural

blank blank blank ( n = 3) recovery % ( n = 3)

Native Mean Mean Mean Mean (ng/mL) Mean S. D

chemical (ng/mL) (ng/mL) (ng/mL)

PFNA 0.01 < 0.01 < 0.01 < 0.01 94 8

Surrogate

13 C5PFNA 0.01 < 0.01 < 0.01 < 0.01 71 1

Supplementary Table S2. specific primers used in qPCR.

Gene symbol Genbank Sequence (5'3') Amplicon Accession no. size (bp) Me1F NM_008615 ACAAGGTGACCAAGGGAC Me1R CAGGGAACACGTAGGAATT 117 Elovl6F NM_130450 TCAGTTACCTGGGAGTGT Elovl6R TCTGTATCTGGCAGTTCTT 76 Apoa4F NM_007468 GGAGCACCTGAAGCCCTAT Apoa4R ATGCGCTGGATGTATGG 96 Apoc3F NM_023114 AAGTAGCGTGCAGGAGTC Apoc3R ATAGCTGGAGTTGGTTGG 150 GapdhF NM_008084 CCTTCCGTGTTCCTACCC GapdhR GCCTGCTTCACCACCTTC 100 Fut8F NM_178155 TTCAAGTGGTCGAGCTTCCC 96 Fut8R GTACAAGTCGATCTGCGAGGT LdhaF NM_005566 ATGGCAACTCTAAAGGATCAGC 86 LdhaR CCAACCCCAACAACTGTAATCT LdlrF NM_010700 GAGGAACTGGCGGCTGAA LdlrR GTGCTGGATGGGGAGGTCT 239 HmgcrF NM_008255 GATTCTGGCAGTCAGTGGGAA HmgcrR GTTGTAGCCGCCTATGCTCC 214 FasnF NM_007988 TGCTCCCAGCTGCAGGC FasnR GCCCGGTAGCTCTGGGTGTA 107 AcacaF NM_133360 TGAAGGGCTACCTCTAATG AcacaR TCACAACCCAAGAACCAC 182 Hmgcs2F NM_008256 CCGTGCTCCCTTCTTAG Hmgcs2R GCTCTTCGTGGGTTCTGT 100 Fdft1F NM_010191 GCCTTTCTCGTCTATTCTC Fdft1R GCTGTAGGGTGTTGGTTATG 261 LplF NM_008509 TCTCCTGATGACGCTGAT LplR CTTGGAGTTGCACCTGTAT 288 GpamF NM_008149 CCGTGGGCATCTCGTAT Gpam R CGGACGTAGCCGTAGTTT 139 Acox1F NM_015729 AGCACTGGTCTCCGTCAT Acox1R TTCCCTCATCTTCTTCACC 244 Acsl1F NM_007981 ATTTCAGGTCGCAGATAGA Acsl1R TGGTACGAGGAGGATTGT 102 MlycdF NM_019966 GGCTGTGATGTGGCGTAT MlycdR TTGGAGCCCAGGTAGGA 135 Scd1F NM_009127 GACCTGAAAGCCGAGAA Scd1R CGTTGAGCACCAGAGTGT 169 Cyp4a10F NM_010011 CCCAAGTGCCTTTCCTA Cyp4a10R GCAAACCATACCCAATCC 149

Abbreviations: Me1, malic 1, NADP(+)dependent, cytosolic; Elovl6,

ELOVL family member 6, elongation of long chain fatty acids; Ldlr, low density lipoprotein receptor; Hmgcr, 3hydroxy3methylglutarylCoenzyme A reductase;

Fasn, fatty acid synthase; Acaca, acetylCoenzyme A carboxylase alpha; Fut8,

Fucosyltransferase 8; Ldha, Lactate dehydrogenase; Fdft1, farnesyl diphosphate farnesyl 1; Lpl, lipoprotein lipase; Gpam, glycerol3phosphate acyltransferase, mitochondrial; Acsl1, acylCoA synthetase longchain family member

1; Hmgcs2, 3hydroxy3methylglutaryl Coenzyme A synthase 2; Scd1, stearoylCoenzyme A desaturase 1; Apoa4, apolipoprotein AIV; Apoc3, apolipoprotein CIII; Acox1, acylCoenzyme A oxidase 1, palmitoyl; Mlycd, malonylCoA decarboxylase; Cyp4a10, cytochrome P450, family 4, subfamily a, polypeptide 10 (Cyp4a10); Gapdh, glyceraldehyde3phosphate dehydrogenase.

Supplementary Table S3. The primers used for 3’ UTR psiCHECK2 vector preparation.

Name Genbank Primer sequence accession no. LdhaF NM_010699 ACCGCTCGAGACACCCTTCTCGTCTGA L dhaR ATAAGAATGCGGCCGCGACTTAACTGGGAACTCG Fut8F NM_016893 ACCGCTCGAGAGAAGACGCAGACTAACA Fut8R ATAAGAATGCGGCCGCGAGGTGGATAAACTGAACT

Abbreviations: Ldha, Lactate dehydrogenase A; Fut8, fucosyltransferase 8. The

XhoI/NotI sites were underlined.

Supplementary Table S4. Significantly altered after 1 mg/kg/d PFNA treatment.

Fold change (1 mg/kg/d Unique Accession Description Score Coverage Proteins PFNA treatment P value Peptides group/Ctrl) Q8VCH0 3ketoacylCoA thiolase B, peroxisomal OS=Mus musculus GN=Acaa1b 1264.18 66.51 1 9 2.72 0.0000 PE=2 SV=1 [THIKB_MOUSE] P97412 Lysosomaltrafficking regulator OS=Mus musculus GN=Lyst PE=1 SV=1 0.00 0.32 1 1 2.48 0.0000 [LYST_MOUSE] Q9DBM2 Peroxisomal bifunctional enzyme OS=Mus musculus GN=Ehhadh PE=1 2744.07 70.33 1 61 2.21 0.0000 SV=4 [ECHP_MOUSE] O35728 Cytochrome P450 4A14 OS=Mus musculus GN=Cyp4a14 PE=2 SV=1 54.29 20.32 1 9 1.93 0.0000 [CP4AE_MOUSE] Q9Z0K8 Pantetheinase OS=Mus musculus GN=Vnn1 PE=1 SV=3 33.64 5.27 1 2 1.89 0.0000 [VNN1_MOUSE] P47740 Fatty aldehyde dehydrogenase OS=Mus musculus GN=Aldh3a2 PE=2 412.74 32.02 4 18 1.81 0.0000 SV=2 [AL3A2_MOUSE] Q9EQ06 Estradiol 17betadehydrogenase 11 OS=Mus musculus GN=Hsd17b11 72.92 20.13 1 4 1.78 0.0075 PE=2 SV=1 [DHB11_MOUSE] Q9R0H0 Peroxisomal acylcoenzyme A oxidase 1 OS=Mus musculus GN=Acox1 588.04 53.4 1 31 1.74 0.0000 PE=1 SV=5 [ACOX1_MOUSE] Q9QYR9 Acylcoenzyme A thioesterase 2, mitochondrial OS=Mus musculus 489.06 60.71 1 10 1.70 0.0001 GN=Acot2 PE=1 SV=2 [ACOT2_MOUSE] P41216 LongchainfattyacidCoA 1 OS=Mus musculus GN=Acsl1 PE=1 569.85 46.35 3 35 1.69 0.0000 SV=2 [ACSL1_MOUSE] O55137 Acylcoenzyme A thioesterase 1 OS=Mus musculus GN=Acot1 PE=1 350.31 62.53 1 6 1.65 0.0002

SV=1 [ACOT1_MOUSE] O88833 Cytochrome P450 4A10 OS=Mus musculus GN=Cyp4a10 PE=2 SV=2 125.23 26.52 1 11 1.64 0.0000 [CP4AA_MOUSE] P47934 Carnitine Oacetyltransferase OS=Mus musculus GN=Crat PE=1 SV=3 49.18 19.33 1 11 1.62 0.0000 [CACP_MOUSE] P12710 Fatty acidbinding , liver OS=Mus musculus GN=Fabp1 PE=1 922.06 70.87 1 13 1.61 0.0000 SV=2 [FABPL_MOUSE] Q08857 Platelet glycoprotein 4 OS=Mus musculus GN=Cd36 PE=1 SV=2 0.00 2.54 1 1 1.60 0.0191 [CD36_MOUSE] P10648 Glutathione Stransferase A2 OS=Mus musculus GN=Gsta2 PE=1 SV=2 387.86 37.39 2 6 1.59 0.0004 [GSTA2_MOUSE] P12791 Cytochrome P450 2B10 OS=Mus musculus GN=Cyp2b10 PE=1 SV=1 32.22 6.2 1 3 1.58 0.0001 [CP2BA_MOUSE] Q8JZR0 LongchainfattyacidCoA ligase 5 OS=Mus musculus GN=Acsl5 PE=2 185.27 33.24 1 21 1.56 0.0000 SV=1 [ACSL5_MOUSE] P55096 ATPbinding cassette subfamily D member 3 OS=Mus musculus 255.43 25.04 2 17 1.56 0.0001 GN=Abcd3 PE=1 SV=2 [ABCD3_MOUSE] Q8BIW1 Protein prune homolog OS=Mus musculus GN=Prune PE=2 SV=1 37.23 11.45 1 4 1.56 0.0003 [PRUNE_MOUSE] P31786 AcylCoAbinding protein OS=Mus musculus GN=Dbi PE=1 SV=2 71.78 70.11 1 7 1.54 0.0000 [ACBP_MOUSE] Q9CYH2 Redoxregulatory protein PAMM OS=Mus musculus PE=1 SV=2 52.76 23.39 1 6 1.54 0.0000 [PAMM_MOUSE] P06801 NADPdependent malic enzyme OS=Mus musculus GN=Me1 PE=1 153.98 28.5 1 16 1.52 0.0000 SV=2 [MAOX_MOUSE] P53808 Phosphatidylcholine transfer protein OS=Mus musculus GN=Pctp PE=1 32.99 22.9 1 4 1.52 0.0026

SV=2 [PPCT_MOUSE] P45952 Mediumchain specific acylCoA dehydrogenase, mitochondrial OS=Mus 624.17 56.29 1 27 1.52 0.0000 musculus GN=Acadm PE=1 SV=1 [ACADM_MOUSE] Q921H8 3ketoacylCoA thiolase A, peroxisomal OS=Mus musculus GN=Acaa1a 1348.55 63.68 1 8 1.52 0.0012 PE=2 SV=1 [THIKA_MOUSE] P00493 Hypoxanthineguanine phosphoribosyltransferase OS=Mus musculus 85.00 24.77 1 5 1.46 0.0001 GN=Hprt1 PE=1 SV=3 [HPRT_MOUSE] Q9WUR2 EnoylCoA delta 2, mitochondrial OS=Mus musculus GN=Eci2 74.73 24.81 1 9 1.45 0.0000 PE=1 SV=2 [ECI2_MOUSE] Q5FW57 Glycine Nacyltransferaselike protein OS=Mus musculus GN=Gm4952 110.86 64.86 1 14 1.45 0.0000 PE=1 SV=2 [GLYAL_MOUSE] P13707 Glycerol3phosphate dehydrogenase [NAD+], cytoplasmic OS=Mus 102.35 46.13 1 15 1.44 0.0000 musculus GN=Gpd1 PE=1 SV=3 [GPDA_MOUSE] Q91V76 Ester C11orf54 homolog OS=Mus musculus PE=2 SV=1 74.61 20.63 1 7 1.43 0.0001 [CK054_MOUSE] Q80XL6 AcylCoA dehydrogenase family member 11 OS=Mus musculus 244.00 33.63 2 27 1.43 0.0001 GN=Acad11 PE=1 SV=2 [ACD11_MOUSE] Q9CQ62 2,4dienoylCoA reductase, mitochondrial OS=Mus musculus GN=Decr1 225.25 47.46 1 18 1.43 0.0000 PE=1 SV=1 [DECR_MOUSE] P58137 Acylcoenzyme A thioesterase 8 OS=Mus musculus GN=Acot8 PE=1 42.74 6.25 1 2 1.43 0.0001 SV=1 [ACOT8_MOUSE] Q9DC50 Peroxisomal carnitine Ooctanoyltransferase OS=Mus musculus GN=Crot 106.12 26.63 1 15 1.42 0.0000 PE=1 SV=1 [OCTC_MOUSE] Q8BWN8 Acylcoenzyme A thioesterase 4 OS=Mus musculus GN=Acot4 PE=2 128.32 29.93 1 6 1.41 0.0015 SV=1 [ACOT4_MOUSE] Q99LB2 Dehydrogenase/reductase SDR family member 4 OS=Mus musculus 103.05 42.29 1 14 1.40 0.0001

GN=Dhrs4 PE=2 SV=2 [DHRS4_MOUSE] P55050 Fatty acidbinding protein, intestinal OS=Mus musculus GN=Fabp2 PE=2 0.00 30.3 1 7 1.39 0.0009 SV=2 [FABPI_MOUSE] P56655 Cytochrome P450 2C38 OS=Mus musculus GN=Cyp2c38 PE=2 SV=1 139.41 9.8 1 1 1.39 0.0006 [CP238_MOUSE] Q2TPA8 Hydroxysteroid dehydrogenaselike protein 2 OS=Mus musculus 180.49 28.16 1 14 1.39 0.0003 GN=Hsdl2 PE=2 SV=1 [HSDL2_MOUSE] Q61133 Glutathione Stransferase theta2 OS=Mus musculus GN=Gstt2 PE=2 157.49 30.33 1 7 1.38 0.0030 SV=3 [GSTT2_MOUSE] P54869 HydroxymethylglutarylCoA synthase, mitochondrial OS=Mus musculus 1099.72 43.31 1 25 1.37 0.0000 GN=Hmgcs2 PE=1 SV=2 [HMCS2_MOUSE] P34914 Epoxide hydrolase 2 OS=Mus musculus GN=Ephx2 PE=1 SV=2 928.65 51.08 1 30 1.37 0.0000 [HYES_MOUSE] P42125 EnoylCoA delta isomerase 1, mitochondrial OS=Mus musculus GN=Eci1 286.03 46.02 1 15 1.37 0.0001 PE=2 SV=1 [ECI1_MOUSE] Q9WUZ9 Ectonucleoside triphosphate diphosphohydrolase 5 OS=Mus musculus 140.46 20.84 1 8 1.37 0.0001 GN=Entpd5 PE=1 SV=1 [ENTP5_MOUSE] Q8CC88 Uncharacterized protein KIAA0564 homolog OS=Mus musculus 301.06 25.25 1 43 1.36 0.0000 GN=Kiaa0564 PE=2 SV=2 [K0564_MOUSE] Q3UUI3 Thioesterase superfamily member 4 OS=Mus musculus GN=Them4 PE=1 26.49 9.13 1 2 1.35 0.0005 SV=1 [THEM4_MOUSE] O35459 Delta(3,5)Delta(2,4)dienoylCoA isomerase, mitochondrial OS=Mus 315.21 50.76 1 15 1.34 0.0000 musculus GN=Ech1 PE=2 SV=1 [ECH1_MOUSE] Q61696 Heat shock 70 kDa protein 1A OS=Mus musculus GN=Hspa1a PE=1 254.99 33.7 2 18 1.33 0.0010 SV=2 [HS71A_MOUSE] P43883 Perilipin2 OS=Mus musculus GN=Plin2 PE=2 SV=2 [PLIN2_MOUSE] 91.91 28.71 1 12 1.33 0.0002

Q99JY0 Trifunctional enzyme subunit beta, mitochondrial OS=Mus musculus 350.99 46.74 4 25 1.33 0.0001 GN=Hadhb PE=1 SV=1 [ECHB_MOUSE] Q8VCT4 Carboxylesterase 3 OS=Mus musculus GN=Ces3 PE=1 SV=1 394.12 41.06 1 22 1.33 0.0000 [CES3_MOUSE] Q9Z2G9 HTATIP2 OS=Mus musculus GN=Htatip2 PE=1 SV=2 85.95 30.58 1 6 1.32 0.0046 [HTAI2_MOUSE] Q91WL5 Cytochrome P450 4A12A OS=Mus musculus GN=Cyp4a12a PE=2 SV=2 171.67 23.82 1 7 1.31 0.0015 [CP4CA_MOUSE] Q8BMS1 Trifunctional enzyme subunit alpha, mitochondrial OS=Mus musculus 1344.03 53.34 2 45 1.31 0.0000 GN=Hadha PE=1 SV=1 [ECHA_MOUSE] Q9CYV5 Transmembrane protein 135 OS=Mus musculus GN=Tmem135 PE=2 31.06 4.8 1 2 1.31 0.0006 SV=1 [TM135_MOUSE] Q9JM62 Receptor expressionenhancing protein 6 OS=Mus musculus GN=Reep6 52.64 25.37 1 4 1.28 0.0006 PE=2 SV=1 [REEP6_MOUSE] Q9QXE0 2hydroxyacylCoA 1 OS=Mus musculus GN=Hacl1 PE=1 SV=2 188.28 28.06 1 16 1.28 0.0000 [HACL1_MOUSE] Q99J08 SEC14like protein 2 OS=Mus musculus GN=Sec14l2 PE=2 SV=1 250.86 40.45 1 19 1.28 0.0001 [S14L2_MOUSE] Q64521 Glycerol3phosphate dehydrogenase, mitochondrial OS=Mus musculus 333.77 38.79 1 30 1.27 0.0000 GN=Gpd2 PE=1 SV=2 [GPDM_MOUSE] Q64FW2 Alltransretinol 13,14reductase OS=Mus musculus GN=Retsat PE=1 91.59 25.29 1 14 1.27 0.0016 SV=3 [RETST_MOUSE] O88844 Isocitrate dehydrogenase [NADP] cytoplasmic OS=Mus musculus 760.46 74.15 1 36 1.26 0.0004 GN=Idh1 PE=1 SV=2 [IDHC_MOUSE] Q9R0M6 Rasrelated protein Rab9A OS=Mus musculus GN=Rab9a PE=1 SV=1 51.17 12.44 1 2 1.26 0.0008 [RAB9A_MOUSE]

P51660 Peroxisomal multifunctional enzyme type 2 OS=Mus musculus 319.88 43.54 1 30 1.25 0.0001 GN=Hsd17b4 PE=1 SV=3 [DHB4_MOUSE] P24549 Retinal dehydrogenase 1 OS=Mus musculus GN=Aldh1a1 PE=1 SV=5 752.65 52.5 2 16 1.25 0.0005 [AL1A1_MOUSE] Q8VCW8 AcylCoA synthetase family member 2, mitochondrial OS=Mus musculus 221.17 38.86 1 26 1.24 0.0001 GN=Acsf2 PE=2 SV=1 [ACSF2_MOUSE] Q9WV68 Peroxisomal 2,4dienoylCoA reductase OS=Mus musculus GN=Decr2 129.80 31.85 1 11 1.24 0.0000 PE=1 SV=1 [DECR2_MOUSE] O08601 Microsomal triglyceride transfer protein large subunit OS=Mus musculus 356.42 34.68 1 30 1.23 0.0001 GN=Mttp PE=2 SV=2 [MTP_MOUSE] P68040 Transcription elongation factor B polypeptide 1 OS=Mus musculus 0.00 17.86 1 1 1.23 0.0064 GN=Tceb1 PE=1 SV=1 [ELOC_MOUSE] O35678 Monoglyceride lipase OS=Mus musculus GN=Mgll PE=1 SV=1 36.50 21.45 1 5 1.23 0.0001 [MGLL_MOUSE] Q9R0N0 Galactokinase OS=Mus musculus GN=Galk1 PE=2 SV=1 0.00 5.12 1 2 1.23 0.0001 [GALK1_MOUSE] Q9JLJ2 4trimethylaminobutyraldehyde dehydrogenase OS=Mus musculus 246.97 36.84 1 17 1.22 0.0000 GN=Aldh9a1 PE=1 SV=1 [AL9A1_MOUSE] P24270 Catalase OS=Mus musculus GN=Cat PE=1 SV=4 [CATA_MOUSE] 1168.83 68.5 2 44 1.22 0.0000 O54984 ATPase Asna1 OS=Mus musculus GN=Asna1 PE=1 SV=2 40.93 5.46 1 2 1.22 0.0008 [ASNA_MOUSE] P36552 CoproporphyrinogenIII oxidase, mitochondrial OS=Mus musculus 57.10 33.18 1 12 1.21 0.0008 GN=Cpox PE=1 SV=2 [HEM6_MOUSE] Q9DD20 Methyltransferaselike protein 7B OS=Mus musculus GN=Mettl7b PE=2 109.27 43.44 1 10 1.21 0.0011 SV=2 [MET7B_MOUSE] Q9DBN5 Lon protease homolog 2, peroxisomal OS=Mus musculus GN=Lonp2 54.81 22.18 1 19 1.21 0.0002

PE=2 SV=1 [LONP2_MOUSE] P38060 HydroxymethylglutarylCoA lyase, mitochondrial OS=Mus musculus 300.83 40.62 2 12 1.21 0.0007 GN=Hmgcl PE=1 SV=2 [HMGCL_MOUSE] P07901 Heat shock protein HSP 90alpha OS=Mus musculus GN=Hsp90aa1 PE=1 662.61 47.61 2 25 1.21 0.0013 SV=4 [HS90A_MOUSE] O70503 Estradiol 17betadehydrogenase 12 OS=Mus musculus GN=Hsd17b12 65.96 7.69 1 2 1.20 0.0018 PE=2 SV=1 [DHB12_MOUSE] Q9DBG1 Sterol 26hydroxylase, mitochondrial OS=Mus musculus GN=Cyp27a1 84.64 24.2 1 11 0.82 0.0019 PE=1 SV=1 [CP27A_MOUSE] Q02788 Collagen alpha2(VI) chain OS=Mus musculus GN=Col6a2 PE=2 SV=3 39.60 11.22 1 11 0.82 0.0161 [CO6A2_MOUSE] Q8VDN2 Sodium/potassiumtransporting ATPase subunit alpha1 OS=Mus 150.62 18.87 6 15 0.82 0.0051 musculus GN=Atp1a1 PE=1 SV=1 [AT1A1_MOUSE] Q9DBE0 28S ribosomal protein S30, mitochondrial OS=Mus musculus 0.00 8.14 1 3 0.81 0.0408 GN=Mrps30 PE=2 SV=1 [RT30_MOUSE] Q61879 Myosin10 OS=Mus musculus GN=Myh10 PE=1 SV=2 37.82 5.41 1 3 0.81 0.0045 [MYH10_MOUSE] P53657 Pyruvate kinase isozymes R/L OS=Mus musculus GN=Pklr PE=2 SV=1 246.80 36.59 1 16 0.80 0.0009 [KPYR_MOUSE] Q01279 Epidermal growth factor receptor OS=Mus musculus GN=Egfr PE=1 71.93 8.51 3 8 0.80 0.0010 SV=1 [EGFR_MOUSE] Q8C196 Carbamoylphosphate synthase [ammonia], mitochondrial OS=Mus 4449.94 63.53 1 123 0.80 0.0000 musculus GN=Cps1 PE=1 SV=2 [CPSM_MOUSE] Q9QY30 Bile salt export pump OS=Mus musculus GN=Abcb11 PE=1 SV=2 32.99 3.79 1 4 0.80 0.0014 [ABCBB_MOUSE] Q8K0E8 Fibrinogen beta chain OS=Mus musculus GN=Fgb PE=2 SV=1 95.12 19.96 2 8 0.78 0.0164

[FIBB_MOUSE] P16460 Argininosuccinate synthase OS=Mus musculus GN=Ass1 PE=1 SV=1 604.08 50.73 1 27 0.78 0.0004 [ASSY_MOUSE] Q9CZS1 Aldehyde dehydrogenase X, mitochondrial OS=Mus musculus 189.61 30.83 2 15 0.77 0.0001 GN=Aldh1b1 PE=2 SV=1 [AL1B1_MOUSE] Q9WU79 Proline dehydrogenase 1, mitochondrial OS=Mus musculus GN=Prodh 229.72 35.23 1 17 0.77 0.0000 PE=2 SV=2 [PROD_MOUSE] P51885 Lumican OS=Mus musculus GN=Lum PE=1 SV=2 [LUM_MOUSE] 45.83 13.31 1 4 0.77 0.0262 P56657 Cytochrome P450 2C40 OS=Mus musculus GN=Cyp2c40 PE=2 SV=2 43.28 8.35 1 2 0.77 0.0227 [CP240_MOUSE] P46656 Adrenodoxin, mitochondrial OS=Mus musculus GN=Fdx1 PE=2 SV=1 27.27 21.28 1 6 0.76 0.0196 [ADX_MOUSE] Q00623 Apolipoprotein AI OS=Mus musculus GN=Apoa1 PE=1 SV=1 161.94 49.62 1 16 0.75 0.0007 [APOA1_MOUSE] Q60605 Myosin light polypeptide 6 OS=Mus musculus GN=Myl6 PE=1 SV=3 126.15 49.01 2 8 0.74 0.0005 [MYL6_MOUSE] P31001 Desmin OS=Mus musculus GN=Des PE=1 SV=3 [DESM_MOUSE] 46.40 25.59 5 10 0.74 0.0152 P14246 Solute carrier family 2, facilitated glucose transporter member 2 OS=Mus 30.19 5.35 1 4 0.71 0.0018 musculus GN=Slc2a2 PE=1 SV=3 [GTR2_MOUSE] O08705 Sodium/bile acid cotransporter OS=Mus musculus GN=Slc10a1 PE=2 84.14 3.87 1 1 0.70 0.0084 SV=1 [NTCP_MOUSE] P58710 Lgulonolactone oxidase OS=Mus musculus GN=Gulo PE=1 SV=3 60.36 18.86 1 9 0.69 0.0002 [GGLO_MOUSE] P21107 Tropomyosin alpha3 chain OS=Mus musculus GN=Tpm3 PE=1 SV=2 40.28 19.37 1 3 0.69 0.0106 [TPM3_MOUSE] P60334 Tropomyosin beta chain OS=Mus musculus GN=Tpm2 PE=1 SV=1 29.70 23.24 1 3 0.65 0.0472

[TPM2_MOUSE] Q75N73 Zinc transporter ZIP14 OS=Mus musculus GN=Slc39a14 PE=1 SV=1 27.98 2.45 1 1 0.60 0.0003 [S39AE_MOUSE] Q283N4 2oxo4hydroxy4carboxy5ureidoimidazoline decarboxylase OS=Mus 80.62 19.66 1 3 0.53 0.0000 musculus GN=Prhoxnb PE=2 SV=1 [URAD_MOUSE] P50462 ADP/ATP 1 OS=Mus musculus GN=Slc25a4 PE=1 SV=4 109.23 29.87 2 1 0.51 0.0393 [ADT1_MOUSE] O88874 CyclinK OS=Mus musculus GN=Ccnk PE=1 SV=3 [CCNK_MOUSE] 0.00 3.07 1 1 0.27 0.0131 When the ratio of a protein between treatment and the control was ≥ 1.2 or ≤ 0.83 (and P < 0.05) in both of the duplicated experiments, the protein was considered to be altered significantly. All the MS data are from one representative result of the duplicated experiments.

Supplementary Table S5. Significantly altered proteins after 5 mg/kg/d PFNA treatment.

Fold change (5 mg/kg/d Unique Accession Description Score Coverage Proteins PFNA treatment P value Peptides group/Ctrl) Q7TNG5 Echinoderm microtubuleassociated proteinlike 2 OS=Mus musculus 0.00 6.01 1 3 3.48 0.0000 GN=Eml2 PE=2 SV=1 [EMAL2_MOUSE] Q9DBM2 Peroxisomal bifunctional enzyme OS=Mus musculus GN=Ehhadh PE=1 3226.15 68.38 1 63 3.18 0.0000 SV=4 [ECHP_MOUSE] Q8VCH0 3ketoacylCoA thiolase B, peroxisomal OS=Mus musculus GN=Acaa1b 867.45 61.79 1 9 2.75 0.0000 PE=2 SV=1 [THIKB_MOUSE] Q9Z0K8 Pantetheinase OS=Mus musculus GN=Vnn1 PE=1 SV=3 55.15 14.45 1 5 2.29 0.0000 [VNN1_MOUSE] O35728 Cytochrome P450 4A14 OS=Mus musculus GN=Cyp4a14 PE=2 SV=1 112.36 20.51 1 9 2.28 0.0052 [CP4AE_MOUSE] P55096 ATPbinding cassette subfamily D member 3 OS=Mus musculus 320.82 29.14 1 19 2.22 0.0019 GN=Abcd3 PE=1 SV=2 [ABCD3_MOUSE] Q924X2 Carnitine Opalmitoyltransferase 1, muscle isoform OS=Mus musculus 24.16 8.94 1 7 2.18 0.0000 GN=Cpt1b PE=2 SV=1 [CPT1B_MOUSE] P47740 Fatty aldehyde dehydrogenase OS=Mus musculus GN=Aldh3a2 PE=2 356.21 26.86 4 15 2.16 0.0000 SV=2 [AL3A2_MOUSE] Q8BIG7 Catechol Omethyltransferase domaincontaining protein 1 OS=Mus 35.13 2.67 1 1 2.14 0.0001 musculus GN=Comtd1 PE=2 SV=1 [CMTD1_MOUSE] O55071 Cytochrome P450 2B19 OS=Mus musculus GN=Cyp2b19 PE=2 SV=1 75.47 8.13 2 2 2.12 0.0001 [CP2BJ_MOUSE] O88833 Cytochrome P450 4A10 OS=Mus musculus GN=Cyp4a10 PE=2 SV=2 94.09 21.22 1 9 2.08 0.0002

[CP4AA_MOUSE] Q9QYR9 Acylcoenzyme A thioesterase 2, mitochondrial OS=Mus musculus 585.32 60.71 1 11 2.06 0.0000 GN=Acot2 PE=1 SV=2 [ACOT2_MOUSE] Q9R0H0 Peroxisomal acylcoenzyme A oxidase 1 OS=Mus musculus GN=Acox1 718.88 48.71 1 30 2.04 0.0000 PE=1 SV=5 [ACOX1_MOUSE] P41216 LongchainfattyacidCoA ligase 1 OS=Mus musculus GN=Acsl1 PE=1 462.13 46.64 1 34 1.95 0.0000 SV=2 [ACSL1_MOUSE] Q8BIW1 Protein prune homolog OS=Mus musculus GN=Prune PE=2 SV=1 0.00 11.45 1 4 1.95 0.0002 [PRUNE_MOUSE] Q2TPA8 Hydroxysteroid dehydrogenaselike protein 2 OS=Mus musculus 67.94 25.31 1 10 1.92 0.0000 GN=Hsdl2 PE=2 SV=1 [HSDL2_MOUSE] Q6PAR0 Kelch domaincontaining protein 10 OS=Mus musculus GN=Klhdc10 0.00 5.01 1 1 1.90 0.0001 PE=2 SV=1 [KLD10_MOUSE] P70269 Cathepsin E OS=Mus musculus GN=Ctse PE=1 SV=2 [CATE_MOUSE] 0.00 2.02 1 1 1.87 0.0000 Q9DD20 Methyltransferaselike protein 7B OS=Mus musculus GN=Mettl7b PE=2 152.68 32.79 1 7 1.83 0.0000 SV=2 [MET7B_MOUSE] Q8C0N2 Glycerol3phosphate acyltransferase 3 OS=Mus musculus GN=Agpat9 39.33 4.57 1 2 1.80 0.0059 PE=1 SV=1 [GPAT3_MOUSE] Q8R2Y0 Monoacylglycerol lipase ABHD6 OS=Mus musculus GN=Abhd6 PE=2 0.00 7.44 1 2 1.79 0.0024 SV=1 [ABHD6_MOUSE] Q9D8S4 Oligoribonuclease, mitochondrial OS=Mus musculus GN=Rexo2 PE=1 0.00 4.22 1 1 1.77 0.0013 SV=2 [ORN_MOUSE] Q924Z4 Ceramide synthase 2 OS=Mus musculus GN=Cers2 PE=1 SV=1 0.00 2.37 1 1 1.76 0.0001 [CERS2_MOUSE] Q9Z2G9 Oxidoreductase HTATIP2 OS=Mus musculus GN=Htatip2 PE=1 SV=2 75.12 21.07 1 6 1.74 0.0000 [HTAI2_MOUSE]

P45952 Mediumchain specific acylCoA dehydrogenase, mitochondrial OS=Mus 507.36 49.88 1 23 1.74 0.0000 musculus GN=Acadm PE=1 SV=1 [ACADM_MOUSE] P09405 Nucleolin OS=Mus musculus GN=Ncl PE=1 SV=2 [NUCL_MOUSE] 373.27 32.39 2 24 1.73 0.0001 Q9DC50 Peroxisomal carnitine Ooctanoyltransferase OS=Mus musculus GN=Crot 98.95 26.63 1 17 1.73 0.0000 PE=1 SV=1 [OCTC_MOUSE] Q99K85 Phosphoserine aminotransferase OS=Mus musculus GN=Psat1 PE=1 49.91 8.65 1 3 1.72 0.0005 SV=1 [SERC_MOUSE] Q8JZR0 LongchainfattyacidCoA ligase 5 OS=Mus musculus GN=Acsl5 PE=2 220.86 24.89 1 13 1.70 0.0000 SV=1 [ACSL5_MOUSE] P47934 Carnitine Oacetyltransferase OS=Mus musculus GN=Crat PE=1 SV=3 44.77 24.92 1 15 1.69 0.0001 [CACP_MOUSE] P20852 Cytochrome P450 2A5 OS=Mus musculus GN=Cyp2a5 PE=2 SV=1 142.10 23.89 1 1 1.68 0.0282 [CP2A5_MOUSE] Q9QYR7 Acylcoenzyme A thioesterase 3 OS=Mus musculus GN=Acot3 PE=2 221.48 26.39 2 3 1.66 0.0005 SV=1 [ACOT3_MOUSE] Q921H8 3ketoacylCoA thiolase A, peroxisomal OS=Mus musculus GN=Acaa1a 961.36 62.03 1 8 1.64 0.0001 PE=2 SV=1 [THIKA_MOUSE] Q5FW57 Glycine Nacyltransferaselike protein OS=Mus musculus GN=Gm4952 58.61 39.53 1 8 1.64 0.0001 PE=1 SV=2 [GLYAL_MOUSE] Q8CGK3 Lon protease homolog, mitochondrial OS=Mus musculus GN=Lonp1 319.33 27.19 1 27 1.63 0.0001 PE=1 SV=2 [LONM_MOUSE] P00493 Hypoxanthineguanine phosphoribosyltransferase OS=Mus musculus 44.74 15.6 1 3 1.62 0.0001 GN=Hprt1 PE=1 SV=3 [HPRT_MOUSE] Q99P72 Reticulon4 OS=Mus musculus GN=Rtn4 PE=1 SV=2 [RTN4_MOUSE] 0.00 2.32 1 2 1.62 0.0001 Q9EQ06 Estradiol 17betadehydrogenase 11 OS=Mus musculus GN=Hsd17b11 77.26 32.55 1 9 1.61 0.0000 PE=2 SV=1 [DHB11_MOUSE]

Q64464 Cytochrome P450 3A13 OS=Mus musculus GN=Cyp3a13 PE=2 SV=1 0.00 4.77 1 2 1.61 0.0000 [CP3AD_MOUSE] O55137 Acylcoenzyme A thioesterase 1 OS=Mus musculus GN=Acot1 PE=1 350.61 49.16 1 5 1.61 0.0002 SV=1 [ACOT1_MOUSE] P53808 Phosphatidylcholine transfer protein OS=Mus musculus GN=Pctp PE=1 0.00 5.61 1 1 1.60 0.0005 SV=2 [PPCT_MOUSE] Q9QUJ7 LongchainfattyacidCoA ligase 4 OS=Mus musculus GN=Acsl4 PE=2 24.36 10.27 2 5 1.58 0.0029 SV=2 [ACSL4_MOUSE] Q64458 Cytochrome P450 2C29 OS=Mus musculus GN=Cyp2c29 PE=1 SV=2 124.19 28.16 3 9 1.58 0.0020 [CP2CT_MOUSE] P12246 Serum amyloid Pcomponent OS=Mus musculus GN=Apcs PE=1 SV=2 29.41 15.63 1 3 1.58 0.0002 [SAMP_MOUSE] P54869 HydroxymethylglutarylCoA synthase, mitochondrial OS=Mus musculus 566.93 37.6 1 24 1.57 0.0000 GN=Hmgcs2 PE=1 SV=2 [HMCS2_MOUSE] Q8BSF4 Phosphatidylserine decarboxylase proenzyme OS=Mus musculus 33.42 6.4 1 2 1.57 0.0287 GN=Pisd PE=2 SV=1 [PISD_MOUSE] P42125 EnoylCoA delta isomerase 1, mitochondrial OS=Mus musculus 259.28 41.87 1 14 1.56 0.0001 GN=Eci1 PE=2 SV=1 [ECI1_MOUSE] P58137 Acylcoenzyme A thioesterase 8 OS=Mus musculus GN=Acot8 PE=1 79.48 22.19 1 5 1.56 0.0001 SV=1 [ACOT8_MOUSE] P61022 Calciumbinding protein p22 OS=Mus musculus GN=Chp PE=2 SV=2 0.00 19.49 1 3 1.56 0.0003 [CHP1_MOUSE] P51660 Peroxisomal multifunctional enzyme type 2 OS=Mus musculus 457.59 38.23 1 26 1.56 0.0000 GN=Hsd17b4 PE=1 SV=3 [DHB4_MOUSE] Q9QXD1 Peroxisomal acylcoenzyme A oxidase 2 OS=Mus musculus GN=Acox2 238.68 34.65 1 22 1.56 0.0001 PE=1 SV=2 [ACOX2_MOUSE]

Q61703 Interalphatrypsin inhibitor heavy chain H2 OS=Mus musculus GN=Itih2 0.00 2.11 1 2 1.53 0.0001 PE=1 SV=1 [ITIH2_MOUSE] Q8BWN8 Acylcoenzyme A thioesterase 4 OS=Mus musculus GN=Acot4 PE=2 211.90 29.45 2 7 1.53 0.0002 SV=1 [ACOT4_MOUSE] P37040 NADPHcytochrome P450 reductase OS=Mus musculus GN=Por PE=1 305.46 29.79 1 19 1.53 0.0001 SV=2 [NCPR_MOUSE] Q9D379 Epoxide hydrolase 1 OS=Mus musculus GN=Ephx1 PE=1 SV=2 75.68 32.09 1 14 1.53 0.0037 [HYEP_MOUSE] P34914 Epoxide hydrolase 2 OS=Mus musculus GN=Ephx2 PE=1 SV=2 786.28 49.46 1 25 1.53 0.0004 [HYES_MOUSE] P12791 Cytochrome P450 2B10 OS=Mus musculus GN=Cyp2b10 PE=1 SV=1 22.42 10 1 2 1.52 0.0025 [CP2BA_MOUSE] Q80XL6 AcylCoA dehydrogenase family member 11 OS=Mus musculus 171.74 29.78 1 24 1.52 0.0000 GN=Acad11 PE=1 SV=2 [ACD11_MOUSE] P14602 Heat shock protein beta1 OS=Mus musculus GN=Hspb1 PE=1 SV=3 38.00 22.49 1 5 1.51 0.0002 [HSPB1_MOUSE] Q08857 Platelet glycoprotein 4 OS=Mus musculus GN=Cd36 PE=1 SV=2 0.00 2.54 1 1 1.49 0.0012 [CD36_MOUSE] Q9D1K2 Vtype proton ATPase subunit F OS=Mus musculus GN=Atp6v1f PE=1 17.49 7.56 1 1 1.49 0.0016 SV=2 [VATF_MOUSE] Q9R0M6 Rasrelated protein Rab9A OS=Mus musculus GN=Rab9a PE=1 SV=1 18.15 12.44 1 2 1.49 0.0001 [RAB9A_MOUSE] Q9JM62 Receptor expressionenhancing protein 6 OS=Mus musculus GN=Reep6 53.64 10.45 1 2 1.49 0.0022 PE=2 SV=1 [REEP6_MOUSE] Q99JY0 Trifunctional enzyme subunit beta, mitochondrial OS=Mus musculus 258.07 41.05 4 22 1.49 0.0000 GN=Hadhb PE=1 SV=1 [ECHB_MOUSE]

P97742 Carnitine Opalmitoyltransferase 1, liver isoform OS=Mus musculus 37.26 7.5 1 5 1.48 0.0035 GN=Cpt1a PE=2 SV=4 [CPT1A_MOUSE] Q9Z0V7 Mitochondrial import inner membrane translocase subunit Tim17B 0.00 8.72 1 1 1.48 0.0000 OS=Mus musculus GN=Timm17b PE=2 SV=1 [TI17B_MOUSE] Q8CC88 Uncharacterized protein KIAA0564 homolog OS=Mus musculus 290.18 23.25 1 39 1.48 0.0000 GN=Kiaa0564 PE=2 SV=2 [K0564_MOUSE] P97872 Dimethylaniline monooxygenase [Noxideforming] 5 OS=Mus musculus 47.56 31.33 1 18 1.48 0.0002 GN=Fmo5 PE=2 SV=4 [FMO5_MOUSE] Q91V01 Lysophospholipid acyltransferase 5 OS=Mus musculus GN=Lpcat3 PE=1 0.00 2.67 1 1 1.48 0.0226 SV=1 [MBOA5_MOUSE] Q9CQ62 2,4dienoylCoA reductase, mitochondrial OS=Mus musculus GN=Decr1 197.61 38.81 1 13 1.48 0.0000 PE=1 SV=1 [DECR_MOUSE] P38647 Stress70 protein, mitochondrial OS=Mus musculus GN=Hspa9 PE=1 848.32 53.9 1 44 1.48 0.0000 SV=2 [GRP75_MOUSE] Q8VCR2 17betahydroxysteroid dehydrogenase 13 OS=Mus musculus 141.92 24.67 1 6 1.47 0.0001 GN=Hsd17b13 PE=1 SV=1 [DHB13_MOUSE] P06728 Apolipoprotein AIV OS=Mus musculus GN=Apoa4 PE=2 SV=3 64.40 27.85 1 10 1.47 0.0004 [APOA4_MOUSE] Q8BHC4 DephosphoCoA kinase domaincontaining protein OS=Mus musculus 0.00 9.09 1 2 1.47 0.0000 GN=Dcakd PE=2 SV=1 [DCAKD_MOUSE] Q8BLF1 Neutral cholesterol ester hydrolase 1 OS=Mus musculus GN=Nceh1 39.87 6.13 1 2 1.46 0.0007 PE=1 SV=1 [ADCL1_MOUSE] Q7TPV4 Mybbinding protein 1A OS=Mus musculus GN=Mybbp1a PE=1 SV=2 65.23 7.29 1 9 1.46 0.0002 [MBB1A_MOUSE] Q922K7 Putative ribosomal RNA methyltransferase NOP2 OS=Mus musculus 22.31 6.94 1 5 1.46 0.0002 GN=Nop2 PE=2 SV=1 [NOP2_MOUSE]

P47911 60S ribosomal protein L6 OS=Mus musculus GN=Rpl6 PE=1 SV=3 47.78 26.35 1 8 1.45 0.0079 [RL6_MOUSE] Q9D1G1 Rasrelated protein Rab1B OS=Mus musculus GN=Rab1b PE=1 SV=1 103.08 25.87 17 2 1.44 0.0054 [RAB1B_MOUSE] O35488 Very longchain acylCoA synthetase OS=Mus musculus GN=Slc27a2 143.83 23.39 1 13 1.44 0.0016 PE=1 SV=2 [S27A2_MOUSE] Q9WV68 Peroxisomal 2,4dienoylCoA reductase OS=Mus musculus GN=Decr2 65.52 27.05 1 9 1.44 0.0001 PE=1 SV=1 [DECR2_MOUSE] Q6ZWV7 60S ribosomal protein L35 OS=Mus musculus GN=Rpl35 PE=2 SV=1 34.77 28.46 1 5 1.44 0.0025 [RL35_MOUSE] Q9Z1D1 Eukaryotic translation initiation factor 3 subunit G OS=Mus musculus 0.00 2.81 1 1 1.43 0.0081 GN=Eif3g PE=1 SV=2 [EIF3G_MOUSE] Q3TW96 UDPNacetylhexosamine pyrophosphorylaselike protein 1 OS=Mus 31.99 8.88 1 4 1.43 0.0003 musculus GN=Uap1l1 PE=2 SV=1 [UAP1L_MOUSE] Q61937 Nucleophosmin OS=Mus musculus GN=Npm1 PE=1 SV=1 44.15 24.66 1 7 1.41 0.0001 [NPM_MOUSE] Q9WUZ9 Ectonucleoside triphosphate diphosphohydrolase 5 OS=Mus musculus 88.19 14.75 1 6 1.41 0.0003 GN=Entpd5 PE=1 SV=1 [ENTP5_MOUSE] Q8VDG7 Plateletactivating factor acetylhydrolase 2, cytoplasmic OS=Mus 26.78 7.69 1 2 1.41 0.0010 musculus GN=Pafah2 PE=2 SV=2 [PAFA2_MOUSE] P26638 SeryltRNA synthetase, cytoplasmic OS=Mus musculus GN=Sars PE=2 79.31 10.55 1 4 1.40 0.0012 SV=3 [SYSC_MOUSE] P12710 Fatty acidbinding protein, liver OS=Mus musculus GN=Fabp1 PE=1 630.87 70.87 1 13 1.40 0.0104 SV=2 [FABPL_MOUSE] Q9D823 60S ribosomal protein L37 OS=Mus musculus GN=Rpl37 PE=2 SV=3 0.00 14.43 1 2 1.40 0.0043 [RL37_MOUSE]

P04919 Band 3 anion transport protein OS=Mus musculus GN=Slc4a1 PE=1 31.23 2.48 1 2 1.40 0.0043 SV=1 [B3AT_MOUSE] Q8VDG5 Phosphopantothenatecysteine ligase OS=Mus musculus GN=Ppcs PE=2 0.00 13.83 1 5 1.40 0.0000 SV=1 [PPCS_MOUSE] P97449 Aminopeptidase N OS=Mus musculus GN=Anpep PE=1 SV=4 67.38 6.42 1 6 1.39 0.0034 [AMPN_MOUSE] P63038 60 kDa heat shock protein, mitochondrial OS=Mus musculus GN=Hspd1 1768.06 72.6 1 43 1.38 0.0000 PE=1 SV=1 [CH60_MOUSE] Q5U405 Transmembrane protease serine 13 OS=Mus musculus GN=Tmprss13 0.00 1.47 1 1 1.38 0.0093 PE=2 SV=2 [TMPSD_MOUSE] Q8K010 5oxoprolinase OS=Mus musculus GN=Oplah PE=2 SV=1 228.85 18.71 1 19 1.38 0.0000 [OPLA_MOUSE] Q8VCH8 UBX domaincontaining protein 4 OS=Mus musculus GN=Ubxn4 PE=1 0.00 8.3 1 3 1.38 0.0054 SV=1 [UBXN4_MOUSE] O08601 Microsomal triglyceride transfer protein large subunit OS=Mus musculus 237.59 30.87 1 27 1.38 0.0000 GN=Mttp PE=2 SV=2 [MTP_MOUSE] Q91WL5 Cytochrome P450 4A12A OS=Mus musculus GN=Cyp4a12a PE=2 SV=2 80.05 20.28 1 6 1.37 0.0021 [CP4CA_MOUSE] Q3UUI3 Thioesterase superfamily member 4 OS=Mus musculus GN=Them4 PE=1 0.00 3.48 1 1 1.37 0.0059 SV=1 [THEM4_MOUSE] Q99LB2 Dehydrogenase/reductase SDR family member 4 OS=Mus musculus 84.73 36.56 1 13 1.37 0.0000 GN=Dhrs4 PE=2 SV=2 [DHRS4_MOUSE] P62075 Mitochondrial import inner membrane translocase subunit Tim13 80.46 25.26 1 2 1.37 0.0009 OS=Mus musculus GN=Timm13 PE=1 SV=1 [TIM13_MOUSE] Q9DBK0 Acylcoenzyme A thioesterase 12 OS=Mus musculus GN=Acot12 PE=2 72.11 7.73 1 4 1.37 0.0045 SV=1 [ACO12_MOUSE]

Q9DCZ4 Apolipoprotein O OS=Mus musculus GN=Apoo PE=2 SV=1 37.26 12.26 1 2 1.35 0.0224 [APOO_MOUSE] Q9CYH2 Redoxregulatory protein PAMM OS=Mus musculus PE=1 SV=2 24.87 14.22 1 4 1.35 0.0003 [PAMM_MOUSE] Q8VC19 5aminolevulinate synthase, nonspecific, mitochondrial OS=Mus 42.52 8.41 1 4 1.35 0.0047 musculus GN=Alas1 PE=2 SV=2 [HEM1_MOUSE] Q8VCI5 Peroxisomal biogenesis factor 19 OS=Mus musculus GN=Pex19 PE=1 26.13 13.38 1 4 1.35 0.0000 SV=1 [PEX19_MOUSE] P50427 Sterylsulfatase OS=Mus musculus GN=Sts PE=2 SV=1 [STS_MOUSE] 0.00 4.97 1 3 1.34 0.0019 P47915 60S ribosomal protein L29 OS=Mus musculus GN=Rpl29 PE=2 SV=2 34.89 20.63 1 4 1.34 0.0071 [RL29_MOUSE] Q8BMS1 Trifunctional enzyme subunit alpha, mitochondrial OS=Mus musculus 842.60 45.87 2 39 1.34 0.0001 GN=Hadha PE=1 SV=1 [ECHA_MOUSE] Q8BGI5 Peroxisome assembly protein 26 OS=Mus musculus GN=Pex26 PE=2 22.95 3.61 1 1 1.34 0.0189 SV=2 [PEX26_MOUSE] Q9CR57 60S ribosomal protein L14 OS=Mus musculus GN=Rpl14 PE=2 SV=3 76.09 11.52 1 2 1.33 0.0371 [RL14_MOUSE] Q921J2 GTPbinding protein Rheb OS=Mus musculus GN=Rheb PE=2 SV=1 0.00 8.7 1 1 1.33 0.0071 [RHEB_MOUSE] O70475 UDPglucose 6dehydrogenase OS=Mus musculus GN=Ugdh PE=1 180.05 45.23 1 16 1.33 0.0068 SV=1 [UGDH_MOUSE] O54782 Epididymisspecific alphamannosidase OS=Mus musculus GN=Man2b2 30.01 1.38 1 1 1.32 0.0004 PE=2 SV=2 [MA2B2_MOUSE] Q8BTY1 Kynurenineoxoglutarate transaminase 1 OS=Mus musculus GN=Ccbl1 56.85 20.52 1 8 1.32 0.0003 PE=2 SV=1 [KAT1_MOUSE] Q9R062 Glycogenin1 OS=Mus musculus GN=Gyg1 PE=2 SV=3 20.46 5.11 1 2 1.32 0.0039

[GLYG_MOUSE] P18572 Basigin OS=Mus musculus GN=Bsg PE=1 SV=2 [BASI_MOUSE] 36.68 12.08 1 4 1.32 0.0004 P08249 Malate dehydrogenase, mitochondrial OS=Mus musculus GN=Mdh2 637.38 52.96 1 18 1.32 0.0001 PE=1 SV=3 [MDHM_MOUSE] Q7TMV3 FAST kinase domaincontaining protein 5 OS=Mus musculus 0.00 1.18 1 1 1.32 0.0142 GN=Fastkd5 PE=2 SV=1 [FAKD5_MOUSE] Q61133 Glutathione Stransferase theta2 OS=Mus musculus GN=Gstt2 PE=2 133.55 41.8 1 8 1.32 0.0002 SV=3 [GSTT2_MOUSE] P59017 Bcl2like protein 13 OS=Mus musculus GN=Bcl2l13 PE=1 SV=2 0.00 2.53 1 1 1.32 0.0207 [B2L13_MOUSE] Q8BG51 Mitochondrial Rho GTPase 1 OS=Mus musculus GN=Rhot1 PE=2 SV=1 33.74 2.69 2 2 1.32 0.0068 [MIRO1_MOUSE] Q64433 10 kDa heat shock protein, mitochondrial OS=Mus musculus GN=Hspe1 221.54 85.29 1 12 1.31 0.0004 PE=1 SV=2 [CH10_MOUSE] P06801 NADPdependent malic enzyme OS=Mus musculus GN=Me1 PE=1 109.49 20.45 1 12 1.31 0.0013 SV=2 [MAOX_MOUSE] O55022 Membraneassociated progesterone receptor component 1 OS=Mus 59.97 23.59 1 6 1.31 0.0298 musculus GN=Pgrmc1 PE=1 SV=4 [PGRC1_MOUSE] Q9QXE0 2hydroxyacylCoA lyase 1 OS=Mus musculus GN=Hacl1 PE=1 SV=2 262.22 26.85 1 16 1.31 0.0001 [HACL1_MOUSE] P62077 Mitochondrial import inner membrane translocase subunit Tim8 B 24.40 18.07 1 2 1.30 0.0017 OS=Mus musculus GN=Timm8b PE=2 SV=1 [TIM8B_MOUSE] O35945 Aldehyde dehydrogenase, cytosolic 1 OS=Mus musculus GN=Aldh1a7 198.26 30.94 5 7 1.30 0.0007 PE=2 SV=1 [AL1A7_MOUSE] P35601 Replication factor C subunit 1 OS=Mus musculus GN=Rfc1 PE=1 SV=2 0.00 1.77 1 1 1.30 0.0180 [RFC1_MOUSE]

P52825 Carnitine Opalmitoyltransferase 2, mitochondrial OS=Mus musculus 223.11 38.91 1 23 1.29 0.0000 GN=Cpt2 PE=1 SV=2 [CPT2_MOUSE] Q6DFW4 Nucleolar protein 58 OS=Mus musculus GN=Nop58 PE=1 SV=1 0.00 7.84 1 4 1.29 0.0051 [NOP58_MOUSE] Q5SSI6 U3 small nucleolar RNAassociated protein 18 homolog OS=Mus 0.00 1.45 1 1 1.29 0.0002 musculus GN=Utp18 PE=1 SV=1 [UTP18_MOUSE] Q99KI0 Aconitate hydratase, mitochondrial OS=Mus musculus GN=Aco2 PE=1 341.31 39.87 1 30 1.28 0.0001 SV=1 [ACON_MOUSE] Q60714 Longchain fatty acid transport protein 1 OS=Mus musculus GN=Slc27a1 0.00 1.08 1 1 1.28 0.0093 PE=1 SV=1 [S27A1_MOUSE] P10852 4F2 cellsurface antigen heavy chain OS=Mus musculus GN=Slc3a2 34.18 3.23 1 1 1.28 0.0002 PE=1 SV=1 [4F2_MOUSE] P24549 Retinal dehydrogenase 1 OS=Mus musculus GN=Aldh1a1 PE=1 SV=5 444.85 45.71 5 15 1.27 0.0099 [AL1A1_MOUSE] P29788 Vitronectin OS=Mus musculus GN=Vtn PE=1 SV=2 [VTNC_MOUSE] 22.91 8.79 1 3 1.27 0.0064 Q8QZT1 AcetylCoA acetyltransferase, mitochondrial OS=Mus musculus 455.78 47.88 1 21 1.27 0.0001 GN=Acat1 PE=1 SV=1 [THIL_MOUSE] Q8K2C7 Protein OS9 OS=Mus musculus GN=Os9 PE=1 SV=2 [OS9_MOUSE] 147.94 5.06 1 4 1.27 0.0006 Q8BKC5 Importin5 OS=Mus musculus GN=Ipo5 PE=1 SV=3 [IPO5_MOUSE] 29.91 0.73 1 1 1.26 0.0002 P62897 Cytochrome c, somatic OS=Mus musculus GN=Cycs PE=1 SV=2 203.11 68.57 2 10 1.26 0.0003 [CYC_MOUSE] Q8BP47 AsparaginyltRNA synthetase, cytoplasmic OS=Mus musculus GN=Nars 51.50 22.36 2 12 1.26 0.0001 PE=1 SV=2 [SYNC_MOUSE] Q99J39 MalonylCoA decarboxylase, mitochondrial OS=Mus musculus 136.77 15.24 1 7 1.26 0.0057 GN=Mlycd PE=2 SV=1 [DCMC_MOUSE] Q8JZN5 AcylCoA dehydrogenase family member 9, mitochondrial OS=Mus 23.33 6.4 1 4 1.25 0.0130

musculus GN=Acad9 PE=2 SV=2 [ACAD9_MOUSE] P49312 Heterogeneous nuclear ribonucleoprotein A1 OS=Mus musculus 43.07 22.5 1 3 1.25 0.0020 GN=Hnrnpa1 PE=1 SV=2 [ROA1_MOUSE] Q91WJ8 Far upstream elementbinding protein 1 OS=Mus musculus GN=Fubp1 0.00 3.53 1 2 1.25 0.0001 PE=1 SV=1 [FUBP1_MOUSE] Q8BJU0 Small glutaminerich tetratricopeptide repeatcontaining protein alpha 54.38 17.46 2 6 1.25 0.0019 OS=Mus musculus GN=Sgta PE=1 SV=2 [SGTA_MOUSE] Q9D6Z1 Nucleolar protein 56 OS=Mus musculus GN=Nop56 PE=1 SV=2 60.90 10 1 4 1.25 0.0023 [NOP56_MOUSE] Q9DCD0 6phosphogluconate dehydrogenase, decarboxylating OS=Mus musculus 104.47 17.39 1 7 1.24 0.0014 GN=Pgd PE=2 SV=3 [6PGD_MOUSE] Q925I1 ATPase family AAA domaincontaining protein 3 OS=Mus musculus 111.66 27.58 1 15 1.24 0.0002 GN=Atad3 PE=1 SV=1 [ATAD3_MOUSE] Q9D1P0 39S ribosomal protein L13, mitochondrial OS=Mus musculus 17.38 18.54 1 3 1.24 0.0137 GN=Mrpl13 PE=2 SV=1 [RM13_MOUSE] Q6ZQI3 Malectin OS=Mus musculus GN=Mlec PE=2 SV=2 [MLEC_MOUSE] 0.00 4.47 1 1 1.24 0.0091 P24270 Catalase OS=Mus musculus GN=Cat PE=1 SV=4 [CATA_MOUSE] 1086.87 62.24 2 41 1.24 0.0003 Q9WUQ2 Prolactin regulatory elementbinding protein OS=Mus musculus GN=Preb 30.70 3.84 1 1 1.24 0.0052 PE=1 SV=1 [PREB_MOUSE] Q8R1G2 Carboxymethylenebutenolidase homolog OS=Mus musculus GN=Cmbl 47.22 26.12 1 5 1.24 0.0001 PE=2 SV=1 [CMBL_MOUSE] P67778 Prohibitin OS=Mus musculus GN=Phb PE=1 SV=1 [PHB_MOUSE] 202.08 66.54 1 17 1.24 0.0001 P27659 60S ribosomal protein L3 OS=Mus musculus GN=Rpl3 PE=2 SV=3 62.56 20.1 1 8 1.24 0.0020 [RL3_MOUSE] P62754 40S ribosomal protein S6 OS=Mus musculus GN=Rps6 PE=1 SV=1 71.62 32.13 1 9 1.24 0.0038 [RS6_MOUSE]

Q62426 CystatinB OS=Mus musculus GN=Cstb PE=1 SV=1 [CYTB_MOUSE] 28.25 18.37 1 2 1.24 0.0033 Q9QYA2 Mitochondrial import receptor subunit TOM40 homolog OS=Mus 21.52 6.09 1 2 1.24 0.0021 musculus GN=Tomm40 PE=1 SV=3 [TOM40_MOUSE] O35678 Monoglyceride lipase OS=Mus musculus GN=Mgll PE=1 SV=1 35.63 9.9 1 3 1.24 0.0014 [MGLL_MOUSE] Q99PT1 Rho GDPdissociation inhibitor 1 OS=Mus musculus GN=Arhgdia PE=1 96.23 21.57 1 4 1.23 0.0116 SV=3 [GDIR1_MOUSE] P19253 60S ribosomal protein L13a OS=Mus musculus GN=Rpl13a PE=1 SV=4 32.81 28.57 1 7 1.23 0.0055 [RL13A_MOUSE] P12970 60S ribosomal protein L7a OS=Mus musculus GN=Rpl7a PE=2 SV=2 124.91 27.44 1 8 1.23 0.0080 [RL7A_MOUSE] P43883 Perilipin2 OS=Mus musculus GN=Plin2 PE=2 SV=2 [PLIN2_MOUSE] 98.34 26.35 1 9 1.23 0.0136 P47802 Metaxin1 OS=Mus musculus GN=Mtx1 PE=1 SV=1 [MTX1_MOUSE] 32.49 12.62 1 4 1.22 0.0208 Q8BSY0 Aspartyl/asparaginyl betahydroxylase OS=Mus musculus GN=Asph 22.52 7.02 1 4 1.22 0.0037 PE=2 SV=1 [ASPH_MOUSE] Q99LC9 Peroxisome assembly factor 2 OS=Mus musculus GN=Pex6 PE=2 SV=1 16.44 5.3 1 5 1.22 0.0019 [PEX6_MOUSE] P62281 40S ribosomal protein S11 OS=Mus musculus GN=Rps11 PE=2 SV=3 30.29 15.82 1 3 1.22 0.0120 [RS11_MOUSE] P47963 60S ribosomal protein L13 OS=Mus musculus GN=Rpl13 PE=2 SV=3 79.87 40.28 1 10 1.22 0.0017 [RL13_MOUSE] Q9QWR8 AlphaNacetylgalactosaminidase OS=Mus musculus GN=Naga PE=2 42.73 8.92 1 3 1.22 0.0261 SV=2 [NAGAB_MOUSE] P31786 AcylCoAbinding protein OS=Mus musculus GN=Dbi PE=1 SV=2 40.19 49.43 1 4 1.21 0.0124 [ACBP_MOUSE] Q9D1N9 39S ribosomal protein L21, mitochondrial OS=Mus musculus 0.00 4.31 1 1 1.21 0.0002

GN=Mrpl21 PE=2 SV=1 [RM21_MOUSE] Q91XE8 Transmembrane protein 205 OS=Mus musculus GN=Tmem205 PE=1 40.80 12.7 1 2 1.21 0.0061 SV=1 [TM205_MOUSE] Q9CQV4 Protein FAM134C OS=Mus musculus GN=Fam134c PE=2 SV=1 0.00 1.93 1 1 1.21 0.0244 [F134C_MOUSE] O09158 Cytochrome P450 3A25 OS=Mus musculus GN=Cyp3a25 PE=2 SV=1 0.00 4.77 1 2 1.21 0.0019 [CP3AP_MOUSE] Q4VAA2 Protein CDV3 OS=Mus musculus GN=Cdv3 PE=1 SV=2 57.68 4.27 1 1 1.21 0.0105 [CDV3_MOUSE] Q99LP6 GrpE protein homolog 1, mitochondrial OS=Mus musculus GN=Grpel1 54.32 33.64 1 9 1.20 0.0353 PE=1 SV=1 [GRPE1_MOUSE] Q9JHW2 Omegaamidase NIT2 OS=Mus musculus GN=Nit2 PE=1 SV=1 145.51 34.78 1 9 0.83 0.0015 [NIT2_MOUSE] P39039 Mannosebinding protein A OS=Mus musculus GN=Mbl1 PE=2 SV=1 0.00 6.69 1 2 0.83 0.0024 [MBL1_MOUSE] Q9CQ75 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 96.08 41.41 1 5 0.83 0.0004 OS=Mus musculus GN=Ndufa2 PE=1 SV=3 [NDUA2_MOUSE] Q91W64 Cytochrome P450 2C70 OS=Mus musculus GN=Cyp2c70 PE=2 SV=2 36.58 14.72 1 6 0.83 0.0173 [CP270_MOUSE] P14824 Annexin A6 OS=Mus musculus GN=Anxa6 PE=1 SV=3 138.59 34.47 1 25 0.83 0.0002 [ANXA6_MOUSE] P00375 Dihydrofolate reductase OS=Mus musculus GN=Dhfr PE=1 SV=3 34.50 17.65 1 3 0.83 0.0020 [DYR_MOUSE] Q61792 LIM and SH3 domain protein 1 OS=Mus musculus GN=Lasp1 PE=1 35.28 32.7 1 9 0.82 0.0056 SV=1 [LASP1_MOUSE] Q8BVI4 Dihydropteridine reductase OS=Mus musculus GN=Qdpr PE=1 SV=2 178.20 50.21 1 9 0.82 0.0013

[DHPR_MOUSE] Q9D7B6 IsobutyrylCoA dehydrogenase, mitochondrial OS=Mus musculus 61.09 24.21 1 10 0.82 0.0000 GN=Acad8 PE=2 SV=2 [ACAD8_MOUSE] P55264 Adenosine kinase OS=Mus musculus GN=Adk PE=1 SV=2 53.47 30.75 1 13 0.82 0.0014 [ADK_MOUSE] P19783 Cytochrome c oxidase subunit 4 isoform 1, mitochondrial OS=Mus 100.69 42.6 1 8 0.82 0.0006 musculus GN=Cox4i1 PE=1 SV=2 [COX41_MOUSE] P01027 Complement C3 OS=Mus musculus GN=C3 PE=1 SV=3 [CO3_MOUSE] 167.25 15.63 1 25 0.82 0.0009 P97823 Acylprotein thioesterase 1 OS=Mus musculus GN=Lypla1 PE=1 SV=1 61.56 16.96 1 4 0.82 0.0022 [LYPA1_MOUSE] Q9WU79 Proline dehydrogenase 1, mitochondrial OS=Mus musculus GN=Prodh 147.47 23.37 1 11 0.82 0.0044 PE=2 SV=2 [PROD_MOUSE] P68368 Tubulin alpha4A chain OS=Mus musculus GN=Tuba4a PE=1 SV=1 95.13 40.63 2 3 0.82 0.0013 [TBA4A_MOUSE] Q9JIL4 Na(+)/H(+) exchange regulatory NHERF3 OS=Mus musculus 50.95 16.76 1 7 0.82 0.0004 GN=Pdzk1 PE=1 SV=1 [NHRF3_MOUSE] Q9CQV5 28S ribosomal protein S24, mitochondrial OS=Mus musculus 0.00 4.79 1 1 0.81 0.0022 GN=Mrps24 PE=2 SV=1 [RT24_MOUSE] Q9EQF5 Dihydropyrimidinase OS=Mus musculus GN=Dpys PE=2 SV=2 197.64 29.87 1 14 0.81 0.0003 [DPYS_MOUSE] Q62425 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4 32.55 37.8 1 5 0.81 0.0050 OS=Mus musculus GN=Ndufa4 PE=1 SV=2 [NDUA4_MOUSE] P33267 Cytochrome P450 2F2 OS=Mus musculus GN=Cyp2f2 PE=2 SV=1 27.34 17.31 1 6 0.81 0.0027 [CP2F2_MOUSE] Q9R111 Guanine deaminase OS=Mus musculus GN=Gda PE=1 SV=1 25.75 9.03 1 4 0.81 0.0015 [GUAD_MOUSE]

Q9WUL7 ADPribosylation factorlike protein 3 OS=Mus musculus GN=Arl3 PE=1 0.00 6.04 1 1 0.80 0.0220 SV=1 [ARL3_MOUSE] Q3U4I7 Pyridine nucleotidedisulfide oxidoreductase domaincontaining protein 2 36.36 7.41 1 4 0.80 0.0344 OS=Mus musculus GN=Pyroxd2 PE=2 SV=2 [PYRD2_MOUSE] Q99KQ4 Nicotinamide phosphoribosyltransferase OS=Mus musculus GN=Nampt 48.12 15.48 1 7 0.80 0.0006 PE=1 SV=1 [NAMPT_MOUSE] Q9CQE3 28S ribosomal protein S17, mitochondrial OS=Mus musculus 0.00 7.5 1 1 0.80 0.0167 GN=Mrps17 PE=2 SV=1 [RT17_MOUSE] Q8VCX1 3oxo5betasteroid 4dehydrogenase OS=Mus musculus GN=Akr1d1 30.57 24.31 1 6 0.80 0.0004 PE=2 SV=1 [AK1D1_MOUSE] Q9CQ91 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 23.58 8.33 1 1 0.80 0.0005 OS=Mus musculus GN=Ndufa3 PE=1 SV=1 [NDUA3_MOUSE] P56656 Cytochrome P450 2C39 OS=Mus musculus GN=Cyp2c39 PE=2 SV=1 48.37 14.08 1 4 0.80 0.0235 [CP239_MOUSE] P51885 Lumican OS=Mus musculus GN=Lum PE=1 SV=2 [LUM_MOUSE] 14.19 14.79 1 5 0.80 0.0226 Q91VD9 NADHubiquinone oxidoreductase 75 kDa subunit, mitochondrial 265.09 37.41 1 24 0.80 0.0001 OS=Mus musculus GN=Ndufs1 PE=1 SV=2 [NDUS1_MOUSE] Q8K3J1 NADH dehydrogenase [ubiquinone] ironsulfur protein 8, mitochondrial 58.00 13.68 1 3 0.79 0.0061 OS=Mus musculus GN=Ndufs8 PE=1 SV=1 [NDUS8_MOUSE] P05201 Aspartate aminotransferase, cytoplasmic OS=Mus musculus GN=Got1 128.99 33.41 1 13 0.79 0.0121 PE=1 SV=3 [AATC_MOUSE] O88587 Catechol Omethyltransferase OS=Mus musculus GN=Comt PE=1 SV=1 46.70 23.4 1 6 0.79 0.0002 [COMT_MOUSE] Q9DCS9 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 49.96 31.82 1 6 0.79 0.0006 OS=Mus musculus GN=Ndufb10 PE=1 SV=3 [NDUBA_MOUSE] Q9D6J6 NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial 162.37 34.68 2 8 0.79 0.0007

OS=Mus musculus GN=Ndufv2 PE=1 SV=2 [NDUV2_MOUSE] Q99JW2 Aminoacylase1 OS=Mus musculus GN=Acy1 PE=1 SV=1 79.55 29.41 1 10 0.79 0.0003 [ACY1_MOUSE] P97364 Selenide, water dikinase 2 OS=Mus musculus GN=Sephs2 PE=1 SV=3 0.00 7.96 1 3 0.79 0.0004 [SPS2_MOUSE] Q9DBA8 Probable imidazolonepropionase OS=Mus musculus GN=Amdhd1 PE=2 111.73 26.29 1 9 0.79 0.0013 SV=1 [HUTI_MOUSE] O09159 Lysosomal alphamannosidase OS=Mus musculus GN=Man2b1 PE=2 0.00 2.57 1 2 0.79 0.0090 SV=4 [MA2B1_MOUSE] Q9DCS2 UPF0585 protein C16orf13 homolog OS=Mus musculus PE=1 SV=1 67.79 31.37 1 6 0.79 0.0006 [CP013_MOUSE] P27773 Protein disulfideisomerase A3 OS=Mus musculus GN=Pdia3 PE=1 256.73 51.09 1 25 0.79 0.0005 SV=2 [PDIA3_MOUSE] Q9D0M5 Dynein light chain 2, cytoplasmic OS=Mus musculus GN=Dynll2 PE=1 29.56 13.48 1 2 0.79 0.0079 SV=1 [DYL2_MOUSE] P11352 Glutathione peroxidase 1 OS=Mus musculus GN=Gpx1 PE=1 SV=2 120.47 70.15 1 11 0.78 0.0004 [GPX1_MOUSE] Q8VCZ9 Probable proline dehydrogenase 2 OS=Mus musculus GN=Prodh2 PE=2 31.30 6.58 1 3 0.78 0.0017 SV=1 [PROD2_MOUSE] Q91WT9 Cystathionine betasynthase OS=Mus musculus GN=Cbs PE=2 SV=3 46.56 12.83 1 7 0.78 0.0001 [CBS_MOUSE] Q9JI75 Ribosyldihydronicotinamide dehydrogenase [quinone] OS=Mus musculus 83.07 24.68 1 7 0.78 0.0000 GN=Nqo2 PE=2 SV=3 [NQO2_MOUSE] Q8R0F9 SEC14like protein 4 OS=Mus musculus GN=Sec14l4 PE=2 SV=1 64.50 26.8 1 9 0.78 0.0024 [S14L4_MOUSE] Q9WVD5 Mitochondrial ornithine transporter 1 OS=Mus musculus GN=Slc25a15 30.76 15.61 1 5 0.78 0.0012

PE=2 SV=1 [ORNT1_MOUSE] P22892 AP1 complex subunit gamma1 OS=Mus musculus GN=Ap1g1 PE=1 32.38 1.82 3 2 0.77 0.0116 SV=3 [AP1G1_MOUSE] P24369 Peptidylprolyl cistrans isomerase B OS=Mus musculus GN=Ppib PE=2 68.97 45.37 3 10 0.77 0.0053 SV=2 [PPIB_MOUSE] Q9DCU9 Probable 4hydroxy2oxoglutarate aldolase, mitochondrial OS=Mus 108.54 16.2 1 5 0.77 0.0001 musculus GN=Hoga1 PE=1 SV=1 [HOGA1_MOUSE] Q8CHR6 Dihydropyrimidine dehydrogenase [NADP+] OS=Mus musculus 102.63 14.54 1 11 0.77 0.0011 GN=Dpyd PE=2 SV=1 [DPYD_MOUSE] P0C0S6 Histone H2A.Z OS=Mus musculus GN=H2afz PE=1 SV=2 145.80 31.25 2 3 0.77 0.0081 [H2AZ_MOUSE] Q00623 Apolipoprotein AI OS=Mus musculus GN=Apoa1 PE=1 SV=1 141.18 47.35 1 14 0.77 0.0064 [APOA1_MOUSE] Q9CXZ1 NADH dehydrogenase [ubiquinone] ironsulfur protein 4, mitochondrial 23.34 19.43 1 3 0.77 0.0126 OS=Mus musculus GN=Ndufs4 PE=1 SV=3 [NDUS4_MOUSE] Q80W21 Glutathione Stransferase Mu 7 OS=Mus musculus GN=Gstm7 PE=1 92.12 44.5 2 4 0.76 0.0256 SV=1 [GSTM7_MOUSE] Q8BK63 Casein kinase I isoform alpha OS=Mus musculus GN=Csnk1a1 PE=2 0.00 2.37 1 1 0.76 0.0204 SV=2 [KC1A_MOUSE] Q8VC12 Urocanate hydratase OS=Mus musculus GN=Uroc1 PE=2 SV=2 158.52 17.31 1 13 0.76 0.0017 [HUTU_MOUSE] P28474 Alcohol dehydrogenase class3 OS=Mus musculus GN=Adh5 PE=1 112.49 20.86 2 7 0.76 0.0002 SV=3 [ADHX_MOUSE] P41317 Mannosebinding protein C OS=Mus musculus GN=Mbl2 PE=2 SV=2 27.12 16.8 1 4 0.76 0.0003 [MBL2_MOUSE] Q8BT60 Copine3 OS=Mus musculus GN=Cpne3 PE=1 SV=2 [CPNE3_MOUSE] 23.18 3.38 1 2 0.76 0.0009

Q9DBB8 Trans1,2dihydrobenzene1,2diol dehydrogenase OS=Mus musculus 58.48 20.12 1 6 0.76 0.0001 GN=Dhdh PE=2 SV=1 [DHDH_MOUSE] Q9CPX6 Ubiquitinlikeconjugating enzyme ATG3 OS=Mus musculus GN=Atg3 0.00 4.14 1 1 0.76 0.0227 PE=1 SV=1 [ATG3_MOUSE] P50247 Adenosylhomocysteinase OS=Mus musculus GN=Ahcy PE=1 SV=3 501.94 44.21 1 17 0.76 0.0005 [SAHH_MOUSE] Q99JB8 Protein kinase C and casein kinase II substrate protein 3 OS=Mus 60.19 12.26 1 4 0.76 0.0000 musculus GN=Pacsin3 PE=1 SV=1 [PACN3_MOUSE] Q9DCT2 NADH dehydrogenase [ubiquinone] ironsulfur protein 3, mitochondrial 91.16 28.14 1 8 0.76 0.0011 OS=Mus musculus GN=Ndufs3 PE=1 SV=2 [NDUS3_MOUSE] Q9D6J5 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, 26.26 31.72 1 4 0.76 0.0028 mitochondrial OS=Mus musculus GN=Ndufb8 PE=1 SV=1 [NDUB8_MOUSE] Q9Z1P6 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 73.53 68.14 1 8 0.76 0.0002 OS=Mus musculus GN=Ndufa7 PE=1 SV=3 [NDUA7_MOUSE] Q99LC3 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, 73.93 22.82 1 7 0.75 0.0004 mitochondrial OS=Mus musculus GN=Ndufa10 PE=1 SV=1 [NDUAA_MOUSE] P34927 Asialoglycoprotein receptor 1 OS=Mus musculus GN=Asgr1 PE=2 SV=3 0.00 6.69 1 2 0.75 0.0030 [ASGR1_MOUSE] P07309 Transthyretin OS=Mus musculus GN=Ttr PE=1 SV=1 [TTHY_MOUSE] 33.00 35.37 1 6 0.75 0.0001 Q9JKR6 Hypoxia upregulated protein 1 OS=Mus musculus GN=Hyou1 PE=1 118.88 28.63 1 25 0.75 0.0009 SV=1 [HYOU1_MOUSE] Q9CPQ1 Cytochrome c oxidase subunit 6C OS=Mus musculus GN=Cox6c PE=1 60.87 36.84 1 4 0.75 0.0000 SV=3 [COX6C_MOUSE] Q91WG8 Bifunctional UDPNacetylglucosamine 37.91 5.82 1 4 0.74 0.0000

2epimerase/Nacetylmannosamine kinase OS=Mus musculus GN=Gne PE=1 SV=1 [GLCNE_MOUSE] P53657 Pyruvate kinase isozymes R/L OS=Mus musculus GN=Pklr PE=2 SV=1 113.70 39.02 1 17 0.74 0.0007 [KPYR_MOUSE] P19536 Cytochrome c oxidase subunit 5B, mitochondrial OS=Mus musculus 109.26 35.94 1 6 0.74 0.0001 GN=Cox5b PE=1 SV=1 [COX5B_MOUSE] P15626 Glutathione Stransferase Mu 2 OS=Mus musculus GN=Gstm2 PE=1 138.99 56.88 2 8 0.74 0.0021 SV=2 [GSTM2_MOUSE] P12787 Cytochrome c oxidase subunit 5A, mitochondrial OS=Mus musculus 50.07 26.71 1 6 0.74 0.0003 GN=Cox5a PE=1 SV=2 [COX5A_MOUSE] Q7TMM9 Tubulin beta2A chain OS=Mus musculus GN=Tubb2a PE=1 SV=1 233.61 45.84 3 3 0.73 0.0002 [TBB2A_MOUSE] Q9CQZ6 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 0.00 10.58 1 1 0.73 0.0027 OS=Mus musculus GN=Ndufb3 PE=1 SV=1 [NDUB3_MOUSE] Q99MZ7 Peroxisomal trans2enoylCoA reductase OS=Mus musculus GN=Pecr 38.61 21.78 1 6 0.73 0.0007 PE=2 SV=1 [PECR_MOUSE] Q9CQA3 Succinate dehydrogenase [ubiquinone] ironsulfur subunit, mitochondrial 83.61 34.4 2 12 0.73 0.0000 OS=Mus musculus GN=Sdhb PE=1 SV=1 [DHSB_MOUSE] P50172 Corticosteroid 11betadehydrogenase isozyme 1 OS=Mus musculus 72.89 20.55 1 8 0.73 0.0050 GN=Hsd11b1 PE=1 SV=3 [DHI1_MOUSE] P14211 Calreticulin OS=Mus musculus GN=Calr PE=1 SV=1 [CALR_MOUSE] 194.80 28.61 1 14 0.73 0.0029 P49442 Inositol polyphosphate 1phosphatase OS=Mus musculus GN=Inpp1 32.04 3.03 1 1 0.73 0.0097 PE=1 SV=2 [INPP_MOUSE] P15105 Glutamine synthetase OS=Mus musculus GN=Glul PE=1 SV=6 67.32 22.79 1 9 0.72 0.0003 [GLNA_MOUSE] Q91XE4 Aspartoacylase2 OS=Mus musculus GN=Acy3 PE=1 SV=1 29.02 4.72 1 2 0.72 0.0002

[ACY3_MOUSE] Q91X52 Lxylulose reductase OS=Mus musculus GN=Dcxr PE=2 SV=2 71.53 42.21 2 10 0.72 0.0002 [DCXR_MOUSE] Q00519 Xanthine dehydrogenase/oxidase OS=Mus musculus GN=Xdh PE=1 37.05 3.6 1 4 0.72 0.0123 SV=5 [XDH_MOUSE] P23953 Liver carboxylesterase N OS=Mus musculus GN=Es1 PE=1 SV=4 66.57 12.82 1 5 0.72 0.0006 [ESTN_MOUSE] Q9DCM0 Protein ETHE1, mitochondrial OS=Mus musculus GN=Ethe1 PE=1 SV=2 122.00 26.38 1 4 0.71 0.0000 [ETHE1_MOUSE] Q7TNG8 Probable Dlactate dehydrogenase, mitochondrial OS=Mus musculus 139.31 19.83 1 10 0.71 0.0006 GN=Ldhd PE=1 SV=1 [LDHD_MOUSE] P28665 Murinoglobulin1 OS=Mus musculus GN=Mug1 PE=1 SV=3 69.07 9.69 2 12 0.71 0.0032 [MUG1_MOUSE] Q922D8 C1tetrahydrofolate synthase, cytoplasmic OS=Mus musculus 371.23 32.62 1 29 0.71 0.0001 GN=Mthfd1 PE=1 SV=4 [C1TC_MOUSE] P52430 Serum paraoxonase/arylesterase 1 OS=Mus musculus GN=Pon1 PE=1 18.55 14.08 1 4 0.71 0.0103 SV=2 [PON1_MOUSE] Q9CY50 Transloconassociated protein subunit alpha OS=Mus musculus GN=Ssr1 28.25 8.04 1 2 0.71 0.0044 PE=1 SV=1 [SSRA_MOUSE] Q9QZ85 Interferoninducible GTPase 1 OS=Mus musculus GN=Iigp1 PE=1 SV=2 86.31 27.12 1 10 0.71 0.0070 [IIGP1_MOUSE] Q9R1Z8 Vinexin OS=Mus musculus GN=Sorbs3 PE=1 SV=1 [VINEX_MOUSE] 0.00 1.09 1 1 0.71 0.0002 Q921I1 Serotransferrin OS=Mus musculus GN=Tf PE=1 SV=1 [TRFE_MOUSE] 122.57 17.93 1 14 0.70 0.0001 Q91YI0 Argininosuccinate lyase OS=Mus musculus GN=Asl PE=2 SV=1 302.91 38.79 2 18 0.70 0.0006 [ARLY_MOUSE] Q9CQC7 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 29.89 27.13 1 4 0.70 0.0003

OS=Mus musculus GN=Ndufb4 PE=1 SV=3 [NDUB4_MOUSE] P56391 Cytochrome c oxidase subunit 6B1 OS=Mus musculus GN=Cox6b1 PE=1 25.74 33.72 1 4 0.70 0.0001 SV=2 [CX6B1_MOUSE] Q9WUK2 Eukaryotic translation initiation factor 4H OS=Mus musculus GN=Eif4h 0.00 8.06 1 2 0.70 0.0034 PE=1 SV=3 [IF4H_MOUSE] P30115 Glutathione Stransferase A3 OS=Mus musculus GN=Gsta3 PE=1 SV=2 391.59 39.82 1 7 0.70 0.0004 [GSTA3_MOUSE] Q64374 Regucalcin OS=Mus musculus GN=Rgn PE=1 SV=1 [RGN_MOUSE] 423.71 47.49 1 13 0.70 0.0000 P14246 Solute carrier family 2, facilitated glucose transporter member 2 OS=Mus 0.00 6.31 1 4 0.70 0.0020 musculus GN=Slc2a2 PE=1 SV=3 [GTR2_MOUSE] P17665 Cytochrome c oxidase subunit 7C, mitochondrial OS=Mus musculus 48.11 23.81 2 2 0.70 0.0062 GN=Cox7c PE=1 SV=1 [COX7C_MOUSE] Q60936 Chaperone activity of bc1 complexlike, mitochondrial OS=Mus 35.93 10.39 1 6 0.70 0.0043 musculus GN=Adck3 PE=2 SV=2 [ADCK3_MOUSE] P16460 Argininosuccinate synthase OS=Mus musculus GN=Ass1 PE=1 SV=1 401.80 57.77 1 26 0.69 0.0000 [ASSY_MOUSE] Q91ZJ5 UTPglucose1phosphate uridylyltransferase OS=Mus musculus 134.96 36.42 1 17 0.69 0.0003 GN=Ugp2 PE=2 SV=3 [UGPA_MOUSE] Q8R0J8 Probable gluconokinase OS=Mus musculus PE=2 SV=2 33.43 14.67 1 2 0.69 0.0316 [GNTK_MOUSE] P35492 Histidine ammonialyase OS=Mus musculus GN=Hal PE=1 SV=1 91.16 16.89 2 11 0.69 0.0002 [HUTH_MOUSE] P23589 Carbonic anhydrase 5A, mitochondrial OS=Mus musculus GN=Ca5a 58.73 12.04 1 3 0.69 0.0002 PE=1 SV=2 [CAH5A_MOUSE] Q8C196 Carbamoylphosphate synthase [ammonia], mitochondrial OS=Mus 3557.58 58 1 100 0.67 0.0000 musculus GN=Cps1 PE=1 SV=2 [CPSM_MOUSE]

Q8R570 Synaptosomalassociated protein 47 OS=Mus musculus GN=Snap47 0.00 7.26 1 2 0.66 0.0081 PE=1 SV=1 [SNP47_MOUSE] P49429 4hydroxyphenylpyruvate dioxygenase OS=Mus musculus GN=Hpd 225.87 41.22 1 15 0.66 0.0000 PE=1 SV=3 [HPPD_MOUSE] A2AJL3 FGGY carbohydrate kinase domaincontaining protein OS=Mus musculus 40.45 2.17 1 1 0.66 0.0158 GN=Fggy PE=2 SV=1 [FGGY_MOUSE] O35490 Betainehomocysteine Smethyltransferase 1 OS=Mus musculus 464.47 56.51 3 21 0.66 0.0003 GN=Bhmt PE=2 SV=1 [BHMT1_MOUSE] Q91WD5 NADH dehydrogenase [ubiquinone] ironsulfur protein 2, mitochondrial 108.23 26.13 1 9 0.66 0.0002 OS=Mus musculus GN=Ndufs2 PE=1 SV=1 [NDUS2_MOUSE] Q8K0E8 Fibrinogen beta chain OS=Mus musculus GN=Fgb PE=2 SV=1 50.84 16.84 2 7 0.65 0.0010 [FIBB_MOUSE] Q9ET01 Glycogen phosphorylase, liver form OS=Mus musculus GN=Pygl PE=1 308.53 34.12 1 26 0.65 0.0000 SV=4 [PYGL_MOUSE] Q8VBW8 Tetratricopeptide repeat protein 36 OS=Mus musculus GN=Ttc36 PE=2 107.19 26.88 1 4 0.65 0.0006 SV=1 [TTC36_MOUSE] P24472 Glutathione Stransferase A4 OS=Mus musculus GN=Gsta4 PE=1 SV=3 32.37 22.97 1 5 0.65 0.0000 [GSTA4_MOUSE] Q78JT3 3hydroxyanthranilate 3,4dioxygenase OS=Mus musculus GN=Haao 174.17 53.15 1 16 0.65 0.0000 PE=1 SV=1 [3HAO_MOUSE] P40936 Indolethylamine Nmethyltransferase OS=Mus musculus GN=Inmt PE=2 27.00 12.5 1 5 0.64 0.0002 SV=1 [INMT_MOUSE] P29758 Ornithine aminotransferase, mitochondrial OS=Mus musculus GN=Oat 222.34 38.04 1 16 0.64 0.0092 PE=1 SV=1 [OAT_MOUSE] Q64442 Sorbitol dehydrogenase OS=Mus musculus GN=Sord PE=1 SV=3 175.55 39.5 1 13 0.64 0.0001 [DHSO_MOUSE]

P22315 Ferrochelatase, mitochondrial OS=Mus musculus GN=Fech PE=1 SV=2 115.38 31.67 1 10 0.64 0.0008 [HEMH_MOUSE] Q921S7 39S ribosomal protein L37, mitochondrial OS=Mus musculus 0.00 2.13 1 1 0.64 0.0101 GN=Mrpl37 PE=2 SV=1 [RM37_MOUSE] Q9CPU0 Lactoylglutathione lyase OS=Mus musculus GN=Glo1 PE=1 SV=3 98.76 38.59 1 8 0.64 0.0001 [LGUL_MOUSE] Q9DBG1 Sterol 26hydroxylase, mitochondrial OS=Mus musculus GN=Cyp27a1 54.53 12.57 1 7 0.64 0.0009 PE=1 SV=1 [CP27A_MOUSE] P01902 H2 class I histocompatibility antigen, KD alpha chain OS=Mus 80.74 20.92 2 5 0.64 0.0149 musculus GN=H2K1 PE=1 SV=1 [HA1D_MOUSE] Q8VC30 Bifunctional ATPdependent dihydroxyacetone kinase/FADAMP lyase 389.80 39.97 1 20 0.64 0.0000 (cyclizing) OS=Mus musculus GN=Dak PE=2 SV=1 [DHAK_MOUSE] P52503 NADH dehydrogenase [ubiquinone] ironsulfur protein 6, mitochondrial 69.45 43.97 1 4 0.63 0.0000 OS=Mus musculus GN=Ndufs6 PE=1 SV=2 [NDUS6_MOUSE] Q9WU19 Hydroxyacid oxidase 1 OS=Mus musculus GN=Hao1 PE=2 SV=1 99.90 34.32 1 12 0.63 0.0005 [HAOX1_MOUSE] P70441 Na(+)/H(+) exchange regulatory cofactor NHERF1 OS=Mus musculus 43.41 12.11 1 4 0.63 0.0002 GN=Slc9a3r1 PE=1 SV=3 [NHRF1_MOUSE] P16331 Phenylalanine4hydroxylase OS=Mus musculus GN=Pah PE=1 SV=4 45.08 28.92 1 14 0.63 0.0011 [PH4H_MOUSE] P56657 Cytochrome P450 2C40 OS=Mus musculus GN=Cyp2c40 PE=2 SV=2 42.93 6.72 1 3 0.62 0.0003 [CP240_MOUSE] Q9QWG7 Sulfotransferase family cytosolic 1B member 1 OS=Mus musculus 46.34 13.38 1 3 0.62 0.0000 GN=Sult1b1 PE=2 SV=2 [ST1B1_MOUSE] Q8BUK6 Protein Hook homolog 3 OS=Mus musculus GN=Hook3 PE=1 SV=2 26.40 1.25 1 1 0.61 0.0028 [HOOK3_MOUSE]

P46656 Adrenodoxin, mitochondrial OS=Mus musculus GN=Fdx1 PE=2 SV=1 23.84 15.96 1 5 0.61 0.0000 [ADX_MOUSE] O35969 Guanidinoacetate Nmethyltransferase OS=Mus musculus GN=Gamt 28.15 16.1 1 2 0.60 0.0010 PE=1 SV=1 [GAMT_MOUSE] Q8VCM7 Fibrinogen gamma chain OS=Mus musculus GN=Fgg PE=2 SV=1 23.78 11.24 1 6 0.60 0.0084 [FIBG_MOUSE] Q8R0Y6 Cytosolic 10formyltetrahydrofolate dehydrogenase OS=Mus musculus 393.11 44.46 2 35 0.60 0.0000 GN=Aldh1l1 PE=2 SV=1 [AL1L1_MOUSE] Q8BGE6 Cysteine protease ATG4B OS=Mus musculus GN=Atg4b PE=1 SV=2 0.00 4.07 1 1 0.59 0.0002 [ATG4B_MOUSE] Q6XVG2 Cytochrome P450 2C54 OS=Mus musculus GN=Cyp2c54 PE=2 SV=1 48.63 12.86 1 1 0.58 0.0262 [CP254_MOUSE] Q9QYY9 Alcohol dehydrogenase 4 OS=Mus musculus GN=Adh4 PE=1 SV=4 25.45 9.81 1 3 0.58 0.0060 [ADH4_MOUSE] P28063 Proteasome subunit beta type8 OS=Mus musculus GN=Psmb8 PE=1 31.54 4.35 1 1 0.57 0.0005 SV=2 [PSB8_MOUSE] P07759 Serine protease inhibitor A3K OS=Mus musculus GN=Serpina3k PE=1 230.58 33.73 4 11 0.57 0.0006 SV=2 [SPA3K_MOUSE] Q61694 3 betahydroxysteroid dehydrogenase type 5 OS=Mus musculus 53.23 11.26 1 4 0.55 0.0274 GN=Hsd3b5 PE=1 SV=4 [3BHS5_MOUSE] P58710 Lgulonolactone oxidase OS=Mus musculus GN=Gulo PE=1 SV=3 48.38 9.32 1 5 0.55 0.0016 [GGLO_MOUSE] Q8VCU1 Liver carboxylesterase 31like OS=Mus musculus GN=Gm4738 PE=2 201.68 17.78 1 3 0.54 0.0011 SV=1 [ES31L_MOUSE] P04939 Major urinary protein 3 OS=Mus musculus GN=Mup3 PE=1 SV=1 27.08 5.98 1 1 0.54 0.0005 [MUP3_MOUSE]

P97328 Ketohexokinase OS=Mus musculus GN=Khk PE=1 SV=1 74.78 15.44 1 5 0.52 0.0000 [KHK_MOUSE] Q9D0J8 Parathymosin OS=Mus musculus GN=Ptms PE=2 SV=3 82.18 22.77 1 2 0.52 0.0000 [PTMS_MOUSE] Q8BM72 Heat shock 70 kDa protein 13 OS=Mus musculus GN=Hspa13 PE=2 0.00 2.12 1 1 0.52 0.0047 SV=1 [HSP13_MOUSE] P70694 Estradiol 17 betadehydrogenase 5 OS=Mus musculus GN=Akr1c6 PE=1 167.32 46.75 1 12 0.51 0.0000 SV=1 [DHB5_MOUSE] Q9JJL3 Solute carrier organic anion transporter family member 1B2 OS=Mus 0.00 2.32 1 1 0.47 0.0016 musculus GN=Slco1b2 PE=1 SV=1 [SO1B2_MOUSE] P52840 Sulfotransferase 1A1 OS=Mus musculus GN=Sult1a1 PE=2 SV=1 0.00 8.93 1 3 0.46 0.0002 [ST1A1_MOUSE] Q9EP75 LeukotrieneB4 omegahydroxylase 3 OS=Mus musculus GN=Cyp4f14 27.40 4.58 2 2 0.44 0.0139 PE=2 SV=1 [CP4FE_MOUSE] P16015 Carbonic anhydrase 3 OS=Mus musculus GN=Ca3 PE=1 SV=3 676.68 64.23 1 15 0.39 0.0000 [CAH3_MOUSE] Q91WR5 Aldoketo reductase family 1 member C21 OS=Mus musculus 0.00 11.76 1 1 0.32 0.0003 GN=Akr1c21 PE=1 SV=2 [AK1CL_MOUSE] P11589 Major urinary protein 2 OS=Mus musculus GN=Mup2 PE=1 SV=1 100.44 51.67 3 1 0.29 0.0116 [MUP2_MOUSE] When the ratio of a protein between treatment and the control was ≥ 1.2 or ≤ 0.83 (and P < 0.05) in both of the duplicated experiments, the protein was considered to be altered significantly. All the MS data are from one representative result of the duplicated experiments.

Supplementary Table S6. Potential regulation of altered proteins by altered miRNAs in 5 mg/kg/d PFNA treatment group.

miRNA geneName targetScanSites picTarSites RNA22Sites PITASites miRandaSites miR107 Cox7a2 0a[0 b,0 c] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR107 Cpne3 1[1,1] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR107 Snap47 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,6] miR130a Bsg 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR130a Mlec 0[0,0] 1[1,3] 0[0,0] 0[0,0] 0[0,0] miR1423p Acsl4 1[1,1] 2[1,2] 1[1,1] 1[1,1] 1[1,1] miR1423p Atp2a2 1[2,9] 1[2,9] 0[0,0] 1[2,9] 1[2,9] miR1423p Crot 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR1423p Dcakd 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR1423p Fubp1 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR1423p Klhdc10 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR1423p Pgrmc1 0[0,0] 0[0,0] 1[1,1] 0[0,0] 1[1,1] miR1423p Rheb 1[1,1] 1[1,1] 0[0,0] 1[1,1] 1[1,1] miR144 Acsl4 1[1,1] 3[1,3] 0[0,0] 1[1,1] 1[1,1] miR144 Arhgdia 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,48] miR144 Fubp1 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR144 Hspa9 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,5] miR144 Rtn4 0[0,0] 2[2,21] 0[0,0] 0[0,0] 1[1,8] miR152 Csnk1a1 0[0,0] 0[0,0] 0[0,0] 0[0,0] 2[1,1] miR152 Dynll2 1[3,14] 2[4,15] 0[0,0] 1[3,14] 0[0,0] miR152 Eif4h 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR152 Pdia3 1[2,13] 1[2,13] 0[0,0] 1[2,13] 1[2,13] miR152 Ssr1 1[1,1] 1[1,1] 0[0,0] 1[1,1] 1[1,1] miR185 Ptms 0[0,0] 2[2,4] 0[0,0] 1[2,4] 1[2,4] miR18a Eif4h 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR18a Ndufs4 0[0,0] 0[0,0] 0[0,0] 0[0,0] 2[1,1] miR193 Bsg 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[2,11] miR200a Crot 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR200a Psat1 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR203 Crot 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR203 Fubp1 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR203 Nceh1 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[2,16] miR203 Pgrmc1 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,13] miR203 Rheb 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,2] miR203 Rpl4 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[2,9] miR203 Rtn4 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,8] miR3383p Fubp1 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,6] miR3383p Rtn4 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[3,30] miR3383p Sars 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR3423p Acsl4 0[0,0] 0[0,0] 0[0,0] 1[1,1] 1[1,1]

miR3423p Fubp1 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR34a Ptms 0[0,0] 1[2,4] 0[0,0] 0[0,0] 0[0,0] miR34a Qdpr 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,5] miR378* Ndufs4 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR93 Inpp1 0[0,0] 0[0,0] 0[0,0] 0[0,0] 1[1,1] miR96 Hook3 0[0,0] 1[1,1] 0[0,0] 0[0,0] 0[0,0] miR96 Hspa13 1[1,9] 2[1,11] 0[0,0] 0[0,0] 0[0,0] a: Target numbers; b: ClipSeq peakcluster numbers; c: Clipseq ReadNum.

A B 200 Ctrl 200 175 0.2 mg/kg/d Ctrl 175 0.2 mg/kg/d 1 mg/kg/d

g/ml) g/gww) 150 1 mg/kg/d

µ 150 µ 5 mg/kg/d 5 mg/kg/d 125 125 100 100 75 75 50 50 25 25

0.2 concentrationPFNA ( 0.2 PFNA concentration ( 0.0 0.0 Liver Serum

Supplementary Fig. S1

A 3.0 B 5 2.5 4 2.0 3 1.5 2 1.0 0.5 1

-Log10(p value) -Log10(pvalue) 0.0 0 -3 -2 -1 0 1 2 3 4 -3-2-1 0 1 2 3 4 5 Log2(1 mg/kg/d/Ctrl) miRNA expression Log2(5 mg/kg/d/Ctrl) miRNA expression

Supplementary Fig. S2

A mRNA-34a 3’-UGUUGGUCGAUUCUGUGACGGU-5’ Mmu 5’-ACAGUCCCACUGUCUC-UGAGACA-CACUGCCAAC----UGCAGGCU-3’ Rno 5’-ACAAUCCCACUGUCUC-CAAGACA-CACUGCCAACUGCAUGCAGGCU-3’ Hsa 5’-AUAGUUCUGCCACCUC-UGACGCACCACUGCCAAUGCUGUACGUACU-3’

B mRNA-34a 3’-UGUUGGUCGAUUCUGUGACGGU-5’ Mmu 5’-CUUUAAAUAUUAUGUCCCCAUUGAACAAACACUGCCACAUUGUGUAA-3’ Rno 5’-CUUUAAAUAUUAUGUCCCCAUUAAACAAACACUGCCACGUUGUGUAA-3’ Hsa 5’-CUUUCAGUAU---GUCCCCAUAAGACAAACACUGCCAUAUUGUGUAA-3’

Supplementary Fig. S3