Figure S1. Quality Control Validation of MS Data. (A‑C) Mass Error Distribution of All Peptides Identified in the Acetylome

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Figure S1. Quality Control Validation of MS Data. (A‑C) Mass Error Distribution of All Peptides Identified in the Acetylome Figure S1. Quality control validation of MS data. (A‑C) Mass error distribution of all peptides identified in the acetylome, succi- nylome and quantitative proteome, respectively. (D‑F) Length distribution of peptides identified in the acetylome, succinylome and quantitative proteome, respectively. Figure S2. Comparison of modification level between breast cancer tissue and normal tissue. Comparison of acetylation level (A) and succinylation level (B) between breast cancer tissue and normal tissue. Data are medians and were analyzed using Wilcoxon Signed Rank Test. **P<0.01. Table SI. Protein sites whose acetylation and succinylation levels were both significantly upregulated in breast cancer tissues (fold change ≥1.5 compared with normal tissues). Protein ID Protein name Modification site P54868 HMCS2 310K Q15063 POSTN 549K Q99715 COCA1 1601K P51572 BAP31 72K P07237 PDLA1 328K Q06830 PRDX1 192K P48735 IDHP 180K P30101 PDIA3 417K P0DMV9 HS71B 526K Q01995 TAGL 21K P06748 NPM1 27K Q00325 MPCP 209K P00488 F13A 69K P02545 LMNA 260K P08133 ANXA6 478K P02452 CO1A1 751K Table SII. Protein sites whose acetylation and succinylation levels were both significantly downregulated in breast cancer tissues (fold change ≥1.5 compared with normal tissues). Protein ID Protein name Modification site RET4 P02753 30K PSG2 P07585 142K HBA P69905 12K IGKC P01834 80K HBA P69905 8K Table SIII. All proteins whose expression level were significantly upregulated in breast cancer tissues (fold change ≥1.5 compared with normal tissues). Protein ID Protein description Ratio (cancer vs. normal) P‑value P29762 Cellular retinoic acid‑binding protein 1 OS=Homo sapiens GN=CRABP1 PE=2 SV=2 4.5485 0.005237 P05787 Keratin, type II cytoskeletal 8 OS=Homo sapiens GN=KRT8 PE=1 SV=7 3.3785 3.49E‑13 Q01105 Protein SET OS=Homo sapiens GN=SET PE=1 SV=3 2.846 0.000294 Q9NZJ9 Diphosphoinositol polyphosphate phosphohydrolase 2 OS=Homo sapiens GN=NUDT4 PE=1 SV=2 2.814 0.002214 P40121 Macrophage-capping protein OS=Homo sapiens GN=CAPG PE=1 SV=2 2.808 0.0001 Q8WX93 Palladin OS=Homo sapiens GN=PALLD PE=1 SV=3 2.7565 5.55E-06 Q9UQP3 Tenascin-N OS=Homo sapiens GN=TNN PE=1 SV=2 2.724 0.00859 P15924 Desmoplakin OS=Homo sapiens GN=DSP PE=1 SV=3 2.7135 3.49E-14 Q13153 Serine/threonine‑protein kinase PAK 1 OS=Homo sapiens GN=PAK1 PE=1 SV=2 2.713 0.003549 P23528 Cofilin‑1 OS=Homo sapiens GN=CFL1 PE=1 SV=3 2.702 1.4E‑08 Q12874 Splicing factor 3A subunit 3 OS=Homo sapiens GN=SF3A3 PE=1 SV=1 2.699 0.009968 Q15063 Periostin OS=Homo sapiens GN=POSTN PE=1 SV=2 2.6945 1.37E‑12 Q13185 Chromobox protein homolog 3 OS=Homo sapiens GN=CBX3 PE=1 SV=4 2.6695 0.00138 Q8TF66 Leucine‑rich repeat‑containing protein 15 OS=Homo sapiens GN=LRRC15 PE=1 SV=2 2.661 0.002947 Q6P996 Pyridoxal‑dependent decarboxylase domain‑containing protein 1 OS=Homo sapiens GN=PDXDC1 PE=1 SV=2 2.635 1.09E‑05 P35442 Thrombospondin‑2 OS=Homo sapiens GN=THBS2 PE=1 SV=2 2.621 7.37E‑05 P13611 Versican core protein OS=Homo sapiens GN=VCAN PE=1 SV=3 2.617 4.99E‑06 Q00688 Peptidyl‑prolyl cis‑trans isomerase FKBP3 OS=Homo sapiens GN=FKBP3 PE=1 SV=1 2.529 0.006514 P08727 Keratin, type I cytoskeletal 19 OS=Homo sapiens GN=KRT19 PE=1 SV=4 2.493 1.01E‑10 Q02790 Peptidyl‑prolyl cis‑trans isomerase FKBP4 OS=Homo sapiens GN=FKBP4 PE=1 SV=3 2.465 8.29E‑05 P22626 Heterogeneous nuclear ribonucleoproteins A2/B1 OS=Homo sapiens GN=HNRNPA2B1 PE=1 SV=2 2.459 2.66E‑07 Q05682 Caldesmon OS=Homo sapiens GN=CALD1 PE=1 SV=3 2.4345 2.5E‑06 Q9P258 Protein RCC2 OS=Homo sapiens GN=RCC2 PE=1 SV=2 2.4015 0.009156 P30520 Adenylosuccinate synthetase isozyme 2 OS=Homo sapiens GN=ADSS PE=1 SV=3 2.391 0.003515 Q5SSJ5 Heterochromatin protein 1‑binding protein 3 OS=Homo sapiens GN=HP1BP3 PE=1 SV=1 2.375 0.001099 P05783 Keratin, type I cytoskeletal 18 OS=Homo sapiens GN=KRT18 PE=1 SV=2 2.3525 1.38E‑08 P21266 Glutathione S‑transferase Mu 3 OS=Homo sapiens GN=GSTM3 PE=1 SV=3 2.348 2.27E‑05 Q6EEV6 Small ubiquitin‑related modifier 4 OS=Homo sapiens GN=SUMO4 PE=1 SV=2 2.311 0.008154 P10253 Lysosomal alpha‑glucosidase OS=Homo sapiens GN=GAA PE=1 SV=4 2.2855 0.001327 P17844 Probable ATP‑dependent RNA helicase DDX5 OS=Homo sapiens GN=DDX5 PE=1 SV=1 2.249 0.000284 P50454 Serpin H1 OS=Homo sapiens GN=SERPINH1 PE=1 SV=2 2.211 6.02E‑06 P23193 Transcription elongation factor A protein 1 OS=Homo sapiens GN=TCEA1 PE=1 SV=2 2.203 0.004442 P39748 Flap endonuclease 1 OS=Homo sapiens GN=FEN1 PE=1 SV=1 2.197 0.005466 Q8TE77 Protein phosphatase Slingshot homolog 3 OS=Homo sapiens GN=SSH3 PE=1 SV=2 2.185 0.0028 P0CW22 40S ribosomal protein S17‑like OS=Homo sapiens GN=RPS17L PE=1 SV=1 2.171 0.007463 Q92544 Transmembrane 9 superfamily member 4 OS=Homo sapiens GN=TM9SF4 PE=1 SV=2 2.17 0.003809 P10155 60 kDa SS‑A/Ro ribonucleoprotein OS=Homo sapiens GN=TROVE2 PE=1 SV=2 2.168 0.000968 P63208 S‑phase kinase‑associated protein 1 OS=Homo sapiens GN=SKP1 PE=1 SV=2 2.165 0.000695 Table SIII. Continued. Protein ID Protein description Ratio (cancer vs. normal) P‑value Q8IV36 Protein HID1 OS=Homo sapiens GN=HID1 PE=1 SV=1 2.1405 0.002398 Q9Y266 Nuclear migration protein nudC OS=Homo sapiens GN=NUDC PE=1 SV=1 2.124 3.41E‑06 P62753 40S ribosomal protein S6 OS=Homo sapiens GN=RPS6 PE=1 SV=1 2.113 0.004002 P15170 Eukaryotic peptide chain release factor GTP‑binding subunit ERF3A OS=Homo sapiens GN=GSPT1 PE=1 SV=1 2.109 0.006605 Q13148 TAR DNA‑binding protein 43 OS=Homo sapiens GN=TARDBP PE=1 SV=1 2.092 5.22E‑05 Q9Y2X3 Nucleolar protein 58 OS=Homo sapiens GN=NOP58 PE=1 SV=1 2.087 0.005814 Q99715 Collagen alpha‑1(XII) chain OS=Homo sapiens GN=COL12A1 PE=1 SV=2 2.084 1.36E‑11 Q9UGI8 Testin OS=Homo sapiens GN=TES PE=1 SV=1 2.08 0.001602 O43390 Heterogeneous nuclear ribonucleoprotein R OS=Homo sapiens GN=HNRNPR PE=1 SV=1 2.069 5.72E‑05 P52272 Heterogeneous nuclear ribonucleoprotein M OS=Homo sapiens GN=HNRNPM PE=1 SV=3 2.066 8.9E‑08 P12830 Cadherin‑1 OS=Homo sapiens GN=CDH1 PE=1 SV=3 2.0585 1.43E‑05 P26373 60S ribosomal protein L13 OS=Homo sapiens GN=RPL13 PE=1 SV=4 2.047 0.006719 P08621 U1 small nuclear ribonucleoprotein 70 kDa OS=Homo sapiens GN=SNRNP70 PE=1 SV=2 2.045 0.000827 Q9UNE7 E3 ubiquitin‑protein ligase CHIP OS=Homo sapiens GN=STUB1 PE=1 SV=2 2.043 0.000282 P22234 Multifunctional protein ADE2 OS=Homo sapiens GN=PAICS PE=1 SV=3 2.04 0.005675 Q15233 Non‑POU domain‑containing octamer‑binding protein OS=Homo sapiens GN=NONO PE=1 SV=4 2.0385 1.4E‑08 P50851 Lipopolysaccharide‑responsive and beige‑like anchor protein OS=Homo sapiens GN=LRBA PE=1 SV=4 2.0365 0.000609 Q13765 Nascent polypeptide‑associated complex subunit alpha OS=Homo sapiens GN=NACA PE=1 SV=1 2.029 0.001067 Q08J23 tRNA (cytosine(34)‑C(5))‑methyltransferase OS=Homo sapiens GN=NSUN2 PE=1 SV=2 2.0205 0.008385 O75223 Gamma‑glutamylcyclotransferase OS=Homo sapiens GN=GGCT PE=1 SV=1 2.006 0.003327 P20700 Lamin‑B1 OS=Homo sapiens GN=LMNB1 PE=1 SV=2 1.982 6.8E‑05 P43487 Ran‑specific GTPase‑activating protein OS=Homo sapiens GN=RANBP1 PE=1 SV=1 1.9695 0.007456 P30050 60S ribosomal protein L12 OS=Homo sapiens GN=RPL12 PE=1 SV=1 1.961 0.000103 P08729 Keratin, type II cytoskeletal 7 OS=Homo sapiens GN=KRT7 PE=1 SV=5 1.96 3.5E‑08 P49585 Choline‑phosphate cytidylyltransferase A OS=Homo sapiens GN=PCYT1A PE=1 SV=2 1.949 0.009506 P15311 Ezrin OS=Homo sapiens GN=EZR PE=1 SV=4 1.937 0.000112 P19338 Nucleolin OS=Homo sapiens GN=NCL PE=1 SV=3 1.9285 4.89E‑05 Q9NR99 Matrix‑remodeling‑associated protein 5 OS=Homo sapiens GN=MXRA5 PE=2 SV=3 1.9275 0.004449 Q8IUX7 Adipocyte enhancer‑binding protein 1 OS=Homo sapiens GN=AEBP1 PE=1 SV=1 1.912 0.004188 Q15459 Splicing factor 3A subunit 1 OS=Homo sapiens GN=SF3A1 PE=1 SV=1 1.911 0.002117 P38919 Eukaryotic initiation factor 4A‑III OS=Homo sapiens GN=EIF4A3 PE=1 SV=4 1.91 0.008213 Q9UHB6 LIM domain and actin‑binding protein 1 OS=Homo sapiens GN=LIMA1 PE=1 SV=1 1.9085 0.001674 P47813 Eukaryotic translation initiation factor 1A, X‑chromosomal OS=Homo sapiens GN=EIF1AX PE=1 SV=2 1.9045 0.008956 Q9NR45 Sialic acid synthase OS=Homo sapiens GN=NANS PE=1 SV=2 1.9025 5.07E‑05 Q14103 Heterogeneous nuclear ribonucleoprotein D0 OS=Homo sapiens GN=HNRNPD PE=1 SV=1 1.893 0.002203 P49207 60S ribosomal protein L34 OS=Homo sapiens GN=RPL34 PE=1 SV=3 1.887 0.005138 Q32P51 Heterogeneous nuclear ribonucleoprotein A1‑like 2 OS=Homo sapiens GN=HNRNPA1L2 PE=2 SV=2 1.885 0.000146 P24821 Tenascin OS=Homo sapiens GN=TNC PE=1 SV=3 1.874 4.26E‑06 Table SIII.
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