Ser18

Site Information
KAGEQQLsEPEDMEM SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 449238

In vivo Characterization
Methods used to characterize site in vivo:	[32P] ATP in vitro ( 22 ) , immunoassay ( 22 ) , immunoprecipitation ( 1 , 22 ) , mass spectrometry ( 2 , 3 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ) , mutation of modification site ( 22 ) , phospho-antibody ( 1 , 22 ) , western blotting ( 1 , 22 )
Disease tissue studied:	bone cancer ( 22 , 37 ) , osteosarcoma ( 37 ) , breast cancer ( 6 , 11 , 12 ) , breast ductal carcinoma ( 11 ) , HER2 positive breast cancer ( 3 ) , luminal A breast cancer ( 3 ) , luminal B breast cancer ( 3 ) , breast cancer, surrounding tissue ( 3 ) , breast cancer, triple negative ( 3 , 11 ) , cervical cancer ( 39 ) , cervical adenocarcinoma ( 39 ) , colorectal cancer ( 22 ) , colorectal carcinoma ( 22 ) , leukemia ( 1 , 23 , 48 ) , acute myelogenous leukemia ( 23 ) , chronic lymphocytic leukemia ( 1 ) , chronic myelogenous leukemia ( 48 ) , hepatocellular carcinoma, surrounding tissue ( 36 ) , lung cancer ( 9 , 15 , 29 , 46 ) , non-small cell lung cancer ( 46 ) , non-small cell lung adenocarcinoma ( 9 , 15 , 29 ) , lymphoma ( 13 ) , Burkitt's lymphoma ( 13 ) , follicular lymphoma ( 13 ) , mantle cell lymphoma ( 13 ) , ovarian cancer ( 11 ) , multiple myeloma ( 35 ) , prostate cancer ( 38 ) , melanoma skin cancer ( 8 )
Relevant cell line - cell type - tissue:	'muscle, skeletal' ( 24 ) , 293 (epithelial) [ADRB1 (human), no information, overexpresses human beta1-adrenergic (ß1AR- HEK293)] ( 49 ) , 293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] ( 33 ) , 293 (epithelial) ( 42 ) , 786-O (renal) [VHL (human), transfection] ( 7 ) , 786-O (renal) ( 7 ) , A498 (renal) ( 34 ) , B lymphocyte-blood ( 35 ) , BJAB (B lymphocyte) ( 13 ) , breast ( 3 , 11 ) , BT-474 (breast cell) ( 6 ) , DG75 (B lymphocyte) ( 32 ) , endothelial-aorta ( 18 ) , FL-18 (B lymphocyte) ( 13 ) , FL-318 (B lymphocyte) ( 13 ) , Flp-In T-Rex-293 (epithelial) [PRKD1 (human), genetic knockin] ( 20 ) , Flp-In T-Rex-293 (epithelial) ( 20 ) , HCT116 (intestinal) ( 22 ) , HeLa (cervical) ( 2 , 10 , 17 , 22 , 31 , 47 , 49 , 50 , 51 ) , HeLa S3 (cervical) ( 39 ) , hepatocyte-liver ( 36 ) , HMLER ('stem, breast cancer') [CXCR4 (human), knockdown] ( 12 ) , HMLER ('stem, breast cancer') ( 12 ) , HUES-7 ('stem, embryonic') ( 41 ) , HUES-9 ('stem, embryonic') ( 30 ) , Jurkat (T lymphocyte) ( 16 , 25 , 26 , 27 , 28 , 45 ) , K562 (erythroid) ( 17 , 40 , 48 ) , KG-1 (myeloid) ( 23 ) , leukocyte-blood ( 37 ) , liver ( 14 ) , LNCaP (prostate cell) ( 38 ) , lung ( 15 ) , MCF-7 (breast cell) ( 5 , 6 ) , MEC1 (B lymphocyte) ( 1 ) , NCEB-1 (B lymphocyte) ( 13 ) , NCI-H1299 (pulmonary) ( 46 ) , NCI-H460 (pulmonary) ( 43 ) , OCI-ly1 (B lymphocyte) ( 13 ) , ovary ( 11 ) , PC9 (pulmonary) ( 9 ) , RAMOS (B lymphocyte) ( 13 ) , REC-1 (B lymphocyte) ( 13 ) , SU-DHL-4 (B lymphocyte) ( 13 ) , T lymphocyte-blood ( 19 ) , TIG-1 (fibroblast) ( 22 ) , U-1810 (pulmonary) [EFNB3 (human), knockdown] ( 29 ) , U-1810 (pulmonary) ( 29 ) , U2OS (bone cell) ( 22 , 37 ) , UPN-1 (B lymphocyte) ( 13 ) , WM115 (melanocyte) ( 44 ) , WM239A (melanocyte) ( 8 )

Upstream Regulation
Regulatory protein:	ATM (human) ( 22 )
Putative in vivo kinases:	CK2A1 (human) ( 1 , 22 )
Kinases, in vitro:	CK2A1 (human) ( 1 , 22 )
Putative upstream phosphatases:	PPM1G (human) ( 22 )
Phosphatases, in vitro:	PPM1G (human) ( 22 )
Treatments:	antibody ( 19 ) , ionizing_radiation ( 22 ) , siRNA ( 22 )

Downstream Regulation
Effects of modification on USP7:	enzymatic activity, induced ( 1 ) , protein stabilization ( 22 )
Effects of modification on biological processes:	cell cycle regulation ( 22 ) , DNA repair, inhibited ( 22 ) , signaling pathway regulation ( 22 )

Disease / Diagnostics Relevance
Relevant diseases:	chronic lymphocytic leukemia ( 1 )

References
1	Carrà G, et al. (2017) Therapeutic inhibition of USP7-PTEN network in chronic lymphocytic leukemia: a strategy to overcome TP53 mutated/deleted clones. Oncotarget 8, 35508-35522 28418900 Curated Info
2	Huang H, et al. (2016) Simultaneous Enrichment of Cysteine-containing Peptides and Phosphopeptides Using a Cysteine-specific Phosphonate Adaptable Tag (CysPAT) in Combination with titanium dioxide (TiO2) Chromatography. Mol Cell Proteomics 15, 3282-3296 27281782 Curated Info
3	Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62 27251275 Curated Info
4	Boeing S, et al. (2016) Multiomic Analysis of the UV-Induced DNA Damage Response. Cell Rep 15, 1597-1610 27184836 Curated Info
5	Sacco F, et al. (2016) Deep Proteomics of Breast Cancer Cells Reveals that Metformin Rewires Signaling Networks Away from a Pro-growth State. Cell Syst 2, 159-71 27135362 Curated Info
6	Carrier M, et al. (2016) Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines. PLoS One 11, e0157290 27362937 Curated Info
7	Malec V, Coulson JM, Urbé S, Clague MJ (2015) Combined Analyses of the VHL and Hypoxia Signaling Axes in an Isogenic Pairing of Renal Clear Cell Carcinoma Cells. J Proteome Res 14, 5263-72 26506913 Curated Info
8	Stuart SA, et al. (2015) A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma Cells. Mol Cell Proteomics 14, 1599-615 25850435 Curated Info
9	Tsai CF, et al. (2015) Large-scale determination of absolute phosphorylation stoichiometries in human cells by motif-targeting quantitative proteomics. Nat Commun 6, 6622 25814448 Curated Info
10	Sharma K, et al. (2014) Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. Cell Rep 8, 1583-94 25159151 Curated Info
11	Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704 24719451 Curated Info
12	Yi T, et al. (2014) Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells. Proc Natl Acad Sci U S A 111, E2182-90 24782546 Curated Info
13	Rolland D, et al. (2014) Global phosphoproteomic profiling reveals distinct signatures in B-cell non-Hodgkin lymphomas. Am J Pathol 184, 1331-42 24667141 Curated Info
14	Bian Y, et al. (2014) An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics 96, 253-62 24275569 Curated Info
15	Schweppe DK, Rigas JR, Gerber SA (2013) Quantitative phosphoproteomic profiling of human non-small cell lung cancer tumors. J Proteomics 91, 286-96 23911959 Curated Info
16	Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7 23749302 Curated Info
17	Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71 23186163 Curated Info
18	Verano-Braga T, et al. (2012) Time-resolved quantitative phosphoproteomics: new insights into Angiotensin-(1-7) signaling networks in human endothelial cells. J Proteome Res 11, 3370-81 22497526 Curated Info
19	Ruperez P, Gago-Martinez A, Burlingame AL, Oses-Prieto JA (2012) Quantitative phosphoproteomic analysis reveals a role for serine and threonine kinases in the cytoskeletal reorganization in early T cell receptor activation in human primary T cells. Mol Cell Proteomics 11, 171-86 22499768 Curated Info
20	Franz-Wachtel M, et al. (2012) Global detection of protein kinase D-dependent phosphorylation events in nocodazole-treated human cells. Mol Cell Proteomics 11, 160-70 22496350 Curated Info
21	Beli P, et al. (2012) Proteomic Investigations Reveal a Role for RNA Processing Factor THRAP3 in the DNA Damage Response. Mol Cell 46, 212-25 22424773 Curated Info
22	Khoronenkova SV, et al. (2012) ATM-dependent downregulation of USP7/HAUSP by PPM1G activates p53 response to DNA damage. Mol Cell 45, 801-13 22361354 Curated Info
23	Weber C, Schreiber TB, Daub H (2012) Dual phosphoproteomics and chemical proteomics analysis of erlotinib and gefitinib interference in acute myeloid leukemia cells. J Proteomics 75, 1343-56 22115753 Curated Info
24	Lundby A, et al. (2012) Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun 3, 876 22673903 Curated Info
25	Mulhern D (2011) CST Curation Set: 12709; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]XP Curated Info
26	Mulhern D (2011) CST Curation Set: 12710; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]XP Curated Info
27	Mulhern D (2011) CST Curation Set: 12712; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]XP Curated Info
28	Guo A (2011) CST Curation Set: 11985; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]XP Curated Info
29	Ståhl S, et al. (2011) Phosphoproteomic profiling of NSCLC cells reveals that ephrin B3 regulates pro-survival signaling through Akt1-mediated phosphorylation of the EphA2 receptor. J Proteome Res 10, 2566-78 21413766 Curated Info
30	Rigbolt KT, et al. (2011) System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal 4, rs3 21406692 Curated Info
31	Kettenbach AN, et al. (2011) Quantitative phosphoproteomics identifies substrates and functional modules of aurora and polo-like kinase activities in mitotic cells. Sci Signal 4, rs5 21712546 Curated Info
32	Iliuk AB, et al. (2010) In-depth analyses of kinase-dependent tyrosine phosphoproteomes based on metal ion-functionalized soluble nanopolymers. Mol Cell Proteomics 9, 2162-72 20562096 Curated Info
33	Christensen GL, et al. (2010) Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists. Mol Cell Proteomics 9, 1540-53 20363803 Curated Info
34	Schreiber TB, et al. (2010) An integrated phosphoproteomics work flow reveals extensive network regulation in early lysophosphatidic acid signaling. Mol Cell Proteomics 9, 1047-62 20071362 Curated Info
35	Ge F, et al. (2010) Phosphoproteomic analysis of primary human multiple myeloma cells. J Proteomics 73, 1381-90 20230923 Curated Info
36	Han G, et al. (2010) Phosphoproteome analysis of human liver tissue by long-gradient nanoflow LC coupled with multiple stage MS analysis. Electrophoresis 31, 1080-9 20166139 Curated Info
37	Raijmakers R, et al. (2010) Exploring the human leukocyte phosphoproteome using a microfluidic reversed-phase-TiO2-reversed-phase high-performance liquid chromatography phosphochip coupled to a quadrupole time-of-flight mass spectrometer. Anal Chem 82, 824-32 20058876 Curated Info
38	Chen L, Giorgianni F, Beranova-Giorgianni S (2010) Characterization of the phosphoproteome in LNCaP prostate cancer cells by in-gel isoelectric focusing and tandem mass spectrometry. J Proteome Res 9, 174-8 20044836 Curated Info
39	Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3 20068231 Curated Info
40	Pan C, Olsen JV, Daub H, Mann M (2009) Global effects of kinase inhibitors on signaling networks revealed by quantitative phosphoproteomics. Mol Cell Proteomics 8, 2796-808 19651622 Curated Info
41	Van Hoof D, et al. (2009) Phosphorylation dynamics during early differentiation of human embryonic stem cells. Cell Stem Cell 5, 214-26 19664995 Curated Info
42	Gauci S, et al. (2009) Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem 81, 4493-501 19413330 Curated Info
43	Nagano K, et al. (2009) Phosphoproteomic analysis of distinct tumor cell lines in response to nocodazole treatment. Proteomics 9, 2861-74 19415658 Curated Info
44	Old WM, et al. (2009) Functional proteomics identifies targets of phosphorylation by B-Raf signaling in melanoma. Mol Cell 34, 115-31 19362540 Curated Info
45	Mayya V, et al. (2009) Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal 2, ra46 19690332 Curated Info
46	Tsai CF, et al. (2008) Immobilized metal affinity chromatography revisited: pH/acid control toward high selectivity in phosphoproteomics. J Proteome Res 7, 4058-69 18707149 Curated Info
47	Dephoure N, et al. (2008) A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A 105, 10762-7 18669648 Curated Info
48	Stokes M (2008) CST Curation Set: 4389; Year: 2008; Biosample/Treatment: cell line, K562/untreated; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]) Curated Info
49	Ruse CI, et al. (2008) Motif-specific sampling of phosphoproteomes. J Proteome Res 7, 2140-50 18452278 Curated Info
50	Fernández-Montalván A, et al. (2007) Biochemical characterization of USP7 reveals post-translational modification sites and structural requirements for substrate processing and subcellular localization. FEBS J 274, 4256-70 17651432 Curated Info
51	Beausoleil SA, et al. (2004) Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A 101, 12130-5 15302935 Curated Info