Ser518

Site Information
LSASPRMsGFIYQGK SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 454356

In vivo Characterization
Methods used to characterize site in vivo:	mass spectrometry ( 1 , 2 , 4 , 5 , 6 , 7 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 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 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ) , mass spectrometry (in vitro) ( 8 ) , mutation of modification site ( 8 ) , western blotting ( 8 )
Disease tissue studied:	adrenal cancer ( 8 ) , pheochromocytoma ( 8 ) , bone cancer ( 44 ) , osteosarcoma ( 44 ) , breast cancer ( 9 , 10 , 21 , 22 ) , breast ductal carcinoma ( 9 ) , HER2 positive breast cancer ( 2 ) , luminal A breast cancer ( 2 ) , luminal B breast cancer ( 2 ) , breast cancer, surrounding tissue ( 2 ) , breast cancer, triple negative ( 2 , 9 ) , cervical cancer ( 46 ) , cervical adenocarcinoma ( 46 ) , leukemia ( 23 , 29 , 31 , 56 , 57 ) , acute myelogenous leukemia ( 23 , 29 ) , acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b) ( 20 , 23 ) , acute megakaryoblastic leukemia (M7) ( 20 ) , acute monoblastic leukemia (M5a) or acute monocytic leukemia (M5b) ( 20 ) , acute myeloblastic leukemia, with granulocytic maturation (M2) ( 20 ) , acute myeloblastic leukemia, without maturation (M1) ( 20 ) , chronic myelogenous leukemia ( 56 , 57 ) , T cell leukemia ( 31 ) , hepatocellular carcinoma, surrounding tissue ( 43 ) , lung cancer ( 6 , 22 , 34 , 39 ) , non-small cell lung cancer ( 22 ) , non-small cell lung adenocarcinoma ( 6 , 34 ) , lymphoma ( 11 ) , B cell lymphoma ( 20 ) , Burkitt's lymphoma ( 11 ) , non-Hodgkin's lymphoma ( 20 ) , follicular lymphoma ( 11 ) , mantle cell lymphoma ( 11 ) , neuroblastoma ( 19 ) , ovarian cancer ( 9 ) , pancreatic ductal adenocarcinoma ( 14 ) , multiple myeloma ( 20 ) , prostate cancer ( 45 ) , melanoma skin cancer ( 5 ) , FTLD ( 37 ) , Parkinson's disease ( 8 )
Relevant cell line - cell type - tissue:	'brain, cerebral cortex' ( 37 ) , 'muscle, skeletal' ( 30 ) , 'pancreatic, ductal'-pancreas ( 14 ) , 'stem, embryonic' ( 48 ) , 293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] ( 41 ) , 293 (epithelial) ( 8 ) , 293E (epithelial) ( 33 ) , 786-O (renal) [VHL (human), transfection] ( 4 ) , A431 (epithelial) ( 66 ) , A498 (renal) ( 42 ) , A549 (pulmonary) ( 15 ) , AML-193 (monocyte) ( 20 , 23 ) , BJAB (B lymphocyte) ( 11 ) , breast ( 2 , 9 ) , BT-20 (breast cell) ( 22 ) , BT-549 (breast cell) ( 22 ) , Calu 6 (pulmonary) ( 22 ) , CL1-0 (pulmonary) ( 39 ) , CL1-1 (pulmonary) ( 39 ) , CL1-2 (pulmonary) ( 39 ) , CL1-5 (pulmonary) ( 39 ) , CMK (megakaryoblast) ( 20 ) , COS (fibroblast) ( 63 ) , CTS (myeloid) ( 20 ) , DG75 (B lymphocyte) ( 40 ) , DOHH2 ('B lymphocyte, precursor') ( 20 ) , endothelial-aorta ( 24 ) , fibroblast-skin ( 64 ) , FL-18 (B lymphocyte) ( 11 ) , Flp-In T-Rex-293 (epithelial) [PRKD1 (human), genetic knockin] ( 25 ) , Flp-In T-Rex-293 (epithelial) ( 25 ) , H2009 (pulmonary) ( 22 ) , H2077 (pulmonary) ( 22 ) , H2887 (pulmonary) ( 22 ) , H322M (pulmonary) ( 22 ) , HCC1359 (pulmonary) ( 22 ) , HCC1937 (breast cell) ( 22 ) , HCC2279 (pulmonary) ( 22 ) , HCC366 (pulmonary) ( 22 ) , HCC4006 (pulmonary) ( 22 ) , HCC78 (pulmonary) ( 22 ) , HCC827 (pulmonary) ( 22 ) , HCT116 (intestinal) ( 49 , 50 ) , HEL (erythroid) ( 20 , 23 ) , HeLa (cervical) ( 7 , 18 , 32 , 36 , 47 , 50 , 51 , 53 , 58 , 59 , 60 , 62 , 65 ) , HeLa S3 (cervical) ( 46 ) , hepatocyte-liver ( 43 ) , HMLER ('stem, breast cancer') [CXCR4 (human), knockdown] ( 10 ) , HMLER ('stem, breast cancer') ( 10 ) , HOP62 (pulmonary) ( 22 ) , HUES-9 ('stem, embryonic') ( 35 ) , JEKO-1 (B lymphocyte) ( 11 ) , Jurkat (T lymphocyte) ( 16 , 27 , 28 , 38 , 52 , 61 ) , K562 (erythroid) ( 18 , 47 , 55 , 56 , 57 ) , Kasumi-1 (myeloid) ( 20 ) , KG-1 (myeloid) ( 20 , 29 ) , Kit225 (T lymphocyte) ( 31 ) , LCLC-103H (pulmonary) ( 22 ) , leukocyte-blood ( 44 ) , liver ( 13 ) , LNCaP (prostate cell) ( 45 ) , LOU-NH91 (squamous) ( 22 ) , MCF-7 (breast cell) ( 22 ) , MDA-MB-231 (breast cell) ( 22 ) , MDA-MB-468 (breast cell) ( 22 ) , MV4-11 (macrophage) ( 20 ) , NB10 (neural crest) ( 19 ) , NCEB-1 (B lymphocyte) ( 11 ) , NCI-H1395 (pulmonary) ( 22 ) , NCI-H1568 (pulmonary) ( 22 ) , NCI-H157 (pulmonary) ( 22 ) , NCI-H1648 (pulmonary) ( 22 ) , NCI-H1666 (pulmonary) ( 22 ) , NCI-H2030 (pulmonary) ( 22 ) , NCI-H2172 (pulmonary) ( 22 ) , NCI-H322 (pulmonary) ( 22 ) , NCI-H460 (pulmonary) ( 22 , 50 ) , NCI-H520 (squamous) ( 22 ) , NCI-H647 (pulmonary) ( 22 ) , NPC (neural crest) ( 19 ) , OCI-ly1 (B lymphocyte) ( 11 ) , OPM-2 (plasma cell) ( 20 ) , ovary ( 9 ) , P31/FUJ (erythroid) ( 20 ) , PC-12 (chromaffin) ( 8 ) , PC9 (pulmonary) ( 6 , 22 ) , RAMOS (B lymphocyte) ( 11 ) , REC-1 (B lymphocyte) ( 11 ) , RL ('B lymphocyte, precursor') ( 20 ) , RPMI-8266 (plasma cell) ( 20 ) , SH-SY5Y (neural crest) [LRRK2 (human), transfection, over-expression of LRRK2(G2019S)] ( 12 ) , SH-SY5Y (neural crest) ( 12 ) , SKBr3 (breast cell) ( 21 ) , SU-DHL-4 (B lymphocyte) ( 11 ) , SU-DHL-6 (B lymphocyte) ( 20 ) , TERT20 ('stem, mesenchymal') ( 54 ) , U-1810 (pulmonary) ( 34 ) , U266 (plasma cell) ( 20 ) , UPN-1 (B lymphocyte) ( 11 ) , Vero E6-S ('epithelial, kidney') ( 1 ) , WM239A (melanocyte) ( 5 )

Upstream Regulation
Putative in vivo kinases:	PKCG (human) ( 8 )
Kinases, in vitro:	PKCG (human) ( 8 )
Treatments:	EGF ( 60 , 62 ) , IL-2 ( 31 ) , metastatic potential ( 39 )

Downstream Regulation
Effects of modification on biological processes:	exocytosis, induced ( 8 )

References
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5	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
6	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
7	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
8	Shirafuji T, et al. (2014) The Role of Pak-Interacting Exchange Factor-β Phosphorylation at Serines 340 and 583 by PKCγ in Dopamine Release. J Neurosci 34, 9268-80 25009260 Curated Info
9	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
10	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
11	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
12	Luerman GC, et al. (2014) Phosphoproteomic evaluation of pharmacological inhibition of leucine-rich repeat kinase 2 reveals significant off-target effects of LRRK-2-IN-1. J Neurochem 128, 561-76 24117733 Curated Info
13	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
14	Britton D, et al. (2014) Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets. PLoS One 9, e90948 24670416 Curated Info
15	Kim JY, et al. (2013) Dissection of TBK1 signaling via phosphoproteomics in lung cancer cells. Proc Natl Acad Sci U S A 110, 12414-9 23836654 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	Shiromizu T, et al. (2013) Identification of missing proteins in the neXtProt database and unregistered phosphopeptides in the PhosphoSitePlus database as part of the Chromosome-centric Human Proteome Project. J Proteome Res 12, 2414-21 23312004 Curated Info
18	Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71 23186163 Curated Info
19	DeNardo BD, et al. (2013) Quantitative phosphoproteomic analysis identifies activation of the RET and IGF-1R/IR signaling pathways in neuroblastoma. PLoS One 8, e82513 24349301 Curated Info
20	Casado P, et al. (2013) Phosphoproteomics data classify hematological cancer cell lines according to tumor type and sensitivity to kinase inhibitors. Genome Biol 14, R37 23628362 Curated Info
21	Imami K, et al. (2012) Temporal profiling of lapatinib-suppressed phosphorylation signals in EGFR/HER2 pathways. Mol Cell Proteomics 11, 1741-57 22964224 Curated Info
22	Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68 22617229 Curated Info
23	Alcolea MP, et al. (2012) Phosphoproteomic analysis of leukemia cells under basal and drug-treated conditions identifies markers of kinase pathway activation and mechanisms of resistance. Mol Cell Proteomics 11, 453-66 22547687 Curated Info
24	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
25	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
26	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
27	Guo A (2012) CST Curation Set: 13865; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Curated Info
28	Mulhern D (2012) CST Curation Set: 13758; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Curated Info
29	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
30	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
31	Osinalde N, et al. (2011) Interleukin-2 signaling pathway analysis by quantitative phosphoproteomics. J Proteomics 75, 177-91 21722762 Curated Info
32	Grosstessner-Hain K, et al. (2011) Quantitative phospho-proteomics to investigate the polo-like kinase 1-dependent phospho-proteome. Mol Cell Proteomics 10, M111.008540 21857030 Curated Info
33	Hsu PP, et al. (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332, 1317-22 21659604 Curated Info
34	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
35	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
36	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
37	Herskowitz JH, et al. (2010) Phosphoproteomic Analysis Reveals Site-Specific Changes in GFAP and NDRG2 Phosphorylation in Frontotemporal Lobar Degeneration. J Proteome Res 9, 6368-79 20886841 Curated Info
38	Possemato A (2010) CST Curation Set: 10868; Year: 2010; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M) Curated Info
39	Wang YT, et al. (2010) An informatics-assisted label-free quantitation strategy that depicts phosphoproteomic profiles in lung cancer cell invasion. J Proteome Res 9, 5582-97 20815410 Curated Info
40	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
41	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
42	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
43	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
44	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
45	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
46	Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3 20068231 Curated Info
47	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
48	Brill LM, et al. (2009) Phosphoproteomic analysis of human embryonic stem cells. Cell Stem Cell 5, 204-13 19664994 Curated Info
49	Oppermann FS, et al. (2009) Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics 8, 1751-64 19369195 Curated Info
50	Nagano K, et al. (2009) Phosphoproteomic analysis of distinct tumor cell lines in response to nocodazole treatment. Proteomics 9, 2861-74 19415658 Curated Info
51	Chen RQ, et al. (2009) CDC25B mediates rapamycin-induced oncogenic responses in cancer cells. Cancer Res 69, 2663-8 19276368 Curated Info
52	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
53	Dephoure N, et al. (2008) A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A 105, 10762-7 18669648 Curated Info
54	Thingholm TE, et al. (2008) TiO2-Based Phosphoproteomic Analysis of the Plasma Membrane and the Effects of Phosphatase Inhibitor Treatment. J Proteome Res 7, 3304-3313 18578522 Curated Info
55	Stokes M (2008) CST Curation Set: 4609; 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
56	Stokes M (2008) CST Curation Set: 4391; 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
57	Stokes M (2008) CST Curation Set: 4393; 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
58	Ruse CI, et al. (2008) Motif-specific sampling of phosphoproteomes. J Proteome Res 7, 2140-50 18452278 Curated Info
59	McNulty DE, Annan RS (2008) Hydrophilic interaction chromatography reduces the complexity of the phosphoproteome and improves global phosphopeptide isolation and detection. Mol Cell Proteomics 7, 971-80 18212344 Curated Info
60	Cantin GT, et al. (2008) Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res 7, 1346-51 18220336 Curated Info
61	Stokes M (2008) CST Curation Set: 3885; Year: 2008; Biosample/Treatment: cell line, Jurkat/pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]) Curated Info
62	Liang X, et al. (2007) Quantitative Comparison of IMAC and TiO(2) Surfaces Used in the Study of Regulated, Dynamic Protein Phosphorylation. J Am Soc Mass Spectrom 18, 1932-44 17870612 Curated Info
63	Wang Y, et al. (2007) Profiling signaling polarity in chemotactic cells. Proc Natl Acad Sci U S A 104, 8328-33 17494752 Curated Info
64	Yang F, et al. (2006) Phosphoproteome profiling of human skin fibroblast cells in response to low- and high-dose irradiation. J Proteome Res 5, 1252-60 16674116 Curated Info
65	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
66	MS This site is one of 509 sites observed by D. Stover et al using MS/FTMS of peptides from lysates of A431 cells grown either in vitro or as xenografts in BALB/c nu/nu mice. These sites were previously unpublished until now (July 27 2006). 66 sites were previously published in: Stover DR, et al. Differential phosphoprofiles of EGF and EGFR kinase inhibitor-treated human tumor cells and mouse xenografts Clin Proteomics 2004 Mar 01; 1(1): 69-80. Curated Info