Ser582

Site Information
PkIERsAsEPsLHRt SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 481007

In vivo Characterization
Methods used to characterize site in vivo:	mass spectrometry ( 1 , 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 12 , 13 , 14 , 15 , 16 , 18 , 19 , 20 , 21 , 22 , 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 ) , mutation of modification site ( 45 ) , phospho-antibody ( 45 )
Disease tissue studied:	breast cancer ( 6 , 14 ) , 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 , 6 ) , cervical cancer ( 35 ) , cervical adenocarcinoma ( 35 ) , leukemia ( 18 , 22 ) , acute myelogenous leukemia ( 18 ) , T cell leukemia ( 22 ) , hepatocellular carcinoma, surrounding tissue ( 34 ) , lung cancer ( 9 , 14 , 29 , 46 ) , non-small cell lung cancer ( 14 , 46 ) , non-small cell lung adenocarcinoma ( 9 ) , neuroblastoma ( 13 ) , pancreatic ductal adenocarcinoma ( 8 )
Relevant cell line - cell type - tissue:	'muscle, skeletal' ( 19 , 37 ) , 'pancreatic, ductal'-pancreas ( 8 ) , 293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] ( 30 ) , 293 (epithelial) ( 21 ) , 786-O (renal) [VHL (human), transfection] ( 4 ) , A498 (renal) ( 33 ) , breast ( 2 , 6 ) , BT-20 (breast cell) ( 14 ) , BT-549 (breast cell) ( 14 ) , CL1-0 (pulmonary) ( 29 ) , CL1-1 (pulmonary) ( 29 ) , CL1-2 (pulmonary) ( 29 ) , CL1-5 (pulmonary) ( 29 ) , COS (fibroblast) ( 45 ) , endothelial-aorta ( 15 ) , Flp-In T-Rex-293 (epithelial) [PRKD1 (human), genetic knockin] ( 16 ) , Flp-In T-Rex-293 (epithelial) ( 16 ) , GM00130 (B lymphocyte) ( 32 ) , H2009 (pulmonary) ( 14 ) , H2077 (pulmonary) ( 14 ) , H2887 (pulmonary) ( 14 ) , H322M (pulmonary) ( 14 ) , HCC1359 (pulmonary) ( 14 ) , HCC1937 (breast cell) ( 14 ) , HCC366 (pulmonary) ( 14 ) , HCC4006 (pulmonary) ( 14 ) , HCC78 (pulmonary) ( 14 ) , HCC827 (pulmonary) ( 14 ) , HCT116 (intestinal) ( 43 ) , HeLa (cervical) ( 1 , 5 , 12 , 20 , 28 , 36 , 49 ) , HeLa S3 (cervical) ( 26 , 35 , 38 , 47 ) , HeLa_Meta (cervical) ( 31 ) , HeLa_Pro (cervical) ( 31 ) , HeLa_Telo (cervical) ( 31 ) , hepatocyte-liver ( 34 ) , HepG2 (hepatic) ( 41 , 42 ) , HOP62 (pulmonary) ( 14 ) , HUES-9 ('stem, embryonic') ( 27 ) , Jurkat (T lymphocyte) ( 10 , 23 , 24 , 25 , 39 ) , K562 (erythroid) ( 12 , 36 ) , KG-1 (myeloid) ( 18 ) , Kit225 (T lymphocyte) ( 22 ) , LCLC-103H (pulmonary) ( 14 ) , liver ( 7 ) , lung ( 9 ) , MCF-7 (breast cell) ( 14 ) , MDA-MB-231 (breast cell) ( 14 ) , MDA-MB-468 (breast cell) ( 14 ) , MV4-11 (macrophage) ( 43 ) , NB10 (neural crest) ( 13 ) , NCI-H1299 (pulmonary) ( 46 ) , NCI-H1568 (pulmonary) ( 14 ) , NCI-H157 (pulmonary) ( 14 ) , NCI-H1666 (pulmonary) ( 14 ) , NCI-H322 (pulmonary) ( 14 ) , NCI-H3255 (pulmonary) ( 40 ) , NCI-H460 (pulmonary) ( 44 ) , NCI-H520 (squamous) ( 14 ) , NCI-H647 (pulmonary) ( 14 ) , NPC (neural crest) ( 13 ) , PC9 (pulmonary) ( 14 ) , SF9 [Lck (human)] ( 45 ) , TERT20 ('stem, mesenchymal') ( 48 )

Upstream Regulation
Treatments:	metastatic potential ( 29 ) , MG132_withdrawal ( 31 )

Downstream Regulation
Effects of modification on ARAF:	enzymatic activity, induced ( 45 )

References
1	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
2	Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62 27251275 Curated Info
3	Boeing S, et al. (2016) Multiomic Analysis of the UV-Induced DNA Damage Response. Cell Rep 15, 1597-1610 27184836 Curated Info
4	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
5	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
6	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
7	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
8	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
9	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
10	Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7 23749302 Curated Info
11	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
12	Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71 23186163 Curated Info
13	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
14	Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68 22617229 Curated Info
15	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
16	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
17	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
18	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
19	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
20	Nishioka T, Nakayama M, Amano M, Kaibuchi K (2012) Proteomic screening for Rho-kinase substrates by combining kinase and phosphatase inhibitors with 14-3-3ζ affinity chromatography. Cell Struct Funct 37, 39-48 22251793 Curated Info
21	Mulhern D (2011) CST Curation Set: 12830; Year: 2011; Biosample/Treatment: cell line, HEK 293/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) AMPK Substrate (P-S/T(2)-102) Rabbit mAb Cat#: 5759, PTMScan(R) Phospho-AMPK Substrate Motif (LXRXXS/T) Immunoaffinity Beads Cat#: 5760 Curated Info
22	Osinalde N, et al. (2011) Interleukin-2 signaling pathway analysis by quantitative phosphoproteomics. J Proteomics 75, 177-91 21722762 Curated Info
23	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
24	Guo A (2011) CST Curation Set: 11983; 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
25	Guo A (2011) CST Curation Set: 11984; 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	Santamaria A, et al. (2011) The Plk1-dependent phosphoproteome of the early mitotic spindle. Mol Cell Proteomics 10, M110.004457 20860994 Curated Info
27	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
28	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
29	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
30	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
31	Dulla K, et al. (2010) Quantitative site-specific phosphorylation dynamics of human protein kinases during mitotic progression. Mol Cell Proteomics 9, 1167-81 20097925 Curated Info
32	Bennetzen MV, et al. (2010) Site-specific phosphorylation dynamics of the nuclear proteome during the DNA damage response. Mol Cell Proteomics 9, 1314-23 20164059 Curated Info
33	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
34	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
35	Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3 20068231 Curated Info
36	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
37	Højlund K, et al. (2009) In vivo phosphoproteome of human skeletal muscle revealed by phosphopeptide enrichment and HPLC-ESI-MS/MS. J Proteome Res 8, 4954-65 19764811 Curated Info
38	Malik R, et al. (2009) Quantitative analysis of the human spindle phosphoproteome at distinct mitotic stages. J Proteome Res 8, 4553-63 19691289 Curated Info
39	Possemato A (2009) CST Curation Set: 8038; Year: 2009; 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 Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) 14-3-3 Binding Motif Antibody Cat#: 9601 Curated Info
40	Possemato A (2009) CST Curation Set: 7415; Year: 2009; Biosample/Treatment: cell line, NCI-H3255/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) PKD Substrate Antibody Cat#: 4381, PTMScan(R) Phospho-PKD Substrate Motif (LXRXXpS/pT) Immunoaffinity Beads Cat#: 1986 Curated Info
41	Possemato A (2009) CST Curation Set: 7408; Year: 2009; Biosample/Treatment: cell line, HepG2/untreated; Disease: hepatocellular carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) PKD Substrate Antibody Cat#: 4381, PTMScan(R) Phospho-PKD Substrate Motif (LXRXXpS/pT) Immunoaffinity Beads Cat#: 1986 Curated Info
42	Possemato A (2009) CST Curation Set: 7407; Year: 2009; Biosample/Treatment: cell line, HepG2/untreated; Disease: hepatocellular carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) PKD Substrate Antibody Cat#: 4381, PTMScan(R) Phospho-PKD Substrate Motif (LXRXXpS/pT) Immunoaffinity Beads Cat#: 1986 Curated Info
43	Oppermann FS, et al. (2009) Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics 8, 1751-64 19369195 Curated Info
44	Nagano K, et al. (2009) Phosphoproteomic analysis of distinct tumor cell lines in response to nocodazole treatment. Proteomics 9, 2861-74 19415658 Curated Info
45	Baljuls A, et al. (2008) Positive regulation of A-RAF by phosphorylation of isoform-specific hinge segment and identification of novel phosphorylation sites. J Biol Chem 283, 27239-54 18662992 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	Daub H, et al. (2008) Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell 31, 438-48 18691976 Curated Info
48	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
49	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