Ser435

Site Information
KKLERNLsFEIKKVP SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 451312

In vivo Characterization
Methods used to characterize site in vivo:	[32P] bio-synthetic labeling ( 49 ) , immunoprecipitation ( 49 ) , mass spectrometry ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 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 , 50 ) , phosphoamino acid analysis ( 49 ) , phosphopeptide mapping ( 49 )
Disease tissue studied:	breast cancer ( 7 , 8 , 17 , 18 ) , breast ductal carcinoma ( 7 ) , HER2 positive breast cancer ( 4 ) , luminal A breast cancer ( 4 ) , luminal B breast cancer ( 4 ) , breast cancer, surrounding tissue ( 4 ) , breast cancer, triple negative ( 4 , 7 ) , cervical cancer ( 36 ) , cervical adenocarcinoma ( 36 ) , leukemia ( 23 , 48 ) , acute myelogenous leukemia ( 23 ) , chronic myelogenous leukemia ( 48 ) , lung cancer ( 11 , 18 , 26 , 27 , 28 , 29 , 30 ) , non-small cell lung cancer ( 18 , 26 , 27 , 28 , 29 , 30 ) , non-small cell lung adenocarcinoma ( 11 , 27 , 29 , 30 ) , non-small cell large cell lung carcinoma ( 26 , 28 ) , neuroblastoma ( 1 , 16 ) , ovarian cancer ( 7 ) , pancreatic ductal adenocarcinoma ( 10 )
Relevant cell line - cell type - tissue:	'muscle, skeletal' ( 24 ) , 'pancreatic, ductal'-pancreas ( 10 ) , 293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] ( 34 ) , 293 (epithelial) [AT1 (human), transfection] ( 33 ) , 293E (epithelial) ( 25 ) , A431 (epithelial) ( 50 ) , A498 (renal) ( 35 ) , A549 (pulmonary) [CD38 (human), transfection, Lentiviral particles containing CD38 vector were transfected] ( 3 ) , A549 (pulmonary) ( 3 , 12 ) , breast ( 4 , 7 ) , BT-20 (breast cell) ( 18 ) , BT-549 (breast cell) ( 18 ) , Calu 6 (pulmonary) ( 18 ) , CLB-Bar ( 1 ) , endothelial-aorta ( 19 ) , Flp-In T-Rex-293 (epithelial) [PRKD1 (human), genetic knockin] ( 21 ) , H2009 (pulmonary) ( 18 ) , H2077 (pulmonary) ( 18 ) , H2887 (pulmonary) ( 18 ) , H322M (pulmonary) ( 18 ) , HCC1359 (pulmonary) ( 18 ) , HCC1937 (breast cell) ( 18 ) , HCC2279 (pulmonary) ( 18 ) , HCC366 (pulmonary) ( 18 ) , HCC4006 (pulmonary) ( 18 ) , HCC78 (pulmonary) ( 18 ) , HCC827 (pulmonary) ( 18 ) , HeLa (cervical) ( 6 , 15 , 32 , 37 , 47 , 49 ) , HeLa S3 (cervical) ( 36 ) , HepG2 (hepatic) ( 45 , 46 ) , HMLER ('stem, breast cancer') [CXCR4 (human), knockdown] ( 8 ) , HMLER ('stem, breast cancer') ( 8 ) , HOP62 (pulmonary) ( 18 ) , HUES-9 ('stem, embryonic') ( 31 ) , Jurkat (T lymphocyte) ( 13 ) , K562 (erythroid) ( 15 , 37 , 48 ) , KG-1 (myeloid) ( 23 ) , LCLC-103H (pulmonary) ( 18 ) , LOU-NH91 (squamous) ( 18 ) , lung ( 11 ) , MCF-7 (breast cell) ( 5 , 18 ) , MDA-MB-231 (breast cell) ( 18 ) , MDA-MB-468 (breast cell) ( 18 ) , NB10 (neural crest) ( 16 ) , NCI-H1395 (pulmonary) ( 18 ) , NCI-H1568 (pulmonary) ( 18 ) , NCI-H157 (pulmonary) ( 18 ) , NCI-H1648 (pulmonary) ( 18 ) , NCI-H1650 (pulmonary) ( 38 , 39 ) , NCI-H1666 (pulmonary) ( 18 ) , NCI-H1975 (pulmonary) ( 30 ) , NCI-H2030 (pulmonary) ( 18 ) , NCI-H2172 (pulmonary) ( 18 ) , NCI-H2228 (pulmonary) ( 41 , 42 ) , NCI-H2342 (pulmonary) ( 29 ) , NCI-H322 (pulmonary) ( 18 ) , NCI-H3255 (pulmonary) ( 40 , 43 , 44 ) , NCI-H441 (pulmonary) ( 27 ) , NCI-H460 (pulmonary) ( 18 , 28 ) , NCI-H520 (squamous) ( 18 ) , NCI-H647 (pulmonary) ( 18 ) , NCI-H661 (pulmonary) ( 26 ) , NPC (neural crest) ( 16 ) , ovary ( 7 ) , PC9 (pulmonary) ( 18 ) , SH-SY5Y (neural crest) [LRRK2 (human), transfection, over-expression of LRRK2(G2019S)] ( 9 ) , SKBr3 (breast cell) ( 17 ) , T lymphocyte-blood ( 20 ) , Vero E6-S ('epithelial, kidney') ( 2 )

Upstream Regulation
Regulatory protein:	CD38 (human) ( 3 ) , TBK1 (human) ( 12 )
Putative in vivo kinases:	PKACA (human) ( 49 ) , PKCA (human) ( 49 )
Kinases, in vitro:	PKACA (human) ( 49 ) , PKCA (human) ( 49 )
Treatments:	angiotensin_2 ( 34 ) , antibody ( 20 ) , colforsin ( 49 ) , HB-EGF ( 35 ) , IBMX ( 49 ) , ischemia ( 7 ) , LPA ( 35 ) , metformin ( 5 ) , nocodazole ( 36 ) , phorbol_ester ( 49 ) , SII_angiotensin_2 ( 34 )

References
1	Borenäs M, et al. (2024) ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition. Proc Natl Acad Sci U S A 121, e2315242121 38154064 Curated Info
2	Bouhaddou M, et al. (2020) The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell 182 32645325 Curated Info
3	Wang W, et al. (2018) Decreased NAD Activates STAT3 and Integrin Pathways to Drive Epithelial-Mesenchymal Transition. Mol Cell Proteomics 29980616 Curated Info
4	Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62 27251275 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	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
7	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
8	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
9	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
10	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
11	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
12	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
13	Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7 23749302 Curated Info
14	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
15	Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71 23186163 Curated Info
16	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
17	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
18	Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68 22617229 Curated Info
19	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
20	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
21	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
22	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
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	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
26	Rikova K (2011) CST Curation Set: 10898; Year: 2011; Biosample/Treatment: cell line, NCI-H661/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]) Curated Info
27	Rikova K (2011) CST Curation Set: 10914; Year: 2011; Biosample/Treatment: cell line, NCI-H441/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]) Curated Info
28	Rikova K (2011) CST Curation Set: 10894; Year: 2011; Biosample/Treatment: cell line, NCI-H460/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]) Curated Info
29	Rikova K (2011) CST Curation Set: 10886; Year: 2011; Biosample/Treatment: cell line, NCI-H2342/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]) Curated Info
30	Rikova K (2011) CST Curation Set: 10890; Year: 2011; Biosample/Treatment: cell line, NCI-H1975/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]) Curated Info
31	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
32	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
33	Xiao K, et al. (2010) Global phosphorylation analysis of beta-arrestin-mediated signaling downstream of a seven transmembrane receptor (7TMR). Proc Natl Acad Sci U S A 107, 15299-304 20686112 Curated Info
34	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
35	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
36	Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3 20068231 Curated Info
37	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
38	Possemato A (2009) CST Curation Set: 8051; Year: 2009; Biosample/Treatment: cell line, NCI-H1650/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Curated Info
39	Possemato A (2009) CST Curation Set: 8050; Year: 2009; Biosample/Treatment: cell line, NCI-H1650/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Curated Info
40	Possemato A (2009) CST Curation Set: 7416; 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: 7391; Year: 2009; Biosample/Treatment: cell line, NCI-H2228/-; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Curated Info
42	Possemato A (2009) CST Curation Set: 7392; Year: 2009; Biosample/Treatment: cell line, NCI-H2228/-; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Curated Info
43	Possemato A (2009) CST Curation Set: 7394; Year: 2009; Biosample/Treatment: cell line, NCI-H3255/-; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Curated Info
44	Possemato A (2009) CST Curation Set: 7393; Year: 2009; Biosample/Treatment: cell line, NCI-H3255/-; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Curated Info
45	Possemato A (2009) CST Curation Set: 7390; Year: 2009; Biosample/Treatment: cell line, HepG2/-; Disease: hepatocellular carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Curated Info
46	Possemato A (2009) CST Curation Set: 7389; Year: 2009; Biosample/Treatment: cell line, HepG2/-; Disease: hepatocellular carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] 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	Moritz A (2005) CST Curation Set: 704; Year: 2005; Biosample/Treatment: cell line, K562/-; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (K/R)XX[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) Akt Substrate Antibody Cat#: 9611 Curated Info
49	Garton AJ, Tonks NK (1994) PTP-PEST: a protein tyrosine phosphatase regulated by serine phosphorylation. EMBO J 13, 3763-71 7520867 Curated Info
50	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