Ser189

Site Information
ySHKGHLsEGLVTkW SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 448267

In vivo Characterization
Methods used to characterize site in vivo:	[32P] bio-synthetic labeling ( 28 , 29 ) , immunoprecipitation ( 19 , 29 ) , mass spectrometry ( 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 13 , 14 , 16 , 17 , 20 , 21 , 22 , 24 , 25 , 26 , 27 ) , mass spectrometry (in vitro) ( 23 ) , mutation of modification site ( 1 , 29 ) , phospho-antibody ( 1 , 18 , 19 ) , phosphoamino acid analysis ( 29 ) , phosphopeptide mapping ( 28 , 29 ) , western blotting ( 1 , 18 , 19 )
Disease tissue studied:	breast cancer ( 1 , 6 , 7 , 14 ) , breast ductal carcinoma ( 6 ) , 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 ) , leukemia ( 16 ) , T cell leukemia ( 16 ) , lung cancer ( 9 , 14 ) , non-small cell lung cancer ( 14 ) , non-small cell lung adenocarcinoma ( 9 ) , melanoma skin cancer ( 4 )
Relevant cell line - cell type - tissue:	293 (epithelial) ( 19 , 29 ) , 3T3 (fibroblast) ( 19 ) , A498 (renal) ( 22 ) , A549 (pulmonary) ( 10 ) , breast ( 2 , 6 ) , BT-20 (breast cell) ( 14 ) , BT-549 (breast cell) ( 14 ) , H2009 (pulmonary) ( 14 ) , H2077 (pulmonary) ( 14 ) , H2887 (pulmonary) ( 14 ) , H322M (pulmonary) ( 14 ) , HCC1359 (pulmonary) ( 14 ) , HCC1937 (breast cell) ( 14 ) , HCC2279 (pulmonary) ( 14 ) , HCC366 (pulmonary) ( 14 ) , HCC4006 (pulmonary) ( 14 ) , HCC78 (pulmonary) ( 14 ) , HCC827 (pulmonary) ( 14 ) , HCT116 (intestinal) ( 26 ) , HeLa (cervical) ( 5 , 13 , 21 , 27 ) , HMEC (endothelial) ( 1 ) , HMLER ('stem, breast cancer') [CXCR4 (human), knockdown] ( 7 ) , HMLER ('stem, breast cancer') ( 7 ) , HOP62 (pulmonary) ( 14 ) , HUES-9 ('stem, embryonic') ( 20 ) , Jurkat (T lymphocyte) ( 11 , 17 , 25 ) , K562 (erythroid) ( 13 , 24 ) , Kit225 (T lymphocyte) ( 16 ) , LCLC-103H (pulmonary) ( 14 ) , LOU-NH91 (squamous) ( 14 ) , lung ( 9 ) , MCF-7 (breast cell) ( 14 ) , MDA-MB-231 (breast cell) ( 1 , 14 ) , MDA-MB-435S (breast cell) ( 26 ) , MDA-MB-468 (breast cell) ( 14 ) , monocyte-blood ( 18 ) , MV4-11 (macrophage) ( 26 ) , NCI-H1568 (pulmonary) ( 14 ) , NCI-H157 (pulmonary) ( 14 ) , NCI-H1666 (pulmonary) ( 14 ) , NCI-H2172 (pulmonary) ( 14 ) , NCI-H322 (pulmonary) ( 14 ) , NCI-H460 (pulmonary) ( 14 ) , NCI-H520 (squamous) ( 14 ) , NCI-H647 (pulmonary) ( 14 ) , PC9 (pulmonary) ( 14 ) , SH-SY5Y (neural crest) [LRRK2 (human), transfection, over-expression of LRRK2(G2019S)] ( 8 ) , WM239A (melanocyte) ( 4 )

Upstream Regulation
Kinases, in vitro:	ERK3 (human) ( 29 ) , PAK2 (human) ( 19 )
Treatments:	EGF ( 1 ) , siRNA ( 1 )

Downstream Regulation
Effects of modification on ERK3:	intracellular localization ( 19 ) , molecular association, regulation ( 19 )
Induce interaction with:	MAPKAPK5 (human) ( 19 )

References
1	Bogucka-Janczi K, et al. (2023) ERK3/MAPK6 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization. Elife 12 37057894 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	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
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	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
8	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
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	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
11	Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7 23749302 Curated Info
12	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
13	Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71 23186163 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	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
16	Osinalde N, et al. (2011) Interleukin-2 signaling pathway analysis by quantitative phosphoproteomics. J Proteomics 75, 177-91 21722762 Curated Info
17	Guo A (2011) CST Curation Set: 12456; 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: (K/R)Xp[ST](I/L/V) Curated Info
18	Wang H, et al. (2011) Convergence of the mammalian target of rapamycin complex 1- and glycogen synthase kinase 3-β-signaling pathways regulates the innate inflammatory response. J Immunol 186, 5217-26 21422248 Curated Info
19	De la Mota-Peynado A, Chernoff J, Beeser A (2011) Identification of the atypical MAPK Erk3 as a novel substrate for p21-activated kinase (Pak) activity. J Biol Chem 286, 13603-11 21317288 Curated Info
20	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
21	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
22	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
23	Tanguay PL, Rodier G, Meloche S (2010) C-terminal domain phosphorylation of ERK3 controlled by Cdk1 and Cdc14 regulates its stability in mitosis. Biochem J 428, 103-11 20236090 Curated Info
24	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
25	Possemato A (2009) CST Curation Set: 8351; 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: (K/R)XX[ST] Curated Info
26	Oppermann FS, et al. (2009) Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics 8, 1751-64 19369195 Curated Info
27	Dephoure N, et al. (2008) A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A 105, 10762-7 18669648 Curated Info
28	Cheng M, et al. (1996) Characterization of a protein kinase that phosphorylates serine 189 of the mitogen-activated protein kinase homolog ERK3. J Biol Chem 271, 12057-62 8662649 Curated Info
29	Cheng M, Boulton TG, Cobb MH (1996) ERK3 is a constitutively nuclear protein kinase. J Biol Chem 271, 8951-8 8621539 Curated Info