Thr219

Site Information
AEHQyFMtEyVAtRW SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 448205

In vivo Characterization
Methods used to characterize site in vivo:	electrophoretic mobility shift ( 43 ) , flow cytometry ( 2 ) , immunoprecipitation ( 1 , 2 , 5 , 43 ) , mass spectrometry ( 3 , 6 , 7 , 8 , 9 , 11 , 12 , 13 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 38 , 39 ) , phospho-antibody ( 1 , 2 , 4 , 5 , 10 , 14 , 40 , 42 , 43 ) , phosphoamino acid analysis ( 36 , 37 ) , western blotting ( 1 , 2 , 4 , 5 , 10 , 14 , 36 , 37 , 40 , 42 , 43 )
Disease tissue studied:	adrenal cancer ( 42 ) , pheochromocytoma ( 42 ) , breast cancer ( 34 , 36 , 43 ) , colorectal cancer ( 37 ) , colorectal carcinoma ( 37 ) , esophageal cancer ( 29 ) , esophageal cancer, surrounding tissue ( 15 , 30 ) , gastric cancer ( 22 , 24 , 32 , 33 ) , gastric carcinoma ( 32 , 33 ) , gastric carcinoma, surrounding tissue ( 23 , 25 ) , kidney cancer ( 35 ) , kidney cancer, surrounding tissue ( 26 ) , leukemia ( 8 , 38 ) , acute myelogenous leukemia ( 38 ) , chronic myelogenous leukemia ( 8 ) , lung cancer ( 6 , 7 , 11 , 12 , 16 , 17 , 18 , 19 , 20 , 27 , 28 , 31 , 39 ) , non-small cell lung cancer ( 6 , 7 , 11 , 12 , 28 , 39 ) , non-small cell lung adenocarcinoma ( 7 ) , non-small cell lung adenocarcinoma, surrounding tissue ( 21 ) , non-small cell squamous cell lung carcinoma ( 27 , 31 ) , ovarian cancer ( 13 ) , prostate cancer ( 5 ) , melanoma skin cancer ( 2 )
Relevant cell line - cell type - tissue:	293 (epithelial) ( 10 ) , 3T3 (fibroblast) ( 36 ) , 703167 (pulmonary) ( 16 ) , A375 (melanocyte) ( 2 ) , bone marrow ( 38 ) , breast ( 34 ) , esophagus ( 15 , 29 , 30 ) , HEK293T (epithelial) ( 2 ) , HeLa (cervical) ( 10 , 37 , 43 ) , HES-3 ('stem, embryonic') ( 9 ) , HT-29 (intestinal) ( 37 ) , K562 (erythroid) ( 8 ) , kidney ( 26 , 35 ) , lung ( 7 , 17 , 18 , 19 , 20 , 21 , 27 , 28 , 31 , 39 ) , MCF-7 (breast cell) ( 43 ) , MDA-MB-231 (breast cell) ( 36 ) , MDA-MB-361 (breast cell) ( 36 ) , mesangial ( 40 ) , myocyte-heart ( 4 ) , NCI-H1650 (pulmonary) ( 6 ) , NCI-H3255 (pulmonary) ( 11 , 12 ) , ovary ( 13 ) , PAE (endothelial) ( 14 ) , PC-12 (chromaffin) ( 42 ) , PC3 (prostate cell) ( 5 ) , Rat1 (fibroblast) ( 36 ) , SK-MEL5 (melanocyte) ( 2 ) , stomach ( 22 , 23 , 24 , 25 , 32 , 33 ) , SU-DIPG-VI (glial) ( 1 )

Upstream Regulation
Regulatory protein:	BRAF (human) ( 2 ) , Brk (human) ( 5 ) , MEK5 (human) ( 2 , 10 ) , PDGFRB (human) ( 14 ) , PTP-SL (human) ( 42 ) , WNK1 (human) ( 37 ) , WNK2 (human) ( 37 )
Kinases, in vitro:	MEK5 (human) ( 41 )
Treatments:	CTGF ( 40 ) , DAPH ( 43 ) , EGF ( 42 , 43 ) , ERK5-IN-1 ( 1 ) , FGF2 ( 9 ) , K252a ( 40 ) , LY294002 ( 14 ) , neuregulin ( 43 ) , nocodazole ( 10 ) , PDGF ( 14 ) , phorbol_ester ( 36 ) , siRNA ( 37 ) , sorbitol ( 10 , 43 ) , SU6656 ( 14 ) , TG02 ( 1 ) , U0126 ( 14 , 43 ) , XMD17-109 ( 1 )

Downstream Regulation
Effects of modification on biological processes:	apoptosis, inhibited ( 14 )

References
1	Koncar RF, et al. (2019) Identification of novel RAS signaling therapeutic vulnerabilities in Diffuse Intrinsic Pontine Gliomas. Cancer Res 31201162 Curated Info
2	Tusa I, et al. (2018) ERK5 is activated by oncogenic BRAF and promotes melanoma growth. Oncogene 29483645 Curated Info
3	Stokes MP, et al. (2012) PTMScan Direct: Identification and Quantification of Peptides from Critical Signaling Proteins by Immunoaffinity Enrichment Coupled with LC-MS/MS. Mol Cell Proteomics 11, 187-201 22322096 Curated Info
4	Le NT, et al. (2012) p90RSK Targets the ERK5-CHIP Ubiquitin E3 Ligase Activity in Diabetic Hearts and Promotes Cardiac Apoptosis and Dysfunction. Circ Res 110, 536-50 22267842 Curated Info
5	Zheng Y, Asara JM, Tyner AL (2012) Protein-tyrosine kinase 6 promotes peripheral adhesion complex formation and cell migration by phosphorylating p130 CRK-associated substrate. J Biol Chem 287, 148-58 22084245 Curated Info
6	Possemato A (2011) CST Curation Set: 11905; Year: 2011; Biosample/Treatment: cell line, NCI-H1650/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
7	Ren H (2011) CST Curation Set: 11781; Year: 2011; Biosample/Treatment: cell line, RP98/untreated; Disease: non-small cell lung adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
8	Moritz A (2011) CST Curation Set: 11306; Year: 2011; Biosample/Treatment: cell line, K562/untreated; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
9	Ding VM, et al. (2011) Tyrosine phosphorylation profiling in fgf-2 stimulated human embryonic stem cells. PLoS One 6, e17538 21437283 Curated Info
10	Iñesta-Vaquera FA, et al. (2010) Alternative ERK5 regulation by phosphorylation during the cell cycle. Cell Signal 22, 1829-37 20667468 Curated Info
11	Moritz A (2010) CST Curation Set: 10599; Year: 2010; Biosample/Treatment: cell line, NCI-H3255/DMSO; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY] Curated Info
12	Moritz A (2010) CST Curation Set: 10598; Year: 2010; Biosample/Treatment: cell line, NCI-H3255/Su11274; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY] Curated Info
13	Ren H (2010) CST Curation Set: 10177; Year: 2010; Biosample/Treatment: tissue, ovary/untreated; Disease: ovarian cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411 Curated Info
14	Lennartsson J, et al. (2010) Erk 5 is necessary for sustained PDGF-induced Akt phosphorylation and inhibition of apoptosis. Cell Signal 22, 955-60 20138986 Curated Info
15	Tucker M (2010) CST Curation Set: 9506; Year: 2010; Biosample/Treatment: tissue, esophagus/untreated; Disease: esophageal cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
16	Hu Y (2010) CST Curation Set: 8751; Year: 2010; Biosample/Treatment: cell line, 703167/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
17	Hu Y (2010) CST Curation Set: 8755; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
18	Hu Y (2010) CST Curation Set: 8935; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
19	Hu Y (2010) CST Curation Set: 8757; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
20	Hu Y (2010) CST Curation Set: 8932; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
21	Ren H (2009) CST Curation Set: 8195; Year: 2009; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
22	Ren H (2009) CST Curation Set: 8028; Year: 2009; Biosample/Treatment: tissue, gastrointestinal tract/untreated; Disease: gastric cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
23	Ren H (2009) CST Curation Set: 8025; Year: 2009; Biosample/Treatment: tissue, gastrointestinal tract/untreated; Disease: gastric cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
24	Ren H (2009) CST Curation Set: 8018; Year: 2009; Biosample/Treatment: tissue, gastrointestinal tract/untreated; Disease: gastric cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
25	Ren H (2009) CST Curation Set: 8019; Year: 2009; Biosample/Treatment: tissue, gastrointestinal tract/untreated; Disease: gastric cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
26	Tucker M (2009) CST Curation Set: 7689; Year: 2009; Biosample/Treatment: tissue, kidney/untreated; Disease: kidney cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
27	Ren H (2009) CST Curation Set: 6961; Year: 2009; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell squamous cell lung carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
28	Ren H (2009) CST Curation Set: 6962; Year: 2009; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
29	Gu T (2009) CST Curation Set: 7076; Year: 2009; Biosample/Treatment: tissue, esophagus/untreated; Disease: esophageal cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
30	Gu T (2009) CST Curation Set: 7078; Year: 2009; Biosample/Treatment: tissue, esophagus/untreated; Disease: esophageal cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
31	Ren H (2009) CST Curation Set: 6479; Year: 2009; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell squamous cell lung carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
32	Ren H (2008) CST Curation Set: 5585; Year: 2008; Biosample/Treatment: tissue, gastrointestinal tract/untreated; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
33	Ren H (2008) CST Curation Set: 5627; Year: 2008; Biosample/Treatment: tissue, gastrointestinal tract/untreated; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
34	Gu T (2008) CST Curation Set: 4237; Year: 2008; Biosample/Treatment: tissue, breast/untreated; Disease: breast cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
35	Rikova K (2007) CST Curation Set: 3485; Year: 2007; Biosample/Treatment: tissue, kidney/untreated; Disease: kidney cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
36	Villa-Moruzzi E (2007) Targeting of FAK Ser910 by ERK5 and PP1delta in non-stimulated and phorbol ester-stimulated cells. Biochem J 408, 7-18 17692050 Curated Info
37	Moniz S, et al. (2007) Protein kinase WNK2 inhibits cell proliferation by negatively modulating the activation of MEK1/ERK1/2. Oncogene 26, 6071-81 17667937 Curated Info
38	Gu T (2007) CST Curation Set: 3109; Year: 2007; Biosample/Treatment: tissue, bone marrow/-; Disease: acute myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
39	Rikova K (2007) CST Curation Set: 2247; Year: 2007; Biosample/Treatment: tissue, lung/-; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
40	Wahab NA, Weston BS, Mason RM (2005) Connective tissue growth factor CCN2 interacts with and activates the tyrosine kinase receptor TrkA. J Am Soc Nephrol 16, 340-51 15601748 Curated Info
41	Mody N, et al. (2003) An analysis of the phosphorylation and activation of extracellular-signal-regulated protein kinase 5 (ERK5) by mitogen-activated protein kinase kinase 5 (MKK5) in vitro. Biochem J 372, 567-75 12628002 Curated Info
42	Buschbeck M, Eickhoff J, Sommer MN, Ullrich A (2002) Phosphotyrosine-specific phosphatase PTP-SL regulates the ERK5 signaling pathway. J Biol Chem 277, 29503-9 12042304 Curated Info
43	Esparís-Ogando A, et al. (2002) Erk5 participates in neuregulin signal transduction and is constitutively active in breast cancer cells overexpressing ErbB2. Mol Cell Biol 22, 270-85 11739740 Curated Info
44	Lee JD, Ulevitch RJ, Han J (1995) Primary structure of BMK1: a new mammalian map kinase. Biochem Biophys Res Commun 213, 715-24 7646528 Curated Info