Ser371

Site Information
VRRVPGssGHLHKTE SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 456506

In vivo Characterization
Methods used to characterize site in vivo:	immunoprecipitation ( 3 ) , mass spectrometry ( 2 , 4 , 5 , 6 , 7 , 9 , 11 , 12 , 14 , 15 , 17 , 18 ) , mutation of modification site ( 3 , 19 ) , phospho-antibody ( 1 , 3 , 10 , 13 , 16 , 19 ) , western blotting ( 1 , 3 , 13 , 16 , 19 )
Disease tissue studied:	melanoma skin cancer ( 4 )
Relevant cell line - cell type - tissue:	'neuron, cortical' ( 1 ) , 293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] ( 12 ) , 293 (epithelial) ( 1 , 3 , 16 , 19 ) , brain ( 11 ) , erythrocyte-blood ( 13 ) , fibroblast-skin ( 3 ) , Flp-In T-Rex-293 (epithelial) [PRKD1 (human), genetic knockin] ( 9 ) , Flp-In T-Rex-293 (epithelial) ( 9 ) , HeLa (cervical) ( 2 , 5 , 14 , 19 ) , Jurkat (T lymphocyte) ( 7 , 18 ) , liver ( 6 ) , MDA-MB-435S (breast cell) ( 15 ) , platelet-blood ( 17 ) , WM239A (melanocyte) ( 4 )

Upstream Regulation
Regulatory protein:	WNK1 (human) ( 13 , 19 )
Putative in vivo kinases:	WNK2 (human) ( 11 )
Kinases, in vitro:	WNK1 (human) ( 20 )
Treatments:	A-769662 ( 13 ) , hypotonic_buffer ( 16 ) , low_chloride ( 3 ) , N-ethylmaleimede ( 1 ) , sorbitol ( 19 ) , sucrose ( 13 )

Downstream Regulation
Effects of modification on STLK3:	enzymatic activity, induced ( 16 )
Effects of modification on biological processes:	signaling pathway regulation ( 11 )

References
1	Conway LC, et al. (2017) N-Ethylmaleimide increases KCC2 cotransporter activity by modulating transporter phosphorylation. J Biol Chem 292, 21253-21263 29092909 Curated Info
2	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
3	Kahle KT, et al. (2016) Peripheral motor neuropathy is associated with defective kinase regulation of the KCC3 cotransporter. Sci Signal 9, ra77 27485015 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	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
7	Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7 23749302 Curated Info
8	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
9	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
10	Thastrup JO, et al. (2012) SPAK/OSR1 regulate NKCC1 and WNK activity: analysis of WNK isoform interactions and activation by T-loop trans-autophosphorylation. Biochem J 441, 325-37 22032326 Curated Info
11	Rinehart J, et al. (2011) WNK2 Kinase Is a Novel Regulator of Essential Neuronal Cation-Chloride Cotransporters. J Biol Chem 286, 30171-80 21733846 Curated Info
12	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
13	Sid B, et al. (2010) Stimulation of human and mouse erythrocyte Na(+)-K(+)-2Cl(-) cotransport by osmotic shrinkage does not involve AMP-activated protein kinase, but is associated with STE20/SPS1-related proline/alanine-rich kinase activation. J Physiol 588, 2315-28 20442269 Curated Info
14	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
15	Oppermann FS, et al. (2009) Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics 8, 1751-64 19369195 Curated Info
16	Richardson C, et al. (2008) Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1. J Cell Sci 121, 675-84 18270262 Curated Info
17	Zahedi RP, et al. (2008) Phosphoproteome of resting human platelets. J Proteome Res 7, 526-34 18088087 Curated Info
18	Possemato A (2008) CST Curation Set: 3661; Year: 2008; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS:pSXXXpS Curated Info
19	Zagórska A, et al. (2007) Regulation of activity and localization of the WNK1 protein kinase by hyperosmotic stress. J Cell Biol 176, 89-100 17190791 Curated Info
20	Vitari AC, Deak M, Morrice NA, Alessi DR (2005) The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases. Biochem J 391, 17-24 16083423 Curated Info