ID STK39_HUMAN Reviewed; 545 AA. AC Q9UEW8; O14774; Q53S90; Q53SL7; Q53SS1; Q9UER4; X5D9C8; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 3. DT 27-MAR-2024, entry version 210. DE RecName: Full=STE20/SPS1-related proline-alanine-rich protein kinase; DE Short=Ste-20-related kinase {ECO:0000303|PubMed:10980603}; DE EC=2.7.11.1 {ECO:0000269|PubMed:16669787, ECO:0000269|PubMed:18270262}; DE AltName: Full=DCHT; DE AltName: Full=Serine/threonine-protein kinase 39; GN Name=STK39; GN Synonyms=PASK {ECO:0000303|PubMed:12740379}, SPAK GN {ECO:0000303|PubMed:10980603}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=10980603; DOI=10.1038/sj.onc.1203784; RA Johnston A.M., Naselli G., Gonez L.J., Martin R.M., Harrison L.C., RA de Aizpurua H.J.; RT "SPAK, a STE20/SPS1-related kinase that activates the p38 pathway."; RL Oncogene 19:4290-4297(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=24722188; DOI=10.1038/ncomms4650; RA Corominas R., Yang X., Lin G.N., Kang S., Shen Y., Ghamsari L., Broly M., RA Rodriguez M., Tam S., Wanamaker S.A., Fan C., Yi S., Tasan M., Lemmens I., RA Kuang X., Zhao N., Malhotra D., Michaelson J.J., Vacic V., Calderwood M.A., RA Roth F.P., Tavernier J., Horvath S., Salehi-Ashtiani K., Korkin D., RA Sebat J., Hill D.E., Hao T., Vidal M., Iakoucheva L.M.; RT "Protein interaction network of alternatively spliced isoforms from brain RT links genetic risk factors for autism."; RL Nat. Commun. 5:3650-3650(2014). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Melnick M.B., Petitt M., Perrimon N., Comb M.J.; RT "New human member of the Ste20 family."; RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 279-545 (ISOFORM 1). RC TISSUE=Testis; RA Baytel D., Don J.; RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases. RN [6] RP FUNCTION, AND MUTAGENESIS OF LYS-92. RX PubMed=12740379; DOI=10.1074/jbc.m301899200; RA Dowd B.F.X., Forbush B.; RT "PASK (proline-alanine-rich STE20-related kinase), a regulatory kinase of RT the Na-K-Cl cotransporter (NKCC1)."; RL J. Biol. Chem. 278:27347-27353(2003). RN [7] RP PHOSPHORYLATION AT SER-309. RX PubMed=14988727; DOI=10.1038/sj.emboj.7600125; RA Li Y., Hu J., Vita R., Sun B., Tabata H., Altman A.; RT "SPAK kinase is a substrate and target of PKCtheta in T-cell receptor- RT induced AP-1 activation pathway."; RL EMBO J. 23:1112-1122(2004). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-477; THR-478; VAL-482; RP GLU-485; LEU-491; VAL-492; ASP-496 AND VAL-500. RX PubMed=16669787; DOI=10.1042/bj20060220; RA Vitari A.C., Thastrup J., Rafiqi F.H., Deak M., Morrice N.A., RA Karlsson H.K., Alessi D.R.; RT "Functional interactions of the SPAK/OSR1 kinases with their upstream RT activator WNK1 and downstream substrate NKCC1."; RL Biochem. J. 397:223-231(2006). RN [9] RP ACTIVITY REGULATION, PHOSPHORYLATION AT THR-231, AND MUTAGENESIS OF RP THR-231. RX PubMed=16832045; DOI=10.1073/pnas.0604607103; RA Anselmo A.N., Earnest S., Chen W., Juang Y.C., Kim S.C., Zhao Y., RA Cobb M.H.; RT "WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter in HeLa cells."; RL Proc. Natl. Acad. Sci. U.S.A. 103:10883-10888(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Prostate cancer; RX PubMed=17487921; DOI=10.1002/elps.200600782; RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.; RT "Toward a global characterization of the phosphoproteome in prostate cancer RT cells: identification of phosphoproteins in the LNCaP cell line."; RL Electrophoresis 28:2027-2034(2007). RN [11] RP ACTIVITY REGULATION, PHOSPHORYLATION AT THR-231 AND SER-371, AND RP MUTAGENESIS OF THR-231 AND SER-371. RX PubMed=17190791; DOI=10.1083/jcb.200605093; RA Zagorska A., Pozo-Guisado E., Boudeau J., Vitari A.C., Rafiqi F.H., RA Thastrup J., Deak M., Campbell D.G., Morrice N.A., Prescott A.R., RA Alessi D.R.; RT "Regulation of activity and localization of the WNK1 protein kinase by RT hyperosmotic stress."; RL J. Cell Biol. 176:89-100(2007). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370; SER-371 AND SER-385, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [14] RP FUNCTION. RX PubMed=19665974; DOI=10.1016/j.cell.2009.05.031; RA Rinehart J., Maksimova Y.D., Tanis J.E., Stone K.L., Hodson C.A., Zhang J., RA Risinger M., Pan W., Wu D., Colangelo C.M., Forbush B., Joiner C.H., RA Gulcicek E.E., Gallagher P.G., Lifton R.P.; RT "Sites of regulated phosphorylation that control K-Cl cotransporter RT activity."; RL Cell 138:525-536(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-349, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [17] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=18270262; DOI=10.1242/jcs.025312; RA Richardson C., Rafiqi F.H., Karlsson H.K., Moleleki N., Vandewalle A., RA Campbell D.G., Morrice N.A., Alessi D.R.; RT "Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK- RT regulated kinases SPAK and OSR1."; RL J. Cell Sci. 121:675-684(2008). RN [18] RP INTERACTION WITH SORL1. RX PubMed=20385770; DOI=10.1128/mcb.01560-09; RA Reiche J., Theilig F., Rafiqi F.H., Carlo A.S., Militz D., Mutig K., RA Todiras M., Christensen E.I., Ellison D.H., Bader M., Nykjaer A., RA Bachmann S., Alessi D., Willnow T.E.; RT "SORLA/SORL1 functionally interacts with SPAK to control renal activation RT of Na(+)-K(+)-Cl(-) cotransporter 2."; RL Mol. Cell. Biol. 30:3027-3037(2010). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [21] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PHOSPHORYLATION AT RP THR-231, AND MUTAGENESIS OF THR-231. RX PubMed=21321328; DOI=10.1242/jcs.077230; RA Richardson C., Sakamoto K., de los Heros P., Deak M., Campbell D.G., RA Prescott A.R., Alessi D.R.; RT "Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and RT -independent pathways."; RL J. Cell Sci. 124:789-800(2011). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-354 AND SER-385, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [24] RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT THR-231, AND MUTAGENESIS RP OF THR-231. RX PubMed=34289367; DOI=10.1016/j.celrep.2021.109416; RA Schiapparelli P., Pirman N.L., Mohler K., Miranda-Herrera P.A., Zarco N., RA Kilic O., Miller C., Shah S.R., Rogulina S., Hungerford W., Abriola L., RA Hoyer D., Turk B.E., Guerrero-Cazares H., Isaacs F.J., RA Quinones-Hinojosa A., Levchenko A., Rinehart J.; RT "Phosphorylated WNK kinase networks in recoded bacteria recapitulate RT physiological function."; RL Cell Rep. 36:109416-109416(2021). CC -!- FUNCTION: Effector serine/threonine-protein kinase component of the CC WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, CC such as ion transport, response to hypertonic stress and blood pressure CC (PubMed:16669787, PubMed:18270262, PubMed:21321328, PubMed:34289367). CC Specifically recognizes and binds proteins with a RFXV motif CC (PubMed:16669787, PubMed:21321328). Acts downstream of WNK kinases CC (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, CC catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, CC SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating CC their activity (PubMed:21321328). Mediates regulatory volume increase CC in response to hyperosmotic stress by catalyzing phosphorylation of ion CC cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream CC of WNK1 and WNK3 kinases (PubMed:12740379, PubMed:16669787, CC PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters CC SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion CC influx; simultaneously, phosphorylation of K-Cl cotransporters CC SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion CC efflux (PubMed:16669787, PubMed:19665974, PubMed:21321328). Acts as a CC regulator of NaCl reabsorption in the distal nephron by mediating CC phosphorylation and activation of the thiazide-sensitive Na-Cl CC cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney CC downstream of WNK4 (PubMed:18270262). Mediates the inhibition of CC SLC4A4, SLC26A6 as well as CFTR activities (By similarity). CC Phosphorylates RELT (By similarity). {ECO:0000250|UniProtKB:Q9Z1W9, CC ECO:0000269|PubMed:12740379, ECO:0000269|PubMed:16669787, CC ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:19665974, CC ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:34289367}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:16669787, CC ECO:0000269|PubMed:18270262}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:Q9Z1W9}; CC -!- ACTIVITY REGULATION: Activated following phosphorylation at Thr-231 by CC WNK kinases (WNK1, WNK2, WNK3 or WNK4) (PubMed:16832045, CC PubMed:17190791, PubMed:21321328, PubMed:34289367). Specifically CC inhibited by YU239252 (YU252) (PubMed:34289367). CC {ECO:0000269|PubMed:16832045, ECO:0000269|PubMed:17190791, CC ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:34289367}. CC -!- SUBUNIT: The phosphorylated form forms a complex with WNK2 (By CC similarity). Interacts with SORL1 (via cytosolic C-terminus) CC (PubMed:20385770). {ECO:0000250|UniProtKB:Q9Z1W9, CC ECO:0000269|PubMed:20385770}. CC -!- INTERACTION: CC Q9UEW8; Q9Y376: CAB39; NbExp=4; IntAct=EBI-2680974, EBI-306905; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Nucleus {ECO:0000305}. CC Note=Nucleus when caspase-cleaved. {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UEW8-1; Sequence=Displayed; CC Name=2; Synonyms=A; CC IsoId=Q9UEW8-2; Sequence=VSP_055889; CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain and pancreas CC followed by heart, lung, kidney, skeletal muscle, liver, placenta and CC testis. {ECO:0000269|PubMed:10980603}. CC -!- DOMAIN: PAPA box (proline-alanine repeats) may target the kinase to a CC specific subcellular location by facilitating interaction with CC intracellular proteins such as actin or actin-like proteins. CC {ECO:0000269|PubMed:10980603}. CC -!- PTM: Phosphorylation at Thr-231 by WNK kinases (WNK1, WNK2, WNK3 or CC WNK4) is required for activation (PubMed:16832045, PubMed:17190791, CC PubMed:21321328, PubMed:34289367). Autophosphorylation at Thr-231 CC positively regulates its activity (By similarity). Phosphorylated at CC Ser-309 by PRKCQ (PubMed:14988727). {ECO:0000250|UniProtKB:Q9Z1W9, CC ECO:0000269|PubMed:14988727, ECO:0000269|PubMed:16832045, CC ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:21321328, CC ECO:0000269|PubMed:34289367}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr CC protein kinase family. STE20 subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF099989; AAC72238.1; -; mRNA. DR EMBL; KJ534948; AHW56588.1; -; mRNA. DR EMBL; AF030403; AAD01901.1; -; mRNA. DR EMBL; AC016723; AAY15003.1; -; Genomic_DNA. DR EMBL; AC017069; AAY14897.1; -; Genomic_DNA. DR EMBL; AC067940; AAY24032.1; -; Genomic_DNA. DR EMBL; AF017635; AAB70552.1; -; mRNA. DR CCDS; CCDS42770.1; -. [Q9UEW8-1] DR RefSeq; NP_037365.2; NM_013233.2. [Q9UEW8-1] DR PDB; 7O86; X-ray; 1.73 A; A/B=441-545. DR PDBsum; 7O86; -. DR AlphaFoldDB; Q9UEW8; -. DR SMR; Q9UEW8; -. DR BioGRID; 118159; 104. DR CORUM; Q9UEW8; -. DR ELM; Q9UEW8; -. DR IntAct; Q9UEW8; 29. DR MINT; Q9UEW8; -. DR STRING; 9606.ENSP00000348278; -. DR BindingDB; Q9UEW8; -. DR ChEMBL; CHEMBL1163108; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; Q9UEW8; -. DR GlyGen; Q9UEW8; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9UEW8; -. DR PhosphoSitePlus; Q9UEW8; -. DR SwissPalm; Q9UEW8; -. DR BioMuta; STK39; -. DR DMDM; 317373508; -. DR EPD; Q9UEW8; -. DR jPOST; Q9UEW8; -. DR MassIVE; Q9UEW8; -. DR MaxQB; Q9UEW8; -. DR PaxDb; 9606-ENSP00000348278; -. DR PeptideAtlas; Q9UEW8; -. DR ProteomicsDB; 84159; -. [Q9UEW8-1] DR Pumba; Q9UEW8; -. DR Antibodypedia; 33792; 877 antibodies from 41 providers. DR DNASU; 27347; -. DR Ensembl; ENST00000355999.5; ENSP00000348278.4; ENSG00000198648.12. [Q9UEW8-1] DR GeneID; 27347; -. DR KEGG; hsa:27347; -. DR MANE-Select; ENST00000355999.5; ENSP00000348278.4; NM_013233.3; NP_037365.2. DR UCSC; uc002uea.4; human. [Q9UEW8-1] DR AGR; HGNC:17717; -. DR DisGeNET; 27347; -. DR GeneCards; STK39; -. DR HGNC; HGNC:17717; STK39. DR HPA; ENSG00000198648; Low tissue specificity. DR MIM; 607648; gene. DR neXtProt; NX_Q9UEW8; -. DR OpenTargets; ENSG00000198648; -. DR PharmGKB; PA38243; -. DR VEuPathDB; HostDB:ENSG00000198648; -. DR eggNOG; KOG0582; Eukaryota. DR GeneTree; ENSGT00940000154621; -. DR HOGENOM; CLU_000288_111_1_1; -. DR InParanoid; Q9UEW8; -. DR OMA; CKFIQKA; -. DR OrthoDB; 152877at2759; -. DR PhylomeDB; Q9UEW8; -. DR TreeFam; TF105339; -. DR BRENDA; 2.7.11.1; 2681. DR PathwayCommons; Q9UEW8; -. DR SignaLink; Q9UEW8; -. DR SIGNOR; Q9UEW8; -. DR BioGRID-ORCS; 27347; 18 hits in 1181 CRISPR screens. DR ChiTaRS; STK39; human. DR GeneWiki; STK39; -. DR GenomeRNAi; 27347; -. DR Pharos; Q9UEW8; Tchem. DR PRO; PR:Q9UEW8; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9UEW8; Protein. DR Bgee; ENSG00000198648; Expressed in endothelial cell and 206 other cell types or tissues. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl. DR GO; GO:0044297; C:cell body; IEA:Ensembl. DR GO; GO:0005938; C:cell cortex; ISS:ParkinsonsUK-UCL. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016301; F:kinase activity; ISS:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0006884; P:cell volume homeostasis; IDA:UniProt. DR GO; GO:0071474; P:cellular hyperosmotic response; IDA:UniProt. DR GO; GO:0071476; P:cellular hypotonic response; IDA:ParkinsonsUK-UCL. DR GO; GO:1990869; P:cellular response to chemokine; IMP:BHF-UCL. DR GO; GO:0035865; P:cellular response to potassium ion; IEA:Ensembl. DR GO; GO:0038146; P:chemokine (C-X-C motif) ligand 12 signaling pathway; IMP:BHF-UCL. DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl. DR GO; GO:0030644; P:intracellular chloride ion homeostasis; IEA:Ensembl. DR GO; GO:0035556; P:intracellular signal transduction; IDA:ParkinsonsUK-UCL. DR GO; GO:0042116; P:macrophage activation; IEA:Ensembl. DR GO; GO:0036438; P:maintenance of lens transparency; ISS:ParkinsonsUK-UCL. DR GO; GO:1905408; P:negative regulation of creatine transmembrane transporter activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0090188; P:negative regulation of pancreatic juice secretion; IEA:Ensembl. DR GO; GO:1901380; P:negative regulation of potassium ion transmembrane transport; IDA:ParkinsonsUK-UCL. DR GO; GO:1901017; P:negative regulation of potassium ion transmembrane transporter activity; IDA:ParkinsonsUK-UCL. DR GO; GO:2000650; P:negative regulation of sodium ion transmembrane transporter activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:ParkinsonsUK-UCL. DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:ParkinsonsUK-UCL. DR GO; GO:0032414; P:positive regulation of ion transmembrane transporter activity; ISS:ParkinsonsUK-UCL. DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IMP:UniProtKB. DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; IMP:BHF-UCL. DR GO; GO:0046777; P:protein autophosphorylation; IMP:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl. DR GO; GO:0050727; P:regulation of inflammatory response; IEA:Ensembl. DR GO; GO:0070294; P:renal sodium ion absorption; IDA:UniProt. DR GO; GO:1904044; P:response to aldosterone; IEA:Ensembl. DR GO; GO:0002021; P:response to dietary excess; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; IDA:ParkinsonsUK-UCL. DR GO; GO:0035725; P:sodium ion transmembrane transport; IEA:Ensembl. DR CDD; cd06610; STKc_OSR1_SPAK; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR024678; Kinase_OSR1/WNK_CCT. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR PANTHER; PTHR48012:SF14; STE20_SPS1-RELATED PROLINE-ALANINE-RICH PROTEIN KINASE; 1. DR PANTHER; PTHR48012; STERILE20-LIKE KINASE, ISOFORM B-RELATED; 1. DR Pfam; PF12202; OSR1_C; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR Genevisible; Q9UEW8; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm; KW Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transferase. FT CHAIN 1..545 FT /note="STE20/SPS1-related proline-alanine-rich protein FT kinase" FT /id="PRO_0000086722" FT DOMAIN 63..337 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 310..536 FT /note="Interaction with RELT" FT /evidence="ECO:0000250|UniProtKB:Q9Z1W9" FT REGION 361..423 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 360..366 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT MOTIF 387..391 FT /note="Caspase cleavage related site" FT COMPBIAS 391..413 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 192 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 69..77 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 92 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 231 FT /note="Phosphothreonine; by WNK1" FT /evidence="ECO:0000269|PubMed:16832045, FT ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:21321328, FT ECO:0000269|PubMed:34289367" FT MOD_RES 235 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1W9" FT MOD_RES 309 FT /note="Phosphoserine; by PKC/PRKCQ" FT /evidence="ECO:0000269|PubMed:14988727" FT MOD_RES 349 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 354 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 370 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18088087" FT MOD_RES 371 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:17190791, FT ECO:0007744|PubMed:18088087" FT MOD_RES 385 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17487921, FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 393 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1W9" FT VAR_SEQ 28..46 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:24722188" FT /id="VSP_055889" FT MUTAGEN 92 FT /note="K->R: Abolished serine/threonine-protein kinase FT activity." FT /evidence="ECO:0000269|PubMed:12740379" FT MUTAGEN 231 FT /note="T->A: Prevents phosphorylation and activation by WNK FT kinases." FT /evidence="ECO:0000269|PubMed:17190791" FT MUTAGEN 231 FT /note="T->E,D: Mimics phosphorylation; promoting kinase FT activity independently of WNK kinases." FT /evidence="ECO:0000269|PubMed:16832045, FT ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:21321328, FT ECO:0000269|PubMed:34289367" FT MUTAGEN 371 FT /note="S->A: Does not affect activation by WNK kinases." FT /evidence="ECO:0000269|PubMed:17190791" FT MUTAGEN 371 FT /note="S->E: Does not greatly affect the kinase activity." FT /evidence="ECO:0000269|PubMed:17190791" FT MUTAGEN 477 FT /note="D->A: Abolished binding to WNK1 and SLC12A2/NKCC1." FT /evidence="ECO:0000269|PubMed:16669787" FT MUTAGEN 478 FT /note="T->A: Decreased binding to SLC12A2/NKCC1." FT /evidence="ECO:0000269|PubMed:16669787" FT MUTAGEN 482 FT /note="V->A: Decreased binding to SLC12A2/NKCC1." FT /evidence="ECO:0000269|PubMed:16669787" FT MUTAGEN 485 FT /note="E->A: Decreased binding to SLC12A2/NKCC1." FT /evidence="ECO:0000269|PubMed:16669787" FT MUTAGEN 491 FT /note="L->A: Abolished binding to WNK1 and SLC12A2/NKCC1." FT /evidence="ECO:0000269|PubMed:16669787" FT MUTAGEN 492 FT /note="V->A: Decreased binding to SLC12A2/NKCC1." FT /evidence="ECO:0000269|PubMed:16669787" FT MUTAGEN 496 FT /note="D->A: Decreased binding to SLC12A2/NKCC1." FT /evidence="ECO:0000269|PubMed:16669787" FT MUTAGEN 500 FT /note="V->A: Decreased binding to SLC12A2/NKCC1." FT /evidence="ECO:0000269|PubMed:16669787" FT CONFLICT 41 FT /note="A -> AAP (in Ref. 1; AAC72238 and 3; AAD01901)" FT /evidence="ECO:0000305" FT CONFLICT 173 FT /note="L -> F (in Ref. 3; AAD01901)" FT /evidence="ECO:0000305" FT CONFLICT 416 FT /note="A -> V (in Ref. 2; AHW56588)" FT /evidence="ECO:0000305" FT STRAND 452..459 FT /evidence="ECO:0007829|PDB:7O86" FT STRAND 465..472 FT /evidence="ECO:0007829|PDB:7O86" FT TURN 474..476 FT /evidence="ECO:0007829|PDB:7O86" FT HELIX 479..488 FT /evidence="ECO:0007829|PDB:7O86" FT HELIX 494..496 FT /evidence="ECO:0007829|PDB:7O86" FT HELIX 497..508 FT /evidence="ECO:0007829|PDB:7O86" FT TURN 511..513 FT /evidence="ECO:0007829|PDB:7O86" FT STRAND 516..520 FT /evidence="ECO:0007829|PDB:7O86" FT STRAND 522..524 FT /evidence="ECO:0007829|PDB:7O86" FT STRAND 526..528 FT /evidence="ECO:0007829|PDB:7O86" FT TURN 533..536 FT /evidence="ECO:0007829|PDB:7O86" FT STRAND 537..544 FT /evidence="ECO:0007829|PDB:7O86" SQ SEQUENCE 545 AA; 59474 MW; 35E68F400A38A861 CRC64; MAEPSGSPVH VQLPQQAAPV TAAAAAAPAA ATAAPAPAAP AAPAPAPAPA AQAVGWPICR DAYELQEVIG SGATAVVQAA LCKPRQERVA IKRINLEKCQ TSMDELLKEI QAMSQCSHPN VVTYYTSFVV KDELWLVMKL LSGGSMLDII KYIVNRGEHK NGVLEEAIIA TILKEVLEGL DYLHRNGQIH RDLKAGNILL GEDGSVQIAD FGVSAFLATG GDVTRNKVRK TFVGTPCWMA PEVMEQVRGY DFKADMWSFG ITAIELATGA APYHKYPPMK VLMLTLQNDP PTLETGVEDK EMMKKYGKSF RKLLSLCLQK DPSKRPTAAE LLKCKFFQKA KNREYLIEKL LTRTPDIAQR AKKVRRVPGS SGHLHKTEDG DWEWSDDEMD EKSEEGKAAF SQEKSRRVKE ENPEIAVSAS TIPEQIQSLS VHDSQGPPNA NEDYREASSC AVNLVLRLRN SRKELNDIRF EFTPGRDTAD GVSQELFSAG LVDGHDVVIV AANLQKIVDD PKALKTLTFK LASGCDGSEI PDEVKLIGFA QLSVS //