STK39_MOUSE
ID STK39_MOUSE Reviewed; 556 AA.
AC Q9Z1W9; Q80W13;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=STE20/SPS1-related proline-alanine-rich protein kinase;
DE Short=Ste-20-related kinase;
DE EC=2.7.11.1;
DE AltName: Full=Serine/threonine-protein kinase 39;
GN Name=Stk39; Synonyms=Spak;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, INTERACTION WITH RELT, MUTAGENESIS OF LYS-104 AND THR-243, AND
RP PHOSPHORYLATION AT THR-243.
RX PubMed=16530727; DOI=10.1016/j.bbrc.2006.02.125;
RA Polek T.C., Talpaz M., Spivak-Kroizman T.;
RT "The TNF receptor, RELT, binds SPAK and uses it to mediate p38 and JNK
RT activation.";
RL Biochem. Biophys. Res. Commun. 343:125-134(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397 AND SER-405, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP TISSUE SPECIFICITY.
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 [6]
RP PHOSPHORYLATION AT THR-366 AND SER-383, AND INTERACTION WITH WNK2.
RX PubMed=21733846; DOI=10.1074/jbc.m111.222893;
RA Rinehart J., Vazquez N., Kahle K.T., Hodson C.A., Ring A.M., Gulcicek E.E.,
RA Louvi A., Bobadilla N.A., Gamba G., Lifton R.P.;
RT "WNK2 is a novel regulator of essential neuronal cation-chloride
RT cotransporters.";
RL J. Biol. Chem. 286:30171-30180(2011).
RN [7]
RP FUNCTION.
RX PubMed=21317537; DOI=10.1172/jci43475;
RA Yang D., Li Q., So I., Huang C.L., Ando H., Mizutani A., Seki G.,
RA Mikoshiba K., Thomas P.J., Muallem S.;
RT "IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK
RT kinase pathway.";
RL J. Clin. Invest. 121:956-965(2011).
RN [8]
RP FUNCTION.
RX PubMed=23542070; DOI=10.1053/j.gastro.2013.03.047;
RA Park S., Shcheynikov N., Hong J.H., Zheng C., Suh S.H., Kawaai K., Ando H.,
RA Mizutani A., Abe T., Kiyonari H., Seki G., Yule D., Mikoshiba K.,
RA Muallem S.;
RT "Irbit mediates synergy between ca(2+) and cAMP signaling pathways during
RT epithelial transport in mice.";
RL Gastroenterology 145:232-241(2013).
CC -!- FUNCTION: May act as a mediator of stress-activated signals. Mediates
CC the inhibition of SLC4A4, SLC26A6 as well as CFTR activities by the WNK
CC scaffolds, probably through phosphorylation (PubMed:21317537,
CC PubMed:23542070). Phosphorylates RELT (PubMed:16530727).
CC {ECO:0000269|PubMed:16530727, ECO:0000269|PubMed:21317537,
CC ECO:0000269|PubMed:23542070}.
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;
CC -!- SUBUNIT: The phosphorylated form forms a complex with WNK2
CC (PubMed:21733846). Interacts with RELT (PubMed:16530727). Interacts
CC with SORL1 (via cytosolic C-terminus) (By similarity).
CC {ECO:0000250|UniProtKB:Q9UEW8, ECO:0000269|PubMed:16530727,
CC ECO:0000269|PubMed:21733846}.
CC -!- INTERACTION:
CC Q9Z1W9; P47811: Mapk14; NbExp=2; IntAct=EBI-444764, EBI-298727;
CC Q9Z1W9; P55012: Slc12a2; NbExp=3; IntAct=EBI-444764, EBI-621078;
CC Q9Z1W9; Q924N4-1: Slc12a6; NbExp=4; IntAct=EBI-444764, EBI-620992;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Nucleus {ECO:0000305}.
CC Note=Nucleus when caspase-cleaved. {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in the kidney, including in epithelial
CC cells of the thick ascending limb of Henle's loop and in the distal
CC convoluted tubule (at protein level). {ECO:0000269|PubMed:20385770}.
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 -!- PTM: Phosphorylated at Ser-321 by PRKCQ (PubMed:21733846).
CC Autophosphorylation at Thr-243 positively regulates its activity
CC (PubMed:16530727). {ECO:0000269|PubMed:16530727,
CC ECO:0000269|PubMed:21733846}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
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DR EMBL; AF099988; AAC72237.1; -; mRNA.
DR EMBL; BC051964; AAH51964.2; -; mRNA.
DR EMBL; BC064443; AAH64443.1; -; mRNA.
DR CCDS; CCDS16084.1; -.
DR RefSeq; NP_058562.1; NM_016866.2.
DR PDB; 5D9H; X-ray; 3.10 A; A/B=63-403.
DR PDB; 5DBX; X-ray; 2.50 A; A/B=63-390.
DR PDBsum; 5D9H; -.
DR PDBsum; 5DBX; -.
DR AlphaFoldDB; Q9Z1W9; -.
DR SMR; Q9Z1W9; -.
DR BioGRID; 207310; 5.
DR DIP; DIP-31911N; -.
DR ELM; Q9Z1W9; -.
DR IntAct; Q9Z1W9; 12.
DR MINT; Q9Z1W9; -.
DR STRING; 10090.ENSMUSP00000099776; -.
DR iPTMnet; Q9Z1W9; -.
DR PhosphoSitePlus; Q9Z1W9; -.
DR EPD; Q9Z1W9; -.
DR jPOST; Q9Z1W9; -.
DR MaxQB; Q9Z1W9; -.
DR PaxDb; Q9Z1W9; -.
DR PRIDE; Q9Z1W9; -.
DR ProteomicsDB; 258762; -.
DR Antibodypedia; 33792; 803 antibodies from 41 providers.
DR DNASU; 53416; -.
DR Ensembl; ENSMUST00000102715; ENSMUSP00000099776; ENSMUSG00000027030.
DR GeneID; 53416; -.
DR KEGG; mmu:53416; -.
DR UCSC; uc008jxo.1; mouse.
DR CTD; 27347; -.
DR MGI; MGI:1858416; Stk39.
DR VEuPathDB; HostDB:ENSMUSG00000027030; -.
DR eggNOG; KOG0582; Eukaryota.
DR GeneTree; ENSGT00940000154621; -.
DR HOGENOM; CLU_000288_111_1_1; -.
DR InParanoid; Q9Z1W9; -.
DR OMA; KEENPEX; -.
DR OrthoDB; 688282at2759; -.
DR PhylomeDB; Q9Z1W9; -.
DR TreeFam; TF105339; -.
DR BRENDA; 2.7.11.1; 3474.
DR BioGRID-ORCS; 53416; 0 hits in 75 CRISPR screens.
DR ChiTaRS; Stk39; mouse.
DR PRO; PR:Q9Z1W9; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9Z1W9; protein.
DR Bgee; ENSMUSG00000027030; Expressed in choroid plexus epithelium and 255 other tissues.
DR ExpressionAtlas; Q9Z1W9; baseline and differential.
DR Genevisible; Q9Z1W9; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:MGI.
DR GO; GO:0044297; C:cell body; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0019898; C:extrinsic component of membrane; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IMP:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IMP:ARUK-UCL.
DR GO; GO:0030644; P:cellular chloride ion homeostasis; IGI:MGI.
DR GO; GO:0071476; P:cellular hypotonic response; IGI:ParkinsonsUK-UCL.
DR GO; GO:1990869; P:cellular response to chemokine; ISO:MGI.
DR GO; GO:0035865; P:cellular response to potassium ion; IDA:MGI.
DR GO; GO:0038146; P:chemokine (C-X-C motif) ligand 12 signaling pathway; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IGI:ParkinsonsUK-UCL.
DR GO; GO:0050801; P:ion homeostasis; IMP:MGI.
DR GO; GO:0042116; P:macrophage activation; IMP:MGI.
DR GO; GO:0036438; P:maintenance of lens transparency; IMP:ParkinsonsUK-UCL.
DR GO; GO:1905408; P:negative regulation of creatine transmembrane transporter activity; ISO:MGI.
DR GO; GO:0090188; P:negative regulation of pancreatic juice secretion; IMP:UniProtKB.
DR GO; GO:1901380; P:negative regulation of potassium ion transmembrane transport; IGI:ParkinsonsUK-UCL.
DR GO; GO:1901017; P:negative regulation of potassium ion transmembrane transporter activity; IGI:ParkinsonsUK-UCL.
DR GO; GO:2000650; P:negative regulation of sodium ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:0032414; P:positive regulation of ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISS:UniProtKB.
DR GO; GO:0043268; P:positive regulation of potassium ion transport; ISO:MGI.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; IMP:MGI.
DR GO; GO:0050727; P:regulation of inflammatory response; IDA:MGI.
DR GO; GO:1904044; P:response to aldosterone; IGI:MGI.
DR GO; GO:0002021; P:response to dietary excess; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IMP:MGI.
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 Pfam; PF12202; OSR1_C; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cytoplasm; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..556
FT /note="STE20/SPS1-related proline-alanine-rich protein
FT kinase"
FT /id="PRO_0000086723"
FT DOMAIN 75..349
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 322..547
FT /note="Interaction with RELT"
FT /evidence="ECO:0000269|PubMed:16530727"
FT REGION 373..434
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 372..378
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 399..403
FT /note="Caspase cleavage related site"
FT COMPBIAS 34..58
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 403..425
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 204
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 81..89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 104
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 243
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:16530727"
FT MOD_RES 321
FT /note="Phosphoserine; by PKC/PRKCQ"
FT /evidence="ECO:0000250|UniProtKB:Q9UEW8"
FT MOD_RES 361
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9UEW8"
FT MOD_RES 366
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21733846"
FT MOD_RES 382
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UEW8"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21733846"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 405
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 104
FT /note="K->E: Loss of kinase activity but no loss of
FT interaction with RELT."
FT /evidence="ECO:0000269|PubMed:16530727"
FT MUTAGEN 243
FT /note="T->Q: Increased kinase activity and
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:16530727"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:5DBX"
FT STRAND 75..83
FT /evidence="ECO:0007829|PDB:5DBX"
FT STRAND 88..94
FT /evidence="ECO:0007829|PDB:5DBX"
FT TURN 95..98
FT /evidence="ECO:0007829|PDB:5DBX"
FT STRAND 99..107
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 114..123
FT /evidence="ECO:0007829|PDB:5DBX"
FT TURN 124..127
FT /evidence="ECO:0007829|PDB:5DBX"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:5DBX"
FT STRAND 145..151
FT /evidence="ECO:0007829|PDB:5DBX"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 158..167
FT /evidence="ECO:0007829|PDB:5DBX"
FT TURN 168..173
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 178..197
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:5DBX"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:5DBX"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 224..228
FT /evidence="ECO:0007829|PDB:5DBX"
FT TURN 230..232
FT /evidence="ECO:0007829|PDB:5D9H"
FT HELIX 233..236
FT /evidence="ECO:0007829|PDB:5D9H"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 253..260
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 265..280
FT /evidence="ECO:0007829|PDB:5DBX"
FT TURN 284..287
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 290..299
FT /evidence="ECO:0007829|PDB:5DBX"
FT TURN 305..308
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 312..315
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 320..329
FT /evidence="ECO:0007829|PDB:5DBX"
FT TURN 334..336
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 340..343
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 347..351
FT /evidence="ECO:0007829|PDB:5DBX"
FT HELIX 355..361
FT /evidence="ECO:0007829|PDB:5DBX"
FT TURN 362..364
FT /evidence="ECO:0007829|PDB:5DBX"
SQ SEQUENCE 556 AA; 60320 MW; 66085A90554311D8 CRC64;
MAEPSGSPVH VQLSQQAAPV TAAAATAPAA ATSAPAPAPA PAPAASAAPA PAPAAAPAPA
PAAQAVGWPI CRDAYELQEV IGSGATAVVQ AALCKPRQER VAIKRINLEK CQTSMDELLK
EIQAMSQCSH PNVVTYYTSF VVKDELWLVM KLLSGGSMLD IIKYIVNRGE HKNGVLEEAI
IATILKEVLE GLDYLHRNGQ IHRDLKAGNI LLGEDGSVQI ADFGVSAFLA TGGDVTRNKV
RKTFVGTPCW MAPEVMEQVR GYDFKADMWS FGITAIELAT GAAPYHKYPP MKVLMLTLQN
DPPTLETGVE DKEMMKKYGK SFRKLLSLCL QKDPSKRPTA AELLKCKFFQ KAKNREYLIE
KLLTRTPDIA QRAKKVRRVP GSSGHLHKTE DGDWEWSDDE MDEKSEEGKA AASQEKSRRV
KEENSEISVN AGGIPEQIQS LSVHDSQAQP NANEDYREGP CAVNLVLRLR NSRKELNDIR
FEFTPGRDTA DGVSQELFSA GLVDGHDVVI VAANLQKIVD DPKALKTLTF KLASGCDGSE
IPDEVKLIGF AQLSVS
