STK39_RAT
ID STK39_RAT Reviewed; 553 AA.
AC O88506; O70541;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 179.
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=Pancreatic serine/threonine-protein kinase;
DE Short=PS/TK;
DE Short=PSTK1;
DE AltName: Full=Serine/threonine-protein kinase 39;
GN Name=Stk39; Synonyms=Pask, Spak;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9675032; DOI=10.1006/abbi.1998.0736;
RA Ushiro H., Tsutsumi T., Suzuki K., Kayahara T., Nakano K.;
RT "Molecular cloning and characterization of a novel Ste20-related protein
RT kinase enriched in neurons and transporting epithelia.";
RL Arch. Biochem. Biophys. 355:233-240(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Pancreas;
RX PubMed=10990492; DOI=10.1177/002215540004801009;
RA Miao N., Fung B., Sanchez R., Lydon J., Barker D., Pang K.;
RT "Isolation and expression of PASK, a serine/threonine kinase, during rat
RT embryonic development, with special emphasis on the pancreas.";
RL J. Histochem. Cytochem. 48:1391-1400(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Insulinoma;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-363 AND SER-394, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. Phosphorylates RELT.
CC {ECO:0000250|UniProtKB:Q9Z1W9}.
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 (By
CC similarity). Interacts with RELT (By similarity). Interacts with SORL1
CC (via cytosolic C-terminus) (By similarity).
CC {ECO:0000250|UniProtKB:Q9UEW8, ECO:0000250|UniProtKB:Q9Z1W9}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Nucleus {ECO:0000305}.
CC Note=Nucleus when caspase-cleaved. {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis followed by pancreas,
CC kidney, heart and brain. Not expressed in skeletal muscle, liver, lung
CC and spleen.
CC -!- DEVELOPMENTAL STAGE: Expressed in the early gut and pancreatic
CC epithelium, at E15 day localized to cells that will eventually become
CC exocrine. Expressed in choroid plexus, developing myocardium,
CC pancreatic epithelium and dorsal root ganglia.
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-318 by PRKCQ. Autophosphorylation at Thr-240
CC positively regulates its activity. {ECO:0000250|UniProtKB:Q9Z1W9}.
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; D88190; BAA26000.1; -; mRNA.
DR EMBL; AF068261; AAC23501.1; -; mRNA.
DR EMBL; AF099990; AAC72239.1; -; mRNA.
DR RefSeq; NP_062235.1; NM_019362.1.
DR AlphaFoldDB; O88506; -.
DR SMR; O88506; -.
DR BioGRID; 248540; 3.
DR ELM; O88506; -.
DR IntAct; O88506; 1.
DR STRING; 10116.ENSRNOP00000034162; -.
DR BindingDB; O88506; -.
DR ChEMBL; CHEMBL4105808; -.
DR iPTMnet; O88506; -.
DR PhosphoSitePlus; O88506; -.
DR SwissPalm; O88506; -.
DR jPOST; O88506; -.
DR PaxDb; O88506; -.
DR PRIDE; O88506; -.
DR Ensembl; ENSRNOT00000098784; ENSRNOP00000089326; ENSRNOG00000024808.
DR GeneID; 54348; -.
DR KEGG; rno:54348; -.
DR UCSC; RGD:621643; rat.
DR CTD; 27347; -.
DR RGD; 621643; Stk39.
DR eggNOG; KOG0582; Eukaryota.
DR GeneTree; ENSGT00940000154621; -.
DR HOGENOM; CLU_000288_111_1_1; -.
DR InParanoid; O88506; -.
DR OMA; KEENPEX; -.
DR OrthoDB; 688282at2759; -.
DR PhylomeDB; O88506; -.
DR TreeFam; TF105339; -.
DR BRENDA; 2.7.11.1; 5301.
DR PRO; PR:O88506; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000024808; Expressed in testis and 19 other tissues.
DR ExpressionAtlas; O88506; baseline and differential.
DR Genevisible; O88506; RN.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0044297; C:cell body; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005856; C:cytoskeleton; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:ParkinsonsUK-UCL.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:RGD.
DR GO; GO:0030644; P:cellular chloride ion homeostasis; IEA:Ensembl.
DR GO; GO:0071476; P:cellular hypotonic response; ISO:RGD.
DR GO; GO:1990869; P:cellular response to chemokine; ISO:RGD.
DR GO; GO:0035865; P:cellular response to potassium ion; ISO:RGD.
DR GO; GO:0038146; P:chemokine (C-X-C motif) ligand 12 signaling pathway; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
DR GO; GO:0050801; P:ion homeostasis; ISO:RGD.
DR GO; GO:0042116; P:macrophage activation; ISO:RGD.
DR GO; GO:0036438; P:maintenance of lens transparency; ISO:RGD.
DR GO; GO:1905408; P:negative regulation of creatine transmembrane transporter activity; ISO:RGD.
DR GO; GO:0090188; P:negative regulation of pancreatic juice secretion; ISO:RGD.
DR GO; GO:1901380; P:negative regulation of potassium ion transmembrane transport; ISO:RGD.
DR GO; GO:1901017; P:negative regulation of potassium ion transmembrane transporter activity; ISO:RGD.
DR GO; GO:2000650; P:negative regulation of sodium ion transmembrane transporter activity; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0032414; P:positive regulation of ion transmembrane transporter activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IMP:UniProtKB.
DR GO; GO:0043268; P:positive regulation of potassium ion transport; IMP:RGD.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; ISO:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0008217; P:regulation of blood pressure; ISO:RGD.
DR GO; GO:0050727; P:regulation of inflammatory response; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:RGD.
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 Acetylation; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..553
FT /note="STE20/SPS1-related proline-alanine-rich protein
FT kinase"
FT /id="PRO_0000086724"
FT DOMAIN 72..346
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 319..544
FT /note="Interaction with RELT"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1W9"
FT REGION 370..431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 369..375
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 396..400
FT /note="Caspase cleavage related site"
FT COMPBIAS 33..55
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 400..422
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 201
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 78..86
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 101
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 240
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1W9"
FT MOD_RES 318
FT /note="Phosphoserine; by PKC/PRKCQ"
FT /evidence="ECO:0000250|UniProtKB:Q9UEW8"
FT MOD_RES 358
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9UEW8"
FT MOD_RES 363
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 379
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UEW8"
FT MOD_RES 380
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UEW8"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 402
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1W9"
FT CONFLICT 11
FT /note="V -> I (in Ref. 2; AAC23501)"
FT /evidence="ECO:0000305"
FT CONFLICT 253
FT /note="M -> I (in Ref. 2; AAC23501)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="E -> Q (in Ref. 2; AAC23501)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 553 AA; 60051 MW; 8BC1458AEA6F90C8 CRC64;
MAEPSGSPVH VQLPQQAAPV TAAAAAPAAA TSAPAPAPAP AAPAAPAPAP AAAPAPAPAA
QAVGWPICRD AYELQEVIGS GATAVVQAAL CKPRQERVAI KRINLEKCQT SMDELLKEIQ
AMSQCSHPNV VTYYTSFVVK DELWLVMKLL SGGSMLDIIK YIVNRGEHKN GVLEEAIIAT
ILKEVLEGLD YLHRNGQIHR DLKAGNILLG EDGSVQIADF GVSAFLATGG DVTRNKVRKT
FVGTPCWMAP EVMEQVRGYD FKADMWSFGI TAIELATGAA PYHKYPPMKV LMLTLQNDPP
TLETGVEDKE MMKKYGKSFR KLLSLCLQKD PSKRPTAAEL LKCKFFQKAK NREYLIEKLL
TRTPDIAQRA KKVRRVPGSS GHLHKTEDGD WEWSDDEMDE KSEEGKAAAS QEKSRRVKEE
NPEISVNAGG IPEQIQSLSV HDSQGQPNAN EDYREGPCAV NLVLRLRNSR KELNDIRFEF
TPGRDTADGV SQELFSAGLV DGHDVVIVAA NLQKIVDDPK ALKTLTFKLA SGCDGAEIPD
EVKLIGFAQL SVS
