STK38_HUMAN
ID STK38_HUMAN Reviewed; 465 AA.
AC Q15208; Q503A1;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Serine/threonine-protein kinase 38;
DE EC=2.7.11.1;
DE AltName: Full=NDR1 protein kinase;
DE AltName: Full=Nuclear Dbf2-related kinase 1;
GN Name=STK38 {ECO:0000312|EMBL:AAH12085.1};
GN Synonyms=NDR1 {ECO:0000303|PubMed:7761441};
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] {ECO:0000305, ECO:0000312|EMBL:CAA84485.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF LYS-118.
RC TISSUE=Fetal brain {ECO:0000312|EMBL:CAA84485.1};
RX PubMed=7761441; DOI=10.1073/pnas.92.11.5022;
RA Millward T.A., Cron P., Hemmings B.A.;
RT "Molecular cloning and characterization of a conserved nuclear
RT serine/threonine protein kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:5022-5026(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3] {ECO:0000312|EMBL:AAH12085.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta, and Uterus {ECO:0000312|EMBL:AAH12085.1};
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 [4]
RP PROTEIN SEQUENCE OF 2-17; 25-44; 51-63; 72-78; 82-97; 110-118; 122-159;
RP 182-239; 248-266; 277-301; 334-391; 394-402 AND 437-454, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Calvo F., Kolch W.;
RL Submitted (MAR-2008) to UniProtKB.
RN [5] {ECO:0000305}
RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT THR-74; SER-281 AND
RP THR-444, AND MUTAGENESIS OF THR-74; LYS-118; SER-281 AND THR-444.
RX PubMed=12493777; DOI=10.1074/jbc.m210590200;
RA Tamaskovic R., Bichsel S.J., Rogniaux H., Stegert M.R., Hemmings B.A.;
RT "Mechanism of Ca2+-mediated regulation of NDR protein kinase through
RT autophosphorylation and phosphorylation by an upstream kinase.";
RL J. Biol. Chem. 278:6710-6718(2003).
RN [6] {ECO:0000305}
RP ACTIVITY REGULATION, AND INTERACTION WITH MOB1 AND MOB2.
RX PubMed=15067004; DOI=10.1074/jbc.m401999200;
RA Devroe E., Erdjument-Bromage H., Tempst P., Silver P.A.;
RT "Human Mob proteins regulate the NDR1 and NDR2 serine-threonine kinases.";
RL J. Biol. Chem. 279:24444-24451(2004).
RN [7] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ACTIVITY REGULATION,
RP AND INTERACTION WITH MOB1 AND MOB2.
RX PubMed=15197186; DOI=10.1074/jbc.m404542200;
RA Bichsel S.J., Tamaskovic R., Stegert M.R., Hemmings B.A.;
RT "Mechanism of activation of NDR (nuclear Dbf2-related) protein kinase by
RT the hMOB1 protein.";
RL J. Biol. Chem. 279:35228-35235(2004).
RN [8]
RP ISGYLATION.
RX PubMed=16884686; DOI=10.1016/j.bbrc.2006.07.076;
RA Takeuchi T., Inoue S., Yokosawa H.;
RT "Identification and Herc5-mediated ISGylation of novel target proteins.";
RL Biochem. Biophys. Res. Commun. 348:473-477(2006).
RN [9]
RP INTERACTION WITH STK3/MST2 AND MOBKL1B, SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION BY STK3/MST2.
RX PubMed=18362890; DOI=10.1038/onc.2008.66;
RA Hirabayashi S., Nakagawa K., Sumita K., Hidaka S., Kawai T., Ikeda M.,
RA Kawata A., Ohno K., Hata Y.;
RT "Threonine 74 of MOB1 is a putative key phosphorylation site by MST2 to
RT form the scaffold to activate nuclear Dbf2-related kinase 1.";
RL Oncogene 27:4281-4292(2008).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MAP3K1 AND MAP3K2.
RX PubMed=17906693; DOI=10.1038/sj.onc.1210828;
RA Enomoto A., Kido N., Ito M., Morita A., Matsumoto Y., Takamatsu N.,
RA Hosoi Y., Miyagawa K.;
RT "Negative regulation of MEKK1/2 signaling by serine-threonine kinase 38
RT (STK38).";
RL Oncogene 27:1930-1938(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP CAUTION.
RX PubMed=19377461; DOI=10.1038/nature07954;
RA Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G.,
RA Kitagawa H., Kato S.;
RT "GlcNAcylation of a histone methyltransferase in retinoic-acid-induced
RT granulopoiesis.";
RL Nature 459:455-459(2009).
RN [13]
RP IDENTIFICATION BY 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-264, 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 [15]
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-264, AND IDENTIFICATION BY
RP 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 [17]
RP CAUTION, AND RETRACTION NOTICE OF PUBMED:23186163.
RX PubMed=24336203; DOI=10.1038/nature12896;
RA Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G.,
RA Kitagawa H., Kato S.;
RT "Retraction: GlcNAcylation of a histone methyltransferase in retinoic-acid-
RT induced granulopoiesis.";
RL Nature 505:574-574(2014).
RN [18] {ECO:0000305}
RP STRUCTURE BY NMR OF 62-84, ACTIVITY REGULATION, AND INTERACTION WITH S100B.
RX PubMed=14661952; DOI=10.1021/bi035089a;
RA Bhattacharya S., Large E., Heizmann C.W., Hemmings B.A., Chazin W.J.;
RT "Structure of the Ca2+/S100B/NDR kinase peptide complex: insights into S100
RT target specificity and activation of the kinase.";
RL Biochemistry 42:14416-14426(2003).
RN [19]
RP VARIANTS [LARGE SCALE ANALYSIS] LYS-18; ASN-145 AND ARG-267.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Negative regulator of MAP3K1/2 signaling. Converts MAP3K2
CC from its phosphorylated form to its non-phosphorylated form and
CC inhibits autophosphorylation of MAP3K2. {ECO:0000269|PubMed:12493777,
CC ECO:0000269|PubMed:15197186, ECO:0000269|PubMed:17906693,
CC ECO:0000269|PubMed:7761441}.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Activated by binding of S100B which releases
CC autoinhibitory N-lobe interactions, enabling ATP to bind and the
CC autophosphorylation of Ser-281. Thr-444 then undergoes calcium-
CC dependent phosphorylation by STK24/MST3. Interactions between
CC phosphorylated Thr-444 and the N-lobe promote additional structural
CC changes that complete the activation of the kinase. Autoinhibition is
CC also released by the binding of MOB1/MOBKL1A and MOB2/HCCA2 to the N-
CC terminal of STK38. {ECO:0000269|PubMed:12493777,
CC ECO:0000269|PubMed:14661952, ECO:0000269|PubMed:15067004,
CC ECO:0000269|PubMed:15197186}.
CC -!- SUBUNIT: Homodimeric S100B binds two molecules of STK38
CC (PubMed:14661952). Interacts with MOB1 and MOB2 (PubMed:15067004,
CC PubMed:15197186). Interacts with MAP3K1 and MAP3K2 (via the kinase
CC catalytic domain) (PubMed:17906693). Forms a tripartite complex with
CC MOBKL1B and STK3/MST2 (PubMed:18362890). Interacts with MICAL1; leading
CC to inhibit the protein kinase activity by antagonizing activation by
CC MST1/STK4 (By similarity). {ECO:0000250|UniProtKB:Q91VJ4,
CC ECO:0000269|PubMed:14661952, ECO:0000269|PubMed:15067004,
CC ECO:0000269|PubMed:15197186, ECO:0000269|PubMed:17906693,
CC ECO:0000269|PubMed:18362890}.
CC -!- INTERACTION:
CC Q15208; P49407: ARRB1; NbExp=3; IntAct=EBI-458376, EBI-743313;
CC Q15208; P32121: ARRB2; NbExp=3; IntAct=EBI-458376, EBI-714559;
CC Q15208; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-458376, EBI-11524452;
CC Q15208; Q03135: CAV1; NbExp=3; IntAct=EBI-458376, EBI-603614;
CC Q15208; P08238: HSP90AB1; NbExp=2; IntAct=EBI-458376, EBI-352572;
CC Q15208; Q9H8S9: MOB1A; NbExp=3; IntAct=EBI-458376, EBI-748229;
CC Q15208; P16333: NCK1; NbExp=3; IntAct=EBI-458376, EBI-389883;
CC Q15208; P30086: PEBP1; NbExp=3; IntAct=EBI-458376, EBI-716384;
CC Q15208; P02638: S100B; Xeno; NbExp=3; IntAct=EBI-458376, EBI-458452;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels observed
CC in peripheral blood leukocytes. {ECO:0000269|PubMed:15197186,
CC ECO:0000269|PubMed:7761441}.
CC -!- PTM: ISGylated. {ECO:0000305|PubMed:16884686}.
CC -!- PTM: Phosphorylated by STK3/MST2 and this is enhanced by MOBKL1B.
CC {ECO:0000269|PubMed:12493777, ECO:0000269|PubMed:18362890}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be part of the MLL5-L complex, at
CC least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and
CC OGT (PubMed:19377461). However, the corresponding article has been
CC retracted (PubMed:24336203). {ECO:0000269|PubMed:19377461,
CC ECO:0000269|PubMed:24336203}.
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DR EMBL; Z35102; CAA84485.1; -; mRNA.
DR EMBL; Z85986; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012085; AAH12085.1; -; mRNA.
DR EMBL; BC095413; AAH95413.1; -; mRNA.
DR CCDS; CCDS4822.1; -.
DR PIR; I38133; I38133.
DR RefSeq; NP_001292031.1; NM_001305102.1.
DR RefSeq; NP_009202.1; NM_007271.3.
DR RefSeq; XP_006715051.1; XM_006714988.3.
DR RefSeq; XP_006715052.1; XM_006714989.3.
DR PDB; 1PSB; NMR; -; C/D=62-87.
DR PDB; 6BXI; X-ray; 2.20 A; A/B=82-414.
DR PDBsum; 1PSB; -.
DR PDBsum; 6BXI; -.
DR AlphaFoldDB; Q15208; -.
DR BMRB; Q15208; -.
DR SMR; Q15208; -.
DR BioGRID; 116457; 121.
DR CORUM; Q15208; -.
DR IntAct; Q15208; 59.
DR MINT; Q15208; -.
DR STRING; 9606.ENSP00000229812; -.
DR BindingDB; Q15208; -.
DR ChEMBL; CHEMBL1075155; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q15208; -.
DR iPTMnet; Q15208; -.
DR MetOSite; Q15208; -.
DR PhosphoSitePlus; Q15208; -.
DR BioMuta; STK38; -.
DR DMDM; 56749457; -.
DR EPD; Q15208; -.
DR jPOST; Q15208; -.
DR MassIVE; Q15208; -.
DR MaxQB; Q15208; -.
DR PaxDb; Q15208; -.
DR PeptideAtlas; Q15208; -.
DR PRIDE; Q15208; -.
DR ProteomicsDB; 60489; -.
DR Antibodypedia; 29688; 452 antibodies from 33 providers.
DR DNASU; 11329; -.
DR Ensembl; ENST00000229812.8; ENSP00000229812.7; ENSG00000112079.9.
DR GeneID; 11329; -.
DR KEGG; hsa:11329; -.
DR MANE-Select; ENST00000229812.8; ENSP00000229812.7; NM_007271.4; NP_009202.1.
DR UCSC; uc003omh.3; human.
DR CTD; 11329; -.
DR DisGeNET; 11329; -.
DR GeneCards; STK38; -.
DR HGNC; HGNC:17847; STK38.
DR HPA; ENSG00000112079; Low tissue specificity.
DR MIM; 606964; gene.
DR neXtProt; NX_Q15208; -.
DR OpenTargets; ENSG00000112079; -.
DR PharmGKB; PA38251; -.
DR VEuPathDB; HostDB:ENSG00000112079; -.
DR eggNOG; KOG0605; Eukaryota.
DR GeneTree; ENSGT00940000153544; -.
DR HOGENOM; CLU_000288_67_0_1; -.
DR InParanoid; Q15208; -.
DR OMA; YTYKKSD; -.
DR OrthoDB; 759391at2759; -.
DR PhylomeDB; Q15208; -.
DR TreeFam; TF105337; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; Q15208; -.
DR Reactome; R-HSA-9013418; RHOBTB2 GTPase cycle.
DR Reactome; R-HSA-9013422; RHOBTB1 GTPase cycle.
DR SignaLink; Q15208; -.
DR SIGNOR; Q15208; -.
DR BioGRID-ORCS; 11329; 15 hits in 1066 CRISPR screens.
DR ChiTaRS; STK38; human.
DR EvolutionaryTrace; Q15208; -.
DR GeneWiki; STK38; -.
DR GenomeRNAi; 11329; -.
DR Pharos; Q15208; Tchem.
DR PRO; PR:Q15208; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q15208; protein.
DR Bgee; ENSG00000112079; Expressed in palpebral conjunctiva and 206 other tissues.
DR ExpressionAtlas; Q15208; baseline and differential.
DR Genevisible; Q15208; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI: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:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0036211; P:protein modification process; IDA:ProtInc.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR IDEAL; IID00172; -.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cytoplasm;
KW Direct protein sequencing; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.4"
FT CHAIN 2..465
FT /note="Serine/threonine-protein kinase 38"
FT /id="PRO_0000086718"
FT DOMAIN 89..382
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000312|EMBL:CAA84485.1"
FT DOMAIN 383..455
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 62..87
FT /note="Interaction with S100B"
FT /evidence="ECO:0000269|PubMed:14661952"
FT ACT_SITE 212
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 95..103
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O95835,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 118
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:12493777, ECO:0000269|PubMed:7761441"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.4"
FT MOD_RES 74
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:12493777"
FT MOD_RES 264
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 281
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12493777"
FT MOD_RES 444
FT /note="Phosphothreonine; by STK24/MST3"
FT /evidence="ECO:0000269|PubMed:12493777"
FT VARIANT 18
FT /note="E -> K (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041196"
FT VARIANT 145
FT /note="D -> N (in dbSNP:rs56005153)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041197"
FT VARIANT 267
FT /note="K -> R (in dbSNP:rs56105564)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041198"
FT MUTAGEN 74
FT /note="T->A: Decreases autophosphorylation and kinase
FT activity. Reduced binding of S100B."
FT /evidence="ECO:0000269|PubMed:12493777"
FT MUTAGEN 118
FT /note="K->A: Loss of autophosphorylation and kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:12493777,
FT ECO:0000269|PubMed:7761441"
FT MUTAGEN 281
FT /note="S->A: Loss of autophosphorylation and kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:12493777"
FT MUTAGEN 444
FT /note="T->A: Decreases autophosphorylation and kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:12493777"
FT HELIX 74..85
FT /evidence="ECO:0007829|PDB:1PSB"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:6BXI"
FT STRAND 89..98
FT /evidence="ECO:0007829|PDB:6BXI"
FT STRAND 101..108
FT /evidence="ECO:0007829|PDB:6BXI"
FT TURN 109..111
FT /evidence="ECO:0007829|PDB:6BXI"
FT STRAND 114..121
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 128..144
FT /evidence="ECO:0007829|PDB:6BXI"
FT STRAND 152..157
FT /evidence="ECO:0007829|PDB:6BXI"
FT STRAND 159..166
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 174..181
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 186..205
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:6BXI"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:6BXI"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:6BXI"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 243..246
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 257..260
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 264..273
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 275..280
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 291..294
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 303..317
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 327..335
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 337..340
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 351..360
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 364..366
FT /evidence="ECO:0007829|PDB:6BXI"
FT TURN 368..371
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 374..377
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 380..382
FT /evidence="ECO:0007829|PDB:6BXI"
FT STRAND 387..389
FT /evidence="ECO:0007829|PDB:6BXI"
FT HELIX 390..392
FT /evidence="ECO:0007829|PDB:6BXI"
SQ SEQUENCE 465 AA; 54190 MW; 7262221DBFFAF83C CRC64;
MAMTGSTPCS SMSNHTKERV TMTKVTLENF YSNLIAQHEE REMRQKKLEK VMEEEGLKDE
EKRLRRSAHA RKETEFLRLK RTRLGLEDFE SLKVIGRGAF GEVRLVQKKD TGHVYAMKIL
RKADMLEKEQ VGHIRAERDI LVEADSLWVV KMFYSFQDKL NLYLIMEFLP GGDMMTLLMK
KDTLTEEETQ FYIAETVLAI DSIHQLGFIH RDIKPDNLLL DSKGHVKLSD FGLCTGLKKA
HRTEFYRNLN HSLPSDFTFQ NMNSKRKAET WKRNRRQLAF STVGTPDYIA PEVFMQTGYN
KLCDWWSLGV IMYEMLIGYP PFCSETPQET YKKVMNWKET LTFPPEVPIS EKAKDLILRF
CCEWEHRIGA PGVEEIKSNS FFEGVDWEHI RERPAAISIE IKSIDDTSNF DEFPESDILK
PTVATSNHPE TDYKNKDWVF INYTYKRFEG LTARGAIPSY MKAAK
