DYR1B_HUMAN
ID DYR1B_HUMAN Reviewed; 629 AA.
AC Q9Y463; O75258; O75788; O75789;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Dual specificity tyrosine-phosphorylation-regulated kinase 1B;
DE EC=2.7.12.1 {ECO:0000269|PubMed:22998443};
DE AltName: Full=Minibrain-related kinase;
DE AltName: Full=Mirk protein kinase;
GN Name=DYRK1B; Synonyms=MIRK;
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] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Testis;
RX PubMed=9918863; DOI=10.1006/bbrc.1998.9967;
RA Leder S., Weber Y., Altafaj X., Estivill X., Joost H.-G., Becker W.;
RT "Cloning and characterization of DYRK1B, a novel member of the DYRK family
RT of protein kinases.";
RL Biochem. Biophys. Res. Commun. 254:474-479(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP PHOSPHORYLATION AT TYR-271 AND TYR-273, AND MUTAGENESIS OF LYS-140; TYR-271
RP AND TYR-273.
RC TISSUE=Colon carcinoma;
RX PubMed=10910078;
RA Lee K., Deng X., Friedman E.;
RT "Mirk protein kinase is a mitogen-activated protein kinase substrate that
RT mediates survival of colon cancer cells.";
RL Cancer Res. 60:3631-3637(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
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 [5]
RP FUNCTION, AND INTERACTION WITH DCOHM; MAP2K3 AND TCF1.
RC TISSUE=Muscle;
RX PubMed=11980910; DOI=10.1074/jbc.m203257200;
RA Lim S., Jin K., Friedman E.;
RT "Mirk protein kinase is activated by MKK3 and functions as a
RT transcriptional activator of HNF1alpha.";
RL J. Biol. Chem. 277:25040-25046(2002).
RN [6]
RP FUNCTION, DIMERIZATION, INTERACTION WITH RANBP9, AND IDENTIFICATION IN A
RP COMPLEX WITH RAN; RANBP9 AND COPS5.
RX PubMed=14500717; DOI=10.1074/jbc.m307556200;
RA Zou Y., Lim S., Lee K., Deng X., Friedman E.;
RT "Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell
RT migration and is negatively regulated by the Met adaptor Ran-binding
RT protein M.";
RL J. Biol. Chem. 278:49573-49581(2003).
RN [7]
RP INTERACTION WITH DCAF7.
RX PubMed=14593110; DOI=10.1074/jbc.m301769200;
RA Skurat A.V., Dietrich A.D.;
RT "Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family
RT protein kinases.";
RL J. Biol. Chem. 279:2490-2498(2004).
RN [8]
RP CATALYTIC ACTIVITY.
RX PubMed=22998443; DOI=10.1021/jm301034u;
RA Tahtouh T., Elkins J.M., Filippakopoulos P., Soundararajan M., Burgy G.,
RA Durieu E., Cochet C., Schmid R.S., Lo D.C., Delhommel F., Oberholzer A.E.,
RA Pearl L.H., Carreaux F., Bazureau J.P., Knapp S., Meijer L.;
RT "Selectivity, cocrystal structures, and neuroprotective properties of
RT leucettines, a family of protein kinase inhibitors derived from the marine
RT sponge alkaloid leucettamine B.";
RL J. Med. Chem. 55:9312-9330(2012).
RN [9]
RP FUNCTION, VARIANTS AOMS3 PRO-90 AND CYS-102, AND CHARACTERIZATION OF
RP VARIANTS AOMS3 PRO-90 AND CYS-102.
RX PubMed=24827035; DOI=10.1056/nejmoa1301824;
RA Keramati A.R., Fathzadeh M., Go G.W., Singh R., Choi M., Faramarzi S.,
RA Mane S., Kasaei M., Sarajzadeh-Fard K., Hwa J., Kidd K.K.,
RA Babaee Bigi M.A., Malekzadeh R., Hosseinian A., Babaei M., Lifton R.P.,
RA Mani A.;
RT "A form of the metabolic syndrome associated with mutations in DYRK1B.";
RL N. Engl. J. Med. 370:1909-1919(2014).
RN [10]
RP INTERACTION WITH RNF169, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=33469661; DOI=10.1093/nar/gkaa1290;
RA Dong C., An L., Yu C.H., Huen M.S.Y.;
RT "A DYRK1B-dependent pathway suppresses rDNA transcription in response to
RT DNA damage.";
RL Nucleic Acids Res. 49:1485-1496(2021).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-239.
RX PubMed=32611815; DOI=10.1073/pnas.2002193117;
RA Dong C., West K.L., Tan X.Y., Li J., Ishibashi T., Yu C.H., Sy S.M.H.,
RA Leung J.W.C., Huen M.S.Y.;
RT "Screen identifies DYRK1B network as mediator of transcription repression
RT on damaged chromatin.";
RL Proc. Natl. Acad. Sci. U.S.A. 117:17019-17030(2020).
RN [12]
RP VARIANTS [LARGE SCALE ANALYSIS] PRO-28; HIS-102; GLY-234 AND ARG-275.
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: Dual-specificity kinase which possesses both serine/threonine
CC and tyrosine kinase activities. Plays an essential role in ribosomal
CC DNA (rDNA) double-strand break repair and rDNA copy number maintenance
CC (PubMed:33469661). During DNA damage, mediates transcription silencing
CC in part via phosphorylating and enforcing DSB accumulation of the
CC histone methyltransferase EHMT2 (PubMed:32611815). Enhances the
CC transcriptional activity of TCF1/HNF1A and FOXO1. Inhibits epithelial
CC cell migration. Mediates colon carcinoma cell survival in mitogen-poor
CC environments. Inhibits the SHH and WNT1 pathways, thereby enhancing
CC adipogenesis. In addition, promotes expression of the gluconeogenic
CC enzyme glucose-6-phosphatase catalytic subunit 1 (G6PC1).
CC {ECO:0000269|PubMed:10910078, ECO:0000269|PubMed:11980910,
CC ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:24827035,
CC ECO:0000269|PubMed:33469661}.
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=2.7.12.1;
CC Evidence={ECO:0000269|PubMed:22998443};
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=2.7.12.1; Evidence={ECO:0000269|PubMed:22998443};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC Evidence={ECO:0000269|PubMed:22998443};
CC -!- ACTIVITY REGULATION: Inhibited by RANBP9.
CC -!- SUBUNIT: Dimer. Interacts with DCOHM, MAP2K3/MKK3, RANBP9 and
CC TCF1/HNF1A (PubMed:11980910). Part of a complex consisting of RANBP9,
CC RAN, DYRK1B and COPS5 (PubMed:14500717). Interacts with DCAF7
CC (PubMed:14593110). Interacts with RNF169 (PubMed:33469661).
CC {ECO:0000269|PubMed:11980910, ECO:0000269|PubMed:14500717,
CC ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:33469661}.
CC -!- INTERACTION:
CC Q9Y463; P61962: DCAF7; NbExp=5; IntAct=EBI-634187, EBI-359808;
CC Q9Y463; O15499: GSC2; NbExp=3; IntAct=EBI-634187, EBI-19954058;
CC Q9Y463; P20823: HNF1A; NbExp=4; IntAct=EBI-634187, EBI-636034;
CC Q9Y463; P08238: HSP90AB1; NbExp=2; IntAct=EBI-634187, EBI-352572;
CC Q9Y463; Q9BRK4: LZTS2; NbExp=4; IntAct=EBI-634187, EBI-741037;
CC Q9Y463; P46734: MAP2K3; NbExp=2; IntAct=EBI-634187, EBI-602462;
CC Q9Y463; Q9H0N5: PCBD2; NbExp=2; IntAct=EBI-634187, EBI-634289;
CC Q9Y463; Q96S59: RANBP9; NbExp=4; IntAct=EBI-634187, EBI-636085;
CC Q9Y463; P06400: RB1; NbExp=4; IntAct=EBI-634187, EBI-491274;
CC Q9Y463; P28749: RBL1; NbExp=4; IntAct=EBI-634187, EBI-971402;
CC Q9Y463; Q12815: TROAP; NbExp=7; IntAct=EBI-634187, EBI-2349743;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:32611815,
CC ECO:0000269|PubMed:33469661}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:33469661}. Chromosome
CC {ECO:0000269|PubMed:32611815}. Note=Localizes to sites of double-strand
CC breaks (DSBs) following DNA damage. {ECO:0000269|PubMed:32611815}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y463-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y463-2; Sequence=VSP_004925;
CC Name=3;
CC IsoId=Q9Y463-3; Sequence=VSP_004926;
CC -!- TISSUE SPECIFICITY: Highest expression in skeletal muscle, testis,
CC heart and brain with little expression in colon or lung. Expressed in a
CC variety of tumor cell lines. {ECO:0000269|PubMed:10910078}.
CC -!- PTM: Autophosphorylated on tyrosine residues. Phosphorylated by MAP
CC kinase. Tyrosine phosphorylation may be required for dimerization.
CC {ECO:0000269|PubMed:10910078}.
CC -!- DISEASE: Abdominal obesity-metabolic syndrome 3 (AOMS3) [MIM:615812]: A
CC form of abdominal obesity-metabolic syndrome, a disorder characterized
CC by abdominal obesity, high triglycerides, low levels of high density
CC lipoprotein cholesterol, high blood pressure, and elevated fasting
CC glucose levels. AOMS3 is characterized by early-onset coronary artery
CC disease, central obesity, hypertension, and diabetes.
CC {ECO:0000269|PubMed:24827035}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MNB/DYRK subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC28914.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/DYRK1BID43235ch19q13.html";
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DR EMBL; Y17999; CAA76991.1; -; mRNA.
DR EMBL; Y17999; CAA76990.1; -; mRNA.
DR EMBL; Y17999; CAA76989.1; -; mRNA.
DR EMBL; AF205861; AAF15893.1; -; mRNA.
DR EMBL; AC005393; AAC28914.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC018751; AAH18751.1; -; mRNA.
DR EMBL; BC025291; AAH25291.1; -; mRNA.
DR CCDS; CCDS12543.1; -. [Q9Y463-1]
DR CCDS; CCDS12544.1; -. [Q9Y463-3]
DR CCDS; CCDS46075.1; -. [Q9Y463-2]
DR PIR; JG0195; JG0195.
DR RefSeq; NP_004705.1; NM_004714.2. [Q9Y463-1]
DR RefSeq; NP_006474.1; NM_006483.2. [Q9Y463-2]
DR RefSeq; NP_006475.1; NM_006484.2. [Q9Y463-3]
DR RefSeq; XP_005259455.1; XM_005259398.4. [Q9Y463-1]
DR AlphaFoldDB; Q9Y463; -.
DR SMR; Q9Y463; -.
DR BioGRID; 114596; 74.
DR ELM; Q9Y463; -.
DR IntAct; Q9Y463; 72.
DR MINT; Q9Y463; -.
DR STRING; 9606.ENSP00000469863; -.
DR BindingDB; Q9Y463; -.
DR ChEMBL; CHEMBL5543; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9Y463; -.
DR GuidetoPHARMACOLOGY; 2010; -.
DR iPTMnet; Q9Y463; -.
DR PhosphoSitePlus; Q9Y463; -.
DR BioMuta; DYRK1B; -.
DR DMDM; 9296963; -.
DR EPD; Q9Y463; -.
DR jPOST; Q9Y463; -.
DR MassIVE; Q9Y463; -.
DR MaxQB; Q9Y463; -.
DR PaxDb; Q9Y463; -.
DR PeptideAtlas; Q9Y463; -.
DR PRIDE; Q9Y463; -.
DR ProteomicsDB; 86110; -. [Q9Y463-1]
DR ProteomicsDB; 86111; -. [Q9Y463-2]
DR ProteomicsDB; 86112; -. [Q9Y463-3]
DR Antibodypedia; 30414; 362 antibodies from 36 providers.
DR DNASU; 9149; -.
DR Ensembl; ENST00000323039.10; ENSP00000312789.4; ENSG00000105204.14. [Q9Y463-1]
DR Ensembl; ENST00000348817.7; ENSP00000221803.4; ENSG00000105204.14. [Q9Y463-3]
DR Ensembl; ENST00000430012.6; ENSP00000403182.1; ENSG00000105204.14. [Q9Y463-2]
DR Ensembl; ENST00000593685.5; ENSP00000469863.1; ENSG00000105204.14. [Q9Y463-1]
DR Ensembl; ENST00000597639.5; ENSP00000472941.1; ENSG00000105204.14. [Q9Y463-3]
DR Ensembl; ENST00000625388.2; ENSP00000486839.1; ENSG00000281320.3. [Q9Y463-3]
DR Ensembl; ENST00000625438.2; ENSP00000487313.1; ENSG00000281320.3. [Q9Y463-3]
DR Ensembl; ENST00000625757.3; ENSP00000485915.1; ENSG00000281320.3. [Q9Y463-1]
DR Ensembl; ENST00000627034.2; ENSP00000487539.1; ENSG00000281320.3. [Q9Y463-2]
DR Ensembl; ENST00000631090.2; ENSP00000486377.1; ENSG00000281320.3. [Q9Y463-1]
DR GeneID; 9149; -.
DR KEGG; hsa:9149; -.
DR MANE-Select; ENST00000323039.10; ENSP00000312789.4; NM_004714.3; NP_004705.1.
DR UCSC; uc002omi.4; human. [Q9Y463-1]
DR CTD; 9149; -.
DR DisGeNET; 9149; -.
DR GeneCards; DYRK1B; -.
DR HGNC; HGNC:3092; DYRK1B.
DR HPA; ENSG00000105204; Tissue enhanced (skeletal muscle, testis).
DR MalaCards; DYRK1B; -.
DR MIM; 604556; gene.
DR MIM; 615812; phenotype.
DR neXtProt; NX_Q9Y463; -.
DR OpenTargets; ENSG00000105204; -.
DR Orphanet; 411969; NON RARE IN EUROPE: Metabolic syndrome.
DR PharmGKB; PA27549; -.
DR VEuPathDB; HostDB:ENSG00000105204; -.
DR eggNOG; KOG0667; Eukaryota.
DR GeneTree; ENSGT00940000160345; -.
DR HOGENOM; CLU_000288_5_6_1; -.
DR InParanoid; Q9Y463; -.
DR OMA; GHSTADY; -.
DR OrthoDB; 1219474at2759; -.
DR PhylomeDB; Q9Y463; -.
DR TreeFam; TF314624; -.
DR BioCyc; MetaCyc:HS02690-MON; -.
DR BRENDA; 2.7.12.1; 2681.
DR PathwayCommons; Q9Y463; -.
DR SignaLink; Q9Y463; -.
DR SIGNOR; Q9Y463; -.
DR BioGRID-ORCS; 9149; 14 hits in 1112 CRISPR screens.
DR ChiTaRS; DYRK1B; human.
DR GeneWiki; DYRK1B; -.
DR GenomeRNAi; 9149; -.
DR Pharos; Q9Y463; Tchem.
DR PRO; PR:Q9Y463; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9Y463; protein.
DR Bgee; ENSG00000105204; Expressed in hindlimb stylopod muscle and 99 other tissues.
DR ExpressionAtlas; Q9Y463; baseline and differential.
DR Genevisible; Q9Y463; HS.
DR GO; GO:0005694; C:chromosome; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0060612; P:adipose tissue development; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0007520; P:myoblast fusion; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:InterPro.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR CDD; cd14226; PKc_DYRK1; 1.
DR InterPro; IPR028318; DYRK1A/B_MNB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR044131; PKc_DYR1A/1B.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24058:SF12; PTHR24058:SF12; 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.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Chromosome; Diabetes mellitus;
KW DNA damage; DNA repair; Kinase; Nucleotide-binding; Nucleus; Obesity;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Tyrosine-protein kinase.
FT CHAIN 1..629
FT /note="Dual specificity tyrosine-phosphorylation-regulated
FT kinase 1B"
FT /id="PRO_0000085934"
FT DOMAIN 111..431
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 67..89
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 380..399
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 436..629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 480..520
FT /note="Interaction with RANBP9"
FT /evidence="ECO:0000269|PubMed:14500717"
FT MOTIF 69..86
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 439..485
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 546..562
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 239
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 117..125
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 140
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 190..193
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 63
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 92
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 111
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 129
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 171
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q63470"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 271
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:10910078"
FT MOD_RES 273
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:10910078"
FT MOD_RES 401
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 624
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT VAR_SEQ 366..405
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9918863"
FT /id="VSP_004925"
FT VAR_SEQ 378..405
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9918863"
FT /id="VSP_004926"
FT VARIANT 28
FT /note="L -> P (in dbSNP:rs34587974)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040454"
FT VARIANT 90
FT /note="H -> P (in AOMS3; expression of glucose-6-
FT phosphatase is significantly higher than wild-type;
FT dbSNP:rs587777380)"
FT /evidence="ECO:0000269|PubMed:24827035"
FT /id="VAR_071773"
FT VARIANT 102
FT /note="R -> C (in AOMS3; accumulation of intracellular
FT lipid is significantly greater than with wild-type protein;
FT cells expressing the variant are able to transform into
FT mature adipocytes without requiring adipogenic medium;
FT expression levels of CEBPA, PPARG forms 1 and 2 and
FT PPARGC1A are higher and those of GLI1 and CDKN1B are lower
FT in cells transfected with the mutant protein compared to
FT wild-type; WNT1 signaling activity is lower in mutant cells
FT compared to wild-type; dbSNP:rs367643250)"
FT /evidence="ECO:0000269|PubMed:24827035"
FT /id="VAR_071774"
FT VARIANT 102
FT /note="R -> H (in dbSNP:rs55687541)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040455"
FT VARIANT 234
FT /note="S -> G (in dbSNP:rs35858874)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040456"
FT VARIANT 275
FT /note="Q -> R (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040457"
FT MUTAGEN 140
FT /note="K->R: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:10910078"
FT MUTAGEN 239
FT /note="D->A: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:32611815"
FT MUTAGEN 271
FT /note="Y->F: Abolishes kinase activity; when associated
FT with F-273."
FT /evidence="ECO:0000269|PubMed:10910078"
FT MUTAGEN 273
FT /note="Y->F: Abolishes kinase activity; when associated
FT with F-271."
FT /evidence="ECO:0000269|PubMed:10910078"
SQ SEQUENCE 629 AA; 69198 MW; D7C354AC55943A8B CRC64;
MAVPPGHGPF SGFPGPQEHT QVLPDVRLLP RRLPLAFRDA TSAPLRKLSV DLIKTYKHIN
EVYYAKKKRR AQQAPPQDSS NKKEKKVLNH GYDDDNHDYI VRSGERWLER YEIDSLIGKG
SFGQVVKAYD HQTQELVAIK IIKNKKAFLN QAQIELRLLE LMNQHDTEMK YYIVHLKRHF
MFRNHLCLVF ELLSYNLYDL LRNTHFRGVS LNLTRKLAQQ LCTALLFLAT PELSIIHCDL
KPENILLCNP KRSAIKIVDF GSSCQLGQRI YQYIQSRFYR SPEVLLGTPY DLAIDMWSLG
CILVEMHTGE PLFSGSNEVD QMNRIVEVLG IPPAAMLDQA PKARKYFERL PGGGWTLRRT
KELRKDYQGP GTRRLQEVLG VQTGGPGGRR AGEPGHSPAD YLRFQDLVLR MLEYEPAARI
SPLGALQHGF FRRTADEATN TGPAGSSAST SPAPLDTCPS SSTASSISSS GGSSGSSSDN
RTYRYSNRYC GGPGPPITDC EMNSPQVPPS QPLRPWAGGD VPHKTHQAPA SASSLPGTGA
QLPPQPRYLG RPPSPTSPPP PELMDVSLVG GPADCSPPHP APAPQHPAAS ALRTRMTGGR
PPLPPPDDPA TLGPHLGLRG VPQSTAASS
