DYRK3_HUMAN
ID DYRK3_HUMAN Reviewed; 588 AA.
AC O43781; D3DT79; Q7Z752; Q9HBY6; Q9HBY7;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 3.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Dual specificity tyrosine-phosphorylation-regulated kinase 3;
DE EC=2.7.12.1 {ECO:0000269|PubMed:23415227, ECO:0000269|PubMed:29634919, ECO:0000269|PubMed:29973724, ECO:0000269|PubMed:9748265};
DE AltName: Full=Regulatory erythroid kinase {ECO:0000303|PubMed:10779429};
DE Short=REDK {ECO:0000303|PubMed:10779429};
GN Name=DYRK3 {ECO:0000312|HGNC:HGNC:3094};
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), CATALYTIC ACTIVITY, AND
RP AUTOPHOSPHORYLATION.
RC TISSUE=Fetal brain;
RX PubMed=9748265; DOI=10.1074/jbc.273.40.25893;
RA Becker W., Weber Y., Wetzel K., Eirmbter K., Tejedor F.J., Joost H.-G.;
RT "Sequence characteristics, subcellular localization, and substrate
RT specificity of DYRK-related kinases, a novel family of dual specificity
RT protein kinases.";
RL J. Biol. Chem. 273:25893-25902(1998).
RN [2]
RP SEQUENCE REVISION TO N-TERMINUS.
RA Becker W.;
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9845759;
RA Xia J., Yang X., Ruan Q., Pan Q., Liu C., Xie W., Deng H.;
RT "Molecular cloning and characterization of novel protein kinase gene
RT DYRK3.";
RL Zhonghua Yi Xue Yi Chuan Xue Za Zhi 15:327-332(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, COFACTOR,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Skeletal muscle;
RX PubMed=10779429;
RA Lord K.A., Creasy C.L., King A.G., King C., Burns B.M., Lee J.C.,
RA Dillon S.B.;
RT "REDK, a novel human regulatory erythroid kinase.";
RL Blood 95:2838-2846(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RA Zhou Z.M.;
RT "Cloning of the human testis-specific dual-specificity tyrosine-(Y)-
RT phosphorylation regulated kinase 5 (DYRK5) gene.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Raya A., de la Luna S.;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
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 [10]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=20167603; DOI=10.1074/jbc.m110.102574;
RA Guo X., Williams J.G., Schug T.T., Li X.;
RT "DYRK1A and DYRK3 promote cell survival through phosphorylation and
RT activation of SIRT1.";
RL J. Biol. Chem. 285:13223-13232(2010).
RN [11]
RP SUBCELLULAR LOCATION, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP LYS-238.
RX PubMed=23415227; DOI=10.1016/j.cell.2013.01.033;
RA Wippich F., Bodenmiller B., Trajkovska M.G., Wanka S., Aebersold R.,
RA Pelkmans L.;
RT "Dual specificity kinase DYRK3 couples stress granule
RT condensation/dissolution to mTORC1 signaling.";
RL Cell 152:791-805(2013).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, UBIQUITINATION, AND
RP MUTAGENESIS OF LYS-238 AND 470-ARG--LYS-474.
RX PubMed=29973724; DOI=10.1038/s41586-018-0279-8;
RA Rai A.K., Chen J.X., Selbach M., Pelkmans L.;
RT "Kinase-controlled phase transition of membraneless organelles in
RT mitosis.";
RL Nature 559:211-216(2018).
RN [13] {ECO:0007744|PDB:5Y86}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH HARMINE, FUNCTION,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, PHOSPHORYLATION AT SER-350, AND
RP MUTAGENESIS OF LYS-238 AND SER-350.
RX PubMed=29634919; DOI=10.1016/j.jmb.2018.04.001;
RA Kim K., Cha J.S., Cho Y.S., Kim H., Chang N., Kim H.J., Cho H.S.;
RT "Crystal structure of human dual-specificity tyrosine-regulated kinase 3
RT reveals new structural features and insights into its auto-
RT phosphorylation.";
RL J. Mol. Biol. 430:1521-1530(2018).
RN [14]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-239.
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 protein kinase that promotes disassembly of
CC several types of membraneless organelles during mitosis, such as stress
CC granules, nuclear speckles and pericentriolar material
CC (PubMed:29973724). Dual-specificity tyrosine-regulated kinases (DYRKs)
CC autophosphorylate a critical tyrosine residue in their activation loop
CC and phosphorylate their substrate on serine and threonine residues
CC (PubMed:9748265, PubMed:29634919). Acts as a central dissolvase of
CC membraneless organelles during the G2-to-M transition, after the
CC nuclear-envelope breakdown: acts by mediating phosphorylation of
CC multiple serine and threonine residues in unstructured domains of
CC proteins, such as SRRM1 and PCM1 (PubMed:29973724). Does not mediate
CC disassembly of all membraneless organelles: disassembly of P-body and
CC nucleolus is not regulated by DYRK3 (PubMed:29973724). Dissolution of
CC membraneless organelles at the onset of mitosis is also required to
CC release mitotic regulators, such as ZNF207, from liquid-unmixed
CC organelles where they are sequestered and keep them dissolved during
CC mitosis (PubMed:29973724). Regulates mTORC1 by mediating the
CC dissolution of stress granules: during stressful conditions, DYRK3
CC partitions from the cytosol to the stress granule, together with mTORC1
CC components, which prevents mTORC1 signaling (PubMed:23415227). When
CC stress signals are gone, the kinase activity of DYRK3 is required for
CC the dissolution of stress granule and mTORC1 relocation to the cytosol:
CC acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1,
CC allowing full reactivation of mTORC1 signaling (PubMed:23415227). Also
CC acts as a negative regulator of EPO-dependent erythropoiesis: may place
CC an upper limit on red cell production during stress erythropoiesis
CC (PubMed:10779429). Inhibits cell death due to cytokine withdrawal in
CC hematopoietic progenitor cells (PubMed:10779429). Promotes cell
CC survival upon genotoxic stress through phosphorylation of SIRT1: this
CC in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603).
CC {ECO:0000269|PubMed:10779429, ECO:0000269|PubMed:20167603,
CC ECO:0000269|PubMed:23415227, ECO:0000269|PubMed:29634919,
CC ECO:0000269|PubMed:29973724, ECO:0000269|PubMed:9748265}.
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:23415227, ECO:0000269|PubMed:29634919,
CC ECO:0000269|PubMed:29973724, ECO:0000269|PubMed:9748265};
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:23415227,
CC ECO:0000269|PubMed:29634919, ECO:0000269|PubMed:29973724,
CC ECO:0000269|PubMed:9748265};
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:23415227, ECO:0000269|PubMed:29634919,
CC ECO:0000269|PubMed:29973724, ECO:0000269|PubMed:9748265};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10779429};
CC -!- ACTIVITY REGULATION: Protein kinase activity is activated following
CC autophosphorylation at Tyr-369 (PubMed:9748265). Inhibited by harmine,
CC an ATP competitive inhibitor (PubMed:29634919). Inhibited by small-
CC compound GSK-626616 (PubMed:29973724). {ECO:0000269|PubMed:29634919,
CC ECO:0000269|PubMed:29973724, ECO:0000269|PubMed:9748265}.
CC -!- SUBUNIT: Interacts with SIRT1. {ECO:0000250|UniProtKB:Q922Y0}.
CC -!- INTERACTION:
CC O43781-2; Q9H8Y8: GORASP2; NbExp=5; IntAct=EBI-13332019, EBI-739467;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10779429,
CC ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:29973724}. Cytoplasm
CC {ECO:0000269|PubMed:29973724}. Nucleus speckle
CC {ECO:0000269|PubMed:29973724}. Cytoplasmic granule
CC {ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:23415227,
CC ECO:0000269|PubMed:29973724}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:29973724}.
CC Note=Associates with membraneless organelles in the cytoplasm and
CC nucleus (PubMed:29973724). Shuttles between cytoplasm and stress
CC granules (PubMed:20167603). Localized predominantly on distinct
CC speckles distributed throughout the cytoplasm of the cell
CC (PubMed:20167603). At low concentration, showns a homogeneous
CC distribution throughout the cytoplasm and does not condense in
CC speckles. During oxidative and osmotic stress, localizes to stress
CC granules (PubMed:20167603). {ECO:0000269|PubMed:20167603,
CC ECO:0000269|PubMed:29973724}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long {ECO:0000303|PubMed:10779429};
CC IsoId=O43781-1; Sequence=Displayed;
CC Name=2; Synonyms=Short {ECO:0000303|PubMed:10779429};
CC IsoId=O43781-2; Sequence=VSP_026178, VSP_026179;
CC -!- TISSUE SPECIFICITY: Isoform 1: Highly expressed in testis and in
CC hematopoietic tissue such as fetal liver, and bone marrow
CC (PubMed:10779429). Isoform 1: Predominant form in fetal liver and bone
CC marrow (PubMed:10779429). Isoform 1: Present at low levels in heart,
CC pancreas, lymph node and thymus (PubMed:10779429). Isoform 2: Highly
CC expressed in testis and in hematopoietic tissue such as fetal liver,
CC and bone marrow (PubMed:10779429). Isoform 2: Predominant form in
CC testis. Isoform 2: Present at low levels in heart, pancreas, lymph node
CC and thymus (PubMed:10779429). {ECO:0000269|PubMed:10779429}.
CC -!- INDUCTION: By EPO/erythropoietin. {ECO:0000269|PubMed:10779429}.
CC -!- DOMAIN: The N-terminal domain, which is intrinsically disordered, is
CC required for stress granule localization.
CC {ECO:0000269|PubMed:23415227}.
CC -!- PTM: Ubiquitinated at anaphase by the anaphase-promoting complex
CC (APC/C), leading to its degradation by the proteasome.
CC {ECO:0000269|PubMed:29973724}.
CC -!- PTM: Protein kinase activity is activated following autophosphorylation
CC at Tyr-369 (Probable). Autophosphorylation at Ser-350 stabilizes the
CC protein and enhances the protein kinase activity (PubMed:9748265).
CC {ECO:0000269|PubMed:9748265, ECO:0000305|PubMed:9748265}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MNB/DYRK subfamily. {ECO:0000305}.
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DR EMBL; Y12735; CAA73266.2; -; mRNA.
DR EMBL; AF186773; AAG17028.1; -; mRNA.
DR EMBL; AF186774; AAG17029.1; -; mRNA.
DR EMBL; AF327561; AAK16443.1; -; mRNA.
DR EMBL; AY590695; AAT06103.1; -; mRNA.
DR EMBL; AL591846; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471100; EAW93533.1; -; Genomic_DNA.
DR EMBL; CH471100; EAW93534.1; -; Genomic_DNA.
DR EMBL; BC015501; AAH15501.1; -; mRNA.
DR CCDS; CCDS30999.1; -. [O43781-1]
DR CCDS; CCDS31000.1; -. [O43781-2]
DR RefSeq; NP_001004023.1; NM_001004023.1. [O43781-2]
DR RefSeq; NP_003573.2; NM_003582.2. [O43781-1]
DR RefSeq; XP_005273372.1; XM_005273315.4. [O43781-2]
DR PDB; 5Y86; X-ray; 1.90 A; A=1-588.
DR PDBsum; 5Y86; -.
DR AlphaFoldDB; O43781; -.
DR SMR; O43781; -.
DR BioGRID; 114022; 10.
DR IntAct; O43781; 28.
DR MINT; O43781; -.
DR STRING; 9606.ENSP00000356076; -.
DR BindingDB; O43781; -.
DR ChEMBL; CHEMBL4575; -.
DR GuidetoPHARMACOLOGY; 2012; -.
DR iPTMnet; O43781; -.
DR PhosphoSitePlus; O43781; -.
DR BioMuta; DYRK3; -.
DR jPOST; O43781; -.
DR MassIVE; O43781; -.
DR MaxQB; O43781; -.
DR PaxDb; O43781; -.
DR PeptideAtlas; O43781; -.
DR PRIDE; O43781; -.
DR ProteomicsDB; 49168; -. [O43781-1]
DR ProteomicsDB; 49169; -. [O43781-2]
DR Antibodypedia; 34587; 238 antibodies from 29 providers.
DR DNASU; 8444; -.
DR Ensembl; ENST00000367106.1; ENSP00000356073.1; ENSG00000143479.18. [O43781-2]
DR Ensembl; ENST00000367108.7; ENSP00000356075.3; ENSG00000143479.18. [O43781-2]
DR Ensembl; ENST00000367109.8; ENSP00000356076.2; ENSG00000143479.18. [O43781-1]
DR GeneID; 8444; -.
DR KEGG; hsa:8444; -.
DR MANE-Select; ENST00000367109.8; ENSP00000356076.2; NM_003582.4; NP_003573.2.
DR UCSC; uc001hei.4; human. [O43781-1]
DR CTD; 8444; -.
DR DisGeNET; 8444; -.
DR GeneCards; DYRK3; -.
DR HGNC; HGNC:3094; DYRK3.
DR HPA; ENSG00000143479; Tissue enhanced (testis).
DR MIM; 603497; gene.
DR neXtProt; NX_O43781; -.
DR OpenTargets; ENSG00000143479; -.
DR PharmGKB; PA27551; -.
DR VEuPathDB; HostDB:ENSG00000143479; -.
DR eggNOG; KOG0667; Eukaryota.
DR GeneTree; ENSGT00940000159878; -.
DR HOGENOM; CLU_000288_5_13_1; -.
DR InParanoid; O43781; -.
DR OMA; CDDPTFI; -.
DR OrthoDB; 870358at2759; -.
DR PhylomeDB; O43781; -.
DR TreeFam; TF314624; -.
DR BRENDA; 2.7.12.1; 2681.
DR PathwayCommons; O43781; -.
DR SignaLink; O43781; -.
DR SIGNOR; O43781; -.
DR BioGRID-ORCS; 8444; 11 hits in 1114 CRISPR screens.
DR ChiTaRS; DYRK3; human.
DR GeneWiki; DYRK3; -.
DR GenomeRNAi; 8444; -.
DR Pharos; O43781; Tchem.
DR PRO; PR:O43781; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O43781; protein.
DR Bgee; ENSG00000143479; Expressed in type B pancreatic cell and 150 other tissues.
DR ExpressionAtlas; O43781; baseline and differential.
DR Genevisible; O43781; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; 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:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000242; C:pericentriolar material; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
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; IDA:UniProtKB.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0030218; P:erythrocyte differentiation; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IEA:Ensembl.
DR GO; GO:0035063; P:nuclear speck organization; IDA:UniProtKB.
DR GO; GO:1903008; P:organelle disassembly; IDA:UniProtKB.
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:1902751; P:positive regulation of cell cycle G2/M phase transition; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0080135; P:regulation of cellular response to stress; IMP:UniProtKB.
DR GO; GO:1903432; P:regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:0035617; P:stress granule disassembly; IDA:UniProtKB.
DR Gene3D; 3.30.10.30; -; 1.
DR InterPro; IPR042521; DYRK.
DR InterPro; IPR011009; Kinase-like_dom_sf.
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 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 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Cell division;
KW Cytoplasm; Cytoskeleton; Kinase; Magnesium; Metal-binding; Mitosis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase;
KW Ubl conjugation.
FT CHAIN 1..588
FT /note="Dual specificity tyrosine-phosphorylation-regulated
FT kinase 3"
FT /id="PRO_0000085938"
FT DOMAIN 209..522
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..188
FT /note="Disordered"
FT /evidence="ECO:0000305|PubMed:23415227"
FT MOTIF 468..481
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:29973724"
FT ACT_SITE 335
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 215..223
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000305|PubMed:29634919"
FT BINDING 238
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:23415227, ECO:0000269|PubMed:29634919"
FT BINDING 288..291
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000305|PubMed:29634919"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:29634919"
FT MOD_RES 369
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q922Y0"
FT VAR_SEQ 1..20
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10779429,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.5"
FT /id="VSP_026178"
FT VAR_SEQ 21..26
FT /note="PPQQRR -> MKWKEK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10779429,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.5"
FT /id="VSP_026179"
FT VARIANT 239
FT /note="M -> L"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040464"
FT MUTAGEN 238
FT /note="K->M: Kinase dead; Induces formation of stress
FT granules-like in absence of stress. Impaired dissolution of
FT membraneless organelles during mitosis, such as stress
FT granules, nuclear speckles and pericentriolar material."
FT /evidence="ECO:0000269|PubMed:23415227,
FT ECO:0000269|PubMed:29634919, ECO:0000269|PubMed:29973724"
FT MUTAGEN 350
FT /note="S->A: Decreased stability of the protein."
FT /evidence="ECO:0000269|PubMed:29634919"
FT MUTAGEN 350
FT /note="S->E,D: Phosphomimetic mutant; increased stability
FT of the protein."
FT /evidence="ECO:0000269|PubMed:29634919"
FT MUTAGEN 470..474
FT /note="RRGKK->AAGAA: Abolishes localization to the nucleus,
FT leading to impaired dissolution of nuclear speckles during
FT mitosis."
FT /evidence="ECO:0000269|PubMed:29973724"
FT CONFLICT 313
FT /note="R -> H (in Ref. 9; AAH15501)"
FT /evidence="ECO:0000305"
FT CONFLICT 396
FT /note="G -> R (in Ref. 1; CAA73266)"
FT /evidence="ECO:0000305"
FT HELIX 143..149
FT /evidence="ECO:0007829|PDB:5Y86"
FT TURN 150..153
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 156..161
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 185..188
FT /evidence="ECO:0007829|PDB:5Y86"
FT TURN 206..208
FT /evidence="ECO:0007829|PDB:5Y86"
FT STRAND 209..218
FT /evidence="ECO:0007829|PDB:5Y86"
FT STRAND 221..228
FT /evidence="ECO:0007829|PDB:5Y86"
FT TURN 229..232
FT /evidence="ECO:0007829|PDB:5Y86"
FT STRAND 233..240
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 244..263
FT /evidence="ECO:0007829|PDB:5Y86"
FT TURN 266..269
FT /evidence="ECO:0007829|PDB:5Y86"
FT STRAND 274..280
FT /evidence="ECO:0007829|PDB:5Y86"
FT STRAND 283..288
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 295..301
FT /evidence="ECO:0007829|PDB:5Y86"
FT TURN 302..304
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 309..328
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 338..340
FT /evidence="ECO:0007829|PDB:5Y86"
FT STRAND 341..345
FT /evidence="ECO:0007829|PDB:5Y86"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 356..358
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 373..375
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 378..382
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 389..404
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 414..425
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 430..434
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 439..441
FT /evidence="ECO:0007829|PDB:5Y86"
FT STRAND 452..456
FT /evidence="ECO:0007829|PDB:5Y86"
FT STRAND 462..465
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 483..486
FT /evidence="ECO:0007829|PDB:5Y86"
FT TURN 487..489
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 493..502
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 507..509
FT /evidence="ECO:0007829|PDB:5Y86"
FT HELIX 513..518
FT /evidence="ECO:0007829|PDB:5Y86"
FT TURN 520..522
FT /evidence="ECO:0007829|PDB:5Y86"
SQ SEQUENCE 588 AA; 65714 MW; 9950F51C39AFED82 CRC64;
MGGTARGPGR KDAGPPGAGL PPQQRRLGDG VYDTFMMIDE TKCPPCSNVL CNPSEPPPPR
RLNMTTEQFT GDHTQHFLDG GEMKVEQLFQ EFGNRKSNTI QSDGISDSEK CSPTVSQGKS
SDCLNTVKSN SSSKAPKVVP LTPEQALKQY KHHLTAYEKL EIINYPEIYF VGPNAKKRHG
VIGGPNNGGY DDADGAYIHV PRDHLAYRYE VLKIIGKGSF GQVARVYDHK LRQYVALKMV
RNEKRFHRQA AEEIRILEHL KKQDKTGSMN VIHMLESFTF RNHVCMAFEL LSIDLYELIK
KNKFQGFSVQ LVRKFAQSIL QSLDALHKNK IIHCDLKPEN ILLKHHGRSS TKVIDFGSSC
FEYQKLYTYI QSRFYRAPEI ILGSRYSTPI DIWSFGCILA ELLTGQPLFP GEDEGDQLAC
MMELLGMPPP KLLEQSKRAK YFINSKGIPR YCSVTTQADG RVVLVGGRSR RGKKRGPPGS
KDWGTALKGC DDYLFIEFLK RCLHWDPSAR LTPAQALRHP WISKSVPRPL TTIDKVSGKR
VVNPASAFQG LGSKLPPVVG IANKLKANLM SETNGSIPLC SVLPKLIS
