DYR1A_HUMAN
ID DYR1A_HUMAN Reviewed; 763 AA.
AC Q13627; O60769; Q92582; Q92810; Q9UNM5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Dual specificity tyrosine-phosphorylation-regulated kinase 1A;
DE EC=2.7.12.1 {ECO:0000269|PubMed:20981014, ECO:0000269|PubMed:22998443, ECO:0000269|PubMed:23665168, ECO:0000269|PubMed:24239188, ECO:0000269|PubMed:30773093};
DE AltName: Full=Dual specificity YAK1-related kinase;
DE AltName: Full=HP86;
DE AltName: Full=Protein kinase minibrain homolog;
DE Short=MNBH;
DE Short=hMNB;
GN Name=DYRK1A; Synonyms=DYRK, MNB, MNBH;
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 LONG), VARIANT PRO-679, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=8975710; DOI=10.1006/geno.1996.0636;
RA Song W.J., Sternberg L.R., Kasten-Sportes C., van Keuren M.L., Chung S.H.,
RA Slack A.C., Miller D.E., Glover T.W., Chiang P.W., Lou L., Kurnit D.W.;
RT "Isolation of human and murine homologues of the Drosophila minibrain gene:
RT human homologue maps to 21q22.2 in the Down syndrome 'critical region'.";
RL Genomics 38:331-339(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), TISSUE SPECIFICITY, AND POSSIBLE
RP INVOLVEMENT IN DOWN SYNDROME.
RX PubMed=8872470; DOI=10.1093/hmg/5.9.1305;
RA Guimera J., Casas C., Pucharcos C., Solans A., Domenech A., Planas A.M.,
RA Ashley J., Lovett M., Estivill X., Pritchard M.A.;
RT "A human homologue of Drosophila minibrain (MNB) is expressed in the
RT neuronal regions affected in Down syndrome and maps to the critical
RT region.";
RL Hum. Mol. Genet. 5:1305-1310(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Fetal brain;
RX PubMed=8769099; DOI=10.1006/bbrc.1996.1135;
RA Shindoh N., Kudoh J., Maeda H., Yamaki A., Minoshima S., Shimizu Y.,
RA Shimizu N.;
RT "Cloning of a human homolog of the Drosophila minibrain/rat Dyrk gene from
RT 'the Down syndrome critical region' of chromosome 21.";
RL Biochem. Biophys. Res. Commun. 225:92-99(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Promyelocytic leukemia;
RX PubMed=9037601; DOI=10.1101/gr.7.1.47;
RA Ohira M., Seki N., Nagase T., Suzuki E., Nomura N., Ohara O., Hattori M.,
RA Sakaki Y., Eki T., Murakami Y., Saito T., Ichikawa H., Ohki M.;
RT "Gene identification in 1.6-Mb region of the Down syndrome region on
RT chromosome 21.";
RL Genome Res. 7:47-58(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), TISSUE SPECIFICITY, POSSIBLE
RP INVOLVEMENT IN DOWN SYNDROME, VARIANTS PHE-415 AND HIS-681, AND ALTERNATIVE
RP SPLICING.
RX PubMed=10329007; DOI=10.1006/geno.1999.5775;
RA Guimera J., Casas C., Estivill X., Pritchard M.A.;
RT "Human minibrain homologue (MNBH/DYRK1): characterization, alternative
RT splicing, differential tissue expression, and overexpression in Down
RT syndrome.";
RL Genomics 57:407-418(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 234-380.
RC TISSUE=Fetal brain;
RX PubMed=9503011; DOI=10.1006/geno.1997.5146;
RA Dahmane N., Ait-Ghezala G., Gosset P., Chamoun Z., Dufresne-Zacharia M.-C.,
RA Lopes C., Rabatel N., Gassanova-Maugenre S., Chettouh Z., Abramowski V.,
RA Fayet E., Yaspo M.-L., Korn B., Blouin J.-L., Lehrach H., Poustka A.,
RA Antonarakis S.E., Sinet P.-M., Creau N., Delabar J.-M.;
RT "Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved
RT in Down syndrome.";
RL Genomics 48:12-23(1998).
RN [7]
RP INTERACTION WITH RANBP9, AND ACTIVITY REGULATION.
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 [8]
RP INTERACTION WITH WDR68.
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-748 AND SER-758, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP POLY-HISTIDINE REPEATS.
RX PubMed=19266028; DOI=10.1371/journal.pgen.1000397;
RA Salichs E., Ledda A., Mularoni L., Alba M.M., de la Luna S.;
RT "Genome-wide analysis of histidine repeats reveals their role in the
RT localization of human proteins to the nuclear speckles compartment.";
RL PLoS Genet. 5:E1000397-E1000397(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-145, AND IDENTIFICATION BY
RP 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 [13]
RP SUBCELLULAR LOCATION.
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 [14]
RP INVOLVEMENT IN MRD7.
RX PubMed=21294719; DOI=10.1111/j.1399-0004.2010.01544.x;
RA van Bon B.W., Hoischen A., Hehir-Kwa J., de Brouwer A.P., Ruivenkamp C.,
RA Gijsbers A.C., Marcelis C.L., de Leeuw N., Veltman J.A., Brunner H.G.,
RA de Vries B.B.;
RT "Intragenic deletion in DYRK1A leads to mental retardation and primary
RT microcephaly.";
RL Clin. Genet. 79:296-299(2011).
RN [15]
RP FUNCTION, AND SUBSTRATE SPECIFICITY.
RX PubMed=21127067; DOI=10.1074/jbc.m110.157909;
RA Papadopoulos C., Arato K., Lilienthal E., Zerweck J., Schutkowski M.,
RA Chatain N., Muller-Newen G., Becker W., de la Luna S.;
RT "Splice variants of the dual specificity tyrosine phosphorylation-regulated
RT kinase 4 (DYRK4) differ in their subcellular localization and catalytic
RT activity.";
RL J. Biol. Chem. 286:5494-5505(2011).
RN [16]
RP INTERACTION WITH SRSF6.
RX PubMed=22767602; DOI=10.1074/jbc.m112.355412;
RA Yin X., Jin N., Gu J., Shi J., Zhou J., Gong C.X., Iqbal K.,
RA Grundke-Iqbal I., Liu F.;
RT "Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A)
RT modulates serine/arginine-rich protein 55 (SRp55)-promoted Tau exon 10
RT inclusion.";
RL J. Biol. Chem. 287:30497-30506(2012).
RN [17]
RP INVOLVEMENT IN MRD7.
RX PubMed=23160955; DOI=10.1126/science.1227764;
RA O'Roak B.J., Vives L., Fu W., Egertson J.D., Stanaway I.B., Phelps I.G.,
RA Carvill G., Kumar A., Lee C., Ankenman K., Munson J., Hiatt J.B.,
RA Turner E.H., Levy R., O'Day D.R., Krumm N., Coe B.P., Martin B.K.,
RA Borenstein E., Nickerson D.A., Mefford H.C., Doherty D., Akey J.M.,
RA Bernier R., Eichler E.E., Shendure J.;
RT "Multiplex targeted sequencing identifies recurrently mutated genes in
RT autism spectrum disorders.";
RL Science 338:1619-1622(2012).
RN [18]
RP SUBCELLULAR LOCATION.
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND TYR-145, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [20]
RP INTERACTION WITH HADV5 E1A (MICROBIAL INFECTION).
RX PubMed=23864635; DOI=10.1128/jvi.00786-13;
RA Cohen M.J., Yousef A.F., Massimi P., Fonseca G.J., Todorovic B., Pelka P.,
RA Turnell A.S., Banks L., Mymryk J.S.;
RT "Dissection of the C-terminal region of E1A redefines the roles of CtBP and
RT other cellular targets in oncogenic transformation.";
RL J. Virol. 87:10348-10355(2013).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-529, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP FUNCTION.
RX PubMed=31024071; DOI=10.1038/s41598-019-42990-5;
RA Guard S.E., Poss Z.C., Ebmeier C.C., Pagratis M., Simpson H., Taatjes D.J.,
RA Old W.M.;
RT "The nuclear interactome of DYRK1A reveals a functional role in DNA damage
RT repair.";
RL Sci. Rep. 9:6539-6539(2019).
RN [23]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30773093; DOI=10.1080/15384101.2019.1577525;
RA Menon V.R., Ananthapadmanabhan V., Swanson S., Saini S., Sesay F.,
RA Yakovlev V., Florens L., DeCaprio J.A., Washburn M.P., Dozmorov M.,
RA Litovchick L.;
RT "DYRK1A regulates the recruitment of 53BP1 to the sites of DNA damage in
RT part through interaction with RNF169.";
RL Cell Cycle 18:531-551(2019).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 126-490 IN COMPLEXES WITH THE
RP SYNTHETIC INHIBITORS HARMINE AND INDY, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=20981014; DOI=10.1038/ncomms1090;
RA Ogawa Y., Nonaka Y., Goto T., Ohnishi E., Hiramatsu T., Kii I., Yoshida M.,
RA Ikura T., Onogi H., Shibuya H., Hosoya T., Ito N., Hagiwara M.;
RT "Development of a novel selective inhibitor of the Down syndrome-related
RT kinase Dyrk1A.";
RL Nat. Commun. 1:86-86(2010).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (3.15 ANGSTROMS) OF 128-485, CATALYTIC ACTIVITY, AND
RP ACTIVITY REGULATION.
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 [26]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 127-485 IN COMPLEX WITH SYNTHETIC
RP INHIBITOR, AND CATALYTIC ACTIVITY.
RX PubMed=24239188; DOI=10.1016/j.bmcl.2013.10.055;
RA Anderson K., Chen Y., Chen Z., Dominique R., Glenn K., He Y., Janson C.,
RA Luk K.C., Lukacs C., Polonskaia A., Qiao Q., Railkar A., Rossman P.,
RA Sun H., Xiang Q., Vilenchik M., Wovkulich P., Zhang X.;
RT "Pyrido[2,3-d]pyrimidines: discovery and preliminary SAR of a novel series
RT of DYRK1B and DYRK1A inhibitors.";
RL Bioorg. Med. Chem. Lett. 23:6610-6615(2013).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 127-485 IN COMPLEXES WITH PEPTIDE
RP SUBSTRATE AND INHIBITOR DJM2005, CATALYTIC ACTIVITY, FUNCTION,
RP AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-188 AND TYR-321, PHOSPHORYLATION AT
RP TYR-111; TYR-140; TYR-159; TYR-177; SER-310; TYR-319; TYR-321; THR-402 AND
RP TYR-449, ACTIVE SITE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23665168; DOI=10.1016/j.str.2013.03.012;
RA Soundararajan M., Roos A.K., Savitsky P., Filippakopoulos P.,
RA Kettenbach A.N., Olsen J.V., Gerber S.A., Eswaran J., Knapp S.,
RA Elkins J.M.;
RT "Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase
RT activation and substrate recognition.";
RL Structure 21:986-996(2013).
RN [28]
RP VARIANT [LARGE SCALE ANALYSIS] PRO-679.
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 important role in double-
CC strand breaks (DSBs) repair following DNA damage (PubMed:31024071).
CC Mechanistically, phosphorylates RNF169 and increases its ability to
CC block accumulation of TP53BP1 at the DSB sites thereby promoting
CC homologous recombination repair (HRR) (PubMed:30773093). May play a
CC role in a signaling pathway regulating nuclear functions of cell
CC proliferation. Modulates alternative splicing by phosphorylating the
CC splice factor SRSF6 (By similarity). Exhibits a substrate preference
CC for proline at position P+1 and arginine at position P-3. Has pro-
CC survival function and negatively regulates the apoptotic process.
CC Promotes cell survival upon genotoxic stress through phosphorylation of
CC SIRT1. This in turn inhibits TP53 activity and apoptosis (By
CC similarity). Phosphorylates SEPTIN4, SEPTIN5 and SF3B1 at 'Thr-434' (By
CC similarity). {ECO:0000250|UniProtKB:Q61214,
CC ECO:0000250|UniProtKB:Q63470, ECO:0000250|UniProtKB:Q9NR20,
CC ECO:0000269|PubMed:20981014, ECO:0000269|PubMed:21127067,
CC ECO:0000269|PubMed:23665168, ECO:0000269|PubMed:8769099}.
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:20981014, ECO:0000269|PubMed:22998443,
CC ECO:0000269|PubMed:23665168, ECO:0000269|PubMed:24239188,
CC ECO:0000269|PubMed:30773093};
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:20981014,
CC ECO:0000269|PubMed:22998443, ECO:0000269|PubMed:23665168,
CC ECO:0000269|PubMed:24239188};
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:20981014, ECO:0000269|PubMed:22998443,
CC ECO:0000269|PubMed:23665168, ECO:0000269|PubMed:24239188};
CC -!- ACTIVITY REGULATION: Inhibited by RANBP9 (PubMed:14500717). Inhibited
CC by harmine, leucettamine B and leucettine L41 (PubMed:22998443).
CC {ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:22998443}.
CC -!- SUBUNIT: Interacts RAD54L2/ARIP4 (By similarity). Interacts with CRY2
CC (By similarity). Interacts with RANBP9 (PubMed:14500717). Interacts
CC with WDR68 (PubMed:14593110). Interacts with SRSF6 (PubMed:22767602).
CC Interacts with SIRT1 (By similarity). Interacts with SEPTIN4 and
CC SEPTIN5 (By similarity). {ECO:0000250|UniProtKB:Q61214,
CC ECO:0000250|UniProtKB:Q63470, ECO:0000269|PubMed:14500717,
CC ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:22767602,
CC ECO:0000269|PubMed:24239188}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human adenovirus 5 E1A
CC protein (PubMed:23864635). {ECO:0000269|PubMed:23864635}.
CC -!- INTERACTION:
CC Q13627; P61962: DCAF7; NbExp=8; IntAct=EBI-1053596, EBI-359808;
CC Q13627; Q5T749: KPRP; NbExp=3; IntAct=EBI-1053596, EBI-10981970;
CC Q13627; Q9BRK4: LZTS2; NbExp=4; IntAct=EBI-1053596, EBI-741037;
CC Q13627; P06400: RB1; NbExp=4; IntAct=EBI-1053596, EBI-491274;
CC Q13627; P28749: RBL1; NbExp=4; IntAct=EBI-1053596, EBI-971402;
CC Q13627; Q12815: TROAP; NbExp=4; IntAct=EBI-1053596, EBI-2349743;
CC Q13627-1; Q13627-1: DYRK1A; NbExp=2; IntAct=EBI-1053617, EBI-1053617;
CC Q13627-2; P31946: YWHAB; NbExp=3; IntAct=EBI-1053621, EBI-359815;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20167603,
CC ECO:0000269|PubMed:23415227}. Nucleus speckle
CC {ECO:0000250|UniProtKB:Q61214}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=Long;
CC IsoId=Q13627-1; Sequence=Displayed;
CC Name=1;
CC IsoId=Q13627-2; Sequence=VSP_004917;
CC Name=2;
CC IsoId=Q13627-3; Sequence=VSP_004918, VSP_004919;
CC Name=3;
CC IsoId=Q13627-4; Sequence=VSP_004920, VSP_004921;
CC Name=4;
CC IsoId=Q13627-5; Sequence=VSP_004922, VSP_004923;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest levels in skeletal muscle,
CC testis, fetal lung and fetal kidney. {ECO:0000269|PubMed:10329007,
CC ECO:0000269|PubMed:8769099, ECO:0000269|PubMed:8872470,
CC ECO:0000269|PubMed:8975710}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing central nervous
CC system. Overexpressed 1.5-fold in fetal Down syndrome brain.
CC {ECO:0000269|PubMed:8769099}.
CC -!- DOMAIN: The polyhistidine repeats act as targeting signals to nuclear
CC speckles. {ECO:0000269|PubMed:19266028}.
CC -!- PTM: Autophosphorylated on numerous tyrosine residues. Can also
CC autophosphorylate on serine and threonine residues (in vitro).
CC {ECO:0000269|PubMed:23665168}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 7
CC (MRD7) [MIM:614104]: A disease characterized by primary microcephaly,
CC severe intellectual disability without speech, anxious autistic
CC behavior, and dysmorphic features, including bitemporal narrowing,
CC deep-set eyes, large simple ears, and a pointed nasal tip. Intellectual
CC disability is characterized by significantly below average general
CC intellectual functioning associated with impairments in adaptive
CC behavior and manifested during the developmental period.
CC {ECO:0000269|PubMed:21294719, ECO:0000269|PubMed:23160955}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MNB/DYRK subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/DYRK1AID43234ch21q22.html";
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DR EMBL; U58496; AAC50939.1; -; mRNA.
DR EMBL; U52373; AAB18639.1; -; mRNA.
DR EMBL; D85759; BAA12866.1; -; mRNA.
DR EMBL; D86550; BAA13110.1; -; mRNA.
DR EMBL; AF108830; AAD31169.1; -; mRNA.
DR EMBL; AJ001870; CAA05059.1; -; mRNA.
DR CCDS; CCDS13653.1; -. [Q13627-2]
DR CCDS; CCDS13654.1; -. [Q13627-3]
DR CCDS; CCDS42925.1; -. [Q13627-1]
DR CCDS; CCDS42926.1; -. [Q13627-5]
DR PIR; JC4898; JC4898.
DR RefSeq; NP_001334650.1; NM_001347721.1. [Q13627-2]
DR RefSeq; NP_001334651.1; NM_001347722.1. [Q13627-2]
DR RefSeq; NP_001387.2; NM_001396.4. [Q13627-1]
DR RefSeq; NP_567824.1; NM_101395.2. [Q13627-5]
DR RefSeq; NP_569120.1; NM_130436.2. [Q13627-2]
DR RefSeq; NP_569122.1; NM_130438.2. [Q13627-3]
DR RefSeq; XP_006724039.1; XM_006723976.3. [Q13627-1]
DR RefSeq; XP_006724040.1; XM_006723977.3. [Q13627-1]
DR RefSeq; XP_006724041.1; XM_006723978.3. [Q13627-1]
DR RefSeq; XP_011527785.1; XM_011529483.2. [Q13627-1]
DR RefSeq; XP_016883773.1; XM_017028284.1. [Q13627-2]
DR PDB; 2VX3; X-ray; 2.40 A; A/B/C/D=127-485.
DR PDB; 2WO6; X-ray; 2.50 A; A/B=127-485.
DR PDB; 3ANQ; X-ray; 2.60 A; A/B/C/D=126-490.
DR PDB; 3ANR; X-ray; 2.60 A; A/B/C/D=126-490.
DR PDB; 4AZE; X-ray; 3.15 A; A/B/C=128-485.
DR PDB; 4MQ1; X-ray; 2.35 A; A/B/C/D=127-485.
DR PDB; 4MQ2; X-ray; 2.80 A; A/B/C/D=127-485.
DR PDB; 4NCT; X-ray; 2.60 A; A/B/C/D=126-490.
DR PDB; 4YLJ; X-ray; 2.58 A; A/B/C/D=127-485.
DR PDB; 4YLK; X-ray; 1.40 A; A=127-485.
DR PDB; 4YLL; X-ray; 1.40 A; A=127-485.
DR PDB; 4YU2; X-ray; 2.90 A; A/B/C/D=127-485.
DR PDB; 5A3X; X-ray; 2.26 A; A/B/C/D=126-490.
DR PDB; 5A4E; X-ray; 2.68 A; A/B/C/D=126-490.
DR PDB; 5A4L; X-ray; 2.73 A; A/B/C/D=126-490.
DR PDB; 5A4Q; X-ray; 2.37 A; A/B/C/D=126-490.
DR PDB; 5A4T; X-ray; 2.15 A; A/B/C/D=126-490.
DR PDB; 5A54; X-ray; 2.63 A; A/B/C/D=126-490.
DR PDB; 5AIK; X-ray; 2.70 A; A/B/C/D=128-485.
DR PDB; 6A1F; X-ray; 1.50 A; A=127-483.
DR PDB; 6A1G; X-ray; 2.15 A; A/B=127-483.
DR PDB; 6EIF; X-ray; 2.22 A; A/B/C/D=126-490.
DR PDB; 6EIJ; X-ray; 2.42 A; A/B/C/D=126-490.
DR PDB; 6EIL; X-ray; 2.46 A; A/B/C/D=126-490.
DR PDB; 6EIP; X-ray; 2.56 A; A/B/C/D=126-490.
DR PDB; 6EIQ; X-ray; 2.30 A; A/B/C/D=126-490.
DR PDB; 6EIR; X-ray; 2.40 A; A/B/C/D=126-490.
DR PDB; 6EIS; X-ray; 2.36 A; A/B/C/D=126-490.
DR PDB; 6EIV; X-ray; 2.68 A; A/B/C/D=126-490.
DR PDB; 6EJ4; X-ray; 2.88 A; A/B/C/D=126-490.
DR PDB; 6LN1; X-ray; 2.70 A; A/B=135-480.
DR PDB; 6QU2; X-ray; 2.90 A; A/B/C/D=127-485.
DR PDB; 6S11; X-ray; 2.44 A; A/B=127-485.
DR PDB; 6S14; X-ray; 1.05 A; A=127-485.
DR PDB; 6S17; X-ray; 1.10 A; A=127-485.
DR PDB; 6S1B; X-ray; 1.30 A; A=127-485.
DR PDB; 6S1H; X-ray; 1.05 A; A=127-485.
DR PDB; 6S1I; X-ray; 2.38 A; A/B/C/D=127-485.
DR PDB; 6S1J; X-ray; 1.41 A; A=127-485.
DR PDB; 6T6A; X-ray; 2.80 A; A/B/C/D=127-485.
DR PDB; 6UIP; X-ray; 3.70 A; A/B/C=127-485.
DR PDB; 6UWY; X-ray; 2.95 A; A/B/C/D=127-485.
DR PDB; 6YF8; X-ray; 3.20 A; A/B/C/D=126-490.
DR PDB; 7A4O; X-ray; 1.90 A; A/B=127-485.
DR PDB; 7A4R; X-ray; 1.80 A; A/B=148-479.
DR PDB; 7A4S; X-ray; 3.10 A; A=148-485.
DR PDB; 7A4W; X-ray; 2.70 A; A/B=127-485.
DR PDB; 7A4Z; X-ray; 1.90 A; A=148-485.
DR PDB; 7A51; X-ray; 1.90 A; A=148-485.
DR PDB; 7A52; X-ray; 2.10 A; A/B=148-479.
DR PDB; 7A53; X-ray; 2.20 A; A/B=148-485.
DR PDB; 7A55; X-ray; 2.20 A; A/B=127-485.
DR PDB; 7A5B; X-ray; 2.60 A; A/B=127-485.
DR PDB; 7A5D; X-ray; 1.80 A; A=148-485.
DR PDB; 7A5L; X-ray; 2.10 A; A=148-485.
DR PDB; 7A5N; X-ray; 2.30 A; A/B=148-485.
DR PDB; 7AJ2; X-ray; 2.10 A; A=148-485.
DR PDB; 7AJ4; X-ray; 2.00 A; A=148-485.
DR PDB; 7AJ5; X-ray; 2.00 A; A=148-485.
DR PDB; 7AJ7; X-ray; 2.90 A; A=148-485.
DR PDB; 7AJ8; X-ray; 2.00 A; A=148-485.
DR PDB; 7AJA; X-ray; 2.20 A; A=148-485.
DR PDB; 7AJM; X-ray; 2.40 A; A/B=148-479.
DR PDB; 7AJS; X-ray; 2.15 A; A/B=148-479.
DR PDB; 7AJV; X-ray; 2.10 A; A/B=148-485.
DR PDB; 7AJW; X-ray; 2.80 A; A=148-485.
DR PDB; 7AJY; X-ray; 2.20 A; A/B=148-485.
DR PDB; 7AK2; X-ray; 2.10 A; A/B=148-485.
DR PDB; 7AKA; X-ray; 1.90 A; A/B=148-485.
DR PDB; 7AKB; X-ray; 2.80 A; A/B=148-485.
DR PDB; 7AKE; X-ray; 2.30 A; A/B=148-485.
DR PDB; 7AKL; X-ray; 2.00 A; A=148-485.
DR PDB; 7FHS; X-ray; 2.42 A; A/B/C/D=127-485.
DR PDB; 7FHT; X-ray; 2.68 A; A/B/C/D=127-485.
DR PDB; 7O7K; X-ray; 1.82 A; A/B=127-485.
DR PDB; 7OY6; X-ray; 2.38 A; C=127-485.
DR PDBsum; 2VX3; -.
DR PDBsum; 2WO6; -.
DR PDBsum; 3ANQ; -.
DR PDBsum; 3ANR; -.
DR PDBsum; 4AZE; -.
DR PDBsum; 4MQ1; -.
DR PDBsum; 4MQ2; -.
DR PDBsum; 4NCT; -.
DR PDBsum; 4YLJ; -.
DR PDBsum; 4YLK; -.
DR PDBsum; 4YLL; -.
DR PDBsum; 4YU2; -.
DR PDBsum; 5A3X; -.
DR PDBsum; 5A4E; -.
DR PDBsum; 5A4L; -.
DR PDBsum; 5A4Q; -.
DR PDBsum; 5A4T; -.
DR PDBsum; 5A54; -.
DR PDBsum; 5AIK; -.
DR PDBsum; 6A1F; -.
DR PDBsum; 6A1G; -.
DR PDBsum; 6EIF; -.
DR PDBsum; 6EIJ; -.
DR PDBsum; 6EIL; -.
DR PDBsum; 6EIP; -.
DR PDBsum; 6EIQ; -.
DR PDBsum; 6EIR; -.
DR PDBsum; 6EIS; -.
DR PDBsum; 6EIV; -.
DR PDBsum; 6EJ4; -.
DR PDBsum; 6LN1; -.
DR PDBsum; 6QU2; -.
DR PDBsum; 6S11; -.
DR PDBsum; 6S14; -.
DR PDBsum; 6S17; -.
DR PDBsum; 6S1B; -.
DR PDBsum; 6S1H; -.
DR PDBsum; 6S1I; -.
DR PDBsum; 6S1J; -.
DR PDBsum; 6T6A; -.
DR PDBsum; 6UIP; -.
DR PDBsum; 6UWY; -.
DR PDBsum; 6YF8; -.
DR PDBsum; 7A4O; -.
DR PDBsum; 7A4R; -.
DR PDBsum; 7A4S; -.
DR PDBsum; 7A4W; -.
DR PDBsum; 7A4Z; -.
DR PDBsum; 7A51; -.
DR PDBsum; 7A52; -.
DR PDBsum; 7A53; -.
DR PDBsum; 7A55; -.
DR PDBsum; 7A5B; -.
DR PDBsum; 7A5D; -.
DR PDBsum; 7A5L; -.
DR PDBsum; 7A5N; -.
DR PDBsum; 7AJ2; -.
DR PDBsum; 7AJ4; -.
DR PDBsum; 7AJ5; -.
DR PDBsum; 7AJ7; -.
DR PDBsum; 7AJ8; -.
DR PDBsum; 7AJA; -.
DR PDBsum; 7AJM; -.
DR PDBsum; 7AJS; -.
DR PDBsum; 7AJV; -.
DR PDBsum; 7AJW; -.
DR PDBsum; 7AJY; -.
DR PDBsum; 7AK2; -.
DR PDBsum; 7AKA; -.
DR PDBsum; 7AKB; -.
DR PDBsum; 7AKE; -.
DR PDBsum; 7AKL; -.
DR PDBsum; 7FHS; -.
DR PDBsum; 7FHT; -.
DR PDBsum; 7O7K; -.
DR PDBsum; 7OY6; -.
DR AlphaFoldDB; Q13627; -.
DR SMR; Q13627; -.
DR BioGRID; 108192; 434.
DR DIP; DIP-39750N; -.
DR ELM; Q13627; -.
DR IntAct; Q13627; 60.
DR MINT; Q13627; -.
DR STRING; 9606.ENSP00000381932; -.
DR BindingDB; Q13627; -.
DR ChEMBL; CHEMBL2292; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB07608; N-(5-{[(2S)-4-amino-2-(3-chlorophenyl)butanoyl]amino}-1H-indazol-3-yl)benzamide.
DR DrugCentral; Q13627; -.
DR GuidetoPHARMACOLOGY; 2009; -.
DR GlyGen; Q13627; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13627; -.
DR PhosphoSitePlus; Q13627; -.
DR BioMuta; DYRK1A; -.
DR DMDM; 3219996; -.
DR EPD; Q13627; -.
DR jPOST; Q13627; -.
DR MassIVE; Q13627; -.
DR MaxQB; Q13627; -.
DR PaxDb; Q13627; -.
DR PeptideAtlas; Q13627; -.
DR PRIDE; Q13627; -.
DR ProteomicsDB; 59619; -. [Q13627-1]
DR ProteomicsDB; 59620; -. [Q13627-2]
DR ProteomicsDB; 59621; -. [Q13627-3]
DR ProteomicsDB; 59622; -. [Q13627-4]
DR ProteomicsDB; 59623; -. [Q13627-5]
DR Antibodypedia; 8587; 426 antibodies from 39 providers.
DR DNASU; 1859; -.
DR Ensembl; ENST00000338785.8; ENSP00000342690.3; ENSG00000157540.22. [Q13627-5]
DR Ensembl; ENST00000398956.2; ENSP00000381929.2; ENSG00000157540.22. [Q13627-3]
DR Ensembl; ENST00000398960.7; ENSP00000381932.2; ENSG00000157540.22. [Q13627-1]
DR Ensembl; ENST00000643624.1; ENSP00000493627.1; ENSG00000157540.22. [Q13627-2]
DR Ensembl; ENST00000644942.1; ENSP00000494544.1; ENSG00000157540.22. [Q13627-1]
DR Ensembl; ENST00000645424.1; ENSP00000494897.1; ENSG00000157540.22. [Q13627-4]
DR Ensembl; ENST00000646548.1; ENSP00000495908.1; ENSG00000157540.22. [Q13627-2]
DR Ensembl; ENST00000647188.2; ENSP00000494572.1; ENSG00000157540.22. [Q13627-2]
DR Ensembl; ENST00000647425.1; ENSP00000496748.1; ENSG00000157540.22. [Q13627-2]
DR GeneID; 1859; -.
DR KEGG; hsa:1859; -.
DR MANE-Select; ENST00000647188.2; ENSP00000494572.1; NM_001347721.2; NP_001334650.1. [Q13627-2]
DR UCSC; uc002ywi.4; human. [Q13627-1]
DR CTD; 1859; -.
DR DisGeNET; 1859; -.
DR GeneCards; DYRK1A; -.
DR GeneReviews; DYRK1A; -.
DR HGNC; HGNC:3091; DYRK1A.
DR HPA; ENSG00000157540; Low tissue specificity.
DR MalaCards; DYRK1A; -.
DR MIM; 600855; gene.
DR MIM; 614104; phenotype.
DR neXtProt; NX_Q13627; -.
DR OpenTargets; ENSG00000157540; -.
DR Orphanet; 268261; DYRK1A-related intellectual disability syndrome due to 21q22.13q22.2 microdeletion.
DR Orphanet; 464311; Intellectual disability syndrome due to a DYRK1A point mutation.
DR PharmGKB; PA27545; -.
DR VEuPathDB; HostDB:ENSG00000157540; -.
DR eggNOG; KOG0667; Eukaryota.
DR GeneTree; ENSGT00940000157408; -.
DR HOGENOM; CLU_000288_5_6_1; -.
DR InParanoid; Q13627; -.
DR OMA; PPIGWTA; -.
DR OrthoDB; 271572at2759; -.
DR PhylomeDB; Q13627; -.
DR TreeFam; TF314624; -.
DR BRENDA; 2.7.12.1; 2681.
DR PathwayCommons; Q13627; -.
DR Reactome; R-HSA-1538133; G0 and Early G1.
DR SignaLink; Q13627; -.
DR SIGNOR; Q13627; -.
DR BioGRID-ORCS; 1859; 113 hits in 1129 CRISPR screens.
DR ChiTaRS; DYRK1A; human.
DR EvolutionaryTrace; Q13627; -.
DR GeneWiki; DYRK1A; -.
DR GenomeRNAi; 1859; -.
DR Pharos; Q13627; Tchem.
DR PRO; PR:Q13627; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; Q13627; protein.
DR Bgee; ENSG00000157540; Expressed in amniotic fluid and 210 other tissues.
DR ExpressionAtlas; Q13627; baseline and differential.
DR Genevisible; Q13627; HS.
DR GO; GO:0030424; C:axon; ISS:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; ISS:ARUK-UCL.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IEA:Ensembl.
DR GO; GO:0003779; F:actin binding; IPI:ARUK-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008092; F:cytoskeletal protein binding; IPI:ARUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:MGI.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0043621; F:protein self-association; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IGI:ARUK-UCL.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0048156; F:tau protein binding; ISS:ARUK-UCL.
DR GO; GO:0050321; F:tau-protein kinase activity; NAS:ARUK-UCL.
DR GO; GO:0003713; F:transcription coactivator activity; IBA:GO_Central.
DR GO; GO:0015631; F:tubulin binding; IPI:ARUK-UCL.
DR GO; GO:0034205; P:amyloid-beta formation; IMP:ARUK-UCL.
DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; ISS:BHF-UCL.
DR GO; GO:0031115; P:negative regulation of microtubule polymerization; ISS:ARUK-UCL.
DR GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; TAS:ARUK-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IGI:ARUK-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:ARUK-UCL.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0090312; P:positive regulation of protein deacetylation; ISS:BHF-UCL.
DR GO; GO:0033120; P:positive regulation of RNA splicing; IDA:ARUK-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS: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:SF121; PTHR24058:SF121; 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 3D-structure; Alternative splicing; ATP-binding; Host-virus interaction;
KW Intellectual disability; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Tyrosine-protein kinase.
FT CHAIN 1..763
FT /note="Dual specificity tyrosine-phosphorylation-regulated
FT kinase 1A"
FT /id="PRO_0000085931"
FT DOMAIN 159..479
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 32..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 115..136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 408..442
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 485..540
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 596..679
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 744..763
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 117..134
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 34..57
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 485..528
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 601..624
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 627..679
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 287
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:23665168"
FT BINDING 165..173
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT BINDING 188
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT BINDING 238..241
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 111
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:23665168"
FT MOD_RES 140
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:23665168"
FT MOD_RES 145
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 159
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:23665168"
FT MOD_RES 177
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:23665168"
FT MOD_RES 219
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q63470"
FT MOD_RES 310
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:23665168"
FT MOD_RES 319
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:23665168"
FT MOD_RES 321
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:23665168"
FT MOD_RES 402
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:23665168"
FT MOD_RES 449
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:23665168"
FT MOD_RES 529
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 538
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61214"
FT MOD_RES 748
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 758
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT VAR_SEQ 70..78
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:8769099,
FT ECO:0000303|PubMed:9037601"
FT /id="VSP_004917"
FT VAR_SEQ 516..529
FT /note="GGSSGTSNSGRARS -> GASAISCSSWLVRH (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004918"
FT VAR_SEQ 516..525
FT /note="GGSSGTSNSG -> GGAALDARCL (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_004920"
FT VAR_SEQ 526..763
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_004921"
FT VAR_SEQ 530..763
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004919"
FT VAR_SEQ 559..584
FT /note="RQQFPAPLGWSGTEAPTQVTVETHPV -> SSHVVHLLVSPAILRWSSTGCQ
FT VPLE (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10329007"
FT /id="VSP_004922"
FT VAR_SEQ 585..763
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10329007"
FT /id="VSP_004923"
FT VARIANT 415
FT /note="Y -> F"
FT /evidence="ECO:0000269|PubMed:10329007"
FT /id="VAR_009395"
FT VARIANT 679
FT /note="A -> P (in dbSNP:rs55720916)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:8975710"
FT /id="VAR_040453"
FT VARIANT 681
FT /note="Q -> H"
FT /evidence="ECO:0000269|PubMed:10329007"
FT /id="VAR_009396"
FT MUTAGEN 188
FT /note="K->R: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:23665168"
FT MUTAGEN 321
FT /note="Y->F: Mildly reduces kinase activity. Does not
FT abolish autophosphorylation on tyrosine residues."
FT /evidence="ECO:0000269|PubMed:23665168"
FT CONFLICT 32
FT /note="G -> A (in Ref. 1; AAC50939)"
FT /evidence="ECO:0000305"
FT CONFLICT 47
FT /note="N -> S (in Ref. 1; AAC50939)"
FT /evidence="ECO:0000305"
FT CONFLICT 57
FT /note="S -> P (in Ref. 1; AAC50939)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="Q -> R (in Ref. 1; AAC50939)"
FT /evidence="ECO:0000305"
FT CONFLICT 266
FT /note="A -> V (in Ref. 6; CAA05059)"
FT /evidence="ECO:0000305"
FT CONFLICT 357
FT /note="G -> R (in Ref. 6; CAA05059)"
FT /evidence="ECO:0000305"
FT CONFLICT 397
FT /note="K -> N (in Ref. 1; AAC50939)"
FT /evidence="ECO:0000305"
FT CONFLICT 592
FT /note="A -> G (in Ref. 1; AAC50939)"
FT /evidence="ECO:0000305"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:6S14"
FT TURN 156..158
FT /evidence="ECO:0007829|PDB:6S14"
FT STRAND 159..168
FT /evidence="ECO:0007829|PDB:6S14"
FT STRAND 171..178
FT /evidence="ECO:0007829|PDB:6S14"
FT TURN 179..182
FT /evidence="ECO:0007829|PDB:6S14"
FT STRAND 183..190
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 194..212
FT /evidence="ECO:0007829|PDB:6S14"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:7AKL"
FT STRAND 219..221
FT /evidence="ECO:0007829|PDB:6S1H"
FT STRAND 224..230
FT /evidence="ECO:0007829|PDB:6S14"
FT STRAND 233..238
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 245..251
FT /evidence="ECO:0007829|PDB:6S14"
FT TURN 252..254
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 259..276
FT /evidence="ECO:0007829|PDB:6S14"
FT TURN 279..281
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:6S14"
FT STRAND 293..297
FT /evidence="ECO:0007829|PDB:6S14"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:7O7K"
FT STRAND 303..305
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 308..310
FT /evidence="ECO:0007829|PDB:2WO6"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:6S1H"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 330..333
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 341..356
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 366..377
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 382..385
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 391..394
FT /evidence="ECO:0007829|PDB:6S14"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:6S14"
FT TURN 399..401
FT /evidence="ECO:0007829|PDB:7A5D"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 409..411
FT /evidence="ECO:0007829|PDB:6S1I"
FT HELIX 423..426
FT /evidence="ECO:0007829|PDB:6S14"
FT TURN 427..432
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 434..436
FT /evidence="ECO:0007829|PDB:6S14"
FT TURN 437..440
FT /evidence="ECO:0007829|PDB:6S14"
FT STRAND 441..443
FT /evidence="ECO:0007829|PDB:7A4R"
FT HELIX 446..459
FT /evidence="ECO:0007829|PDB:6S14"
FT TURN 464..466
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 470..475
FT /evidence="ECO:0007829|PDB:6S14"
FT HELIX 477..479
FT /evidence="ECO:0007829|PDB:4YLK"
SQ SEQUENCE 763 AA; 85584 MW; 7C3A52A3CBB04FB5 CRC64;
MHTGGETSAC KPSSVRLAPS FSFHAAGLQM AGQMPHSHQY SDRRQPNISD QQVSALSYSD
QIQQPLTNQV MPDIVMLQRR MPQTFRDPAT APLRKLSVDL IKTYKHINEV YYAKKKRRHQ
QGQGDDSSHK KERKVYNDGY DDDNYDYIVK NGEKWMDRYE IDSLIGKGSF GQVVKAYDRV
EQEWVAIKII KNKKAFLNQA QIEVRLLELM NKHDTEMKYY IVHLKRHFMF RNHLCLVFEM
LSYNLYDLLR NTNFRGVSLN LTRKFAQQMC TALLFLATPE LSIIHCDLKP ENILLCNPKR
SAIKIVDFGS SCQLGQRIYQ YIQSRFYRSP EVLLGMPYDL AIDMWSLGCI LVEMHTGEPL
FSGANEVDQM NKIVEVLGIP PAHILDQAPK ARKFFEKLPD GTWNLKKTKD GKREYKPPGT
RKLHNILGVE TGGPGGRRAG ESGHTVADYL KFKDLILRML DYDPKTRIQP YYALQHSFFK
KTADEGTNTS NSVSTSPAME QSQSSGTTSS TSSSSGGSSG TSNSGRARSD PTHQHRHSGG
HFTAAVQAMD CETHSPQVRQ QFPAPLGWSG TEAPTQVTVE THPVQETTFH VAPQQNALHH
HHGNSSHHHH HHHHHHHHHG QQALGNRTRP RVYNSPTNSS STQDSMEVGH SHHSMTSLSS
STTSSSTSSS STGNQGNQAY QNRPVAANTL DFGQNGAMDV NLTVYSNPRQ ETGIAGHPTY
QFSANTGPAH YMTEGHLTMR QGADREESPM TGVCVQQSPV ASS
