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 27-MAR-2024, entry version 228. DE RecName: Full=Dual specificity tyrosine-phosphorylation-regulated kinase 1A; DE EC=2.7.11.23 {ECO:0000269|PubMed:25620562}; 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 {ECO:0000303|PubMed:8872470, ECO:0000303|PubMed:8975710}; DE Short=MNBH; DE Short=hMNB; GN Name=DYRK1A {ECO:0000303|PubMed:25620562, ECO:0000312|HGNC:HGNC:3091}; GN Synonyms=DYRK, MNB {ECO:0000303|PubMed:8872470}, 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, FUNCTION, 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 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] 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 [26] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP LYS-188. RX PubMed=25620562; DOI=10.1016/j.molcel.2014.12.026; RA Di Vona C., Bezdan D., Islam A.B., Salichs E., Lopez-Bigas N., Ossowski S., RA de la Luna S.; RT "Chromatin-wide profiling of DYRK1A reveals a role as a gene-specific RNA RT polymerase II CTD kinase."; RL Mol. Cell 57:506-520(2015). RN [27] RP FUNCTION, AND DOMAIN. RX PubMed=29849146; DOI=10.1038/s41586-018-0174-3; RA Lu H., Yu D., Hansen A.S., Ganguly S., Liu R., Heckert A., Darzacq X., RA Zhou Q.; RT "Phase-separation mechanism for C-terminal hyperphosphorylation of RNA RT polymerase II."; RL Nature 558:318-323(2018). RN [28] 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 [29] 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 (PubMed:21127067, PubMed:8769099, CC PubMed:30773093, PubMed:20981014, PubMed:23665168). Exhibits a CC substrate preference for proline at position P+1 and arginine at CC position P-3 (PubMed:23665168). 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). Also acts as a CC positive regulator of transcription by acting as a CTD kinase that CC mediates phosphorylation of the CTD (C-terminal domain) of the large CC subunit of RNA polymerase II (RNAP II) POLR2A (PubMed:25620562, CC PubMed:29849146). May play a role in a signaling pathway regulating CC nuclear functions of cell proliferation (PubMed:14500717). Modulates CC alternative splicing by phosphorylating the splice factor SRSF6 (By CC similarity). Has pro-survival function and negatively regulates the CC apoptotic process (By similarity). Promotes cell survival upon CC genotoxic stress through phosphorylation of SIRT1 (By similarity). This CC in turn inhibits p53/TP53 activity and apoptosis (By similarity). CC Phosphorylates SEPTIN4, SEPTIN5 and SF3B1 at 'Thr-434' (By similarity). CC {ECO:0000250|UniProtKB:Q61214, ECO:0000250|UniProtKB:Q63470, CC ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:20981014, CC ECO:0000269|PubMed:21127067, ECO:0000269|PubMed:23665168, CC ECO:0000269|PubMed:25620562, ECO:0000269|PubMed:29849146, CC ECO:0000269|PubMed:30773093, ECO:0000269|PubMed:31024071, CC 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 -!- CATALYTIC ACTIVITY: CC Reaction=[DNA-directed RNA polymerase] + ATP = ADP + H(+) + phospho- CC [DNA-directed RNA polymerase]; Xref=Rhea:RHEA:10216, Rhea:RHEA- CC COMP:11321, Rhea:RHEA-COMP:11322, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546, CC ChEBI:CHEBI:456216; EC=2.7.11.23; CC Evidence={ECO:0000269|PubMed:25620562}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10217; CC Evidence={ECO:0000269|PubMed:25620562}; 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 with RAD54L2/ARIP4 (By similarity). Interacts with CC CRY2 (By similarity). Interacts with RANBP9 (PubMed:14500717). CC Interacts with WDR68 (PubMed:14593110). Interacts with SIRT1 (By CC similarity). {ECO:0000250|UniProtKB:Q61214, CC ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:14593110}. 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; Q12933: TRAF2; NbExp=3; IntAct=EBI-1053596, EBI-355744; 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, ECO:0000269|PubMed:25620562}. Nucleus CC speckle {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 -!- DOMAIN: The histidine-rich domain (HRD) region is intrinsically CC disordered and promotes the formation of phase-separated liquid CC droplets that enhance its ability to phosphorylate the CTD (C-terminal CC domain) of the large subunit of RNA polymerase II (RNA Pol II). CC {ECO:0000269|PubMed:29849146}. 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="https://atlasgeneticsoncology.org/gene/43234/DYRK1A"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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. DR RefSeq; XP_006724040.1; XM_006723977.3. DR RefSeq; XP_006724041.1; XM_006723978.3. DR RefSeq; XP_011527785.1; XM_011529483.2. DR RefSeq; XP_016883773.1; XM_017028284.1. 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 PDB; 7Z5N; X-ray; 2.77 A; A/B/C/D/E/F/G/H=126-489. DR PDB; 7ZH8; X-ray; 2.30 A; A/B/C/D=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 PDBsum; 7Z5N; -. DR PDBsum; 7ZH8; -. DR AlphaFoldDB; Q13627; -. DR SMR; Q13627; -. DR BioGRID; 108192; 448. DR DIP; DIP-39750N; -. DR ELM; Q13627; -. DR IntAct; Q13627; 174. DR MINT; Q13627; -. DR STRING; 9606.ENSP00000340373; -. 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; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q13627; -. DR PhosphoSitePlus; Q13627; -. DR BioMuta; DYRK1A; -. DR DMDM; 3219996; -. DR CPTAC; CPTAC-2879; -. DR EPD; Q13627; -. DR jPOST; Q13627; -. DR MassIVE; Q13627; -. DR MaxQB; Q13627; -. DR PaxDb; 9606-ENSP00000381932; -. DR PeptideAtlas; 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 Pumba; Q13627; -. DR Antibodypedia; 8587; 457 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 AGR; HGNC:3091; -. 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; YNFAEIS; -. DR OrthoDB; 452107at2759; -. 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; 127 hits in 1228 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 212 other cell types or tissues. DR ExpressionAtlas; Q13627; baseline and differential. 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:0140857; F:histone H3T45 kinase activity; IDA:GO_Central. 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; IDA:UniProt. 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:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IDA: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:0090310; P:negative regulation of DNA methylation-dependent heterochromatin formation; IDA:GO_Central. 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:0045893; P:positive regulation of DNA-templated transcription; IBA:GO_Central. 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:0046777; P:protein autophosphorylation; ISS:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR CDD; cd14226; PKc_DYRK1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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; DUAL SPECIFICITY PROTEIN KINASE; 1. DR PANTHER; PTHR24058:SF121; DUAL SPECIFICITY TYROSINE-PHOSPHORYLATION-REGULATED KINASE 1A; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q13627; HS. 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 Transcription; Transcription regulation; Transferase; KW 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 595..625 FT /note="Histidine-rich domain (HRD)" FT /evidence="ECO:0000269|PubMed:29849146" FT REGION 596..679 FT /note="Disordered" FT /evidence="ECO:0000269|PubMed:29849146" 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: Abolished protein kinase activity." FT /evidence="ECO:0000269|PubMed:23665168, FT ECO:0000269|PubMed:25620562" 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:7OY6" 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 //