Dual specificity tyrosine-phosphorylation-regulated kinase 1A

Details

Name
Dual specificity tyrosine-phosphorylation-regulated kinase 1A
Synonyms
  • 2.7.12.1
  • Dual specificity YAK1-related kinase
  • DYRK
  • hMNB
  • HP86
  • MNB
  • MNBH
  • Protein kinase minibrain homolog
Gene Name
DYRK1A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0007671|Dual specificity tyrosine-phosphorylation-regulated kinase 1A
MHTGGETSACKPSSVRLAPSFSFHAAGLQMAGQMPHSHQYSDRRQPNISDQQVSALSYSD
QIQQPLTNQVMPDIVMLQRRMPQTFRDPATAPLRKLSVDLIKTYKHINEVYYAKKKRRHQ
QGQGDDSSHKKERKVYNDGYDDDNYDYIVKNGEKWMDRYEIDSLIGKGSFGQVVKAYDRV
EQEWVAIKIIKNKKAFLNQAQIEVRLLELMNKHDTEMKYYIVHLKRHFMFRNHLCLVFEM
LSYNLYDLLRNTNFRGVSLNLTRKFAQQMCTALLFLATPELSIIHCDLKPENILLCNPKR
SAIKIVDFGSSCQLGQRIYQYIQSRFYRSPEVLLGMPYDLAIDMWSLGCILVEMHTGEPL
FSGANEVDQMNKIVEVLGIPPAHILDQAPKARKFFEKLPDGTWNLKKTKDGKREYKPPGT
RKLHNILGVETGGPGGRRAGESGHTVADYLKFKDLILRMLDYDPKTRIQPYYALQHSFFK
KTADEGTNTSNSVSTSPAMEQSQSSGTTSSTSSSSGGSSGTSNSGRARSDPTHQHRHSGG
HFTAAVQAMDCETHSPQVRQQFPAPLGWSGTEAPTQVTVETHPVQETTFHVAPQQNALHH
HHGNSSHHHHHHHHHHHHHGQQALGNRTRPRVYNSPTNSSSTQDSMEVGHSHHSMTSLSS
STTSSSTSSSSTGNQGNQAYQNRPVAANTLDFGQNGAMDVNLTVYSNPRQETGIAGHPTY
QFSANTGPAHYMTEGHLTMRQGADREESPMTGVCVQQSPVASS
Number of residues
763
Molecular Weight
85583.41
Theoretical pI
8.98
GO Classification
Functions
ATP binding / non-membrane spanning protein tyrosine kinase activity / protein kinase activity / protein self-association / protein serine/threonine kinase activity / protein serine/threonine/tyrosine kinase activity / protein tyrosine kinase activity / tau protein binding
Processes
circadian rhythm / mitotic cell cycle / negative regulation of DNA damage response, signal transduction by p53 class mediator / negative regulation of mRNA splicing, via spliceosome / nervous system development / peptidyl-serine phosphorylation / peptidyl-threonine phosphorylation / peptidyl-tyrosine phosphorylation / positive regulation of protein deacetylation / protein autophosphorylation / protein phosphorylation / regulation of alternative mRNA splicing, via spliceosome
Components
nuclear speck / nucleoplasm / nucleus / ribonucleoprotein complex
General Function
Tau protein binding
Specific Function
May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity). Phosphorylates serine, threonine and tyrosine residues in its sequence and in exogenous substrates such as CRY2, FOXO1, SRSF6 and SIRT1. Exhibits a sugstrate preference for proline at position P+1 and arginine at position P-3.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus speckle
Gene sequence
>lcl|BSEQ0012797|Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A)
ATGCATACAGGAGGAGAGACTTCAGCATGCAAACCTTCATCTGTTCGGCTTGCACCGTCA
TTTTCATTCCATGCTGCTGGCCTTCAGATGGCTGGACAGATGCCCCATTCACATCAGTAC
AGTGACCGTCGCCAGCCAAACATAAGTGACCAACAGGTTTCTGCCTTATCATATTCTGAC
CAGATTCAGCAACCTCTAACTAACCAGGTGATGCCTGATATTGTCATGTTACAGAGGCGG
ATGCCCCAAACCTTCCGTGACCCAGCAACTGCTCCCCTGAGAAAACTTTCTGTTGACTTG
ATCAAAACATACAAGCATATTAATGAGGTTTACTATGCAAAAAAGAAGCGAAGACACCAA
CAGGGCCAGGGAGACGATTCTAGTCATAAGAAGGAACGGAAGGTTTACAATGATGGTTAT
GATGATGATAACTATGATTATATTGTAAAAAACGGAGAAAAGTGGATGGATCGTTACGAA
ATTGACTCCTTGATAGGCAAAGGTTCCTTTGGACAGGTTGTAAAGGCATATGATCGTGTG
GAGCAAGAATGGGTTGCCATTAAAATAATAAAGAACAAGAAGGCTTTTCTGAATCAAGCA
CAGATAGAAGTGCGACTTCTTGAGCTCATGAACAAACATGACACTGAAATGAAATACTAC
ATAGTGCATTTGAAACGCCACTTTATGTTTCGAAACCATCTCTGTTTAGTTTTTGAAATG
CTGTCCTACAACCTCTATGACTTGCTGAGAAACACCAATTTCCGAGGGGTCTCTTTGAAC
CTAACACGAAAGTTTGCGCAACAGATGTGCACTGCACTGCTTTTCCTTGCGACTCCAGAA
CTTAGTATCATTCACTGTGATCTAAAACCTGAAAATATCCTTCTTTGTAACCCCAAACGC
AGTGCAATCAAGATAGTTGACTTTGGCAGTTCTTGTCAGTTGGGGCAGAGGATATACCAG
TATATTCAGAGTCGCTTTTATCGGTCTCCAGAGGTGCTACTGGGAATGCCTTATGACCTT
GCCATTGATATGTGGTCCCTCGGGTGTATTTTGGTTGAAATGCACACTGGAGAACCTCTG
TTCAGTGGTGCCAATGAGGTAGATCAGATGAATAAAATAGTGGAAGTTCTGGGTATTCCA
CCTGCTCATATTCTTGACCAAGCACCAAAAGCAAGAAAGTTCTTTGAGAAGTTGCCAGAT
GGCACTTGGAACTTAAAGAAGACCAAAGATGGAAAACGGGAGTACAAACCACCAGGAACC
CGTAAACTTCATAACATTCTTGGAGTGGAAACAGGAGGACCTGGTGGGCGACGTGCTGGG
GAGTCAGGTCATACGGTCGCTGACTACTTGAAGTTCAAAGACCTCATTTTAAGGATGCTT
GATTATGACCCCAAAACTCGAATTCAACCTTATTATGCTCTGCAGCACAGTTTCTTCAAG
AAAACAGCTGATGAAGGTACAAATACAAGTAATAGTGTATCTACAAGCCCCGCCATGGAG
CAGTCTCAGTCTTCGGGCACCACCTCCAGTACATCGTCAAGCTCAGGTGGCTCATCGGGG
ACAAGCAACAGTGGGAGAGCCCGGTCGGATCCGACGCACCAGCATCGGCACAGTGGTGGG
CACTTCACAGCTGCCGTGCAGGCCATGGACTGCGAGACACACAGTCCCCAGGTGCGTCAG
CAATTTCCTGCTCCTCTTGGTTGGTCAGGCACTGAAGCTCCTACACAGGTCACTGTTGAA
ACTCATCCTGTTCAAGAAACAACCTTTCATGTAGCCCCTCAACAGAATGCATTGCATCAT
CACCATGGTAACAGTTCCCATCACCATCACCACCACCACCACCATCACCACCACCATGGA
CAACAAGCCTTGGGTAACCGGACCAGGCCAAGGGTCTACAATTCTCCAACGAATAGCTCC
TCTACCCAAGATTCTATGGAGGTTGGCCACAGTCACCACTCCATGACATCCCTGTCTTCC
TCAACGACTTCTTCCTCGACATCTTCCTCCTCTACTGGTAACCAAGGCAATCAGGCCTAC
CAGAATCGCCCAGTGGCTGCTAATACCTTGGACTTTGGACAGAATGGAGCTATGGACGTT
AATTTGACCGTCTACTCCAATCCCCGCCAAGAGACTGGCATAGCTGGACATCCAACATAC
CAATTTTCTGCTAATACAGGTCCTGCACATTACATGACTGAAGGACATCTGACAATGAGG
CAAGGGGCTGATAGAGAAGAGTCCCCCATGACAGGAGTTTGTGTGCAACAGAGTCCTGTA
GCTAGCTCGTGA
Chromosome Location
21
Locus
21q22.13
External Identifiers
ResourceLink
UniProtKB IDQ13627
UniProtKB Entry NameDYR1A_HUMAN
GenBank Protein ID1381156
GenBank Gene IDU58496
HGNC IDHGNC:3091
General References
  1. Song WJ, Sternberg LR, Kasten-Sportes C, Keuren ML, Chung SH, Slack AC, Miller DE, Glover TW, Chiang PW, Lou L, Kurnit DM: Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome "critical region". Genomics. 1996 Dec 15;38(3):331-9. [Article]
  2. Guimera J, Casas C, Pucharcos C, Solans A, Domenech A, Planas AM, Ashley J, Lovett M, Estivill X, Pritchard MA: A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region. Hum Mol Genet. 1996 Sep;5(9):1305-10. [Article]
  3. Shindoh N, Kudoh J, Maeda H, Yamaki A, Minoshima S, Shimizu Y, Shimizu N: Cloning of a human homolog of the Drosophila minibrain/rat Dyrk gene from "the Down syndrome critical region" of chromosome 21. Biochem Biophys Res Commun. 1996 Aug 5;225(1):92-9. [Article]
  4. Ohira M, Seki N, Nagase T, Suzuki E, Nomura N, Ohara O, Hattori M, Sakaki Y, Eki T, Murakami Y, Saito T, Ichikawa H, Ohki M: Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21. Genome Res. 1997 Jan;7(1):47-58. [Article]
  5. Guimera J, Casas C, Estivill X, Pritchard M: Human minibrain homologue (MNBH/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome. Genomics. 1999 May 1;57(3):407-18. [Article]
  6. Dahmane N, Ghezala GA, Gosset P, Chamoun Z, Dufresne-Zacharia MC, Lopes C, Rabatel N, Gassanova-Maugenre S, Chettouh Z, Abramowski V, Fayet E, Yaspo ML, Korn B, Blouin JL, Lehrach H, Poutska A, Antonarakis SE, Sinet PM, Creau N, Delabar JM: Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved in Down syndrome. Genomics. 1998 Feb 15;48(1):12-23. [Article]
  7. Zou Y, Lim S, Lee K, Deng X, Friedman E: Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell migration and is negatively regulated by the Met adaptor Ran-binding protein M. J Biol Chem. 2003 Dec 5;278(49):49573-81. Epub 2003 Sep 18. [Article]
  8. Skurat AV, Dietrich AD: Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family protein kinases. J Biol Chem. 2004 Jan 23;279(4):2490-8. Epub 2003 Oct 30. [Article]
  9. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. [Article]
  10. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  11. Salichs E, Ledda A, Mularoni L, Alba MM, de la Luna S: Genome-wide analysis of histidine repeats reveals their role in the localization of human proteins to the nuclear speckles compartment. PLoS Genet. 2009 Mar;5(3):e1000397. doi: 10.1371/journal.pgen.1000397. Epub 2009 Mar 6. [Article]
  12. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  13. van Bon BW, Hoischen A, Hehir-Kwa J, de Brouwer AP, Ruivenkamp C, Gijsbers AC, Marcelis CL, de Leeuw N, Veltman JA, Brunner HG, de Vries BB: Intragenic deletion in DYRK1A leads to mental retardation and primary microcephaly. Clin Genet. 2011 Mar;79(3):296-9. doi: 10.1111/j.1399-0004.2010.01544.x. [Article]
  14. Papadopoulos C, Arato K, Lilienthal E, Zerweck J, Schutkowski M, Chatain N, Muller-Newen G, Becker W, de la Luna S: Splice variants of the dual specificity tyrosine phosphorylation-regulated kinase 4 (DYRK4) differ in their subcellular localization and catalytic activity. J Biol Chem. 2011 Feb 18;286(7):5494-505. doi: 10.1074/jbc.M110.157909. Epub 2010 Dec 2. [Article]
  15. Yin X, Jin N, Gu J, Shi J, Zhou J, Gong CX, Iqbal K, Grundke-Iqbal I, Liu F: Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) modulates serine/arginine-rich protein 55 (SRp55)-promoted Tau exon 10 inclusion. J Biol Chem. 2012 Aug 31;287(36):30497-506. doi: 10.1074/jbc.M112.355412. Epub 2012 Jul 5. [Article]
  16. Cohen MJ, Yousef AF, Massimi P, Fonseca GJ, Todorovic B, Pelka P, Turnell AS, Banks L, Mymryk JS: Dissection of the C-terminal region of E1A redefines the roles of CtBP and other cellular targets in oncogenic transformation. J Virol. 2013 Sep;87(18):10348-55. doi: 10.1128/JVI.00786-13. Epub 2013 Jul 17. [Article]
  17. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  18. Ogawa Y, Nonaka Y, Goto T, Ohnishi E, Hiramatsu T, Kii I, Yoshida M, Ikura T, Onogi H, Shibuya H, Hosoya T, Ito N, Hagiwara M: Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A. Nat Commun. 2010 Oct 5;1:86. doi: 10.1038/ncomms1090. [Article]
  19. Tahtouh T, Elkins JM, Filippakopoulos P, Soundararajan M, Burgy G, Durieu E, Cochet C, Schmid RS, Lo DC, Delhommel F, Oberholzer AE, Pearl LH, Carreaux F, Bazureau JP, Knapp S, Meijer L: Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B. J Med Chem. 2012 Nov 8;55(21):9312-30. doi: 10.1021/jm301034u. Epub 2012 Oct 8. [Article]
  20. Anderson K, Chen Y, Chen Z, Dominique R, Glenn K, He Y, Janson C, Luk KC, Lukacs C, Polonskaia A, Qiao Q, Railkar A, Rossman P, Sun H, Xiang Q, Vilenchik M, Wovkulich P, Zhang X: Pyrido[2,3-d]pyrimidines: discovery and preliminary SAR of a novel series of DYRK1B and DYRK1A inhibitors. Bioorg Med Chem Lett. 2013 Dec 15;23(24):6610-5. doi: 10.1016/j.bmcl.2013.10.055. Epub 2013 Nov 1. [Article]
  21. Soundararajan M, Roos AK, Savitsky P, Filippakopoulos P, Kettenbach AN, Olsen JV, Gerber SA, Eswaran J, Knapp S, Elkins JM: Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition. Structure. 2013 Jun 4;21(6):986-96. doi: 10.1016/j.str.2013.03.012. Epub 2013 May 9. [Article]
  22. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB07608N-(5-{[(2S)-4-amino-2-(3-chlorophenyl)butanoyl]amino}-1H-indazol-3-yl)benzamideexperimentalunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails