DYRK1A

DYRK1A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2VX3, 2WO6, 3ANQ, 3ANR, 4AZE, 4MQ1, 4MQ2, 4NCT, 4YLJ, 4YLK, 4YLL, 4YU2, 5AIK, 5A4Q, 5A4E, 5A3X, 5A4T, 5A54, 5A4L
Identifiers
Aliases	DYRK1A, DYRK, DYRK1, HP86, MNB, MNBH, MRD7, dual specificity tyrosine phosphorylation regulated kinase 1A
External IDs	OMIM: 600855 MGI: 1330299 HomoloGene: 55576 GeneCards: DYRK1A
Genetically Related Diseases
human immunodeficiency virus infectious disease[1]
Gene ontology Molecular function • transferase activity • protein kinase activity • nucleotide binding • non-membrane spanning protein tyrosine kinase activity • kinase activity • protein self-association • protein serine/threonine kinase activity • protein binding • identical protein binding • protein serine/threonine/tyrosine kinase activity • protein tyrosine kinase activity • tau protein binding • ATP binding Cellular component • nuclear speck • intracellular ribonucleoprotein complex • nucleoplasm • nucleus Biological process • positive regulation of protein deacetylation • phosphorylation • regulation of alternative mRNA splicing, via spliceosome • nervous system development • protein phosphorylation • negative regulation of mRNA splicing, via spliceosome • negative regulation of DNA damage response, signal transduction by p53 class mediator • peptidyl-serine phosphorylation • circadian rhythm • protein autophosphorylation • peptidyl-tyrosine phosphorylation • peptidyl-threonine phosphorylation Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1859	13548
Ensembl	ENSG00000157540	ENSMUSG00000022897
UniProt	Q13627	Q61214
RefSeq (mRNA)	NM_001396 NM_101395 NM_130436 NM_130437 NM_130438	NM_001113389 NM_007890
RefSeq (protein)	NP_001387.2 NP_567824.1 NP_569120.1 NP_569122.1	NP_001106860.1 NP_031916.1
Location (UCSC)	Chr 21: 37.37 – 37.52 Mb	Chr 16: 94.57 – 94.7 Mb
PubMed search	[2]	[3]
Wikidata

View/Edit Human

View/Edit Mouse

Dual specificity tyrosine-phosphorylation-regulated kinase 1A is an enzyme that in humans is encoded by the DYRK1A gene.^[4] Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region.^[5] These variants encode at least five different isoforms.^[6]

Function

DYRK1A is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. This member contains a nuclear targeting signal sequence, a protein kinase domain, a leucine zipper motif, and a highly conservative 13-consecutive-histidine repeat. It catalyzes its autophosphorylation on serine/threonine and tyrosine residues. It may play a significant role in a signaling pathway regulating cell proliferation and may be involved in brain development. This gene is a homolog of Drosophila mnb (minibrain) gene and rat Dyrk gene.^[6]

Dyrk1a has also been shown to modulate plasma homocysteine level in a mouse model of overexpression.^[7]

Clinical significance

DYRK1A is localized in the Down syndrome critical region of chromosome 21, and is considered to be a strong candidate gene for learning defects associated with Down syndrome.^[6] In addition, a polymorphism (SNP) in DYRK1A was found to be associated with HIV-1 replication in monocyte-derived macrophages, as well as with slower progression to AIDS in two independent cohorts of HIV-1-infected individuals.^[5] Mutations in DYRK1A are also associated with Autism spectrum disorder.^[8]

Interactions

DYRK1A has been shown to interact with WDR68.^[9]

References

1. "Diseases that are genetically associated with DYRK1A view/edit references on wikidata".
2. "Human PubMed Reference:".
3. "Mouse PubMed Reference:".
4. Guimera J, Pritchard M, Nadal M, Estivill X (Sep 1997). "Minibrain (MNBH) is a single copy gene mapping to human chromosome 21q22.2". Cytogenet Cell Genet. 77 (3–4): 182–4. doi:10.1159/000134571. PMID 9284911.
5. Bol SM, Moerland PD, Limou S, van Remmerden Y, Coulonges C, van Manen D, Herbeck JT, Fellay J, Sieberer M, Sietzema JG, van 't Slot R, Martinson J, Zagury JF, Schuitemaker H, van 't Wout AB (2011). "Genome-wide association study identifies single nucleotide polymorphism in DYRK1A associated with replication of HIV-1 in monocyte-derived macrophages". PLoS ONE. 6 (2): e17190. doi:10.1371/journal.pone.0017190. PMC 3045405. PMID 21364930.
6. "Entrez Gene: DYRK1A dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A".
7. Noll C, Planque C, Ripoll C, Guedj F, Diez A, Ducros V, Belin N, Duchon A, Paul JL, Badel A, de Freminville B, Grattau Y, Bléhaut H, Herault Y, Janel N, Delabar JM (2009). "DYRK1A, a novel determinant of the methionine-homocysteine cycle in different mouse models overexpressing this Down-syndrome-associated kinase". PLoS ONE. 4 (10): e7540. doi:10.1371/journal.pone.0007540. PMC 2760102. PMID 19844572.
8. O'Roak BJ, Vives L, Fu W, Egertson JD, Stanaway IB, Phelps IG, Carvill G, Kumar A, Lee C, Ankenman K, Munson J, Hiatt JB, Turner EH, Levy R, O'Day DR, Krumm N, Coe BP, Martin BK, Borenstein E, Nickerson DA, Mefford HC, Doherty D, Akey JM, Bernier R, Eichler EE, Shendure J (December 2012). "Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders". Science. 338 (6114): 1619–22. doi:10.1126/science.1227764. PMID 23160955.
9. Skurat AV, Dietrich AD (January 2004). "Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family protein kinases". J. Biol. Chem. 279 (4): 2490–8. doi:10.1074/jbc.M301769200. PMID 14593110.

Further reading

• Hämmerle B, Elizalde C, Galceran J, et al. (2004). "The MNB/DYRK1A protein kinase: neurobiological functions and Down syndrome implications". J. Neural Transm. Suppl. (67): 129–37. doi:10.1007/978-3-7091-6721-2_11. PMID 15068245.
• Galceran J, de Graaf K, Tejedor FJ, Becker W (2004). "The MNB/DYRK1A protein kinase: genetic and biochemical properties". J. Neural Transm. Suppl. (67): 139–48. doi:10.1007/978-3-7091-6721-2_12. PMID 15068246.
• Schultz SJ, Nigg EA (1994). "Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans". Cell Growth Differ. 4 (10): 821–30. PMID 8274451.
• Shindoh N, Kudoh J, Maeda H, et al. (1996). "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. 225 (1): 92–9. doi:10.1006/bbrc.1996.1135. PMID 8769099.
• Guimerá J, Casas C, Pucharcòs C, et al. (1997). "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. 5 (9): 1305–10. doi:10.1093/hmg/5.9.1305. PMID 8872470.
• Song WJ, Sternberg LR, Kasten-Sportès C, et al. (1997). "Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome "critical region"". Genomics. 38 (3): 331–9. doi:10.1006/geno.1996.0636. PMID 8975710.
• Ohira M, Seki N, Nagase T, et al. (1997). "Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21". Genome Res. 7 (1): 47–58. doi:10.1101/gr.7.1.47. PMID 9037601.
• Chen H, Antonarakis SE (1997). "Localisation of a human homologue of the Drosophila mnb and rat Dyrk genes to chromosome 21q22.2". Hum. Genet. 99 (2): 262–5. doi:10.1007/s004390050350. PMID 9048932.
• Smith DJ, Stevens ME, Sudanagunta SP, et al. (1997). "Functional screening of 2 Mb of human chromosome 21q22.2 in transgenic mice implicates minibrain in learning defects associated with Down syndrome". Nat. Genet. 16 (1): 28–36. doi:10.1038/ng0597-28. PMID 9140392.
• Dahmane N, Ghezala GA, Gosset P, et al. (1998). "Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved in Down syndrome". Genomics. 48 (1): 12–23. doi:10.1006/geno.1997.5146. PMID 9503011.
• Xu X, Rich ES, Seldin DC (1998). "Murine protein kinase CK2 alpha': cDNA and genomic cloning and chromosomal mapping". Genomics. 48 (1): 79–86. doi:10.1006/geno.1997.5154. PMID 9503019.
• Becker W, Weber Y, Wetzel K, et al. (1998). "Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases". J. Biol. Chem. 273 (40): 25893–902. doi:10.1074/jbc.273.40.25893. PMID 9748265.
• Wang J, Kudoh J, Shintani A, et al. (1998). "Identification of two novel 5' noncoding exons in human MNB/DYRK gene and alternatively spliced transcripts". Biochem. Biophys. Res. Commun. 250 (3): 704–10. doi:10.1006/bbrc.1998.9392. PMID 9784410.
• Guimera J, Casas C, Estivill X, Pritchard M (1999). "Human minibrain homologue (MNBH/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome". Genomics. 57 (3): 407–18. doi:10.1006/geno.1999.5775. PMID 10329007.
• Hattori M, Fujiyama A, Taylor TD, et al. (2000). "The DNA sequence of human chromosome 21". Nature. 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953.
• Woods YL, Rena G, Morrice N, et al. (2001). "The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site". Biochem. J. 355 (Pt 3): 597–607. PMC 1221773. PMID 11311120.
• Mao J, Maye P, Kogerman P, et al. (2002). "Regulation of Gli1 transcriptional activity in the nucleus by Dyrk1". J. Biol. Chem. 277 (38): 35156–61. doi:10.1074/jbc.M206743200. PMID 12138125.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Martí E, Altafaj X, Dierssen M, et al. (2003). "Dyrk1A expression pattern supports specific roles of this kinase in the adult central nervous system". Brain Res. 964 (2): 250–63. doi:10.1016/S0006-8993(02)04069-6. PMID 12576186.