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
Gene location (Human) Chr. Chromosome 21 (human) [1] Band 21q22.13 Start 37,365,573 bp [1] End 37,526,358 bp [1]
Gene location (Mouse) Chr. Chromosome 16 (mouse) [2] Band 16 C4|16 55.3 cM Start 94,370,869 bp [2] End 94,496,376 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in amniotic fluid biceps brachii Brodmann area 23 bronchial epithelial cell tibialis anterior muscle middle temporal gyrus germinal epithelium visceral pleura spongy bone Achilles tendon Top expressed in secondary oocyte extensor digitorum longus muscle triceps surae gastrocnemius muscle cumulus cell triceps brachii muscle plantaris muscle extraocular muscle soleus muscle quadriceps femoris muscle More reference expression data BioGPS More reference expression data
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 protein serine/threonine/tyrosine kinase activity protein tyrosine kinase activity tau protein binding ATP binding identical protein binding tau-protein kinase activity Cellular component nuclear speck nucleoplasm nucleus cytoplasm cytoskeleton axon dendrite ribonucleoprotein complex 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 viral process negative regulation of microtubule polymerization positive regulation of RNA splicing amyloid-beta formation peptidyl-serine autophosphorylation peptidyl-tyrosine autophosphorylation Sources:Amigo / QuickGO
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_001347721 NM_001347722 NM_001347723 NM_001113389 NM_007890 NM_001347731 RefSeq (protein) NP_001334650 NP_001334651 NP_001334652 NP_001387 NP_567824 NP_569120 NP_569122 NP_001106860 NP_001334660 NP_031916 NP_001389720 NP_001389721 NP_001389722 Location (UCSC) Chr 21: 37.37 – 37.53 Mb Chr 16: 94.37 – 94.5 Mb PubMed search [3] [4]
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. ^[5] Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region. ^[6] These variants encode for at least five different isoforms. ^[7]

Function

See also: Dual-specificity kinase

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 the Drosophila mnb (minibrain) gene. ^[7]

DYRK1A has also been shown to modulate plasma homocysteine levesl in a mouse model of overexpression. ^[8]

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. ^[7] 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. ^[6] Mutations in DYRK1A are also associated with autism spectrum disorder. ^[9]

Interactions

DYRK1A has been shown to interact with WDR68. ^[10]

In popular culture

Rosie, the protagonist of BBC sitcom There She Goes , has the DYRK1A gene, as revealed in the show's final episode. ^[11]

See also

• DYRK1B
• DYRK2
• DYRK3

References

1. GRCh38: Ensembl release 89: ENSG00000157540 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022897 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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. Bibcode:2011PLoSO...617190B. doi: 10.1371/journal.pone.0017190 . PMC   3045405 . PMID   21364930.
7. "Entrez Gene: DYRK1A dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A".
8. 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. Bibcode:2009PLoSO...4.7540N. doi: 10.1371/journal.pone.0007540 . PMC   2760102 . PMID   19844572.
9. 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. Bibcode:2012Sci...338.1619O. doi:10.1126/science.1227764. PMC   3528801 . PMID   23160955.
10. 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.
11. "There She Goes creator explains family cameo in special episode". Radio Times . 21 June 2023. Retrieved 6 July 2023.

Further reading

• Hämmerle B, Elizalde C, Galceran J, et al. (2004). "The MNB/DYRK1A protein kinase: Neurobiological functions and Down syndrome implications". Advances in Down Syndrome Research. Journal of Neural Transmission Supplement 67. Vol. 67. pp. 129–37. doi:10.1007/978-3-7091-6721-2_11. ISBN   978-3-211-40776-9. PMID   15068245.{{cite book}}: |journal= ignored (help)
• Galceran J, de Graaf K, Tejedor FJ, Becker W (2004). "The MNB/DYRK1A protein kinase: Genetic and biochemical properties". Advances in Down Syndrome Research. Journal of Neural Transmission Supplement 67. Vol. 67. pp. 139–48. doi:10.1007/978-3-7091-6721-2_12. ISBN   978-3-211-40776-9. PMID   15068246.{{cite book}}: |journal= ignored (help)
• 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. S2CID   26729330.
• 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. S2CID   29490013.
• 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. Bibcode:2000Natur.405..311H. 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. doi:10.1042/bj3550597. 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 . hdl: 10261/333520 . 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. Bibcode:2002PNAS...9916899M. 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. S2CID   35092325.
• Jarhad DB, Mashelkar KK, Kim HR, Noh M, Jeong LS (2018). "Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitors as potential therapeutics". Journal of Medicinal Chemistry. 61 (22): 9791–9810. doi:10.1021/acs.jmedchem.8b00185. PMID   29985601. S2CID   51606533.

External links

• Overview of all the structural information available in the PDB for UniProt : Q13627 (Dual specificity tyrosine-phosphorylation-regulated kinase 1A) at the PDBe-KB .