DYRK1A
Dual specificity tyrosine-phosphorylation-regulated kinase 1A is an enzyme that in humans is encoded by the DYRK1A gene. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region. These variants encode for at least five different isoforms.
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 the Drosophila mnb (minibrain) gene.
DYRK1A has also been shown to modulate plasma homocysteine levels in a mouse model of overexpression.
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. 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. Mutations in DYRK1A are also associated with autism spectrum disorder.
Interactions
In popular culture
Rosie, the learning-disabled protagonist of BBC sitcom There She Goes, has DYRK1A syndrome, as revealed in the show's final episode.
See also
References
- 1 2 3 GRCh38: Ensembl release 89: ENSG00000157540 – Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022897 – Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ 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.
- 1 2 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.
- 1 2 3 "Entrez Gene: DYRK1A dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A".
- ↑ 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.
- ↑ 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.
- ↑ Courraud J, Quartier A, Drouot N, Zapata-Bodalo I, Gilet J, Benchoua A, Mandel JL, Piton A (March 2025). "DYRK1A roles in human neural progenitors". Frontiers in Neuroscience. 19 (13) 1533253. doi:10.3389/fnins.2025.1533253. PMC 11966461. PMID 40182141.
- ↑ 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.
- ↑ "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, Becker W, Tejedor FJ (2004). "The MNB/DYRK1A protein kinase: neurobiological functions and Down syndrome implications". Journal of Neural Transmission. Supplementum. 67: 129–137. doi:10.1007/978-3-7091-6721-2_11. ISBN 978-3-211-40776-9. PMID 15068245.
{{cite journal}}: CS1 maint: periodical has ISBN (link) - Galceran J, de Graaf K, Tejedor FJ, Becker W (2004). "The MNB/DYRK1A protein kinase: genetic and biochemical properties". Journal of Neural Transmission. Supplementum. 67 (67): 139–148. doi:10.1007/978-3-7091-6721-2_12. ISBN 978-3-211-40776-9. PMID 15068246.
{{cite journal}}: CS1 maint: periodical has ISBN (link) - Schultz SJ, Nigg EA (October 1993). "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 & Differentiation. 4 (10): 821–830. PMID 8274451.
- Shindoh N, Kudoh J, Maeda H, Yamaki A, Minoshima S, Shimizu Y, Shimizu N (August 1996). "Cloning of a human homolog of the Drosophila minibrain/rat Dyrk gene from "the Down syndrome critical region" of chromosome 21". Biochemical and Biophysical Research Communications. 225 (1): 92–99. Bibcode:1996BBRC..225...92S. doi:10.1006/bbrc.1996.1135. PMID 8769099.
- Guimerá J, Casas C, Pucharcòs C, Solans A, Domènech A, Planas AM, Ashley J, Lovett M, Estivill X, Pritchard MA (September 1996). "A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region". Human Molecular Genetics. 5 (9): 1305–1310. doi:10.1093/hmg/5.9.1305. PMID 8872470.
- Song WJ, Sternberg LR, Kasten-Sportès C, Keuren ML, Chung SH, Slack AC, Miller DE, Glover TW, Chiang PW, Lou L, Kurnit DM (December 1996). "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): 331–339. doi:10.1006/geno.1996.0636. PMID 8975710.
- 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 (January 1997). "Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21". Genome Research. 7 (1): 47–58. doi:10.1101/gr.7.1.47. PMID 9037601.
- Chen H, Antonarakis SE (February 1997). "Localisation of a human homologue of the Drosophila mnb and rat Dyrk genes to chromosome 21q22.2". Human Genetics. 99 (2): 262–265. doi:10.1007/s004390050350. PMID 9048932. S2CID 26729330.
- Smith DJ, Stevens ME, Sudanagunta SP, Bronson RT, Makhinson M, Watabe AM, O'Dell TJ, Fung J, Weier HU, Cheng JF, Rubin EM (May 1997). "Functional screening of 2 Mb of human chromosome 21q22.2 in transgenic mice implicates minibrain in learning defects associated with Down syndrome". Nature Genetics. 16 (1): 28–36. doi:10.1038/ng0597-28. PMID 9140392. S2CID 29490013.
- 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, Créau N, Delabar JM (February 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 (February 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, Eirmbter K, Tejedor FJ, Joost HG (October 1998). "Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases". The Journal of Biological Chemistry. 273 (40): 25893–25902. doi:10.1074/jbc.273.40.25893. PMID 9748265.
- Wang J, Kudoh J, Shintani A, Minoshima S, Shimizu N (September 1998). "Identification of two novel 5' noncoding exons in human MNB/DYRK gene and alternatively spliced transcripts". Biochemical and Biophysical Research Communications. 250 (3): 704–710. Bibcode:1998BBRC..250..704W. doi:10.1006/bbrc.1998.9392. PMID 9784410.
- Guimera J, Casas C, Estivill X, Pritchard M (May 1999). "Human minibrain homologue (MNBH/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome". Genomics. 57 (3): 407–418. doi:10.1006/geno.1999.5775. PMID 10329007.
- Woods YL, Rena G, Morrice N, Barthel A, Becker W, Guo S, Unterman TG, Cohen P (May 2001). "The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site". The Biochemical Journal. 355 (Pt 3): 597–607. doi:10.1042/bj3550597. PMC 1221773. PMID 11311120.
- Mao J, Maye P, Kogerman P, Tejedor FJ, Toftgard R, Xie W, Wu G, Wu D (September 2002). "Regulation of Gli1 transcriptional activity in the nucleus by Dyrk1". The Journal of Biological Chemistry. 277 (38): 35156–35161. doi:10.1074/jbc.M206743200. hdl:10261/333520. PMID 12138125.
- Martí E, Altafaj X, Dierssen M, de la Luna S, Fotaki V, Alvarez M, Pérez-Riba M, Ferrer I, Estivill X (February 2003). "Dyrk1A expression pattern supports specific roles of this kinase in the adult central nervous system". Brain Research. 964 (2): 250–263. doi:10.1016/S0006-8993(02)04069-6. PMID 12576186. S2CID 35092325.
- Jarhad DB, Mashelkar KK, Kim HR, Noh M, Jeong LS (November 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.