Biology:DYRK1A
 Generic protein structure example |
Dual specificity tyrosine-phosphorylation-regulated kinase 1A is an enzyme that in humans is encoded by the DYRK1A gene.[1] Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region.[2] These variants encode at least five different isoforms.[3]
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.[3]
Dyrk1a has also been shown to modulate plasma homocysteine level in a mouse model of overexpression.[4]
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.[3] 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.[2] Mutations in DYRK1A are also associated with Autism spectrum disorder.[5]
Interactions
DYRK1A has been shown to interact with WDR68.[6]
In a computational analysis, compounds from a library of in-house synthesized pyrrolone-fused benzosuberene compounds exhibited higher ligand efficiency, binding affinity, lipophilic ligand efficiency, and favorable torsion values as compared to 2C3 (co-crystallized compound).[7]
See also
References
- ↑ "Minibrain (MNBH) is a single copy gene mapping to human chromosome 21q22.2". Cytogenet Cell Genet 77 (3–4): 182–4. Sep 1997. doi:10.1159/000134571. PMID 9284911.
- ↑ 2.0 2.1 "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. 2011. doi:10.1371/journal.pone.0017190. PMID 21364930. Bibcode: 2011PLoSO...617190B.
- ↑ 3.0 3.1 3.2 "Entrez Gene: DYRK1A dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1859.
- ↑ "DYRK1A, a novel determinant of the methionine-homocysteine cycle in different mouse models overexpressing this Down-syndrome-associated kinase". PLOS ONE 4 (10): e7540. 2009. doi:10.1371/journal.pone.0007540. PMID 19844572. Bibcode: 2009PLoSO...4.7540N.
- ↑ "Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders". Science 338 (6114): 1619–22. December 2012. doi:10.1126/science.1227764. PMID 23160955. Bibcode: 2012Sci...338.1619O.
- ↑ "Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family protein kinases". J. Biol. Chem. 279 (4): 2490–8. January 2004. doi:10.1074/jbc.M301769200. PMID 14593110.
- ↑ "Structural based study to identify new potential inhibitors for dual specificity tyrosine-phosphorylation- regulated kinase". Computer Methods Programs in Biomedicine. 194 (1): 105494. October 2020. doi:10.1016/j.cmpb.2020.105494. PMID 32447145.
Further reading
- "The MNB/DYRK1A protein kinase: neurobiological functions and Down syndrome implications". J. Neural Transm. Suppl.. Journal of Neural Transmission Supplement 67 67 (67): 129–37. 2004. doi:10.1007/978-3-7091-6721-2_11. ISBN 978-3-211-40776-9. PMID 15068245.
- "The MNB/DYRK1A protein kinase: genetic and biochemical properties". J. Neural Transm. Suppl.. Journal of Neural Transmission Supplement 67 67 (67): 139–48. 2004. doi:10.1007/978-3-7091-6721-2_12. ISBN 978-3-211-40776-9. PMID 15068246.
- "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. 1994. PMID 8274451.
- "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. 1996. doi:10.1006/bbrc.1996.1135. PMID 8769099.
- "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. 1997. doi:10.1093/hmg/5.9.1305. PMID 8872470.
- "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. 1997. doi:10.1006/geno.1996.0636. PMID 8975710.
- "Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21". Genome Res. 7 (1): 47–58. 1997. doi:10.1101/gr.7.1.47. PMID 9037601.
- "Localisation of a human homologue of the Drosophila mnb and rat Dyrk genes to chromosome 21q22.2". Hum. Genet. 99 (2): 262–5. 1997. doi:10.1007/s004390050350. PMID 9048932.
- "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. 1997. doi:10.1038/ng0597-28. PMID 9140392.
- "Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved in Down syndrome". Genomics 48 (1): 12–23. 1998. doi:10.1006/geno.1997.5146. PMID 9503011.
- "Murine protein kinase CK2 alpha': cDNA and genomic cloning and chromosomal mapping". Genomics 48 (1): 79–86. 1998. doi:10.1006/geno.1997.5154. PMID 9503019.
- "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. 1998. doi:10.1074/jbc.273.40.25893. PMID 9748265.
- "Identification of two novel 5' noncoding exons in human MNB/DYRK gene and alternatively spliced transcripts". Biochem. Biophys. Res. Commun. 250 (3): 704–10. 1998. doi:10.1006/bbrc.1998.9392. PMID 9784410.
- "Human minibrain homologue (MNBH/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome". Genomics 57 (3): 407–18. 1999. doi:10.1006/geno.1999.5775. PMID 10329007.
- "The DNA sequence of human chromosome 21". Nature 405 (6784): 311–9. 2000. doi:10.1038/35012518. PMID 10830953. Bibcode: 2000Natur.405..311H.
- "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. 2001. doi:10.1042/bj3550597. PMID 11311120.
- "Regulation of Gli1 transcriptional activity in the nucleus by Dyrk1". J. Biol. Chem. 277 (38): 35156–61. 2002. doi:10.1074/jbc.M206743200. PMID 12138125.
- "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. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Dyrk1A expression pattern supports specific roles of this kinase in the adult central nervous system". Brain Res. 964 (2): 250–63. 2003. doi:10.1016/S0006-8993(02)04069-6. PMID 12576186.
- "Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitors as potential therapeutics". Journal of Medicinal Chemistry 61 (22): 9791–9810. 2018. doi:10.1021/acs.jmedchem.8b00185. PMID 29985601.
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.
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