DYRK1A

Protein-coding gene in the species Homo sapiens
DYRK1A
Available structures
PDBOrtholog 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
AliasesDYRK1A, DYRK, DYRK1, HP86, MNB, MNBH, MRD7, dual specificity tyrosine phosphorylation regulated kinase 1A
External IDsOMIM: 600855 MGI: 1330299 HomoloGene: 55576 GeneCards: DYRK1A
Gene location (Human)
Chromosome 21 (human)
Chr.Chromosome 21 (human)[1]
Chromosome 21 (human)
Genomic location for DYRK1A
Genomic location for DYRK1A
Band21q22.13Start37,365,573 bp[1]
End37,526,358 bp[1]
Gene location (Mouse)
Chromosome 16 (mouse)
Chr.Chromosome 16 (mouse)[2]
Chromosome 16 (mouse)
Genomic location for DYRK1A
Genomic location for DYRK1A
Band16 C4|16 55.3 cMStart94,370,869 bp[2]
End94,496,376 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • amniotic fluid

  • biceps brachii

  • Brodmann area 23

  • bronchial epithelial cell

  • tibialis anterior muscle

  • middle temporal gyrus

  • germinal epithelium

  • visceral pleura

  • trabecular 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
SpeciesHumanMouse
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 MbChr 16: 94.37 – 94.5 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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

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

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000157540 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b 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. ^ a b c "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.


  • v
  • t
  • e