8c2z

Structural highlights

Disease

DYR1B_HUMAN NON RARE IN EUROPE: Metabolic syndrome. The disease is caused by variants affecting the gene represented in this entry.

Function

DYR1B_HUMAN Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Plays an essential role in ribosomal DNA (rDNA) double-strand break repair and rDNA copy number maintenance (PubMed:33469661). During DNA damage, mediates transcription silencing in part via phosphorylating and enforcing DSB accumulation of the histone methyltransferase EHMT2 (PubMed:32611815). Enhances the transcriptional activity of TCF1/HNF1A and FOXO1. Inhibits epithelial cell migration. Mediates colon carcinoma cell survival in mitogen-poor environments. Inhibits the SHH and WNT1 pathways, thereby enhancing adipogenesis. In addition, promotes expression of the gluconeogenic enzyme glucose-6-phosphatase catalytic subunit 1 (G6PC1).^{[1] [2] [3] [4] [5]}

References

1. ↑ Lee K, Deng X, Friedman E. Mirk protein kinase is a mitogen-activated protein kinase substrate that mediates survival of colon cancer cells. Cancer Res. 2000 Jul 1;60(13):3631-7 PMID:10910078
2. ↑ Lim S, Jin K, Friedman E. Mirk protein kinase is activated by MKK3 and functions as a transcriptional activator of HNF1alpha. J Biol Chem. 2002 Jul 12;277(28):25040-6. PMID:11980910 doi:10.1074/jbc.M203257200
3. ↑ Zou Y, Lim S, Lee K, Deng X, Friedman E. Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell migration and is negatively regulated by the Met adaptor Ran-binding protein M. J Biol Chem. 2003 Dec 5;278(49):49573-81. Epub 2003 Sep 18. PMID:14500717 doi:http://dx.doi.org/10.1074/jbc.M307556200
4. ↑ Keramati AR, Fathzadeh M, Go GW, Singh R, Choi M, Faramarzi S, Mane S, Kasaei M, Sarajzadeh-Fard K, Hwa J, Kidd KK, Babaee Bigi MA, Malekzadeh R, Hosseinian A, Babaei M, Lifton RP, Mani A. A form of the metabolic syndrome associated with mutations in DYRK1B. N Engl J Med. 2014 May 15;370(20):1909-1919. PMID:24827035 doi:10.1056/NEJMoa1301824
5. ↑ Dong C, An L, Yu CH, Huen MSY. A DYRK1B-dependent pathway suppresses rDNA transcription in response to DNA damage. Nucleic Acids Res. 2021 Feb 22;49(3):1485-1496. PMID:33469661 doi:10.1093/nar/gkaa1290