DYRK1B explained

Dual specificity tyrosine-phosphorylation-regulated kinase 1B is an enzyme that in humans is encoded by the DYRK1B gene.^{[1] [2]}

Function

DYRK1B is a member of the DYRK family of protein kinases. DYRK1B contains a bipartite nuclear localization signal and is found mainly in muscle and testis. The protein is proposed to be involved in the regulation of nuclear functions. Three isoforms of DYRK1B have been identified differing in the presence of two alternatively spliced exons within the catalytic domain.^[2]

Interactions

DYRK1B has been shown to interact with:

• PCBD1^[3] and
• RANBP9.^[4]

Clinical significance

One lone missense mutation in Dyrk1B gene (R102C) was found associated with an autosomal dominant early onset Coronary Artery Disease, juvenile-onset truncal obesity, severe hypertension, and type II diabetes mellitus - seen in subjects from a nomadic group in Iran.^[5]

See also

• DYRK1A
• DYRK2

Further reading

• Mercer SE, Friedman E . Mirk/Dyrk1B: a multifunctional dual-specificity kinase involved in growth arrest, differentiation, and cell survival. . Cell Biochem. Biophys. . 45 . 3 . 303–15 . 2006 . 16845176 . 10.1385/CBB:45:3:303 .
• 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. . 60 . 13 . 3631–7 . 2000 . 10910078 .
• Lim S, Jin K, Friedman E . Mirk protein kinase is activated by MKK3 and functions as a transcriptional activator of HNF1alpha. . J. Biol. Chem. . 277 . 28 . 25040–6 . 2002 . 11980910 . 10.1074/jbc.M203257200 . free .
• Lim S, Zou Y, Friedman E . The transcriptional activator Mirk/Dyrk1B is sequestered by p38alpha/beta MAP kinase. . J. Biol. Chem. . 277 . 51 . 49438–45 . 2003 . 12384504 . 10.1074/jbc.M206840200 . free .
• 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. . 278 . 49 . 49573–81 . 2004 . 14500717 . 10.1074/jbc.M307556200 . free .
• Skurat AV, Dietrich AD . Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family protein kinases. . J. Biol. Chem. . 279 . 4 . 2490–8 . 2004 . 14593110 . 10.1074/jbc.M301769200 . free .
• Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC . Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry. . Anal. Chem. . 76 . 10 . 2763–72 . 2004 . 15144186 . 10.1021/ac035352d .
• Deng X, Ewton DZ, Mercer SE, Friedman E . Mirk/dyrk1B decreases the nuclear accumulation of class II histone deacetylases during skeletal muscle differentiation. . J. Biol. Chem. . 280 . 6 . 4894–905 . 2005 . 15546868 . 10.1074/jbc.M411894200 . free .
• Mercer SE, Ewton DZ, Deng X, Lim S, Mazur TR, Friedman E . Mirk/Dyrk1B mediates survival during the differentiation of C2C12 myoblasts. . J. Biol. Chem. . 280 . 27 . 25788–801 . 2005 . 15851482 . 1201501 . 10.1074/jbc.M413594200 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Deng X, Ewton DZ, Li S, Naqvi A, Mercer SE, Landas S, Friedman E . The kinase Mirk/Dyrk1B mediates cell survival in pancreatic ductal adenocarcinoma. . Cancer Res. . 66 . 8 . 4149–58 . 2006 . 16618736 . 10.1158/0008-5472.CAN-05-3089 .
• Takahashi-Yanaga F, Mori J, Matsuzaki E, Watanabe Y, Hirata M, Miwa Y, Morimoto S, Sasaguri T . Involvement of GSK-3beta and DYRK1B in differentiation-inducing factor-3-induced phosphorylation of cyclin D1 in HeLa cells. . J. Biol. Chem. . 281 . 50 . 38489–97 . 2007 . 17046823 . 10.1074/jbc.M605205200 . free .

Notes and References

1. Leder S, Weber Y, Altafaj X, Estivill X, Joost HG, Becker W . Cloning and characterization of DYRK1B, a novel member of the DYRK family of protein kinases . Biochem Biophys Res Commun . 254 . 2 . 474–9 . Feb 1999 . 9918863 . 10.1006/bbrc.1998.9967 .
2. Web site: Entrez Gene: DYRK1B dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1B.
3. Lim S, Jin K, Friedman E . Mirk protein kinase is activated by MKK3 and functions as a transcriptional activator of HNF1alpha . J. Biol. Chem. . 277 . 28 . 25040–6 . Jul 2002 . 11980910 . 10.1074/jbc.M203257200 . free .
4. 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. . 278 . 49 . 49573–81 . Dec 2003 . 14500717 . 10.1074/jbc.M307556200 . free .
5. Keramati AR . Identification of a Novel Disease Gene for Early Onset Atherosclerosis, Diabetes and Metabolic Syndrome by Whole Exome Sequencing and Linkage Analysis . Circulation . 128 . 22 Supplement . 2013 . etal.