Hepatocyte nuclear factor 1-alpha (HNF1A, TCF1) and hepatocyte nuclear factor 1-beta (HNF1B, TCF2) are homeodomain-containing transcription factors expressed in the pancreas, liver, kidney, and intestine, where they direct tissue-specific gene regulation [, ]. They play an essential role in the development and differentiation of pancreatic precursor cells [, ]. Mutations in HNF1beta and HNF1alpha cause autosomal dominant diabetes maturity-onset diabetes of the young (MODY), which is a monogenic form of non-insulin-dependent type 2 diabetes. Mutations in HNF1A are responsible for type 3 MODY (MODY3) [], whereas the HNF1B gene is linked to a rare case of type 5 MODY (MODY5) [].
Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) () phosphorylates serine, threonine and tyrosine residues in proteins such as CRY2, FOXO1 and SIRT1 [, , , ]. It can be activated by tyrosine autophosphorylation [, ]. DYRK1A play a role in a signaling pathway regulating nuclear functions of cell proliferation. DYRK1A is a neurogenesis regulator and plays an important role in altered brain development in Down syndrome [, ]. Dual specificity tyrosine-phosphorylation-regulated kinase 1B (DYRK1B also known as Mirk) also phosphorylates serine, threonine and tyrosine residues, and has been shown to enhance the transcriptional activity of HNF1A and FOXO1 []. Mirk is reported to be an inhibitor of epithelial cell migration [], and appears to mediate carcinoma cell survival in specific environments [].This entry also includes mnb from Drosophila melanogaster. It plays a role in the specific control of proper proliferation of optic lobe neuronal progeny [].
Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) () phosphorylates serine, threonine and tyrosine residues in proteins such as CRY2, FOXO1 and SIRT1 [, , , ]. It can be activated by tyrosine autophosphorylation [, ]. DYRK1A play a role in a signaling pathway regulating nuclear functions of cell proliferation. DYRK1A is a neurogenesis regulator and plays an important role in altered brain development in Down syndrome [, ]. Dual specificity tyrosine-phosphorylation-regulated kinase 1B (DYRK1B also known as Mirk) also phosphorylates serine, threonine and tyrosine residues, and has been shown to enhance the transcriptional activity of HNF1A and FOXO1 []. Mirk is reported to be an inhibitor of epithelial cell migration [], and appears to mediate carcinoma cell survival in specific environments [].This entry also includes mnb from Drosophila melanogaster. It plays a role in the specific control of proper proliferation of optic lobe neuronal progeny [].This entry represents the catalytic domain found in DYRK1A and DYRK1B.
HNF4A (also known as TCF14) is a member of the steroid-thyroid hormone receptor superfamily. HNF4A interacts with regulatory elements in promoters and enhancers of the genes involved in cholesterol fatty acid and glucose metabolism [, ]. It is an upstream regulator of HNF1A expression []. HNF4A regulates the expression of genes in the liver, pancreas, kidney, intestine, and other tissues. It is essential for development of the liver [, ]and regulates growth and function of islet beta-cells in the pancreas [, ]. Mutations in the HFN4A gene result in type 1 MODY (MODY1), a monogenic form of non-insulin-dependent type 2 diabetes [, ]. HNF4A is also involved in circadian rhythm maintenance in liver and colon cells as it transrepresses CLOCK:BMAL1 heterodimer activity [].
