Recombinant Human Hepatocyte nuclear factor 4-alpha (HNF4A)

Function

Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes (PubMed:30597922). Activates the transcription of CYP2C38 (By similarity). Represses the CLOCK-BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698)

Subcellular Location

Nucleus

Disease Association

Maturity-onset diabetes of the young 1 (MODY1) : A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. [The disease is caused by variants affecting the gene represented in this entry] | Type 2 diabetes mellitus (T2D) : A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. [Disease susceptibility may be associated with variants affecting the gene represented in this entry] | Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young (FRTS4) : An autosomal dominant disease characterized by Fanconi syndrome associated with a beta cell phenotype of neonatal hyperinsulinism with macrosomia and young onset diabetes. Fanconi syndrome is a proximal tubulopathy resulting in generalized aminoaciduria, low molecular weight proteinuria, glycosuria, hyperphosphaturia and hypouricemia. Some FRTS4 patients have nephrocalcinosis, renal impairment, hypercalciuria with relative hypocalcemia, and hypermagnesemia. [The disease is caused by variants affecting the gene represented in this entry]

Subunit

Homodimerization is required for HNF4-alpha to bind to its recognition site (PubMed:14982928). Interacts with CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2 (PubMed:30530698). Interacts with NR0B2/SHP; the resulting heterodimer is transcriptionally inactive (PubMed:28128295). Interacts with DDX3X; this interaction disrupts the interaction between HNF4 and NR0B2 that forms inactive heterodimers and enhances the formation of active HNF4 homodimers (PubMed:28128295)

• Kritis A.A. et al. Isolation and characterization of a third isoform of human hepatocyte nuclear factor 4. — Gene (1996)
• Drewes T. et al. Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes. — Mol. Cell. Biol. (1996)
• Yamagata K. et al. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). — Nature (1996)
• Tanaka T. et al. Variation in P1 and P2 promoter-driven hepatocyte nuclear factor-4a (HNF4a) expression in human tissues: implications for carcinogenesis. (JUL-)
• PubMed: CI-8451K69U65QGO (MAY-)
• Deloukas P. et al. The DNA sequence and comparative analysis of human chromosome 20. — Nature (2001)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)