HNF-4-alpha

Domain

The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

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-ARNTL/BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698).

Involvement in disease

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Diabetes mellitus, non-insulin-dependent

NIDDM

A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own 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.

None

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylated on tyrosine residue(s); phosphorylation is important for its DNA-binding activity. Phosphorylation may directly or indirectly play a regulatory role in the subnuclear distribution. Phosphorylation at Ser-313 by AMPK reduces the ability to form homodimers and bind DNA.

Acetylation at Lys-458 lowers transcriptional activation by about two-fold.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR2 subfamily.

Cellular localization

• Nucleus

Alternative names

• Hepatocyte nuclear factor 4-alpha
• HNF-4-alpha
• Nuclear receptor subfamily 2 group A member 1
• Transcription factor 14
• Transcription factor HNF-4
• TCF-14
• NR2A1
• HNF4A
• HNF4
• TCF14

Database links

• entrezGene:3172
• omim:600281
• swissprot:P41235

Target type

Proteins

Primary research area

Epigenetics

Molecular weight

52785Da