Biology:Hepatocyte nuclear factor 4
| Hepatocyte nuclear factor 4 alpha | |
|---|---|
| Identifiers | |
| Symbol | HNF4A |
| Alt. symbols | TCF14, MODY, MODY1 |
| NCBI gene | 3172 |
| HGNC | 5024 |
| OMIM | 600281 |
| PDB | 1M7W |
| RefSeq | NM_001030004 |
| UniProt | P41235 |
| Other data | |
| Locus | Chr. 20 q12-20q13.1 |
| Hepatocyte nuclear factor 4 gamma | |
|---|---|
| Identifiers | |
| Symbol | HNF4G |
| NCBI gene | 3174 |
| HGNC | 5026 |
| OMIM | 605966 |
| PDB | 1LV2 |
| RefSeq | NM_004133 |
| UniProt | Q14541 |
| Other data | |
| Locus | Chr. 8 q21-q22 |
HNF4 (Hepatocyte Nuclear Factor 4) is a nuclear receptor protein mostly expressed in the liver, gut, kidney, and pancreatic beta cells that is critical for liver development. In humans, there are two paralogs of HNF4, HNF4α and HNF4γ, encoded by two separate genes HNF4A and HNF4G respectively.[1]
Ligands
HNF4 was originally classified as an orphan receptor that exhibits constitutive transactivation activity apparently by being continuously bound to a variety of fatty acids.[2][3] The existence of a ligand for HNF4 has been somewhat controversial, but linoleic acid (LA) has been identified as the endogenous ligand of native HNF4 expressed in mouse liver; the binding of LA to HNF4 is reversible.[4]
The ligand binding domain of HNF4, as with other nuclear receptors, adopts a canonical alpha helical sandwich fold[5][6] and interacts with co-activator proteins.[7]
HNF4 binds to the consensus sequence AGGTCAaAGGTCA in order to activate transcription.
Pathology
Mutations in the HNF4A gene have been linked to maturity onset diabetes of the young 1 (MODY1).[8]
This seems to be caused by HNF4-a's [1] role in the synthesis of SHBG, which is known to be severely diminished in patients with insulin-resistance.
See also
- Hepatocyte nuclear factors
- Hepatocyte nuclear factor 4A
References
- ↑ "Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver". Gene 147 (2): 269–72. 1994. doi:10.1016/0378-1119(94)90079-5. PMID 7926813.
- ↑ Sladek F (August 2002). "Desperately seeking...something". Mol. Cell 10 (2): 219–21. doi:10.1016/S1097-2765(02)00605-6. PMID 12191466.
- ↑ "Fatty acid regulation of hepatic gene transcription". J. Nutr. 135 (11): 2503–6. November 2005. doi:10.1093/jn/135.11.2503. PMID 16251601.
- ↑ Laudet, Vincent, ed (2009). "Identification of an endogenous ligand bound to a native orphan nuclear receptor". PLOS ONE 4 (5): e5609. doi:10.1371/journal.pone.0005609. PMID 19440305. Bibcode: 2009PLoSO...4.5609Y.
- ↑ "Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids". Structure 10 (9): 1225–34. September 2002. doi:10.1016/S0969-2126(02)00829-8. PMID 12220494.
- ↑ "Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand". J. Biol. Chem. 277 (41): 37973–6. October 2002. doi:10.1074/jbc.C200420200. PMID 12193589.
- ↑ "Structural basis for HNF-4alpha activation by ligand and coactivator binding". J. Biol. Chem. 279 (22): 23311–6. May 2004. doi:10.1074/jbc.M400864200. PMID 14982928.
- ↑ "Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young". N Engl J Med 345 (13): 971–80. 2001. doi:10.1056/NEJMra002168. PMID 11575290.
External links
- Hepatocyte+Nuclear+Factor+4 at the US National Library of Medicine Medical Subject Headings (MeSH)
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