HNF4 (HepatocyteNuclearFactor 4) is anuclear receptorprotein mostly expressed in theliver, gut, kidney, and pancreaticbeta cells that is critical for liver development. In humans, there are two paralogs of HNF4,HNF4αandHNF4γ,encoded by two separate genesHNF4A andHNF4G respectively.[1]
HNF4 was originally classified as anorphan 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, butlinoleic 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 sandwichfold[5][6] and interacts withco-activator proteins.[7]
HNF4 binds to the consensus sequence AGGTCAaAGGTCA in order to activate transcription.
^Chartier FL, Bossu JP, Laudet V, Fruchart JC, Laine B (1994). "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.doi:10.1016/0378-1119(94)90079-5.PMID7926813.
^Fajans SS, Bell GI, Polonsky KS (2001). "Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young".N Engl J Med.345 (13):971–80.doi:10.1056/NEJMra002168.PMID11575290.
