HNF4 (Hepatocyte Nuclear Factor 4) is a
nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These intracellular receptors work with other proteins to regulate the ex ...
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
mostly expressed in the
liver
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
, 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 and respectively.
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.
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.
The ligand binding domain of HNF4, as with other nuclear receptors, adopts a canonical alpha helical sandwich
fold and interacts with
co-activator proteins.
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).
This seems to be caused by HNF4-a'
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
External links
*
{{Transcription factors, g2
Intracellular receptors
Transcription factors