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 steroid hormone, steroids, thyroid hormone, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to ...
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
mostly expressed in the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
, gut, kidney, and pancreatic
beta cell
Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are di ...
s that is critical for liver development. In humans, there are two isoforms of HNF4,
HNF4α and
HNF4γ, encoded by two separate genes and respectively.
Ligands
HNF4 was originally classified as an
orphan receptor
In biochemistry, an orphan receptor is a protein that has a similar structure to other identified receptors but whose endogenous ligand has not yet been identified. If a ligand for an orphan receptor is later discovered, the receptor is referred to ...
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
Linoleic acid (LA) is an organic compound with the formula COOH(CH2)7CH=CHCH2CH=CH(CH2)4CH3. Both alkene groups are ''cis''. It is a fatty acid sometimes denoted 18:2 (n-6) or 18:2 ''cis''-9,12. A linoleate is a salt or ester of this 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
A coactivator is a type of transcriptional coregulator that binds to an activator (a transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA ...
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
Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it has also been called androgen ...
, which is known to be severely diminished in patients with
insulin-resistance.
See also
*
Hepatocyte nuclear factors
Hepatocyte nuclear factors (HNFs) are a group of phylogenetically unrelated transcription factors that regulate the transcription of a diverse group of genes into proteins. These proteins include blood clotting factors and in addition, enzymes a ...
*
Hepatocyte nuclear factor 4A
References
External links
*
Intracellular receptors
Transcription factors
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