Hnf4
Encyclopedia
HNF4 is a nuclear receptor
Nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...

 protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 mostly expressed in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

, gut, kidney, and pancreatic beta cell
Beta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...

s that is critical for liver development. In humans, there are two isoforms of HNF4, alpha
Hepatocyte nuclear factor 4 alpha
Hepatocyte nuclear factor 4 alpha also known as NR2A1 is a nuclear receptor that in humans is encoded by the HNF4A gene.- Function :...

and gamma
Hepatocyte nuclear factor 4 gamma
Hepatocyte nuclear factor 4 gamma also known as NR2A2 is a nuclear receptor that in humans is encoded by the HNF4G gene....

encoded by two separate genes and respectively.

Ligands

HNF4 was originally classified as an orphan receptor
Orphan receptor
An orphan receptor is an apparent receptor 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 as an "adopted orphan".-Examples:Examples of orphan...

 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
Linoleic acid is an unsaturated n-6 fatty acid. It is a colorless liquid at room temperature. In physiological literature, it has a lipid number of 18:2...

 (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
Coactivation (Transcription)
Coactivation is a process by which the transcription of RNA is increased. Proteins called coactivators are recruited to DNA-binding transcription factors through their activation domains and increase transcription by relaxing the chromatin structure to allow greater access to a gene or by bringing...

 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).
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