HNF4 ( H epatocyte N uclear F actor 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.
4-471: 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
8-547: A canonical alpha helical sandwich fold and interacts with co-activator proteins. HNF4 binds to the consensus sequence AGGTCAaAGGTCA in order to activate transcription. 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's [1] role in the synthesis of SHBG , which is known to be severely diminished in patients with insulin-resistance . Orphan receptor In biochemistry , an orphan receptor
12-407: 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 as an "adopted orphan". Conversely, the term orphan ligand refers to a biological ligand whose cognate receptor has not yet been identified. Examples of orphan receptors are found in
16-601: The G protein-coupled receptor (GPCR) and nuclear receptor families. If an endogenous ligand is found, the orphan receptor is "adopted" or "de-orphanized". An example is the nuclear receptor farnesoid X receptor (FXR) and the GPCR TGR5/GPCR19/G protein-coupled bile acid receptor , both of which are activated by bile acids . Adopted orphan receptors in the nuclear receptor group include FXR, liver X receptor (LXR), and peroxisome proliferator-activated receptor (PPAR). Another example of an orphan receptor site
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