Hepatocyte nuclear factor 4 alpha
Encyclopedia
Hepatocyte nuclear factor 4 alpha (HNF4A) also known as NR2A1 (nuclear receptor subfamily 2, group A, member 1) is a nuclear receptor
that in humans is encoded by the HNF4A gene.
that binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha
, a transcription factor which regulates the expression of several hepatic genes. This gene plays a role in development of the , , and . Alternative splicing of this gene results in multiple transcript variants.
HNF4A is required for the PXR
and CAR
-mediated transcriptional activation of CYP3A4
.
The alkaloid berberine
upregulates the expression of HNF4A.
type II.
with:
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...
that in humans is encoded by the HNF4A gene.
Function
HNF-4α is a nuclear transcription factorTranscription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
that binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha
HNF1A
HNF1 homeobox A , also known as HNF1A, is a human gene.The protein encoded by this gene is a transcription factor that is highly expressed in the liver and is involved in the regulation of the expression of several liver-specific genes.-Interactions:HNF1A has been shown to interact with PCAF, Src,...
, a transcription factor which regulates the expression of several hepatic genes. This gene plays a role in development of the , , and . Alternative splicing of this gene results in multiple transcript variants.
HNF4A is required for the PXR
Pregnane X receptor
In the field of molecular biology, the pregnane X receptor , also known as the steroid and xenobiotic sensing nuclear receptor or nuclear receptor subfamily 1, group I, member 2 is a protein that in humans is encoded by the NR1I2 gene.PXR is a nuclear receptor whose primary function is to sense...
and CAR
Constitutive androstane receptor
The constitutive androstane receptor also known as nuclear receptor subfamily 1, group I, member 3 is a protein that in humans is encoded by the NR1I3 gene...
-mediated transcriptional activation of CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...
.
The alkaloid berberine
Berberine
Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants as Berberis Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants as Berberis Berberine is a quaternary...
upregulates the expression of HNF4A.
Clinical significance
Mutations in this gene have been associated with monogenic autosomal dominant non-insulin-dependent diabetes mellitusDiabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
type II.
Interactions
Hepatocyte nuclear factor 4 alpha has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with:
- Beta-cateninBeta-cateninBeta-catenin is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo...
, - CREB binding proteinCREB binding proteinCREB-binding protein, also known as CREBBP or CBP, is a protein that in humans is encoded by the CREBBP gene.The CREB protein carries out its function by activating transcription, where interaction with transcription factors is managed by one or more of p300 domains: the nuclear receptor...
, - MED1MED1Mediator of RNA polymerase II transcription subunit 1 is a protein that in humans is encoded by the MED1 gene.- Function :The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with...
, - MED14MED14Mediator of RNA polymerase II transcription subunit 14 is an enzyme that in humans is encoded by the MED14 gene.-Interactions:MED14 has been shown to interact with PPARGC1A, Estrogen receptor alpha, STAT2, Cyclin-dependent kinase 8, Glucocorticoid receptor and Hepatocyte nuclear factor 4...
, - Small heterodimer partnerSmall heterodimer partnerThe small heterodimer partner also known as NR0B2 is a protein that in humans is encoded by the NR0B2 gene. SHP is a member of the nuclear receptor family of intracellular transcription factors. SHP is unusual for a nuclear receptor in that it lacks a DNA binding domain...
- Testicular receptor 4Testicular receptor 4Testicular receptor 4 also known as NR2C2 is a protein that in humans is encoded by the NR2C2 gene.The testicular receptor 4 is a member of the nuclear receptor family of transcription factors....
,