Aryl hydrocarbon receptor nuclear translocator
Encyclopedia
The ARNT gene
encodes the aryl hydrocarbon receptor nuclear translocator protein
that forms a complex with ligand-bound aryl hydrocarbon receptor
(AhR), and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF1). A t(1;12)(q21;p13) translocation, which results in a TEL-ARNT fusion protein
, is associated with acute myeloblastic leukemia
. Three alternatively spliced variants encoding different isoforms have been described for this gene.
The aryl hydrocarbon receptor (AhR) is involved in the induction of several enzyme
s that participate in xenobiotic
metabolism. The ligand-free, cytosolic form of the aryl hydrocarbon receptor
is complexed to heat shock protein 90
. Binding of ligand, which includes dioxin and polycyclic aromatic hydrocarbon
s, results in translocation of the ligand-binding subunit only to the nucleus. Induction of enzymes involved in xenobiotic metabolism occurs through binding of the ligand-bound AhR to xenobiotic responsive elements in the promoters of genes for these enzymes.
with HIF1A
, SRC-1, AIP
, SIM1
, Aryl hydrocarbon receptor
, EPAS1
, SIM2
and Nuclear receptor coactivator 2
.
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
encodes the aryl hydrocarbon receptor nuclear translocator 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...
that forms a complex with ligand-bound aryl hydrocarbon receptor
Aryl hydrocarbon receptor
The Aryl hydrocarbon receptor is a member of the family of basic-helix-loop-helix transcription factors. AhR is a cytosolic transcription factor that is normally inactive, bound to several co-chaperones...
(AhR), and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF1). A t(1;12)(q21;p13) translocation, which results in a TEL-ARNT fusion protein
Fusion protein
Fusion proteins or chimeric proteins are proteins created through the joining of two or more genes which originally coded for separate proteins. Translation of this fusion gene results in a single polypeptide with functional properties derived from each of the original proteins...
, is associated with acute myeloblastic leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
. Three alternatively spliced variants encoding different isoforms have been described for this gene.
The aryl hydrocarbon receptor (AhR) is involved in the induction of several enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s that participate in xenobiotic
Xenobiotic
A xenobiotic is a chemical which is found in an organism but which is not normally produced or expected to be present in it. It can also cover substances which are present in much higher concentrations than are usual...
metabolism. The ligand-free, cytosolic form of the aryl hydrocarbon receptor
Aryl hydrocarbon receptor
The Aryl hydrocarbon receptor is a member of the family of basic-helix-loop-helix transcription factors. AhR is a cytosolic transcription factor that is normally inactive, bound to several co-chaperones...
is complexed to heat shock protein 90
Hsp90
Hsp90 is a molecular chaperone and is one of the most abundant proteins expressed in cells. It is a member of the heat shock protein family, which is upregulated in response to stress...
. Binding of ligand, which includes dioxin and polycyclic aromatic hydrocarbon
Aromatic hydrocarbon
An aromatic hydrocarbon or arene is a hydrocarbon with alternating double and single bonds between carbon atoms. The term 'aromatic' was assigned before the physical mechanism determining aromaticity was discovered, and was derived from the fact that many of the compounds have a sweet scent...
s, results in translocation of the ligand-binding subunit only to the nucleus. Induction of enzymes involved in xenobiotic metabolism occurs through binding of the ligand-bound AhR to xenobiotic responsive elements in the promoters of genes for these enzymes.
Interactions
Aryl hydrocarbon receptor nuclear translocator 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 HIF1A
HIF1A
Hypoxia-inducible factor 1, alpha subunit , also known as HIF1A, is a protein that in humans is encoded by the HIF1A gene...
, SRC-1, AIP
AIP (gene)
AH receptor-interacting protein also known as aryl-hydrocarbon receptor-interacting protein, immunophilin homolog ARA9, or HBV X-associated protein 2 is a protein that in humans is encoded by the AIP gene.- Function :...
, SIM1
SIM1
Single-minded homolog 1 also known as class E basic helix-loop-helix protein 14 is a protein that in humans is encoded by the SIM1 gene.- Function :...
, Aryl hydrocarbon receptor
Aryl hydrocarbon receptor
The Aryl hydrocarbon receptor is a member of the family of basic-helix-loop-helix transcription factors. AhR is a cytosolic transcription factor that is normally inactive, bound to several co-chaperones...
, EPAS1
EPAS1
Endothelial PAS domain-containing protein 1 is a protein that in humans is encoded by the EPAS1 gene.- Function :This gene encodes a transcription factor involved in the induction of genes regulated by oxygen, which is induced as oxygen levels fall...
, SIM2
SIM2
Single-minded homolog 2 is a protein that in humans is encoded by the SIM2 gene.- Function :SIM1 and SIM2 genes are Drosophila single-minded gene homologs. The Drosophila sim gene encodes a transcription factor that is a master regulator of neurogenesis of midline cells in the central nervous...
and Nuclear receptor coactivator 2
Nuclear receptor coactivator 2
The nuclear receptor coactivator 2 is a transcriptional coregulatory protein which contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA2 is recruited to DNA promotion sites by ligand activated nuclear receptors. NCOA2 in turn acylates...
.