Androgen receptor
Encyclopedia
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor
that is activated by binding of either of the androgen
ic hormones testosterone
or dihydrotestosterone
in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor
, and progestin
s in higher dosages can block the androgen receptor.
The main function of the androgen receptor is as a DNA-binding transcription factor
that regulates gene expression; however, the androgen receptor has other functions as well. Androgen regulated genes are critical for the development and maintenance of the male sexual phenotype
.
to dihydrotestosterone, an even more potent agonist
for androgen receptor activation. Testosterone appears to be the primary androgen receptor-activating hormone in the Wolffian duct
, whereas dihydrotestosterone is the main androgenic hormone in the urogenital sinus
, urogenital tubercle, and hair follicle
s. Hence, testosterone is responsible primarily for the development of male primary sexual characteristics
, whereas dihydrotestosterone is responsible for secondary male characteristics
.
Androgens cause slow epiphysis
, or maturation of the bones, but more of the potent epiphysis
effect comes from the estrogen produced by aromatization of androgens. Steroid users of teen age may find that their growth had been stunted by androgen and/or estrogen excess. People with too little sex hormones can be short during puberty but end up taller as adults as in androgen insensitivity syndrome
or estrogen insensitivity syndrome
.
Also, AR knockout-mice studies have shown that AR is essential for normal female fertility, being required for development and full functionality of the ovarian follicle
s and ovulation, working through both intra-ovarian and neuroendocrine mechanisms.
. The binding of an androgen
to the androgen receptor results in a conformational change in the receptor that, in turn, causes dissociation of heat shock protein
s, transport from the cytosol
into the cell nucleus
, and dimerization. The androgen receptor dimer binds to a specific sequence of DNA
known as a hormone response element
. Androgen receptors interact with other proteins in the nucleus, resulting in up- or down-regulation of specific gene
transcription
. Up-regulation or activation of transcription results in increased synthesis of messenger RNA
, which, in turn, is translated by ribosomes to produce specific proteins. One of the known target genes of androgen receptor activation is insulin-like growth factor I (IGF-1). Thus, changes in levels of specific proteins in cells is one way that androgen receptors control cell behavior.
One function of androgen receptor that is independent of direct binding to its target DNA sequence, is facilitated by recruitment via other DNA-binding proteins. One example is serum response factor
, a protein that activates several genes that cause muscle growth.
s, androgen receptors can have actions that are independent of their interactions with DNA. Androgen receptors interact with certain signal transduction
proteins in the cytoplasm. Androgen binding to cytoplasmic androgen receptors can cause rapid changes in cell function independent of changes in gene transcription, such as changes in ion transport
. Regulation of signal transduction pathways by cytoplasmic androgen receptors can indirectly lead to changes in gene transcription, for example, by leading to phosphorylation of other transcription factors.
located on the X chromosome
at Xq11-12.
, formerly known as testicular feminization, is caused by a mutation of the Androgen Receptor gene located on the X chromosome (locus:Xq11-Xq12).
The androgen receptor seems to affect neuron physiology and is defective in Kennedy disease
. In addition, point mutations and trinucleotide repeat polymorphisms has been linked to a number of additional disorders.
of the androgen receptor (A and B) have been identified:
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 is activated by binding of either of the androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
ic hormones testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
or dihydrotestosterone
Dihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor
Progesterone receptor
The progesterone receptor also known as NR3C3 , is an intracellular steroid receptor that specifically binds progesterone...
, and progestin
Progestin
A progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
s in higher dosages can block the androgen receptor.
The main function of the androgen receptor is as a DNA-binding transcription factor
Transcription 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 regulates gene expression; however, the androgen receptor has other functions as well. Androgen regulated genes are critical for the development and maintenance of the male sexual phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
.
Effect on development
In some cell types, testosterone interacts directly with androgen receptors, whereas, in others, testosterone is converted by 5-alpha-reductase5-alpha reductase
5α-reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in 3 metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism, and prostate cancer....
to dihydrotestosterone, an even more potent agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
for androgen receptor activation. Testosterone appears to be the primary androgen receptor-activating hormone in the Wolffian duct
Wolffian duct
The mesonephric duct is a paired organ found in mammals including humans during embryogenesis....
, whereas dihydrotestosterone is the main androgenic hormone in the urogenital sinus
Urogenital sinus
The definitive urogenital sinus is a part of the human body only present in the development of the urinary and reproductive organs...
, urogenital tubercle, and hair follicle
Hair follicle
A hair follicle is a skin organ that produces hair. Hair production occurs in phases, including a growth phase , and cessation phase , and a rest phase . Stem cells are principally responsible for the production of hair....
s. Hence, testosterone is responsible primarily for the development of male primary sexual characteristics
Sex organ
A sex organ, or primary sexual characteristic, as narrowly defined, is any of the anatomical parts of the body which are involved in sexual reproduction and constitute the reproductive system in a complex organism; flowers are the reproductive organs of flowering plants, cones are the reproductive...
, whereas dihydrotestosterone is responsible for secondary male characteristics
Secondary sex characteristic
Secondary sex characteristics are features that distinguish the two sexes of a species, but that are not directly part of the reproductive system. They are believed to be the product of sexual selection for traits which give an individual an advantage over its rivals in courtship and aggressive...
.
Androgens cause slow epiphysis
Epiphysis
The epiphysis is the rounded end of a long bone, at its joint with adjacent bone. Between the epiphysis and diaphysis lies the metaphysis, including the epiphyseal plate...
, or maturation of the bones, but more of the potent epiphysis
Epiphysis
The epiphysis is the rounded end of a long bone, at its joint with adjacent bone. Between the epiphysis and diaphysis lies the metaphysis, including the epiphyseal plate...
effect comes from the estrogen produced by aromatization of androgens. Steroid users of teen age may find that their growth had been stunted by androgen and/or estrogen excess. People with too little sex hormones can be short during puberty but end up taller as adults as in androgen insensitivity syndrome
Androgen insensitivity syndrome
Androgen insensitivity syndrome is a condition that results in the partial or complete inability of the cell to respond to androgens. The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as...
or estrogen insensitivity syndrome
Estrogen insensitivity syndrome
The estrogen insensitivity syndrome or estrogen resistance is a form of congenital estrogen deficiency caused by a defective estrogen receptor . Thus, estrogens cannot be recognized and initiate their biological action....
.
Also, AR knockout-mice studies have shown that AR is essential for normal female fertility, being required for development and full functionality of the ovarian follicle
Ovarian follicle
Ovarian follicles are the basic units of female reproductive biology, each of which is composed of roughly spherical aggregations of cells found in the ovary. They contain a single oocyte . These structures are periodically initiated to grow and develop, culminating in ovulation of usually a single...
s and ovulation, working through both intra-ovarian and neuroendocrine mechanisms.
Genomic
The primary mechanism of action for androgen receptors is direct regulation of gene transcriptionTranscription 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...
. The binding of an androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
to the androgen receptor results in a conformational change in the receptor that, in turn, causes dissociation of heat shock protein
Heat shock protein
Heat shock proteins are a class of functionally related proteins involved in the folding and unfolding of other proteins. Their expression is increased when cells are exposed to elevated temperatures or other stress. This increase in expression is transcriptionally regulated...
s, transport from the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
into the cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, and dimerization. The androgen receptor dimer binds to a specific sequence of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
known as a hormone response element
Hormone response element
A hormone response element is a response element for hormones, a short sequence of DNA within the promoter of a gene that is able to bind a specific hormone receptor complex and therefore regulate transcription...
. Androgen receptors interact with other proteins in the nucleus, resulting in up- or down-regulation of specific gene
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...
transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
. Up-regulation or activation of transcription results in increased synthesis of messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
, which, in turn, is translated by ribosomes to produce specific proteins. One of the known target genes of androgen receptor activation is insulin-like growth factor I (IGF-1). Thus, changes in levels of specific proteins in cells is one way that androgen receptors control cell behavior.
One function of androgen receptor that is independent of direct binding to its target DNA sequence, is facilitated by recruitment via other DNA-binding proteins. One example is serum response factor
Serum response factor
Serum response factor , also known as SRF, is a transcription factor.It is a member of the MADS box superfamily of transcription factors. This protein binds to the serum response element in the promoter region of target genes...
, a protein that activates several genes that cause muscle growth.
Non-genomic
More recently, androgen receptors have been shown to have a second mode of action. As has been also found for other steroid hormone receptors such as estrogen receptorEstrogen receptor
Estrogen receptor refers to a group of receptors that are activated by the hormone 17β-estradiol . Two types of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and the estrogen G protein-coupled receptor GPR30 , which is a G protein-coupled...
s, androgen receptors can have actions that are independent of their interactions with DNA. Androgen receptors interact with certain signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
proteins in the cytoplasm. Androgen binding to cytoplasmic androgen receptors can cause rapid changes in cell function independent of changes in gene transcription, such as changes in ion transport
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
. Regulation of signal transduction pathways by cytoplasmic androgen receptors can indirectly lead to changes in gene transcription, for example, by leading to phosphorylation of other transcription factors.
Gene
In humans, the androgen receptor is encoded by the AR geneGene
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...
located on the X chromosome
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
at Xq11-12.
AR deficiencies
The androgen insensitivity syndromeAndrogen insensitivity syndrome
Androgen insensitivity syndrome is a condition that results in the partial or complete inability of the cell to respond to androgens. The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as...
, formerly known as testicular feminization, is caused by a mutation of the Androgen Receptor gene located on the X chromosome (locus:Xq11-Xq12).
The androgen receptor seems to affect neuron physiology and is defective in Kennedy disease
Kennedy disease
Kennedy's disease or X-linked Spinal and Bulbar Muscular Atrophy or Spinobulbar Muscular Atrophy or X-Linked Bulbo-Spinal Atrophy is an X-linked recessive, slow progressing, neurodegenerative disease associated with mutation of the androgen receptor...
. In addition, point mutations and trinucleotide repeat polymorphisms has been linked to a number of additional disorders.
Structure
Isoforms
Two isoformsProtein isoform
A protein isoform is any of several different forms of the same protein. Different forms of a protein may be produced from related genes, or may arise from the same gene by alternative splicing. A large number of isoforms are caused by single-nucleotide polymorphisms or SNPs, small genetic...
of the androgen receptor (A and B) have been identified:
- AR-A - 87 kDaAtomic mass unitThe unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...
- N-terminus truncated (lacks the first 187 amino acids), which results from in vitro proteolysis. - AR-B - 110 kDa - full length
Domains
Like other nuclear receptors, the androgen receptor is modular in structure and is composed of the following functional domains labeled A through F:- A/B) - N-terminal regulatory domain contains:
- activation function 1 (AF-1) between residues 101 and 370 required for full ligand activated transcriptional activity
- activation function 5 (AF-5) between residues 360-485 is responsible for the constitutive activity (activity without bound ligand)
- dimerization surface involving residues 1-36 (containing the FXXLF motif where F = phenylalaninePhenylalaninePhenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
, L = leucineLeucineLeucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
, and X = any amino acid residue) and 370-494, both of which interact with the LBD in an intramolecular head-to-tail interaction
- C) - DNA binding domain (DBD)
- D) - Hinge region - flexible region that connects the DBD with the LBD; along with the DBD, contains a ligand dependent nuclear localization signalNuclear localization signalA nuclear localization signal or sequence is an amino acid sequence which 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface. Different...
- E) - LigandLigandIn coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
binding domain (LBD) containing- activation function 2 (AF-2), responsible for agonist induced activity (activity in the presence of bound agonist)
- AF-2 binds either the N-terminal FXXFL motif intramolecularIntramolecularIntramolecular in chemistry describes a process or characteristic limited within the structure of a single molecule, a property or phenomenon limited to the extent of a single molecule.- Examples :...
ly or coactivatorCoactivator (genetics)A coactivator is a protein that increases gene expression by binding to an activator which contains a DNA binding domain. The coactivator is unable to bind DNA by itself....
proteins (containing the LXXLL or preferably FXXFL motifs) - A ligand dependent nuclear export signalNuclear export signalA nuclear export signal is a short amino acid sequence of 4 hydrophobic residues in a protein that targets it for export from the cell nucleus to the cytoplasm through the nuclear pore complex using nuclear transport. It has the opposite effect of a nuclear localization signal, which targets a...
- F) - C-terminal domain
Interactions
Androgen receptor 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:
- AKT1AKT1RAC-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1 gene. Multiple alternatively spliced transcript variants have been found for this gene.- Function :...
, - BAG1BAG1BAG family molecular chaperone regulator 1 is a protein that in humans is encoded by the BAG1 gene.BAG gene has been implicated in age related neurodegenerative diseases as Alzheimer's...
, - Beta-cateninBeta-cateninBeta-catenin is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo...
, - BRCA1BRCA1BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
, - C-junC-junc-Jun is the name of a gene and protein that, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the...
, - Calmodulin 1Calmodulin 1Calmodulin 1 is a protein that in humans is encoded by the CALM1 gene.- Function :Calmodulin 1 is the archetype of the family of calcium-modulated proteins of which nearly 20 members have been found. They are identified by their occurrence in the cytosol or on membranes facing the cytosol and by a...
, - Caveolin 1,
- CDK9CDK9CDK9 or cyclin-dependent kinase 9 is a cyclin-dependent kinase associated with P-TEFb.CDK9 is also known to associate with other proteins such as TRAF2, and be involved in differentiation of skeletal muscle...
, - COX5BCOX5BCytochrome c oxidase subunit 5B, mitochondrial is an enzyme that in humans is encoded by the COX5B gene.-Interactions:COX5B has been shown to interact with Androgen receptor.-External links:* in PROSITE...
, - CREB-binding protein,
- Cyclin D1Cyclin D1G1/S-specific cyclin-D1 is a protein that in humans is encoded by the CCND1 gene.Immunohistochemical staining of cyclin D1 antibodies is used to diagnose mantle cell lymphoma.-Interactions:...
, - Cyclin-dependent kinase 7Cyclin-dependent kinase 7Cell division protein kinase 7 is an enzyme that in humans is encoded by the CDK7 gene.The protein encoded by this gene is a member of the cyclin-dependent protein kinase family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces...
, - Death associated protein 6Death associated protein 6Death-associated protein 6 also known as DAXX is a protein that in humans is encoded by the DAXX gene.- Function :DAXX, a death-domain-associated protein, was first discovered through its cytoplasmic interaction with the classical death receptor Fas...
, - Deleted in Colorectal CancerDeleted in Colorectal CancerDeleted in Colorectal Carcinoma, also known as DCC, is a protein which in humans is encoded by the DCC gene. DCC has long been implicated in colorectal cancer. While the official, full name of this gene is Deleted in Colorectal Carcinoma, it is almost universally called Deleted in Colorectal Cancer...
, - EFCAB6EFCAB6EF-hand calcium-binding domain-containing protein 6 is a protein that in humans is encoded by the EFCAB6 gene.-Interactions:EFCAB6 has been shown to interact with PARK7 and Androgen receptor.-Further reading:...
, - Epidermal growth factor receptorEpidermal growth factor receptorThe epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
, - FOXO1FOXO1Forkhead box protein O1 also known as forkhead in rhabdomyosarcoma is a protein that in humans is encoded by the FOXO1 gene.- Function :...
, - GAPDHGlyceraldehyde 3-phosphate dehydrogenaseGlyceraldehyde 3-phosphate dehydrogenase is an enzyme of ~37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules...
, - GelsolinGelsolinGelsolin is an actin-binding protein that is a key regulator of actin filament assembly and disassembly. Gelsolin is one of the most potent members of the actin-severing gelsolin/villin superfamily, as it severs with nearly 100% efficiency...
, - GNB2L1GNB2L1Guanine nucleotide-binding protein subunit beta-2-like 1 is a protein that in humans is encoded by the GNB2L1 gene.-Interactions:GNB2L1 has been shown to interact with PDE4D, STAT1, Tyrosine kinase 2, Src, Androgen receptor, AGTRAP, Janus kinase 1, FYN, Cyclin A1, IFNAR2, PRKCE, P73, RAS p21...
, - GSK3BGSK3BGlycogen synthase kinase 3 beta, also known as GSK3B, is an enzyme that in humans is encoded by the GSK3B gene.- Function :Glycogen synthase kinase-3 is a proline-directed serine-threonine kinase that was initially identified as a phosphorylating and inactivating glycogen synthase. Two isoforms,...
, - HDAC1HDAC1Histone deacetylase 1 is an enzyme that in humans is encoded by the HDAC1 gene.-Interactions:HDAC1 has been shown to interact with RAD9A, DNMT3L, MTA1, FKBP3, CDC20, CDH1, Host cell factor C1, BUB3, Nuclear receptor co-repressor 2, IKZF1, Prohibitin, EVI1, DDX5, DNMT3A, Mothers against...
, - HSP90AA1,
- HTATIPHTATIPHistone acetyltransferase KAT5 is an enzyme that in humans is encoded by the KAT5 gene.- Function :The protein encoded by this gene belongs to the MYST family of histone acetyl transferases and was originally isolated as an HIV-1 TAT-interactive protein...
, - MAGEA11MAGEA11Melanoma-associated antigen 11 is a protein that in humans is encoded by the MAGEA11 gene.-Interactions:MAGEA11 has been shown to interact with TCEA2, Androgen receptor and SH2D4A.-Further reading:...
, - 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...
, - MYST2MYST2Histone acetyltransferase MYST2 is an enzyme that in humans is encoded by the MYST2 gene.-Interactions:MYST2 has been shown to interact with Androgen receptor, ORC1L and Vimentin.-Further reading:...
, - NCOA1Nuclear receptor coactivator 1The nuclear receptor coactivator 1 is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity . NCOA1 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA1, in turn, acylates...
, - NCOA2Nuclear receptor coactivator 2The 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...
, - NCOA3Nuclear receptor coactivator 3The nuclear receptor coactivator 3 also known as NCOA3 is a protein that, in humans, is encoded by the NCOA3 gene. NCOA3 is also frequently called 'amplified in breast 1' , steroid receptor coactivator-3 , or thyroid hormone receptor activator molecule 1 .-Function:NCOA3 is a transcriptional...
, - NCOA4NCOA4Nuclear receptor coactivator 4 is a protein that in humans is encoded by the NCOA4 gene.-Interactions:NCOA4 has been shown to interact with Peroxisome proliferator-activated receptor gamma and Androgen receptor.-Further reading:...
, - NCOA6NCOA6Nuclear receptor coactivator 6 is a protein that in humans is encoded by the NCOA6 gene.-Interactions:NCOA6 has been shown to interact with Ku70, RBBP5, E2F1, Retinoblastoma protein, CREB-binding protein, Activating transcription factor 2, HSF1, HBXIP, TGS1, TUBB, TUBA4A, Thyroid hormone receptor...
, - NCOR2Nuclear receptor co-repressor 2The nuclear receptor co-repressor 2 is a transcriptional coregulatory protein that contains several nuclear receptor-interacting domains. In addition, NCOR2 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR2 assists nuclear receptors in the down regulation of target...
, - NONONONONon-POU domain-containing octamer-binding protein is a protein that in humans is encoded by the NONO gene.-Interactions:NONO has been shown to interact with SFPQ, SPI1 and Androgen receptor.-Further reading:...
, - PA2G4PA2G4Proliferation-associated protein 2G4 is a protein that in humans is encoded by the PA2G4 gene.-Interactions:PA2G4 has been shown to interact with ERBB3, Retinoblastoma protein and Androgen receptor.-Further reading:...
, - PAK6PAK6Serine/threonine-protein kinase PAK 6 is an enzyme that in humans is encoded by the PAK6 gene.-Interactions:PAK6 has been shown to interact with Androgen receptor.-Further reading:...
, - PATZ1PATZ1POZ-, AT hook-, and zinc finger-containing protein 1 is a protein that in humans is encoded by the PATZ1 gene.-Interactions:PATZ1 has been shown to interact with RNF4, Microphthalmia-associated transcription factor and Androgen receptor....
, - PIAS2Protein inhibitor of activated STAT2E3 SUMO-protein ligase PIAS2 is an enzyme that in humans is encoded by the PIAS2 gene.-Interactions:Protein inhibitor of activated STAT2 has been shown to interact with Androgen receptor, DNMT3A, PARK7 and UBE2I.-Further reading:...
, - PRPF6PRPF6Pre-mRNA-processing factor 6 is a protein that in humans is encoded by the PRPF6 gene.-Interactions:PRPF6 has been shown to interact with TXNL4B, ARAF and Androgen receptor.-External links:*...
, - PTENPTEN (gene)Phosphatase and tensin homolog is a protein that, in humans, is encoded by the PTEN gene. Mutations of this gene are a step in the development of many cancers....
, - RAD9ARAD9ACell cycle checkpoint control protein RAD9A is a protein that in humans is encoded by the RAD9A gene.-Interactions:RAD9A has been shown to interact with RAD17, HDAC1, TOPBP1, RAD1 homolog, BCL2-like 1, Bcl-2, Androgen receptor, DNAJC7, HUS1 and Abl gene.-Further reading:...
, - RANBP9RANBP9Ran-binding protein 9 is a protein that in humans is encoded by the RANBP9 gene.-Interactions:RANBP9 has been shown to interact with C-Met, DYRK1B, USP11, DISC1, Androgen receptor, Glucocorticoid receptor, S100A7, HIPK2 and MKLN1.-Further reading:...
, - RCHY1RCHY1RING finger and CHY zinc finger domain-containing protein 1 is a protein that in humans is encoded by the RCHY1 gene.-Interactions:RCHY1 has been shown to interact with P53 and Androgen receptor.-Further reading:...
, - Retinoblastoma proteinRetinoblastoma proteinThe retinoblastoma protein is a tumor suppressor protein that is dysfunctional in the majority types of cancer. One highly studied function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide...
, - RNF14RNF14E3 ubiquitin-protein ligase RNF14 is an enzyme that in humans is encoded by the RNF14 gene.-Interactions:RNF14 has been shown to interact with Androgen receptor.-Further reading:...
, - RNF4RNF4RING finger protein 4 is a protein that in humans is encoded by the RNF4 gene.The protein encoded by this gene contains a RING finger domain and acts as a transcription factor. This protein has been shown to interact with, and inhibit the activity of, TRPS1, a transcription suppressor of...
, - SART3SART3Squamous cell carcinoma antigen recognized by T-cells 3 is a protein that in humans is encoded by the SART3 gene.The protein encoded by this gene is an RNA-binding nuclear protein that is a tumor-rejection antigen...
, - SMAD3Mothers against decapentaplegic homolog 3Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene. SMAD3 is a member of the SMAD family of proteins.The human SMAD3 gene is located on chromosome 15...
, - 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...
, - SrcSrc (gene)Proto-oncogene tyrosine-protein kinase Src is an enzyme that in humans is encoded by the SRC gene.Src is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine. It belongs to a...
, - SRYSRYSRY is a sex-determining gene on the Y chromosome in the therians .This intronless gene encodes a transcription factor that is a member of the SOX gene family of DNA-binding proteins...
, - STAT3STAT3Signal transducer and activator of transcription 3 also known as STAT3 is a transcription factor which in humans is encoded by the STAT3 gene.- Function :The protein encoded by this gene is a member of the STAT protein family...
, - SVILSVILSupervillin is a protein that in humans is encoded by the SVIL gene.-Interactions:SVIL has been shown to interact with Androgen receptor.-Further reading:...
, - Testicular receptor 2Testicular receptor 2The testicular receptor 2 also known as NR2C1 is protein that in humans is encoded by the NR2C1 gene...
, - 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....
, - TGFB1I1TGFB1I1Transforming growth factor beta-1-induced transcript 1 protein is a protein that in humans is encoded by the TGFB1I1 gene.-Interactions:TGFB1I1 has been shown to interact with PTPN12, PTK2, Androgen receptor, PTK2B, Dopamine transporter and Hsp27....
, - TMF1TMF1TATA element modulatory factor is a protein that in humans is encoded by the TMF1 gene.-Interactions:TMF1 has been shown to interact with FER and Androgen receptor.-Further reading:...
, - TRIM68TRIM68Tripartite motif-containing protein 68 is a protein that in humans is encoded by the TRIM68 gene.-Interactions:TRIM68 has been shown to interact with Androgen receptor.-Further reading:...
, - UBE2IUBE2ISUMO-conjugating enzyme UBC9 is a protein that in humans is encoded by the UBE2I gene.-Interactions:UBE2I has been shown to interact with WT1, TOP1, RAD51, Activating transcription factor 2, PIAS1, SALL1, FHIT, RANBP2, Protein inhibitor of activated STAT2, DNMT3A, DNMT3B, Small ubiquitin-related...
, - UXTUXTProtein UXT also known as androgen receptor trapped clone 27 protein is a protein that in humans is encoded by the UXT gene.- Function :...
, and - ZMIZ1ZMIZ1Zinc finger MIZ domain-containing protein 1 is a protein that in humans is encoded by the ZMIZ1 gene.-Interactions:ZMIZ1 has been shown to interact with Androgen receptor.-Further reading:...
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External links
- GeneReviews/NCBI/NIH/UW entry on Androgen Insensitivity Syndrome
- OMIM entries on Androgen Insensitivity Syndrome
- GeneReviews/NIH/NCBI/UW entry on Spinal and Bulbar Muscular Atrophy, Kennedy's Disease, SBMA, X-Linked Spinal and Bulbar Muscular Atrophy
- OMIM entries on Spinal and Bulbar Muscular Atrophy, Kennedy's Disease, SBMA, X-Linked Spinal and Bulbar Muscular Atrophy