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 any of the
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
ic
hormones, including
testosterone
Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...
and
dihydrotestosterone
Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues includ ...
in the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
and then translocating into the
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
* Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucl ...
. The androgen receptor is most closely related to the
progesterone receptor, and
progestins in higher dosages can block the androgen receptor.
The main function of the androgen receptor is as a
DNA-binding transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
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
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...
.
Function
Effect on development
In some cell types, testosterone interacts directly with androgen receptors, whereas, in others, testosterone is converted by
5-alpha-reductase 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
The urogenital sinus is a part of the human body only present in the development of the urinary and reproductive organs. It is the ventral part of the cloaca, formed after the cloaca separates from the anal canal during the fourth to seventh w ...
,
urogenital tubercle, and
hair follicles.
Testosterone is therefore responsible primarily for the development of male
primary sexual characteristics
Sexual characteristics are physical traits of an organism (typically of a sexually dimorphic organism) which are indicative of its biological sex. These can include sex organs used for reproduction and secondary sex characteristics which disting ...
, whilst dihydrotestosterone is responsible for
secondary male characteristics.
Androgens cause slow maturation of the bones, but more of the potent maturation effect comes from the
estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
produced by
aromatization
Aromatization is a chemical reaction in which an aromatic system is formed from a single nonaromatic precursor. Typically aromatization is achieved by dehydrogenation of existing cyclic compounds, illustrated by the conversion of cyclohexane int ...
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 (AIS) is a difference in sex development involving hormonal resistance due to androgen receptor dysfunction.
It affects 1 in 20,000 to 64,000 XY ( karyotypically male) births. The condition results in the partial ...
or
estrogen insensitivity syndrome
Estrogen insensitivity syndrome (EIS), or estrogen resistance, is a form of congenital estrogen deficiency or hypoestrogenism which is caused by a defective estrogen receptor (ER) – specifically, the estrogen receptor alpha (ERα) – that res ...
.
Knockout-mice
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "Gene knockout, knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They ...
studies have shown that the androgen receptor is essential for normal female fertility, being required for development and full functionality of the
ovarian follicle
An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries. It secretes hormones that influence stages of the menstrual cycle. At the time of puberty, women have approximately 200,000 to 300,000 follicles, each with t ...
s and
ovulation
Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilize ...
, working through both intra-ovarian and
neuroendocrine
Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules (hormones) into the blood. In this way they bri ...
mechanisms.
Maintenance of male skeletal integrity
Via the androgen receptor, androgens play a key role in the maintenance of male skeletal integrity. The regulation of this integrity by androgen receptor (AR) signaling can be attributed to both
osteoblasts
Osteoblasts (from the Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function ...
and
osteocytes
An osteocyte, an oblate shaped type of bone cell with dendritic processes, is the most commonly found cell in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide and ...
.
Role in females
The AR plays a role in regulating female sexual, somatic, and behavioral functions. Experimental data using AR
knockout female mice, provides evidence that the promotion of cardiac growth, kidney hypertrophy, cortical bone growth and regulation of
trabecular bone structure is a result of DNA-binding-dependent actions of the AR in females.
Moreover, the importance of understanding female androgen receptors lies in their role in several genetic disorders including androgen insensitivity syndrome (AIS).
Complete (CAIS) and
partial (PAIS) which are a result of
mutations in the genes that code for AR. These mutations cause the inactivation of AR due to mutations conferring resistance to circulating testosterone, with more than 400 different AR mutations reported.
Mechanism of action
Genomic
The primary mechanism of action for androgen receptors is
direct regulation of
gene transcription
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called ...
. 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
Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including expo ...
s, transport from the
cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
into the
cell nucleus, and
dimerization. The androgen receptor dimer binds to a specific sequence of DNA known as a
hormone response element Response elements are short sequences of DNA within a gene promoter or enhancer region that are able to bind specific transcription factors and regulate transcription of genes.
Under conditions of stress, a transcription activator protein binds ...
. Androgen receptors interact with other proteins in the nucleus, resulting in up- or down-regulation of specific
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
transcription.
Up-regulation or activation of transcription results in increased synthesis of
messenger RNA, which, in turn, is translated by
ribosomes
Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...
to produce specific proteins. One of the known target genes of androgen receptor activation is the
insulin-like growth factor 1 receptor
The insulin-like growth factor 1 (IGF-1) receptor is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called insulin-like growth factor 1 (IGF-1) and by a related hormone called IGF-2. It ...
(IGF-1R).
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
DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for DNA#Base pairing, single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove ...
. One example is
serum response factor
Serum response factor, also known as SRF, is a transcription factor protein.
Function
Serum response factor is a member of the MADS (MCM1, Agamous, Deficiens, and SRF) box superfamily of transcription factors. This protein binds to the serum ...
, a protein that activates several genes that cause muscle growth.
Androgen receptor is modified by
post-translational modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribos ...
through
acetylation, which directly promotes AR-mediated
transactivation In the context of gene regulation: transactivation is the increased rate of gene expression triggered either by biological processes or by artificial means, through the expression of an intermediate transactivator protein.
In the context of recep ...
,
apoptosis and contact-independent growth of
prostate cancer cells. AR acetylation is induced by androgens and determines recruitment into
chromatin
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
. The AR acetylation site is a key target of
NAD-dependent and
TSA-dependent
histone deacetylases
Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around his ...
and
long non-coding RNA
Long non-coding RNAs (long ncRNAs, lncRNA) are a type of RNA, generally defined as transcripts more than 200 nucleotides that are not translated into protein. This arbitrary limit distinguishes long ncRNAs from small non-coding RNAs, such as mi ...
.
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 receptor
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...
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.
Genetics
Gene
In humans, the androgen receptor is encoded by the ''AR''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
located on the
X chromosome
The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex ...
at Xq11–12.
Deficiencies
At least 165 disease-causing mutations in this gene have been discovered.
The
androgen insensitivity syndrome
Androgen insensitivity syndrome (AIS) is a difference in sex development involving hormonal resistance due to androgen receptor dysfunction.
It affects 1 in 20,000 to 64,000 XY ( karyotypically male) births. The condition results in the partial ...
, formerly known as testicular feminization, is caused by a mutation in the androgen receptor gene on the
X chromosome
The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex ...
(locus: Xq11–Xq12).
The androgen receptor seems to affect neuron physiology and is defective in
Kennedy's disease.
In addition,
point mutations
A point mutation is a genetic mutation where a single nucleotide base is changed, inserted or deleted from a DNA or RNA sequence of an organism's genome. Point mutations have a variety of effects on the downstream protein product—consequence ...
and
trinucleotide repeat polymorphisms have been linked to a number of additional disorders.
CAG repeats
The AR gene contains
CAG repeats that affect receptor function, where fewer repeats leads to increased receptor sensitivity to circulating androgens and more repeats leads to decreased receptor sensitivity. Studies have shown that racial variation in CAG repeats exists,
with African-Americans having fewer repeats than non-Hispanic white Americans.
The racial trends in CAG repeats parallels the incidence and mortality of prostate cancer in these groups.
Structure
Isoforms
Two
isoforms
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some iso ...
of the androgen receptor (A and B) have been identified:
* AR-A – 87
kDa
The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...
;
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
In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...
-activated transcriptional activity
** activation function 5 (AF-5) between residues 360–485 is responsible for the
constitutive activity
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a recepto ...
(activity without bound ligand)
** dimerization surface involving residues 1–36 (containing the FXXLF motif; where F =
phenylalanine, L =
leucine
Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α- amino group (which is in the protonated −NH3+ form under biological conditions), an α- ...
, and X = any amino acid residue) and 370–494, both of which interact with the ligand binding domain (LBD) in an intramolecular
head-to-tail interaction
* C) –
DNA binding domain
A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a genera ...
(DBD)
* D) – Hinge region; flexible region that connects the DBD with the LBD; along with the DBD, contains a ligand dependent
nuclear localization signal A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that '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 o ...
* E) – Ligand 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
intramolecularly or
coactivator
A coactivator is a type of transcriptional coregulator that binds to an activator (a transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA ...
proteins (containing the LXXLL or preferably FXXFL motifs)
** A ligand dependent
nuclear export signal
* F) –
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
domain
Splice variants
AR-V7 is an androgen receptor
splice variant
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be in ...
that can be detected in
circulating tumor cells of metastatic
prostate cancer patients
and is predictive of resistance to some drugs.
Clinical significance
High expression in androgen receptor has been linked to aggression and sex drive by affecting the HPA and HPG axis
Aberrant androgen receptor
coregulator activity may contribute to the progression of
prostate cancer.
Ligands
Agonists
*
Endogenous androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
s (e.g.,
testosterone
Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...
,
dihydrotestosterone
Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues includ ...
,
androstenedione,
androstenediol
Androstenediol, or 5-androstenediol (abbreviated as A5 or Δ5-diol), also known as androst-5-ene-3β,17β-diol, is an endogenous weak androgen and estrogen steroid hormone and intermediate in the biosynthesis of testosterone from dehydroepia ...
,
dehydroepiandrosterone
Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It fun ...
)
*
Synthetic androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
s (e.g.,
methyltestosterone,
metandienone
Metandienone, also known as methandienone or methandrostenolone and sold under the brand name Dianabol (D-Bol) among others, is an androgen and anabolic steroid (AAS) medication which is still quite often used because of its affordability and eff ...
,
nandrolone
Nandrolone, also known as 19-nortestosterone, is an androgen and anabolic steroid (AAS) which is used in the form of esters such as nandrolone decanoate (brand name Deca-Durabolin) and nandrolone phenylpropionate (brand name Durabolin). Nandrolon ...
,
trenbolone
Trenbolone is an androgen and anabolic steroid (AAS) of the nandrolone group which itself was never marketed. Trenbolone ester prodrugs, including trenbolone acetate (brand names Finajet, Finaplix, others) and trenbolone hexahydrobenzylcarbonate ...
,
oxandrolone
Oxandrolone, sold under the brand names Oxandrin and Anavar, among others, is an androgen and anabolic steroid (AAS) medication which is used to help promote weight gain in various situations, to help offset protein catabolism caused by long-ter ...
,
stanozolol
Stanozolol ( abbrev. Stz), sold under many brand names, is an androgen and anabolic steroid (AAS) medication derived from dihydrotestosterone (DHT). It is used to treat hereditary angioedema. It was developed by American pharmaceutical company W ...
)
Mixed
*
Selective androgen receptor modulator
Selective Androgen Receptor Modulators or SARMs are a class of androgen receptor ligands that maintain some of the desirable effects of androgens, such as preventing osteoporosis and muscle loss while reducing risks of developing prostate cance ...
s (e.g.,
andarine,
enobosarm
Enobosarm, also known as ostarine or MK-2866, is an investigational selective androgen receptor modulator (SARM) developed by GTx, Inc. for the treatment of conditions such as muscle wasting and osteoporosis, formerly under development by Merc ...
)
Antagonists
*
Steroidal antiandrogens (e.g.,
cyproterone acetate
Cyproterone acetate (CPA), sold alone under the brand name Androcur or with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the treatment of androgen-dependent condition ...
,
chlormadinone acetate
Chlormadinone acetate (CMA), sold under the brand names Belara, Gynorelle, Lutéran, and Prostal among others, is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy, as a component of menopausal hor ...
,
spironolactone
Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood press ...
,
oxendolone
Oxendolone, sold under the brand names Prostetin and Roxenone, is an antiandrogen and progestin medication which is used in Japan in the treatment of enlarged prostate. However, this use is controversial due to concerns about its clinical effic ...
)
*
Nonsteroidal antiandrogen
A nonsteroidal antiandrogen (NSAA) is an antiandrogen with a nonsteroidal chemical structure. They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the effects of androgens like ...
s (e.g.,
flutamide
Flutamide, sold under the brand name Eulexin among others, is a nonsteroidal antiandrogen (NSAA) which is used primarily to treat prostate cancer. It is also used in the treatment of androgen-dependent conditions like acne, excessive hair grow ...
,
nilutamide
Nilutamide, sold under the brand names Nilandron and Anandron, is a nonsteroidal antiandrogen (NSAA) which is used in the treatment of prostate cancer.https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020169s008lbl.pdf It has also been ...
,
bicalutamide
Bicalutamide, sold under the brand name Casodex among others, is an antiandrogen medication that is primarily used to treat prostate cancer. It is typically used together with a gonadotropin-releasing hormone (GnRH) analogue or surgical remo ...
,
enzalutamide
Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castrat ...
,
apalutamide,
RU-58841
__NOTOC__
RU-58841, also known as PSK-3841 or HMR-3841, is a nonsteroidal antiandrogen (NSAA) which was initially developed in the 1980s by Roussel Uclaf, the French pharmaceutical company from which it received its name. It was formerly under in ...
)
*
N-Terminal domain antiandrogens (e.g.,
bisphenol A,
EPI-001,
ralaniten, JN compounds)
As a drug target
The AR is an important therapeutic target in
prostate cancer. Thus many different
antiandrogen
Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the ...
s have been developed, primarily targeting the
ligand-binding domain of the protein.
AR
ligands can either be classified based on their structure (
steroidal
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
or
nonsteroidal A nonsteroidal compound is a drug that is not a steroid nor a steroid derivative. Nonsteroidal anti-inflammatory drugs (NSAIDs) are distinguished from corticosteroids as a class of anti-inflammatory agents.
List of nonsteroidal steroid receptor mo ...
) or based on their ability to activate or inhibit transcription (
agonists
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agon ...
or
antagonists).
Inhibitors that target alternative functional domains (
N-terminal domain,
DNA-binding domain
A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a gener ...
) of the protein are still under development.
Interactions
Androgen receptor has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
AKT1
RAC(Rho family)-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the ''AKT1'' gene. This enzyme belongs to the AKT subfamily of serine/threonine kinases that contain SH2 (Src homology 2-like) protein domains. It ...
,
*
BAG1
BAG family molecular chaperone regulator 1 is a protein that in humans is encoded by the ''BAG1'' gene.
Function
The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The protei ...
,
*
Beta-catenin
Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcrip ...
,
* BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a ...
,
* C-jun,
* Calmodulin 1
Calmodulin 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 (calmodulin) proteins of which nearly 20 members have been found. They are identified by their ...
,
* Caveolin 1
Caveolin-1 is a protein that in humans is encoded by the ''CAV1'' gene.
Function
The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits ...
,
* CDK9
Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb.
Function
The protein encoded by this gene is a member of the cyclin-dependent kinase (CDK) family. CDK family members are highly similar to the gene produc ...
,
* COX5B,
* CREB-binding protein,
* Cyclin D1,
* Cyclin-dependent kinase 7
Cyclin-dependent kinase 7, or cell 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 (CDK) family. CDK family members are h ...
,
* DACH1
Dachshund homolog 1, also known as DACH1, is a protein which in humans is encoded by the ''DACH1'' gene. DACH1 has been shown to interact with Ubc9, Smad4, and NCoR.
Structure
Gene structure . This protein coding gene has 760 amino acid protei ...
,
* Death associated protein 6
Death-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 rece ...
,
* L-DOPA
-DOPA, also known as levodopa and -3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DOPA ...
,
* EFCAB6,
* Epidermal growth factor receptor
The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands.
The epidermal growth factor rece ...
,
* FOXO1,
* GAPDH
Glyceraldehyde 3-phosphate dehydrogenase (abbreviated GAPDH) () is an enzyme of about 37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. In addition to this long establishe ...
,
* Gelsolin
Gelsolin 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.
Cell ...
,
* GNB2L1
Receptor for activated C kinase 1 (RACK1), also known as guanine nucleotide-binding protein subunit beta-2-like 1 (GNB2L1), is a 35 kDa protein that in humans is encoded by the RACK1 gene.
Function
RACK1 was originally isolated and identified a ...
,
* GSK3B
Glycogen synthase kinase-3 beta, (GSK-3 beta), is an enzyme that in humans is encoded by the ''GSK3B'' gene. In mice, the enzyme is encoded by the Gsk3b gene. Abnormal regulation and expression of GSK-3 beta is associated with an increased suscept ...
,
* HDAC1
Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the ''HDAC1'' gene.
Function
Histone acetylation and deacetylation, catalyzed by multisubunit complexes, play a key role in the regulation of eukaryotic gene expression. Th ...
,
* HSP90AA1,
* HTATIP
Histone acetyltransferase KAT5 is an enzyme that in humans is encoded by the ''KAT5'' gene. It is also commonly identified as TIP60.
The protein encoded by this gene belongs to the MYST family of histone acetyl transferases (HATs) and was origina ...
,[
* ]MAGEA11
Melanoma-associated antigen 11 is a protein that in humans is encoded by the ''MAGEA11'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generat ...
,
* MED1
Mediator of RNA polymerase II transcription subunit 1 also known as DRIP205 or Trap220 is a subunit of the Mediator complex and is a protein that in humans is encoded by the ''MED1'' gene. MED1 functions as a nuclear receptor coactivator.
Fun ...
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* MYST2
Histone acetyltransferase KAT7 is an enzyme that in humans is encoded by the ''KAT7'' gene. It specifically acetylates H4 histones at the lysine12 residue (H4K12) and is necessary for origin licensing and DNA replication. KAT7 associates with o ...
,
* NCOA1,
* NCOA2,
* NCOA3,
* NCOA4,
* NCOA6
Nuclear receptor coactivator 6 is a protein that in humans is encoded by the ''NCOA6'' gene.
Function
The protein encoded by this gene is a transcriptional coactivator that can interact with nuclear hormone receptors to enhance their transcrip ...
,
* NCOR2,
* NONO
Nono may refer to:
Places
* Nono, Argentina, a municipality in the Province of Córdoba
* Nono, Ecuador, a parish in the municipality of Quito in the province of Pichincha
* Nono, Illubabor, Oromia (woreda), Ethiopia, or Nono Sele
** Nono, Illub ...
,[
* p300,]
* PA2G4,
* PAK6
Serine/threonine-protein kinase PAK 6 is an enzyme that in humans is encoded by the ''PAK6'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''gene ...
,
* PATZ1
POZ-, AT hook-, and zinc finger-containing protein 1 is a protein that in humans is encoded by the ''PATZ1'' gene.
Function
The protein encoded by this gene contains an AT-hook DNA binding motif, which usually binds to other DNA binding struct ...
,
* PIAS2
E3 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
SUMO-conjugat ...
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* PRPF6,
* PTEN,
* RAD9A
Cell cycle checkpoint control protein RAD9A is a protein that in humans is encoded by the ''RAD9A'' gene.''Rad9'' has been shown to induce G2 arrest in the cell cycle in response to DNA damage in yeast cells. ''Rad9'' was originally found in buddin ...
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* RANBP9,
* RCHY1,
* Retinoblastoma protein
The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated ''Rb'', ''RB'' or ''RB1'') is a proto-oncogenic tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive ...
,
* RNF14,
* RNF4,
* SART3
Squamous 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. This antigen possesses tu ...
,
* SIRT1
Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene.
SIRT1 stands for sirtuin (silent mating type information regulation 2 homolog) 1 ('' S. cerevisiae''), referring to the fact ...
,
* SMAD3
Mothers 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. It acts as a mediator of the signals initiated by t ...
,
* Small heterodimer partner
The small heterodimer partner (SHP) also known as NR0B2 (nuclear receptor subfamily 0, group B, member 2) is a protein that in humans is encoded by the ''NR0B2'' gene. SHP is a member of the nuclear receptor family of intracellular transcription ...
,
* Src,
* SRY,
* STAT3
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the ''STAT3'' gene. It is a member of the STAT protein family.
Function
STAT3 is a member of the STAT protein family. In respons ...
,
* SVIL,
* Testicular receptor 2,
* Testicular receptor 4
Testicular receptor 4 also known as NR2C2 (nuclear receptor subfamily 2, group C, member 2) 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 factor ...
,
* TGFB1I1
Transforming growth factor beta-1-induced transcript 1 protein is a protein that in humans is encoded by the ''TGFB1I1'' gene. Often put together with and studied alongside TGFB1I1 is the mouse homologue HIC-5 ( Hydrogen Peroxide-Inducible Clone ...
,
* TMF1,
* TRIM68,
* UBE2I
SUMO-conjugating enzyme UBC9 is an enzyme that in humans is encoded by the ''UBE2I'' gene. It is also sometimes referred to as "ubiquitin conjugating enzyme E2I" or "ubiquitin carrier protein 9", even though these names do not accurately describe ...
,
* UXT, and
* ZMIZ1.
See also
* Membrane androgen receptor Membrane androgen receptors (mARs) are a group of G protein-coupled receptors (GPCRs) which bind and are activated by testosterone and/or other androgens. Unlike the androgen receptor (AR), a nuclear receptor which mediates its effects via genomic m ...
* Discovery and development of antiandrogens
References
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
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{{DEFAULTSORT:Androgen Receptor
Genes on human chromosome X
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