AR

The androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]

Androgen Receptor

Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).
Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024).
Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Isoform 3: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones.
Isoform 4: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones.

Activation of prostate induction by androgen receptor signaling pathway Source: Ensembl
Androgen receptor signaling pathway Source: UniProtKB
Animal organ formation Source: Ensembl
Cell-cell signaling Source: ProtInc
Cellular response to estrogen stimulus Source: ARUK-UCL
Cellular response to steroid hormone stimulus Source: CAFA
Cellular response to testosterone stimulus Source: ARUK-UCL
Epithelial cell differentiation involved in prostate gland development Source: Ensembl
Epithelial cell morphogenesis Source: Ensembl
Intracellular estrogen receptor signaling pathway Source: ARUK-UCL
Intracellular receptor signaling pathway Source: BHF-UCL
Intracellular steroid hormone receptor signaling pathway Source: GO_Central
In utero embryonic development Source: Ensembl
Lateral sprouting involved in mammary gland duct morphogenesis Source: Ensembl
Leydig cell differentiation Source: Ensembl
Male genitalia morphogenesis Source: Ensembl
Male gonad development Source: GO_Central
Male somatic sex determination Source: Ensembl
Mammary gland alveolus development Source: Ensembl
Morphogenesis of an epithelial fold Source: Ensembl
Multicellular organism growth Source: Ensembl
Negative regulation of cell population proliferation Source: UniProtKB
Negative regulation of epithelial cell proliferation Source: Ensembl
Negative regulation of extrinsic apoptotic signaling pathway Source: BHF-UCL
Negative regulation of integrin biosynthetic process Source: BHF-UCL
Negative regulation of transcription by RNA polymerase II Source: CAFA
Positive regulation of cell differentiation Source: UniProtKB
Positive regulation of cell population proliferation Source: BHF-UCL
Positive regulation of epithelial cell proliferation involved in prostate gland development Source: Ensembl
Positive regulation of gene expression Source: UniProtKB
Positive regulation of insulin-like growth factor receptor signaling pathway Source: Ensembl
Positive regulation of integrin biosynthetic process Source: BHF-UCL
Positive regulation of intracellular estrogen receptor signaling pathway Source: Ensembl
Positive regulation of MAPK cascade Source: Ensembl
Positive regulation of NF-kappaB transcription factor activity Source: BHF-UCL
Positive regulation of phosphorylation Source: BHF-UCL
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of transcription by RNA polymerase III Source: BHF-UCL
Prostate gland epithelium morphogenesis Source: Ensembl
Prostate gland growth Source: Ensembl
Protein deubiquitination Source: Reactome
Regulation of androgen receptor signaling pathway Source: Reactome
Regulation of developmental growth Source: Ensembl
Regulation of protein localization to plasma membrane Source: BHF-UCL
Regulation of systemic arterial blood pressure Source: Ensembl
Regulation of transcription by RNA polymerase II Source: GO_Central
Seminiferous tubule development Source: Ensembl
Signal transduction Source: ProtInc
Single fertilization Source: Ensembl
Spermatogenesis Source: Ensembl
Tertiary branching involved in mammary gland duct morphogenesis Source: Ensembl
Transcription initiation from RNA polymerase II promoter Source: Reactome

Cytoplasm; Nucleus. Detected at the promoter of target genes (PubMed:25091737). Predominantly cytoplasmic in unligated form but translocates to the nucleus upon ligand-binding. Can also translocate to the nucleus in unligated form in the presence of RACK1.

Androgen insensitivity syndrome (AIS): An X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype.
Spinal and bulbar muscular atrophy X-linked 1 (SMAX1): The disease is caused by variants affecting the gene represented in this entry. Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease. An X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor.
Androgen insensitivity, partial (PAIS): A disorder that is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations.
Hypospadias 1, X-linked (HYSP1): A common malformation in which the urethra opens on the ventral side of the penis, due to developmental arrest of urethral fusion. The opening can be located glandular, penile, or even more posterior in the scrotum or perineum. Hypospadias is a feature of several syndromic disorders, including the androgen insensitivity syndrome and Opitz syndrome.

Sumoylated on Lys-388 (major) and Lys-521. Ubiquitinated. Deubiquitinated by USP26. 'Lys-6' and 'Lys-27'-linked polyubiquitination by RNF6 modulates AR transcriptional activity and specificity.
Phosphorylated in prostate cancer cells in response to several growth factors including EGF. Phosphorylation is induced by c-Src kinase (CSK). Tyr-535 is one of the major phosphorylation sites and an increase in phosphorylation and Src kinase activity is associated with prostate cancer progression. Phosphorylation by TNK2 enhances the DNA-binding and transcriptional activity and may be responsible for androgen-independent progression of prostate cancer. Phosphorylation at Ser-83 by CDK9 regulates AR promoter selectivity and cell growth. Phosphorylation by PAK6 leads to AR-mediated transcription inhibition.
Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation.