Androgen receptor

Homo sapiensTaxon: 9606

3D-structureActivatorAlternative splicingCytoplasmDisease variantDNA-bindingIsopeptide bondLipid-bindingLipoproteinMetal-bindingNeurodegenerationNucleus+13

Sequence Length

920

amino acids

Molecular Weight

99.2 kDa

theoretical

Experimental Structures

PDB entries

Related Diseases

recorded

Function

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 Lacks the C-terminal ligand-binding domain and therefore constitutively regulates the transcription of a specific set of canonical AR-target genes, including PSA/KLK3 and TMPRSS2, independently of steroid hormones (PubMed:19244107, PubMed:25008967). However, some genes are differentially regulated by full-length AR (isoform 1) and isoform 3. Isoform 3-specific target genes may be regulated independently of FOXA1 expression (PubMed:25008967) Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones

Localization & Distribution

Tissue Specificity

Expressed in basal and stromal cells of the prostate (at protein level)

Related Diseases

Androgen insensitivity syndrome

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

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.

Prostate cancer, hereditary, X-linked 3

A condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma.

Androgen insensitivity, partial

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

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.

Amino Acid Sequence

MEVQLGLGRVYPRPPSKTYRGAFQNLFQSVREVIQNPGPRHPEAASAAPPGASLLLLQQQ
QQQQQQQQQQQQQQQQQQQQETSPRQQQQQQGEDGSPQAHRRGPTGYLVLDEEQQPSQPQ
SALECHPERGCVPEPGAAVAASKGLPQQLPAPPDEDDSAAPSTLSLLGPTFPGLSSCSAD
LKDILSEASTMQLLQQQQQEAVSEGSSSGRAREASGAPTSSKDNYLGGTSTISDNAKELC

FASTA format · 920 amino acids · mass 99.2 kDa

Experimental Structures

50 PDB entries

1E3G1GS41T5Z1T631T651XJ71XOW1XQ31Z952AM92AMA2AMB2AO62AX62AX72AX82AX92AXA2HVC2OZ72PIO2PIP2PIQ2PIR2PIT2PIU2PIV2PIW2PIX2PKL2PNU2Q7I2Q7J2Q7K2Q7L2YHD2YLO2YLP2YLQ2Z4J3B5R3B653B663B673B683BTR3L3X3L3Z3RLJ3RLL

Post-Translational Modifications

•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