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

Binds DNA as a homodimer. Part of a ternary complex containing AR, EFCAB6/DJBP and PARK7. Interacts with HIPK3 and NR0B2 in the presence of androgen.

The ligand binding domain interacts with KAT7/HBO1 in the presence of dihydrotestosterone. Interacts with EFCAB6/DJBP, PQBP1, RANBP9, RBAK, SPDEF, SRA1, TGFB1I1 and RREB1. Interacts with ZMIZ1/ZIMP10 and ZMIZ2/ZMIP7 which both enhance its transactivation activity.

Interacts with SLC30A9 and RAD54L2/ARIP4. Interacts with MACROD1 (via macro domain) (PubMed:19022849). Interacts via the ligand-binding domain with LXXLL and FXXLF motifs from NCOA1, NCOA2, NCOA3 and MAGEA11.

Interacts (via nuclear receptor DNA binding domain and nuclear receptor ligand binding domain) with NCOA4 (PubMed:15563469, PubMed:8643607). The AR N-terminal poly-Gln region binds Ran resulting in enhancement of AR-mediated transactivation. Ran-binding decreases as the poly-Gln length increases.

Interacts with HIP1 (via coiled coil domain). Interacts (via ligand-binding domain) with TRIM68. Interacts with TNK2.

Interacts with USP26. Interacts with RNF6. Interacts (regulated by RNF6 probably through polyubiquitination) with RNF14; regulates AR transcriptional activity.

Interacts with PRMT2 and TRIM24. Interacts with RACK1. Interacts with RANBP10; this interaction enhances dihydrotestosterone-induced AR transcriptional activity.

Interacts with PRPF6 in a hormone-independent way; this interaction enhances dihydrotestosterone-induced AR transcriptional activity. Interacts with STK4/MST1. Interacts with ZIPK/DAPK3.

Interacts with LPXN. Interacts with MAK. Part of a complex containing AR, MAK and NCOA3.

Interacts with CRY1. Interacts with CCAR1 and GATA2. Interacts with ZNF318 (By similarity).

Interacts with BUD31 (PubMed:25091737). Interacts with ARID4A (PubMed:23487765). Interacts with ARID4B (By similarity).

Interacts (via NR LBD domain) with ZBTB7A; the interaction is direct and androgen-dependent (PubMed:20812024). Interacts with NCOR1 (PubMed:20812024). Interacts with NCOR2 (PubMed:20812024).

Interacts with CRY2 in a ligand-dependent manner (By similarity). Interacts (via NR LBD domain) with RWDD1; the interaction is direct and may stimulate AR activity (PubMed:22406838)

Mainly expressed in heart and skeletal muscle

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

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. In the presence of bound steroid the ligand-binding domain interacts with the N-terminal modulating domain, and thereby activates AR transcription factor activity. Agonist binding is required for dimerization and binding to target DNA.

The transcription factor activity of the complex formed by ligand-activated AR and DNA is modulated by interactions with coactivator and corepressor proteins (PubMed:25091737). Interaction with RANBP9 is mediated by both the N-terminal domain and the DNA-binding domain. Interaction with EFCAB6/DJBP is mediated by the DNA-binding domain

• 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)

  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 (HPCX3)

  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.

• Unknown disease
• 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.