Receptor nomenclature | NR2B1 |
Receptor code | 4.10.1:AG:3:C4 |
Other names | AIS, DHTR, dihydrotestosterone receptor, HUMARA, KD, NR3C4, SBMA, SMAX1, TFM |
Molecular information | Hs: 919aa, P10275, chr. Xq111,2 |
Rn: 902aa, P15207, chr. Xq223 | |
Mm: 899aa, P19091, chr. X C34–6 | |
DNA binding | |
Structure | Homodimer |
HRE core sequence | GGTACANNNTGTTCT (GRE, palindrome) |
Partners | HSP90 (physical): cellular localization, specify protein stability7,8; HMGB (physical, functional): DNA binding9,10 |
Agonists | Mibolerone (1.65 nM),* DHT (2.23 nM), androstenedione (2.75 nM), methyltrienolone (3.07 nM),* testosterone (15.9 nM)* [IC50]2 |
Fluoxymesterone | |
Antagonists | Hydroxyflutamide, bicalutamide, nilutamide, mifepristone, cyproterone acetate |
Coactivators | RNF14, NCOA2, NCOA4, Fhl2, TGFB1I1, RAN11–24 |
Biologically important isoforms | AR-A {Hs}:187aa truncated from the N terminus25–28; AR-B {Hs}: 110 kDa25–28 |
Tissue distribution | Bone marrow, mammary gland, muscle, prostate, stem cells, testes, preputial gland, scrotal skin, vagina {Rn} [Western blot]29 |
Functional assay | Treatment of castrated rats with AR ligands possessing anabolic activity results in increased skeletal muscle mass {Rn}30; androgen treatment causes increased expression of sex hormone-binding globulin in the hepatocarcinoma cell line HepG2 {Hs}31; treatment of castrated rats with AR ligands possessing anabolic activity results in increased weight of prostate and seminal vesicles {Rn}30 |
Main target genes | Activated: PSA {Hs, Rn, Mm},32,33 probasin {Rn},34 Slp {Mm},35 prostatein C3 {Rn},36 SC {Hs}37,38 |
Mutant phenotype | Male mice lacking AR–/– exhibit insulin resistance and impaired glucose tolerance {Mm} [knockout]39–41; male mice lacking AR in Sertoli cells exhibit infertility with defective spermatogenesis and hypotestosteronemia {Mm} [knockout]42 |
Human disease | Prostate cancer: mutations of AR affecting ligand binding as well as gene amplification of AR have been described43; androgen insensitivity syndrome: mutations of AR affecting ligand binding, DNA binding or nuclear localization44,45; Kennedy's disease (poly-Q): spinobulbar muscular atrophy is an X-linked form of motor neuron disease characterized by progressive atrophy of the muscles, dysphagia, dysarthria, and mild androgen insensitivity caused by CAG repeat expansion in the AR gene46–48; Klinefelter's syndrome (47, XXY, hypogonadism): characterized by undeveloped testes and sterility, skewed inactivation of the X-chromosome seems to contribute to reduced AR expression49,50 |
aa, amino acids; chr., chromosome; HRE, hormone response element; DHT, dihydrotestosterone; GRE, glucocorticoid response element
↵* Radioligand
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