Androgen receptor

Function

Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. 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. Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.

Classification

Family (Pfam)

PF02166 Androgen_recep, PF00104 Hormone_recep, PF00105 zf-C4

InterPro

Andrgn_rcpt, NHR-like_dom_sf, Nucl_hrmn_rcpt_lig-bd, Nuclear_hormone_rcpt_NR3, Znf_hrmn_rcpt, Znf_NHR/GATA

Functional cluster

Homeobox & Zinc-Finger Transcription Factors

Experimental structures · PDB · 94

• 1E3G X-ray 2.40A
• 1GS4 X-ray 1.95A
• 1T5Z X-ray 2.30A
• 1T63 X-ray 2.07A
• 1T65 X-ray 1.66A
• 1XJ7 X-ray 2.70A
• 1XOW X-ray 1.80A
• 1XQ3 X-ray 2.25A
• 1Z95 X-ray 1.80A
• 2AM9 X-ray 1.64A
• 2AMA X-ray 1.90A
• 2AMB X-ray 1.75A
• … and 82 more

A predicted model is available from AlphaFold.

Gene Ontology · 56

• GO:0000785 chromatin
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0016607 nuclear speck
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005886 plasma membrane
• GO:0032991 protein-containing complex
• GO:0005497 androgen binding
• GO:0051117 ATPase binding
• GO:0008013 beta-catenin binding
• GO:0003682 chromatin binding
• GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
• GO:0003700 DNA-binding transcription factor activity
• GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
• GO:0019899 enzyme binding
• GO:0034056 estrogen response element binding
• GO:0060090 molecular adaptor activity
• GO:0140693 molecular condensate scaffold activity
• GO:0004879 nuclear receptor activity
• GO:0003707 nuclear steroid receptor activity
• GO:0070974 POU domain binding
• GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
• GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding
• GO:0001091 RNA polymerase II general transcription initiation factor binding
• GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding
• GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
• GO:0005102 signaling receptor binding
• GO:0005496 steroid binding
• GO:0000976 transcription cis-regulatory region binding
• GO:0001223 transcription coactivator binding
• GO:0008270 zinc ion binding
• GO:0030521 androgen receptor signaling pathway
• GO:0007267 cell-cell signaling
• GO:0071391 cellular response to estrogen stimulus
• GO:0071383 cellular response to steroid hormone stimulus
• GO:0071394 cellular response to testosterone stimulus
• GO:0006351 DNA-templated transcription
• GO:0030520 estrogen receptor signaling pathway
• GO:0030522 intracellular receptor signaling pathway
• GO:0008584 male gonad development
• GO:0140694 membraneless organelle assembly
• GO:0008285 negative regulation of cell population proliferation
• GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0045597 positive regulation of cell differentiation
• GO:0008284 positive regulation of cell population proliferation
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0010628 positive regulation of gene expression
• GO:0045726 positive regulation of integrin biosynthetic process
• GO:1902895 positive regulation of miRNA transcription
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0045945 positive regulation of transcription by RNA polymerase III
• GO:1903076 regulation of protein localization to plasma membrane
• GO:0007165 signal transduction
• GO:0007283 spermatogenesis

Disease associations

• androgen insensitivity syndrome MONDO:0019154
• hypospadias 1, X-linked MONDO:0010384
• prostate cancer, hereditary, X-linked 3 MONDO:0971170
• partial androgen insensitivity syndrome MONDO:0010720
• Kennedy disease MONDO:0010735

Drugs targeting this protein · 39

• ENZALUTAMIDE antagonist
• TESTOSTERONE PROPIONATE agonist
• TESTOSTERONE ENANTHATE agonist
• NANDROLONE PHENPROPIONATE agonist
• OXANDROLONE agonist
• OXYMETHOLONE agonist
• ETHYLESTRENOL agonist
• NANDROLONE DECANOATE agonist
• DROMOSTANOLONE PROPIONATE agonist
• TESTOSTERONE CYPIONATE agonist
• NILUTAMIDE antagonist
• DIMETHYLCURCUMIN degrader
• METHYLTESTOSTERONE agonist
• CYPROTERONE ACETATE antagonist
• METHANDROSTENOLONE agonist
• FLUOXYMESTERONE agonist
• DANAZOL agonist
• ENOBOSARM modulator
• STANOZOLOL agonist
• GALETERONE antagonist
• TESTOSTERONE UNDECANOATE agonist
• GLPG0492 modulator
• AZD3514 modulator
• ABIRATERONE antagonist
• APALUTAMIDE antagonist
• MK-0773 modulator
• SEVITERONEL antagonist
• LY2452473 modulator
• HE3235 modulator
• CLASCOTERONE antagonist
• APC-100 antagonist
• TESTOSTERONE agonist
• BICALUTAMIDE antagonist
• DAROLUTAMIDE antagonist
• PRUXELUTAMIDE antagonist
• REZVILUTAMIDE antagonist
• LGD-2941 modulator
• VK5211 modulator
• FLUTAMIDE antagonist

Related proteins · sequence + function similarity

• Androgen receptor 1.00
• Androgen receptor 0.99
• Androgen receptor 0.99
• Androgen receptor 0.99
• Androgen receptor 0.98
• Androgen receptor 0.98
• Androgen receptor 0.97
• Androgen receptor 0.97
• Androgen receptor 0.96
• Androgen receptor 0.96
• Androgen receptor 0.93
• Progesterone receptor 0.88

Co-cited proteins · studied together in the literature

• Nuclear receptor coactivator 4 2 shared papers
• Ras-responsive element-binding protein 1 1 shared papers
• Serine/threonine-protein kinase PAK 6 1 shared papers
• Zinc finger MIZ domain-containing protein 1 1 shared papers
• SAM pointed domain-containing Ets transcription factor 1 shared papers
• Androgen receptor 1 shared papers
• Protein BUD31 homolog 1 shared papers
• Ubiquitin carboxyl-terminal hydrolase 26 1 shared papers
• RB-associated KRAB zinc finger protein 1 shared papers
• Activated CDC42 kinase 1 2 shared papers
• Androgen receptor 4 shared papers
• E3 ubiquitin-protein ligase RNF6 1 shared papers

Literature · 213 cited papers

• Shorter androgen receptor polyQ alleles protect against life-threatening COVID-19 disease in European males. EBioMedicine · 2021
• Analysis of protein-coding genetic variation in 60,706 humans. Nature · 2016
• Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis. Mol. Oncol. · 2014
• Androgen receptor and its splice variant, AR-V7, differentially regulate FOXA1 sensitive genes in LNCaP prostate cancer cells. Int. J. Biochem. Cell Biol. · 2014
• AR and SRD5A2 gene mutations in a series of 51 Turkish 46,XY DSD children with a clinical diagnosis of androgen insensitivity. Andrology · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• CCAR1 promotes chromatin loading of androgen receptor (AR) transcription complex by stabilizing the association between AR and GATA2. Nucleic Acids Res. · 2013
• ARID4A and ARID4B regulate male fertility, a functional link to the AR and RB pathways. Proc. Natl. Acad. Sci. U.S.A. · 2013
• RWDD1 interacts with the ligand binding domain of the androgen receptor and acts as a coactivator of androgen-dependent transactivation. Mol. Cell. Endocrinol. · 2012
• The androgen receptor gene mutations database: 2012 update. Hum. Mutat. · 2012
• Cryptochromes mediate rhythmic repression of the glucocorticoid receptor. Nature · 2011
• DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors. Mol. Biol. Cell · 2012
• … and 201 more in the literature graph