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MGP000189

UniProt Annotations

Entry Information
Gene Nameandrogen receptor
Protein EntryANDR_HUMAN
UniProt IDP10275
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; Synonyms=AR-B; IsoId=P10275-1; Sequence=Displayed; Name=2; Synonyms=AR-A, Variant AR45; IsoId=P10275-2; Sequence=VSP_036889, VSP_036890;
DiseaseAndrogen insensitivity, partial (PAIS) [MIM:312300]: 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. {ECO:0000269|PubMed:10022458, ECO:0000269|PubMed:10221692, ECO:0000269|PubMed:10470409, ECO:0000269|PubMed:10502786, ECO:0000269|PubMed:10543676, ECO:0000269|PubMed:11587068, ECO:0000269|PubMed:1303262, ECO:0000269|PubMed:1307250, ECO:0000269|PubMed:1316540, ECO:0000269|PubMed:1424203, ECO:0000269|PubMed:1430233, ECO:0000269|PubMed:2010552, ECO:0000269|PubMed:7581399, ECO:0000269|PubMed:7649358, ECO:0000269|PubMed:7671849, ECO:0000269|PubMed:7909256, ECO:0000269|PubMed:7910529, ECO:0000269|PubMed:7929841, ECO:0000269|PubMed:7970939, ECO:0000269|PubMed:7981687, ECO:0000269|PubMed:8033918, ECO:0000269|PubMed:8097257, ECO:0000269|PubMed:8126121, ECO:0000269|PubMed:8205256, ECO:0000269|PubMed:8281139, ECO:0000269|PubMed:8325932, ECO:0000269|PubMed:8325950, ECO:0000269|PubMed:8446106, ECO:0000269|PubMed:8550758, ECO:0000269|PubMed:8809734, ECO:0000269|PubMed:8823308, ECO:0000269|PubMed:8824883, ECO:0000269|PubMed:9039340, ECO:0000269|PubMed:9196614, ECO:0000269|PubMed:9302173, ECO:0000269|PubMed:9329414, ECO:0000269|PubMed:9543136, ECO:0000269|PubMed:9607727, ECO:0000269|PubMed:9768671, ECO:0000269|PubMed:9856504, ECO:0000269|Ref.115}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseAndrogen insensitivity syndrome (AIS) [MIM:300068]: 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. {ECO:0000269|PubMed:10022458, ECO:0000269|PubMed:10221692, ECO:0000269|PubMed:10221770, ECO:0000269|PubMed:10404311, ECO:0000269|PubMed:10458483, ECO:0000269|PubMed:10571951, ECO:0000269|PubMed:10590024, ECO:0000269|PubMed:10690872, ECO:0000269|PubMed:11587068, ECO:0000269|PubMed:11744994, ECO:0000269|PubMed:1307250, ECO:0000269|PubMed:1316540, ECO:0000269|PubMed:1426313, ECO:0000269|PubMed:1430233, ECO:0000269|PubMed:1464650, ECO:0000269|PubMed:1480178, ECO:0000269|PubMed:1487249, ECO:0000269|PubMed:1569163, ECO:0000269|PubMed:1609793, ECO:0000269|PubMed:1775137, ECO:0000269|PubMed:1999491, ECO:0000269|PubMed:2082179, ECO:0000269|PubMed:2594783, ECO:0000269|PubMed:7537149, ECO:0000269|PubMed:7581399, ECO:0000269|PubMed:7633398, ECO:0000269|PubMed:7641413, ECO:0000269|PubMed:7671849, ECO:0000269|PubMed:7929841, ECO:0000269|PubMed:7962294, ECO:0000269|PubMed:7970939, ECO:0000269|PubMed:7981687, ECO:0000269|PubMed:7981689, ECO:0000269|PubMed:7993455, ECO:0000269|PubMed:8040309, ECO:0000269|PubMed:8096390, ECO:0000269|PubMed:8103398, ECO:0000269|PubMed:8162033, ECO:0000269|PubMed:8224266, ECO:0000269|PubMed:8281140, ECO:0000269|PubMed:8325950, ECO:0000269|PubMed:8413310, ECO:0000269|PubMed:8446106, ECO:0000269|PubMed:8626869, ECO:0000269|PubMed:8647313, ECO:0000269|PubMed:8683794, ECO:0000269|PubMed:8723113, ECO:0000269|PubMed:8768864, ECO:0000269|PubMed:8809734, ECO:0000269|PubMed:8830623, ECO:0000269|PubMed:8918984, ECO:0000269|PubMed:8990010, ECO:0000269|PubMed:9001799, ECO:0000269|PubMed:9007482, ECO:0000269|PubMed:9039340, ECO:0000269|PubMed:9106550, ECO:0000269|PubMed:9160185, ECO:0000269|PubMed:9252933, ECO:0000269|PubMed:9255042, ECO:0000269|PubMed:9302173, ECO:0000269|PubMed:9328206, ECO:0000269|PubMed:9544375, ECO:0000269|PubMed:9554754, ECO:0000269|PubMed:9610419, ECO:0000269|PubMed:9627582, ECO:0000269|PubMed:9698822, ECO:0000269|PubMed:9788719, ECO:0000269|PubMed:9851768, ECO:0000269|PubMed:9856504, ECO:0000269|Ref.107, ECO:0000269|Ref.173}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseNote=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.
DiseaseSpinal and bulbar muscular atrophy X-linked 1 (SMAX1) [MIM:313200]: 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. {ECO:0000269|PubMed:15851746}. Note=The disease is caused by mutations 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.
DomainComposed 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. 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.
Enzyme RegulationAIM-100 (4-amino-5,6-biaryl-furo[2,3- d]pyrimidine) suppresses TNK2-mediated phosphorylation at Tyr-267. Inhibits the binding of the Tyr-267 phosphorylated form to androgen-responsive enhancers (AREs) and its transcriptional activity. {ECO:0000269|PubMed:20623637}.
FunctionSteroid 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. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3. {ECO:0000269|PubMed:14664718, ECO:0000269|PubMed:15563469, ECO:0000269|PubMed:17591767, ECO:0000269|PubMed:17911242, ECO:0000269|PubMed:18084323, ECO:0000269|PubMed:19345326, ECO:0000269|PubMed:20980437}.
InteractionP00519:ABL1; NbExp=2; IntAct=EBI-608057, EBI-375543; P51451:BLK; NbExp=3; IntAct=EBI-608057, EBI-2105445; Q8WV28:BLNK; NbExp=2; IntAct=EBI-608057, EBI-2623522; P78543:BTG2; NbExp=4; IntAct=EBI-608057, EBI-1047576; O89110:Casp8 (xeno); NbExp=2; IntAct=EBI-608057, EBI-851690; Q92793:CREBBP; NbExp=2; IntAct=EBI-608057, EBI-81215; O14595:CTDSP2; NbExp=3; IntAct=EBI-608057, EBI-2802973; P35222:CTNNB1; NbExp=8; IntAct=EBI-608057, EBI-491549; Q9UER7:DAXX; NbExp=5; IntAct=EBI-608057, EBI-77321; P20711:DDC; NbExp=2; IntAct=EBI-608057, EBI-1632155; P11308:ERG; NbExp=3; IntAct=EBI-608057, EBI-79704; P07332:FES; NbExp=3; IntAct=EBI-608057, EBI-1055635; P09769:FGR; NbExp=3; IntAct=EBI-608057, EBI-1383732; O75593:FOXH1; NbExp=3; IntAct=EBI-608057, EBI-1759806; Q9R1E0:Foxo1 (xeno); NbExp=4; IntAct=EBI-608057, EBI-1371343; Q14451:GRB7; NbExp=3; IntAct=EBI-608057, EBI-970191; P56524:HDAC4; NbExp=4; IntAct=EBI-608057, EBI-308629; Q16665:HIF1A; NbExp=2; IntAct=EBI-608057, EBI-447269; Q16666:IFI16; NbExp=3; IntAct=EBI-608057, EBI-2867186; O15357:INPPL1; NbExp=3; IntAct=EBI-608057, EBI-1384248; Q15652:JMJD1C; NbExp=2; IntAct=EBI-608057, EBI-1224969; O95251:KAT7; NbExp=5; IntAct=EBI-608057, EBI-473199; P07288:KLK3; NbExp=3; IntAct=EBI-608057, EBI-1220791; P06239:LCK; NbExp=7; IntAct=EBI-608057, EBI-1348; P07948:LYN; NbExp=5; IntAct=EBI-608057, EBI-79452; P20794:MAK; NbExp=5; IntAct=EBI-608057, EBI-3911321; P42679:MATK; NbExp=4; IntAct=EBI-608057, EBI-751664; Q00987:MDM2; NbExp=2; IntAct=EBI-608057, EBI-389668; Q15596:NCOA2; NbExp=2; IntAct=EBI-608057, EBI-81236; Q14686:NCOA6; NbExp=2; IntAct=EBI-608057, EBI-78670; Q99497:PARK7; NbExp=6; IntAct=EBI-608057, EBI-1164361; P27986:PIK3R1; NbExp=5; IntAct=EBI-608057, EBI-79464; O00459:PIK3R2; NbExp=14; IntAct=EBI-608057, EBI-346930; Q92569:PIK3R3; NbExp=37; IntAct=EBI-608057, EBI-79893; P19174:PLCG1; NbExp=22; IntAct=EBI-608057, EBI-79387; P16885:PLCG2; NbExp=6; IntAct=EBI-608057, EBI-617403; Q06830:PRDX1; NbExp=3; IntAct=EBI-608057, EBI-353193; Q06124:PTPN11; NbExp=12; IntAct=EBI-608057, EBI-297779; P20936:RASA1; NbExp=16; IntAct=EBI-608057, EBI-1026476; Q9UBS8:RNF14; NbExp=2; IntAct=EBI-608057, EBI-2130308; Q9Y252:RNF6; NbExp=10; IntAct=EBI-608057, EBI-2341483; O14796:SH2D1B; NbExp=3; IntAct=EBI-608057, EBI-3923013; Q9NP31:SH2D2A; NbExp=6; IntAct=EBI-608057, EBI-490630; P29353:SHC1; NbExp=14; IntAct=EBI-608057, EBI-78835; Q6S5L8:SHC4; NbExp=3; IntAct=EBI-608057, EBI-9453524; Q5VZ18:SHE; NbExp=3; IntAct=EBI-608057, EBI-3956977; Q06986:Siah2 (xeno); NbExp=6; IntAct=EBI-608057, EBI-957413; Q15797:SMAD1; NbExp=6; IntAct=EBI-608057, EBI-1567153; O14544:SOCS6; NbExp=4; IntAct=EBI-608057, EBI-3929549; P12931:SRC; NbExp=7; IntAct=EBI-608057, EBI-621482; Q9ULZ2:STAP1; NbExp=2; IntAct=EBI-608057, EBI-6083058; P63165:SUMO1; NbExp=7; IntAct=EBI-608057, EBI-80140; Q9HBL0:TNS1; NbExp=3; IntAct=EBI-608057, EBI-3389814; O96028:WHSC1; NbExp=5; IntAct=EBI-608057, EBI-2693298; P07947:YES1; NbExp=5; IntAct=EBI-608057, EBI-515331;
MiscellaneousIn the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity. The hormone- receptor complex appears to recognize discrete DNA sequences upstream of transcriptional start sites.
MiscellaneousThe level of tyrosine phosphorylation may serve as a diagnostic tool to predict patient outcome in response to hormone-ablation therapy. Inhibition of tyrosine phosphorylation may be an effective intervention target for hormone-refractory prostate cancer.
MiscellaneousTranscriptional activity is enhanced by binding to RANBP9.
PolymorphismThe poly-Gln region of AR is highly polymorphic and the number of Gln varies in the population (from 17 to 26). A smaller size of the poly-Gln region may be associated with the development of prostate cancer.
PolymorphismThe poly-Gly region of AR is polymorphic and ranges from 24 to 31 Gly. A poly-Gly region shorter or equal to 23 may be associated with the development of androgenetic alopecia.
PtmPalmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation. {ECO:0000269|PubMed:22031296}.
PtmPhosphorylated in prostate cancer cells in response to several growth factors including EGF. Phosphorylation is induced by c-Src kinase (CSK). Tyr-534 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-81 by CDK9 regulates AR promoter selectivity and cell growth. Phosphorylation by PAK6 leads to AR- mediated transcription inhibition. {ECO:0000269|PubMed:14573606, ECO:0000269|PubMed:17045208, ECO:0000269|PubMed:17494760, ECO:0000269|PubMed:20623637, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:21406692, ECO:0000269|PubMed:21512132}.
PtmSumoylated on Lys-386 (major) and Lys-520. Ubiquitinated. Deubiquitinated by USP26. 'Lys-6' and 'Lys-27'-linked polyubiquitination by RNF6 modulates AR transcriptional activity and specificity. {ECO:0000269|PubMed:11121022, ECO:0000269|PubMed:19345326, ECO:0000269|PubMed:20501646}.
SimilarityBelongs to the nuclear hormone receptor family. NR3 subfamily. {ECO:0000305}.
SimilarityContains 1 nuclear receptor DNA-binding domain. {ECO:0000255|PROSITE-ProRule:PRU00407}.
Subcellular LocationNucleus. Cytoplasm. Note=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 GNB2L1.
SubunitBinds 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, PELP1, PQBP1, RANBP9, RBAK, SPDEF, SRA1, TGFB1I1, ZNF318 and RREB1. Interacts with ZMIZ1/ZIMP10 and ZMIZ2/ZMIP7 which both enhance its transactivation activity. Interacts with SLC30A9 and RAD54L2/ARIP4. Interacts via the ligand-binding domain with LXXLL and FXXLF motifs from NCOA1, NCOA2, NCOA3, NCOA4 and MAGEA11. 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 GNB2L1/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. {ECO:0000269|PubMed:10075738, ECO:0000269|PubMed:10332029, ECO:0000269|PubMed:10383460, ECO:0000269|PubMed:10400640, ECO:0000269|PubMed:10625666, ECO:0000269|PubMed:10930412, ECO:0000269|PubMed:12039962, ECO:0000269|PubMed:12361945, ECO:0000269|PubMed:12415108, ECO:0000269|PubMed:12612053, ECO:0000269|PubMed:12958311, ECO:0000269|PubMed:14609956, ECO:0000269|PubMed:14664718, ECO:0000269|PubMed:15525515, ECO:0000269|PubMed:15563469, ECO:0000269|PubMed:16027218, ECO:0000269|PubMed:16051670, ECO:0000269|PubMed:16951154, ECO:0000269|PubMed:17311914, ECO:0000269|PubMed:17494760, ECO:0000269|PubMed:17550981, ECO:0000269|PubMed:17587566, ECO:0000269|PubMed:17591767, ECO:0000269|PubMed:17711855, ECO:0000269|PubMed:17911242, ECO:0000269|PubMed:18007036, ECO:0000269|PubMed:18084323, ECO:0000269|PubMed:18222118, ECO:0000269|PubMed:18451096, ECO:0000269|PubMed:18451177, ECO:0000269|PubMed:19345326, ECO:0000269|PubMed:19909775, ECO:0000269|PubMed:20501646, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:21512132, ECO:0000269|PubMed:22170608}.
Tissue SpecificityIsoform 2 is mainly expressed in heart and skeletal muscle. {ECO:0000269|PubMed:15634333}.
Web ResourceName=Androgen receptor gene mutations database; URL="http://androgendb.mcgill.ca";
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ARID685chXq12.html";
Web ResourceName=Wikipedia; Note=Androgen receptor entry; URL="http://en.wikipedia.org/wiki/Androgen_receptor";
Web ResourceName=X-chromosome gene database, androgen receptor (AR); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/AR";
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