Gene/Proteome Database (LMPD)

LMPD ID
LMP006676
Gene ID
367
Species
Homo sapiens (Human)
Gene Name
androgen receptor
Gene Symbol
AR
Synonyms
AIS; DHTR; HUMARA; HYSP1; KD; NR3C4; SBMA; SMAX1; TFM
Chromosome
X
Map Location
Xq12
Summary
The androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract causes spinal bulbar muscular atrophy (Kennedy disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Two alternatively spliced variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
Orthologs
View orthologs and multiple alignments for AR

Proteins

androgen receptor isoform 1
Refseq ID NP_000035
Protein GI 21322252
UniProt ID P10275
mRNA ID NM_000044
Length 920
RefSeq Status REVIEWED
MEVQLGLGRVYPRPPSKTYRGAFQNLFQSVREVIQNPGPRHPEAASAAPPGASLLLLQQQQQQQQQQQQQQQQQQQQQQQETSPRQQQQQQGEDGSPQAHRRGPTGYLVLDEEQQPSQPQSALECHPERGCVPEPGAAVAASKGLPQQLPAPPDEDDSAAPSTLSLLGPTFPGLSSCSADLKDILSEASTMQLLQQQQQEAVSEGSSSGRAREASGAPTSSKDNYLGGTSTISDNAKELCKAVSVSMGLGVEALEHLSPGEQLRGDCMYAPLLGVPPAVRPTPCAPLAECKGSLLDDSAGKSTEDTAEYSPFKGGYTKGLEGESLGCSGSAAAGSSGTLELPSTLSLYKSGALDEAAAYQSRDYYNFPLALAGPPPPPPPPHPHARIKLENPLDYGSAWAAAAAQCRYGDLASLHGAGAAGPGSGSPSAAASSSWHTLFTAEEGQLYGPCGGGGGGGGGGGGGGGGGGGGGGGEAGAVAPYGYTRPPQGLAGQESDFTAPDVWYPGGMVSRVPYPSPTCVKSEMGPWMDSYSGPYGDMRLETARDHVLPIDYYFPPQKTCLICGDEASGCHYGALTCGSCKVFFKRAAEGKQKYLCASRNDCTIDKFRRKNCPSCRLRKCYEAGMTLGARKLKKLGNLKLQEEGEASSTTSPTEETTQKLTVSHIEGYECQPIFLNVLEAIEPGVVCAGHDNNQPDSFAALLSSLNELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNVNSRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEFGWLQITPQEFLCMKALLLFSIIPVDGLKNQKFFDELRMNYIKELDRIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAEIISVQVPKILSGKVKPIYFHTQ
androgen receptor isoform 2
Refseq ID NP_001011645
Protein GI 58535455
UniProt ID P10275
mRNA ID NM_001011645
Length 388
RefSeq Status REVIEWED
MILWLHSLETARDHVLPIDYYFPPQKTCLICGDEASGCHYGALTCGSCKVFFKRAAEGKQKYLCASRNDCTIDKFRRKNCPSCRLRKCYEAGMTLGARKLKKLGNLKLQEEGEASSTTSPTEETTQKLTVSHIEGYECQPIFLNVLEAIEPGVVCAGHDNNQPDSFAALLSSLNELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNVNSRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEFGWLQITPQEFLCMKALLLFSIIPVDGLKNQKFFDELRMNYIKELDRIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAEIISVQVPKILSGKVKPIYFHTQ

Gene Information

Entrez Gene ID
367
Gene Name
androgen receptor
Gene Symbol
AR
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005737 IDA:UniProtKB C cytoplasm
GO:0000790 IDA:BHF-UCL C nuclear chromatin
GO:0005654 TAS:Reactome C nucleoplasm
GO:0005634 IDA:UniProtKB C nucleus
GO:0043234 IDA:MGI C protein complex
GO:0003677 NAS:UniProtKB F DNA binding
GO:0000978 IDA:NTNU_SB F RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0001077 IDA:NTNU_SB F RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0001085 IPI:BHF-UCL F RNA polymerase II transcription factor binding
GO:0005497 NAS:UniProtKB F androgen binding
GO:0004882 IDA:UniProtKB F androgen receptor activity
GO:0008013 IDA:BHF-UCL F beta-catenin binding
GO:0003682 IDA:UniProtKB F chromatin binding
GO:0019899 IPI:UniProtKB F enzyme binding
GO:0004879 IDA:BHF-UCL F ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity
GO:0046983 NAS:UniProtKB F protein dimerization activity
GO:0005102 IPI:UniProtKB F receptor binding
GO:0003700 IDA:UniProtKB F sequence-specific DNA binding transcription factor activity
GO:0008134 IPI:BHF-UCL F transcription factor binding
GO:0044212 IDA:UniProtKB F transcription regulatory region DNA binding
GO:0008270 IEA:InterPro F zinc ion binding
GO:0030521 IDA:UniProtKB P androgen receptor signaling pathway
GO:0008219 IEA:UniProtKB-KW P cell death
GO:0016049 NAS:UniProtKB P cell growth
GO:0008283 NAS:UniProtKB P cell proliferation
GO:0007267 TAS:ProtInc P cell-cell signaling
GO:0010467 TAS:Reactome P gene expression
GO:0030522 IDA:BHF-UCL P intracellular receptor signaling pathway
GO:2001237 IDA:BHF-UCL P negative regulation of extrinsic apoptotic signaling pathway
GO:0045720 IDA:BHF-UCL P negative regulation of integrin biosynthetic process
GO:0051092 IMP:BHF-UCL P positive regulation of NF-kappaB transcription factor activity
GO:0008284 IDA:BHF-UCL P positive regulation of cell proliferation
GO:0045726 IDA:BHF-UCL P positive regulation of integrin biosynthetic process
GO:0042327 IMP:BHF-UCL P positive regulation of phosphorylation
GO:0045944 IDA:UniProtKB P positive regulation of transcription from RNA polymerase II promoter
GO:0045945 IDA:BHF-UCL P positive regulation of transcription from RNA polymerase III promoter
GO:0045893 IDA:UniProtKB P positive regulation of transcription, DNA-templated
GO:0030850 NAS:UniProtKB P prostate gland development
GO:0051259 IDA:MGI P protein oligomerization
GO:0090003 IDA:BHF-UCL P regulation of establishment of protein localization to plasma membrane
GO:0007548 NAS:UniProtKB P sex differentiation
GO:0007165 TAS:ProtInc P signal transduction
GO:0006367 TAS:Reactome P transcription initiation from RNA polymerase II promoter
GO:0006351 IDA:UniProtKB P transcription, DNA-templated
GO:0006810 TAS:ProtInc P transport

KEGG Pathway Links

KEGG Pathway ID Description
hsa04114 Oocyte meiosis

Domain Information

InterPro Annotations

Accession Description
IPR001103 Androgen receptor
IPR008946 Nuclear hormone receptor, ligand-binding
IPR000536 Nuclear hormone receptor, ligand-binding, core
IPR013088 Zinc finger, NHR/GATA-type
IPR001628 Zinc finger, nuclear hormone receptor-type

UniProt Annotations

Entry Information

Gene Name
androgen receptor
Protein Entry
ANDR_HUMAN
UniProt ID
P10275
Species
Human

Comments

Comment Type Description
Alternative Products Event=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;
Disease Androgen insensitivity syndrome (AIS) [MIM
Disease Androgen insensitivity, partial (PAIS) [MIM
Disease Note=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.
Disease Spinal and bulbar muscular atrophy X-linked 1 (SMAX1) [MIM
Domain 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. 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 Regulation AIM-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.
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. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3. {ECO
Interaction P00519: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;
Miscellaneous In 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.
Miscellaneous The 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.
Miscellaneous Transcriptional activity is enhanced by binding to RANBP9.
Polymorphism The 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.
Polymorphism The 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.
Ptm 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.
Ptm Phosphorylated 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
Ptm Sumoylated 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
Similarity Belongs to the nuclear hormone receptor family. NR3 subfamily.
Similarity Contains 1 nuclear receptor DNA-binding domain.
Subcellular Location Nucleus. 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.
Subunit 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, 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
Tissue Specificity Isoform 2 is mainly expressed in heart and skeletal muscle.
Web Resource Name=Androgen receptor gene mutations database; URL="http://androgendb.mcgill.ca";
Web Resource Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ARID685chXq12.html";
Web Resource Name=Wikipedia; Note=Androgen receptor entry; URL="http://en.wikipedia.org/wiki/Androgen_receptor";
Web Resource Name=X-chromosome gene database, androgen receptor (AR); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/AR";

Identical and Related Proteins

Unique RefSeq proteins for LMP006676 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
21322252 RefSeq NP_000035 920 androgen receptor isoform 1
58535455 RefSeq NP_001011645 388 androgen receptor isoform 2

Identical Sequences to LMP006676 proteins

Reference Database Accession Length Protein Name
GI:58535455 EMBL CAH89502.1 388 hypothetical protein [Pongo abelii]
GI:21322252 EMBL CCV20035.1 920 unnamed protein product [Homo sapiens]
GI:58535455 GenBank ADZ17334.1 388 androgen nuclear receptor variant 2 [Homo sapiens]
GI:21322252 GenBank AFD45320.1 920 Sequence 28 from patent US 8129125
GI:21322252 GenBank AFL33673.1 920 Sequence 55 from patent US 8173861
GI:21322252 GenBank AGN43277.1 920 Sequence 83 from patent US 8450290
GI:21322252 GenBank AGV97421.1 920 Sequence 2 from patent US 8513210
GI:21322252 GenBank AHD80469.1 920 Sequence 32815 from patent US 8586006
GI:58535455 GenBank AHD80470.1 388 Sequence 32816 from patent US 8586006
GI:58535455 RefSeq NP_001124649.1 388 androgen receptor [Pongo abelii]

Related Sequences to LMP006676 proteins

Reference Database Accession Length Protein Name
GI:58535455 EMBL CAM97358.1 388 androgen receptor [Macaca fascicularis]
GI:21322252 GenBank ADB54358.1 920 androgen receptor isoform 1 transcript variant 1 [Homo sapiens]
GI:58535455 GenBank ADC18416.1 919 Sequence 59 from patent US 7635753
GI:21322252 GenBank ADD26777.1 920 androgen receptor isoform 1 transcript variant 1 [Homo sapiens]
GI:21322252 GenBank ADD26778.1 920 androgen receptor isoform 1 transcript variant 1 [Homo sapiens]
GI:21322252 GenBank ADD26779.1 920 androgen receptor isoform 1 transcript variant 1 [Homo sapiens]
GI:21322252 GenBank ADD26780.1 920 androgen receptor isoform 1 transcript variant 1 [Homo sapiens]
GI:21322252 GenBank ADD26781.1 920 androgen receptor isoform 1 transcript variant 1 [Homo sapiens]
GI:58535455 GenBank ADH04800.1 388 androgen receptor variant [Callithrix jacchus]
GI:58535455 RefSeq XP_003272754.1 392 PREDICTED: androgen receptor [Nomascus leucogenys]
GI:58535455 RefSeq XP_008987670.1 388 PREDICTED: androgen receptor isoform X2 [Callithrix jacchus]
GI:58535455 RefSeq XP_010369130.1 392 PREDICTED: androgen receptor [Rhinopithecus roxellana]