Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Androgen receptor

Gene

AR

Organism
Pan troglodytes (Chimpanzee)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei697 – 6971Androgen
Binding sitei744 – 7441Androgen
Binding sitei869 – 8691Androgen

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi551 – 62373Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri551 – 57121NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri587 – 61125NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Lipid-binding, Metal-binding, Steroid-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Androgen receptor
Alternative name(s):
Dihydrotestosterone receptor
Nuclear receptor subfamily 3 group C member 4
Gene namesi
Name:AR
Synonyms:NR3C4
OrganismiPan troglodytes (Chimpanzee)
Taxonomic identifieri9598 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePan
Proteomesi
  • UP000002277 Componenti: Unplaced

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity

  • 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 RACK1.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 911911Androgen receptorPRO_0000053708Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei81 – 811Phosphoserine; by CDK9By similarity
Modified residuei93 – 931PhosphoserineBy similarity
Modified residuei222 – 2221Phosphotyrosine; by CSKBy similarity
Modified residuei255 – 2551PhosphoserineBy similarity
Modified residuei266 – 2661Phosphotyrosine; by CSK and TNK2By similarity
Modified residuei306 – 3061Phosphotyrosine; by CSKBy similarity
Modified residuei345 – 3451Phosphotyrosine; by CSKBy similarity
Modified residuei356 – 3561Phosphotyrosine; by CSKBy similarity
Modified residuei361 – 3611Phosphotyrosine; by CSKBy similarity
Modified residuei362 – 3621Phosphotyrosine; by CSK and TNK2By similarity
Cross-linki385 – 385Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei392 – 3921Phosphotyrosine; by CSKBy similarity
Cross-linki512 – 512Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei526 – 5261Phosphotyrosine; by CSKBy similarity
Modified residuei543 – 5431Phosphotyrosine; by CSKBy similarity
Modified residuei642 – 6421Phosphoserine; by STK4/MST1By similarity
Cross-linki837 – 837Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki839 – 839Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei907 – 9071Phosphotyrosine; by CSKBy similarity

Post-translational modificationi

Phosphorylated in prostate cancer cells in response to several growth factors including EGF. Phosphorylation is induced by c-Src kinase (CSK). Tyr-526 is one of the major phosphorylation sites and an increase in phosphorylation and Src kinase activity is associated with prostate cancer progression (By similarity). Phosphorylation by TNK2 enhances the DNA-binding and transcriptional activity. Phosphorylation at Ser-81 by CDK9 regulates AR promoter selectivity and cell growth (By similarity).By similarity
Sumoylated on Lys-385 (major) and Lys-512 (By similarity). Ubiquitinated. Deubiquitinated by USP26 (By similarity). 'Lys-6' and 'Lys-27'-linked polyubiquitination by RNF6 modulates AR transcriptional activity and specificity (By similarity).By similarity
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 (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

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 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 (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei712 – 7121Interaction with coactivator LXXL motif
Sitei889 – 8891Interaction with coactivator FXXLF motif

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-46077N.

Structurei

Secondary structure

1
911
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi664 – 6729Combined sources
Helixi689 – 71224Combined sources
Helixi717 – 7193Combined sources
Helixi722 – 74928Combined sources
Beta strandi752 – 7576Combined sources
Beta strandi760 – 7623Combined sources
Helixi764 – 7696Combined sources
Helixi773 – 78816Combined sources
Helixi793 – 80412Combined sources
Beta strandi806 – 8094Combined sources
Helixi816 – 83520Combined sources
Helixi841 – 87434Combined sources
Helixi876 – 8794Combined sources
Helixi885 – 8939Combined sources
Helixi895 – 8995Combined sources
Beta strandi902 – 9054Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1T73X-ray2.20A654-911[»]
1T74X-ray2.00A654-911[»]
1T76X-ray2.10A654-911[»]
1T79X-ray1.80A654-911[»]
1T7FX-ray1.60A654-911[»]
1T7MX-ray1.60A654-911[»]
1T7RX-ray1.40A654-911[»]
1T7TX-ray1.70A654-911[»]
ProteinModelPortaliO97775.
SMRiO97775. Positions 547-620, 655-910.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO97775.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 549549ModulatingBy similarityAdd
BLAST
Regioni543 – 911369Interaction with LPXNBy similarityAdd
BLAST
Regioni563 – 65391Interaction with HIPK3By similarityAdd
BLAST
Regioni583 – 911329Interaction with CCAR1By similarityAdd
BLAST
Regioni616 – 911296Interaction with KAT7By similarityAdd
BLAST
Regioni682 – 911230Ligand-bindingAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi57 – 7822Poly-GlnAdd
BLAST
Compositional biasi84 – 885Poly-Gln
Compositional biasi192 – 1965Poly-Gln
Compositional biasi371 – 38010Poly-Pro
Compositional biasi395 – 4017Poly-Ala
Compositional biasi448 – 46417Poly-GlyAdd
BLAST

Domaini

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 (By similarity).By similarity

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri551 – 57121NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri587 – 61125NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

HOVERGENiHBG007583.
InParanoidiO97775.
KOiK08557.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR001103. Andrgn_rcpt.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF02166. Androgen_recep. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00521. ANDROGENR.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O97775-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEVQLGLGRV YPRPPSKTYR GAFQNLFQSV REVIQNPGPR HPEAASAAPP
60 70 80 90 100
GASLLLQQQQ QQQQQQQQQQ QQQQQQQQET SPRQQQQQGE DGSPQAHRRG
110 120 130 140 150
PTGYLVLDEE QQPSQPQSAP ECHPERGCVP EPGAAVAASK GLPQQLPAPP
160 170 180 190 200
DEDDSAAPST LSLLGPTFPG LSSCSADLKD ILSEASTMQL LQQQQQEAVS
210 220 230 240 250
EGSSSGRARE ASGAPTSSKD NYLGGTSTIS DSAKELCKAV SVSMGLGVEA
260 270 280 290 300
LEHLSPGEQL RGDCMYAPLL GVPPAVRPTP CAPLAECKGS LLDDSAGKST
310 320 330 340 350
EDTAEYSPFK GGYTKGLEGE SLGCSGSAAA GSSGTLELPS TLSLYKSGAL
360 370 380 390 400
DEAAAYQSRD YYNFPLALAG PPPPPPPPHP HARIKLENPL DYGSAWAAAA
410 420 430 440 450
AQCRYGDLAS LHGAGAAGPG SGSPSAAASS SWHTLFTAEE GQLYGPCGGG
460 470 480 490 500
GGGGGGGGGG GGGGEAGAVA PYGYTRPPQG LAGQEGDFTA PDVWYPGGMV
510 520 530 540 550
SRVPYPSPTC VKSEMGPWMD SYSGPYGDMR LETARDHVLP IDYYFPPQKT
560 570 580 590 600
CLICGDEASG CHYGALTCGS CKVFFKRAAE GKQKYLCASR NDCTIDKFRR
610 620 630 640 650
KNCPSCRLRK CYEAGMTLGA RKLKKLGNLK LQEEGEASST TSPTEETTQK
660 670 680 690 700
LTVSHIEGYE CQPIFLNVLE AIEPGVVCAG HDNNQPDSFA ALLSSLNELG
710 720 730 740 750
ERQLVHVVKW AKALPGFRNL HVDDQMAVIQ YSWMGLMVFA MGWRSFTNVN
760 770 780 790 800
SRMLYFAPDL VFNEYRMHKS RMYSQCVRMR HLSQEFGWLQ ITPQEFLCMK
810 820 830 840 850
ALLLFSIIPV DGLKNQKFFD ELRMNYIKEL DRIIACKRKN PTSCSRRFYQ
860 870 880 890 900
LTKLLDSVQP IARELHQFTF DLLIKSHMVS VDFPEMMAEI ISVQVPKILS
910
GKVKPIYFHT Q
Length:911
Mass (Da):98,403
Last modified:May 1, 1999 - v1
Checksum:i601B9BD4E697DAA4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U94177 mRNA. Translation: AAC73048.1.
RefSeqiNP_001009012.1. NM_001009012.1.
UniGeneiPtr.6188.

Genome annotation databases

GeneIDi747460.
KEGGiptr:747460.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U94177 mRNA. Translation: AAC73048.1.
RefSeqiNP_001009012.1. NM_001009012.1.
UniGeneiPtr.6188.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1T73X-ray2.20A654-911[»]
1T74X-ray2.00A654-911[»]
1T76X-ray2.10A654-911[»]
1T79X-ray1.80A654-911[»]
1T7FX-ray1.60A654-911[»]
1T7MX-ray1.60A654-911[»]
1T7RX-ray1.40A654-911[»]
1T7TX-ray1.70A654-911[»]
ProteinModelPortaliO97775.
SMRiO97775. Positions 547-620, 655-910.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-46077N.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi747460.
KEGGiptr:747460.

Organism-specific databases

CTDi367.

Phylogenomic databases

HOVERGENiHBG007583.
InParanoidiO97775.
KOiK08557.

Miscellaneous databases

EvolutionaryTraceiO97775.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR001103. Andrgn_rcpt.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF02166. Androgen_recep. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00521. ANDROGENR.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Evolution of the primate androgen receptor: a structural basis for disease."
    Choong C.S., Kemppainen J.A., Wilson E.M.
    J. Mol. Evol. 47:334-342(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Recognition and accommodation at the androgen receptor coactivator binding interface."
    Hur E., Pfaff S.J., Payne E.S., Groen H., Buehrer B.M., Fletterick R.J.
    PLoS Biol. 2:E274-E274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 654-911 IN COMPLEXES WITH DIHYDROTESTOSTERONE AND COACTIVATOR-BASED PEPTIDES.

Entry informationi

Entry nameiANDR_PANTR
AccessioniPrimary (citable) accession number: O97775
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1999
Last modified: June 8, 2016
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.
Transcriptional activity is enhanced by binding to RANBP9.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.