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Protein

Androgen receptor

Gene

Ar

Organism
Rattus norvegicus (Rat)
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).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei688Androgen1
Binding sitei735Androgen1
Binding sitei860Androgen1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi541 – 614Nuclear receptorPROSITE-ProRule annotationAdd BLAST74
Zinc fingeri542 – 562NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri578 – 602NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

  • androgen binding Source: UniProtKB
  • androgen receptor activity Source: UniProtKB
  • androgen receptor binding Source: RGD
  • beta-catenin binding Source: UniProtKB
  • chromatin binding Source: RGD
  • DNA binding Source: RGD
  • protein domain specific binding Source: RGD
  • receptor binding Source: UniProtKB
  • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding Source: BHF-UCL
  • sequence-specific DNA binding Source: RGD
  • steroid binding Source: UniProtKB-KW
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: RGD
  • transcription regulatory region DNA binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • androgen receptor signaling pathway Source: RGD
  • cellular response to steroid hormone stimulus Source: RGD
  • copulation Source: RGD
  • intracellular receptor signaling pathway Source: BHF-UCL
  • male courtship behavior Source: RGD
  • male sex differentiation Source: RGD
  • negative regulation of extrinsic apoptotic signaling pathway Source: BHF-UCL
  • negative regulation of integrin biosynthetic process Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: RGD
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of phosphorylation Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • prostate gland growth Source: RGD
  • regulation of establishment of protein localization to plasma membrane Source: UniProtKB
  • response to insulin Source: RGD
  • single-organism reproductive behavior Source: RGD
  • skeletal muscle hypertrophy Source: RGD
  • spermatogenesis Source: RGD
  • transcription, DNA-templated Source: UniProtKB
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2147. Ar.

Subcellular locationi

  • Nucleus By similarity1 Publication
  • 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

  • axon Source: RGD
  • cytoplasm Source: UniProtKB
  • dendrite Source: RGD
  • nuclear chromatin Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in Ar are a cause of androgen insensitivity. Rats with this syndrome are called testicular feminized (TFM).

Keywords - Diseasei

Disease mutation

Chemistry databases

ChEMBLiCHEMBL3072.
GuidetoPHARMACOLOGYi628.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000537121 – 902Androgen receptorAdd BLAST902

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei61Phosphoserine; by CDK9By similarity1
Modified residuei75PhosphoserineBy similarity1
Modified residuei221Phosphotyrosine; by CSKBy similarity1
Modified residuei254PhosphoserineBy similarity1
Modified residuei265Phosphotyrosine; by CSK and TNK2By similarity1
Modified residuei290PhosphoserineCombined sources1
Modified residuei305Phosphotyrosine; by CSKBy similarity1
Modified residuei344Phosphotyrosine; by CSKBy similarity1
Modified residuei355Phosphotyrosine; by CSKBy similarity1
Modified residuei360Phosphotyrosine; by CSKBy similarity1
Modified residuei361Phosphotyrosine; by CSK and TNK2By similarity1
Cross-linki384Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei391Phosphotyrosine; by CSKBy similarity1
Cross-linki503Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei517Phosphotyrosine; by CSKBy similarity1
Modified residuei534Phosphotyrosine; by CSKBy similarity1
Modified residuei633PhosphoserineCombined sources1
Cross-linki828Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki830Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei898Phosphotyrosine; by CSKBy similarity1

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-517 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-61 by CDK9 regulates AR promoter selectivity and cell growth. Phosphorylation by PAK6 leads to AR-mediated transcription inhibition (By similarity).By similarity
Sumoylated on Lys-384 (major) and Lys-503 (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

Proteomic databases

PaxDbiP15207.
PRIDEiP15207.

PTM databases

iPTMnetiP15207.
PhosphoSitePlusiP15207.

Expressioni

Tissue specificityi

Highest levels in the seminal vesicle, ventral prostate and coagulating gland with lower levels in the kidney and levator ani muscle.

Gene expression databases

BgeeiENSRNOG00000005639.

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 similarity7 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei703Interaction with coactivator LXXL motifBy similarity1
Sitei880Interaction with coactivator FXXLF motifBy similarity1

GO - Molecular functioni

  • androgen receptor binding Source: RGD
  • beta-catenin binding Source: UniProtKB
  • protein domain specific binding Source: RGD
  • receptor binding Source: UniProtKB
  • transcription factor binding Source: RGD

Protein-protein interaction databases

BioGridi246396. 3 interactors.
DIPiDIP-5963N.
IntActiP15207. 1 interactor.
STRINGi10116.ENSRNOP00000009129.

Chemistry databases

BindingDBiP15207.

Structurei

Secondary structure

1902
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi543 – 545Combined sources3
Beta strandi551 – 553Combined sources3
Beta strandi556 – 558Combined sources3
Helixi560 – 570Combined sources11
Beta strandi579 – 582Combined sources4
Turni588 – 593Combined sources6
Helixi595 – 605Combined sources11
Helixi655 – 663Combined sources9
Beta strandi674 – 676Combined sources3
Helixi680 – 703Combined sources24
Helixi708 – 710Combined sources3
Helixi713 – 740Combined sources28
Beta strandi743 – 748Combined sources6
Beta strandi751 – 753Combined sources3
Helixi755 – 760Combined sources6
Helixi764 – 779Combined sources16
Helixi784 – 795Combined sources12
Beta strandi797 – 800Combined sources4
Helixi807 – 826Combined sources20
Beta strandi827 – 829Combined sources3
Helixi833 – 866Combined sources34
Helixi867 – 869Combined sources3
Helixi876 – 884Combined sources9
Helixi886 – 890Combined sources5
Beta strandi893 – 896Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1I37X-ray2.00A647-902[»]
1I38X-ray2.00A647-902[»]
1R4IX-ray3.10A/B533-637[»]
1XNNX-ray2.20A647-902[»]
2IHQX-ray2.00A647-902[»]
2NW4X-ray3.00A647-902[»]
3G0WX-ray1.95A647-902[»]
ProteinModelPortaliP15207.
SMRiP15207.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15207.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 540ModulatingAdd BLAST540
Regioni534 – 902Interaction with LPXNBy similarityAdd BLAST369
Regioni554 – 644Interaction with HIPK31 PublicationAdd BLAST91
Regioni574 – 902Interaction with CCAR1By similarityAdd BLAST329
Regioni607 – 902Interaction with KAT7By similarityAdd BLAST296
Regioni673 – 902Ligand-bindingAdd BLAST230

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi63 – 67Poly-Arg5
Compositional biasi174 – 195Poly-GlnAdd BLAST22
Compositional biasi370 – 376Poly-Pro7
Compositional biasi394 – 400Poly-Ala7
Compositional biasi444 – 450Poly-Gly7

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)DescriptionActionsGraphical viewLength
Zinc fingeri542 – 562NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri578 – 602NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
HOGENOMiHOG000254783.
HOVERGENiHBG007583.
InParanoidiP15207.
KOiK08557.
PhylomeDBiP15207.
TreeFamiTF350286.

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.

P15207-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEVQLGLGRV YPRPPSKTYR GAFQNLFQSV REAIQNPGPR HPEAASIAPP
60 70 80 90 100
GACLQQRQET SPRRRRRQQH PEDGSPQAHI RGTTGYLALE EEQQPSQQQS
110 120 130 140 150
ASEGHPESGC LPEPGAATAP GKGLPQQPPA PPDQDDSAAP STLSLLGPTF
160 170 180 190 200
PGLSSCSADI KDILSEAGTM QLLQQQQQQQ QQQQQQQQQQ QQQQQEVISE
210 220 230 240 250
GSSSVRAREA TGAPSSSKDS YLGGNSTISD SAKELCKAVS VSMGLGVEAL
260 270 280 290 300
EHLSPGEQLR GDCMYASLLG GPPAVRPTPC APLAECKGLS LDEGPGKGTE
310 320 330 340 350
ETAEYSSFKG GYAKGLEGES LGCSGSSEAG SSGTLEIPSS LSLYKSGAVD
360 370 380 390 400
EAAAYQNRDY YNFPLALSGP PHPPPPTHPH ARIKLENPSD YGSAWAAAAA
410 420 430 440 450
QCRYGDLASL HGGSVAGPST GSPPATASSS WHTLFTAEEG QLYGPGGGGG
460 470 480 490 500
SSSPSDAGPV APYGYTRPPQ GLASQEGDFS ASEVWYPGGV VNRVPYPSPS
510 520 530 540 550
CVKSEMGPWM ENYSGPYGDM RLDSTRDHVL PIDYYFPPQK TCLICGDEAS
560 570 580 590 600
GCHYGALTCG SCKVFFKRAA EGKQKYLCAS RNDCTIDKFR RKNCPSCRLR
610 620 630 640 650
KCYEAGMTLG ARKLKKLGNL KLQEEGENSS AGSPTEDPSQ KMTVSHIEGY
660 670 680 690 700
ECQPIFLNVL EAIEPGVVCA GHDNNQPDSF AALLSSLNEL GERQLVHVVK
710 720 730 740 750
WAKALPGFRN LHVDDQMAVI QYSWMGLMVF AMGWRSFTNV NSRMLYFAPD
760 770 780 790 800
LVFNEYRMHK SRMYSQCVRM RHLSQEFGWL QITPQEFLCM KALLLFSIIP
810 820 830 840 850
VDGLKNQKFF DELRMNYIKE LDRIIACKRK NPTSCSRRFY QLTKLLDSVQ
860 870 880 890 900
PIARELHQFT FDLLIKSHMV SVDFPEMMAE IISVQVPKIL SGKVKPIYFH

TQ
Length:902
Mass (Da):98,218
Last modified:April 1, 1990 - v1
Checksum:i43F4064759FDCBED
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti195Missing in AAA40734 (PubMed:2341409).Curated1
Sequence conflicti389S → L in AAA40759 (PubMed:3174628).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti735R → Q in TFM; has only 10-15% of the androgen-binding capacity of wild-type AR. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20133 mRNA. Translation: AAA40733.1.
M23264 mRNA. Translation: AAA40759.1.
J05454 Genomic DNA. Translation: AAA40734.1.
PIRiB40494.
RefSeqiNP_036634.1. NM_012502.1.
UniGeneiRn.9813.

Genome annotation databases

GeneIDi24208.
KEGGirno:24208.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20133 mRNA. Translation: AAA40733.1.
M23264 mRNA. Translation: AAA40759.1.
J05454 Genomic DNA. Translation: AAA40734.1.
PIRiB40494.
RefSeqiNP_036634.1. NM_012502.1.
UniGeneiRn.9813.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1I37X-ray2.00A647-902[»]
1I38X-ray2.00A647-902[»]
1R4IX-ray3.10A/B533-637[»]
1XNNX-ray2.20A647-902[»]
2IHQX-ray2.00A647-902[»]
2NW4X-ray3.00A647-902[»]
3G0WX-ray1.95A647-902[»]
ProteinModelPortaliP15207.
SMRiP15207.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246396. 3 interactors.
DIPiDIP-5963N.
IntActiP15207. 1 interactor.
STRINGi10116.ENSRNOP00000009129.

Chemistry databases

BindingDBiP15207.
ChEMBLiCHEMBL3072.
GuidetoPHARMACOLOGYi628.

PTM databases

iPTMnetiP15207.
PhosphoSitePlusiP15207.

Proteomic databases

PaxDbiP15207.
PRIDEiP15207.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24208.
KEGGirno:24208.

Organism-specific databases

CTDi367.
RGDi2147. Ar.

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
HOGENOMiHOG000254783.
HOVERGENiHBG007583.
InParanoidiP15207.
KOiK08557.
PhylomeDBiP15207.
TreeFamiTF350286.

Miscellaneous databases

EvolutionaryTraceiP15207.
PROiP15207.

Gene expression databases

BgeeiENSRNOG00000005639.

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...

Entry informationi

Entry nameiANDR_RAT
AccessioniPrimary (citable) accession number: P15207
Secondary accession number(s): Q63049
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: November 30, 2016
This is version 182 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.