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Protein

Androgen receptor

Gene

Ar

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 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.By similarity

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei685AndrogenCombined sources1 Publication1
Binding sitei732AndrogenCombined sources1 Publication1
Binding sitei857AndrogenCombined sources1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi538 – 611Nuclear receptorPROSITE-ProRule annotationAdd BLAST74
Zinc fingeri539 – 559NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri575 – 599NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandLipid-binding, Metal-binding, Steroid-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-MMU-383280 Nuclear Receptor transcription pathway
R-MMU-4090294 SUMOylation of intracellular receptors
R-MMU-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
R-MMU-5689880 Ub-specific processing proteases
R-MMU-8940973 RUNX2 regulates osteoblast differentiation

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:88064 Ar

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3056

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000537071 – 899Androgen receptorAdd BLAST899

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei61Phosphoserine; by CDK9By similarity1
Modified residuei75PhosphoserineBy similarity1
Modified residuei218Phosphotyrosine; by CSKBy similarity1
Modified residuei251PhosphoserineBy similarity1
Modified residuei262Phosphotyrosine; by CSK and TNK2By similarity1
Modified residuei302Phosphotyrosine; by CSKBy similarity1
Modified residuei341Phosphotyrosine; by CSKBy similarity1
Modified residuei352Phosphotyrosine; by CSKBy similarity1
Modified residuei357Phosphotyrosine; by CSKBy similarity1
Modified residuei358Phosphotyrosine; by CSK and TNK2By similarity1
Cross-linki381Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei388Phosphotyrosine; by CSKBy similarity1
Cross-linki500Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei514Phosphotyrosine; by CSKBy similarity1
Modified residuei531Phosphotyrosine; by CSKBy similarity1
Modified residuei630PhosphoserineCombined sources1
Cross-linki825Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki827Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei895Phosphotyrosine; 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-514 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-381 (major) and Lys-500 (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

PaxDbiP19091
PRIDEiP19091

PTM databases

iPTMnetiP19091
PhosphoSitePlusiP19091

Expressioni

Gene expression databases

BgeeiENSMUSG00000046532 Expressed in 211 organ(s), highest expression level in lacrimal gland
CleanExiMM_AR
GenevisibleiP19091 MM

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, SPDEF, SRA1, TGFB1I1, ZNF318 and RREB1. 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 ZMIZ1/ZIMP10 and ZMIZ2/ZMIP7 which both enhance its transactivation activity. Interacts with RBAK. Interacts via the ligand-binding domain with LXXLL and FXXLF motifs from NCOA1, NCOA2, NCOA3, NCOA4 and MAGEA11. Interacts with HIP1 (via coiled coil domain). Interacts with SLC30A9 and RAD54L2/ARIP4. Interacts with MACROD1. 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 hormone-induced AR transcriptional activity. Interacts with PRPF6 in a hormone-independent way; this interaction enhances hormone-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). Interacts with BUD31 (By similarity). Interacts with ARID4A (PubMed:23487765). Interacts with ARID4B (PubMed:23487765). Interacts (via NR LBD domain) with ZBTB7A; the interaction is direct and androgen-dependent (By similarity). Interacts with NCOR1 (By similarity). Interacts with NCOR2 (By similarity).By similarity8 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei700Interaction with coactivator LXXL and FXXFY motifsBy similarity1
Sitei877Interaction with coactivator FXXLF and FXXFY motifsBy similarity1

Binary interactionsi

WithEntry#Exp.IntActNotes
Casp8O891102EBI-1776062,EBI-851690

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198179, 21 interactors
DIPiDIP-41803N
IntActiP19091, 9 interactors
MINTiP19091
STRINGi10090.ENSMUSP00000052648

Chemistry databases

BindingDBiP19091

Structurei

Secondary structure

1899
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP19091
SMRiP19091
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP19091

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini648 – 879NR LBDPROSITE-ProRule annotationAdd BLAST232

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 566Interaction with ZNF3181 PublicationAdd BLAST566
Regioni1 – 537ModulatingBy similarityAdd BLAST537
Regioni531 – 898Interaction with LPXNBy similarityAdd BLAST368
Regioni551 – 641Interaction with HIPK3By similarityAdd BLAST91
Regioni571 – 898Interaction with CCAR1By similarityAdd BLAST328
Regioni604 – 898Interaction with KAT7By similarityAdd BLAST295

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi63 – 67Poly-Arg5
Compositional biasi174 – 193Poly-GlnAdd BLAST20
Compositional biasi367 – 373Poly-Pro7
Compositional biasi391 – 397Poly-Ala7
Compositional biasi441 – 447Poly-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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri539 – 559NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri575 – 599NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00760000118887
HOGENOMiHOG000254783
HOVERGENiHBG007583
InParanoidiP19091
KOiK08557
OMAiFPAPDVW
OrthoDBiEOG091G032J
PhylomeDBiP19091
TreeFamiTF350286

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR001103 Andrgn_rcpt
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF02166 Androgen_recep, 1 hit
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00521 ANDROGENR
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequencei

Sequence statusi: Complete.

P19091-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEVQLGLGRV YPRPPSKTYR GAFQNLFQSV REAIQNPGPR HPEAANIAPP
60 70 80 90 100
GACLQQRQET SPRRRRRQQH TEDGSPQAHI RGPTGYLALE EEQQPSQQQA
110 120 130 140 150
ASEGHPESSC LPEPGAATAP GKGLPQQPPA PPDQDDSAAP STLSLLGPTF
160 170 180 190 200
PGLSSCSADI KDILNEAGTM QLLQQQQQQQ QHQQQHQQHQ QQQEVISEGS
210 220 230 240 250
SARAREATGA PSSSKDSYLG GNSTISDSAK ELCKAVSVSM GLGVEALEHL
260 270 280 290 300
SPGEQLRGDC MYASLLGGPP AVRPTPCAPL PECKGLPLDE GPGKSTEETA
310 320 330 340 350
EYSSFKGGYA KGLEGESLGC SGSSEAGSSG TLEIPSSLSL YKSGALDEAA
360 370 380 390 400
AYQNRDYYNF PLALSGPPHP PPPTHPHARI KLENPLDYGS AWAAAAAQCR
410 420 430 440 450
YGDLGSLHGG SVAGPSTGSP PATTSSSWHT LFTAEEGQLY GPGGGGGSSS
460 470 480 490 500
PSDAGPVAPY GYTRPPQGLT SQESDYSASE VWYPGGVVNR VPYPSPNCVK
510 520 530 540 550
SEMGPWMENY SGPYGDMRLD STRDHVLPID YYFPPQKTCL ICGDEASGCH
560 570 580 590 600
YGALTCGSCK VFFKRAAEGK QKYLCASRND CTIDKFRRKN CPSCRLRKCY
610 620 630 640 650
EAGMTLGARK LKKLGNLKLQ EEGENSNAGS PTEDPSQKMT VSHIEGYECQ
660 670 680 690 700
PIFLNVLEAI EPGVVCAGHD NNQPDSFAAL LSSLNELGER QLVHVVKWAK
710 720 730 740 750
ALPGFRNLHV DDQMAVIQYS WMGLMVFAMG WRSFTNVNSR MLYFAPDLVF
760 770 780 790 800
NEYRMHKSRM YSQCVRMRHL SQEFGWLQIT PQEFLCMKAL LLFSIIPVDG
810 820 830 840 850
LKNQKFFDEL RMNYIKELDR IIACKRKNPT SCSRRFYQLT KLLDSVQPIA
860 870 880 890
RELHQFTFDL LIKSHMVSVD FPEMMAEIIS VQVPKILSGK VKPIYFHTQ
Length:899
Mass (Da):98,194
Last modified:November 1, 1990 - v1
Checksum:iFD9EE07C07F7A568
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S56585 mRNA Translation: AAB19916.1
X53779 mRNA Translation: CAA37795.1
M37890 mRNA Translation: AAA37234.1
X59592 mRNA Translation: CAA42160.1
CCDSiCCDS30294.1
PIRiA35895
RefSeqiNP_038504.1, NM_013476.4
UniGeneiMm.39005
Mm.394224
Mm.439657

Genome annotation databases

EnsembliENSMUST00000052837; ENSMUSP00000052648; ENSMUSG00000046532
GeneIDi11835
KEGGimmu:11835
UCSCiuc009tuv.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S56585 mRNA Translation: AAB19916.1
X53779 mRNA Translation: CAA37795.1
M37890 mRNA Translation: AAA37234.1
X59592 mRNA Translation: CAA42160.1
CCDSiCCDS30294.1
PIRiA35895
RefSeqiNP_038504.1, NM_013476.4
UniGeneiMm.39005
Mm.394224
Mm.439657

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QPYX-ray2.50A649-899[»]
ProteinModelPortaliP19091
SMRiP19091
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198179, 21 interactors
DIPiDIP-41803N
IntActiP19091, 9 interactors
MINTiP19091
STRINGi10090.ENSMUSP00000052648

Chemistry databases

BindingDBiP19091
ChEMBLiCHEMBL3056

PTM databases

iPTMnetiP19091
PhosphoSitePlusiP19091

Proteomic databases

PaxDbiP19091
PRIDEiP19091

Protocols and materials databases

DNASUi11835
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000052837; ENSMUSP00000052648; ENSMUSG00000046532
GeneIDi11835
KEGGimmu:11835
UCSCiuc009tuv.1 mouse

Organism-specific databases

CTDi367
MGIiMGI:88064 Ar

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00760000118887
HOGENOMiHOG000254783
HOVERGENiHBG007583
InParanoidiP19091
KOiK08557
OMAiFPAPDVW
OrthoDBiEOG091G032J
PhylomeDBiP19091
TreeFamiTF350286

Enzyme and pathway databases

ReactomeiR-MMU-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-MMU-383280 Nuclear Receptor transcription pathway
R-MMU-4090294 SUMOylation of intracellular receptors
R-MMU-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
R-MMU-5689880 Ub-specific processing proteases
R-MMU-8940973 RUNX2 regulates osteoblast differentiation

Miscellaneous databases

ChiTaRSiCyp19a1 mouse
EvolutionaryTraceiP19091
PROiPR:P19091
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000046532 Expressed in 211 organ(s), highest expression level in lacrimal gland
CleanExiMM_AR
GenevisibleiP19091 MM

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR001103 Andrgn_rcpt
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF02166 Androgen_recep, 1 hit
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00521 ANDROGENR
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiANDR_MOUSE
AccessioniPrimary (citable) accession number: P19091
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: November 7, 2018
This is version 203 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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