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Q9TT90 (ANDR_CANFA) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Androgen receptor
Alternative name(s):
Dihydrotestosterone receptor
Nuclear receptor subfamily 3 group C member 4
Gene names
Name:AR
Synonyms:NR3C4
OrganismCanis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]
Taxonomic identifier9615 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis

Protein attributes

Sequence length907 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

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 By similarity.

Subunit structure

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 SLC30A9 and RAD54L2/ARIP4. Interacts with HIP1 (via coiled coil domain). 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 GNB2L1/RACK1 By similarity. Interacts with RANBP10; this interaction enhances hormone-induced AR transcriptional activity By similarity. Interacts with PRPF6 in a hormone-independent way; this interaction enhances hormone-induced AR transcriptional activity. Interacts with STK4/MST1 By similarity. Interacts with ZIPK/DAPK3 By similarity. Interacts with LPXN By similarity. Interacts with MAK By similarity. Part of a complex containing AR, MAK and NCOA3 By similarity.

Subcellular location

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 GNB2L1 By similarity.

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 By similarity.

Post-translational modification

Phosphorylated in prostate cancer cells in response to several growth factors including EGF. Phosphorylation is induced by c-Src kinase (CSK). Tyr-522 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-67 by CDK9 regulates AR promoter selectivity and cell growth By similarity.

Sumoylated on Lys-389 (major) and Lys-508 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.

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.

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.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR3 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DomainZinc-finger
   LigandDNA-binding
Lipid-binding
Metal-binding
Steroid-binding
Zinc
   Molecular functionReceptor
   PTMIsopeptide bond
Lipoprotein
Palmitate
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processandrogen receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular receptor signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of extrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of integrin biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of establishment of protein localization to plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear chromatin

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionandrogen receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

beta-catenin binding

Inferred from sequence or structural similarity. Source: UniProtKB

ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from sequence or structural similarity. Source: BHF-UCL

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

steroid binding

Inferred from electronic annotation. Source: UniProtKB-KW

transcription regulatory region DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 907907Androgen receptor
PRO_0000053701

Regions

DNA binding546 – 61974Nuclear receptor
Zinc finger547 – 56721NR C4-type
Zinc finger583 – 60725NR C4-type
Region1 – 545545Modulating By similarity
Region539 – 907369Interaction with LPXN By similarity
Region559 – 64991Interaction with HIPK3 By similarity
Region612 – 907296Interaction with KAT7 By similarity
Region678 – 907230Ligand-binding
Compositional bias55 – 6410Poly-Gln
Compositional bias70 – 767Poly-Gln
Compositional bias131 – 1344Poly-Gln
Compositional bias180 – 20223Poly-Gln
Compositional bias329 – 3324Poly-Ser
Compositional bias375 – 38410Poly-Pro
Compositional bias399 – 4057Poly-Ala

Sites

Binding site6931Androgen By similarity
Binding site7401Androgen By similarity
Binding site8651Androgen By similarity
Site7081Interaction with coactivator LXXL motif By similarity
Site8851Interaction with coactivator FXXLF motif By similarity

Amino acid modifications

Modified residue671Phosphoserine; by CDK9 By similarity
Modified residue811Phosphoserine By similarity
Modified residue2281Phosphotyrosine; by CSK By similarity
Modified residue2721Phosphotyrosine; by CSK and TNK2 By similarity
Modified residue3101Phosphotyrosine; by CSK By similarity
Modified residue3491Phosphotyrosine; by CSK By similarity
Modified residue3601Phosphotyrosine; by CSK By similarity
Modified residue3651Phosphotyrosine; by CSK By similarity
Modified residue3661Phosphotyrosine; by CSK and TNK2 By similarity
Modified residue3961Phosphotyrosine; by CSK By similarity
Modified residue5221Phosphotyrosine; by CSK By similarity
Modified residue5391Phosphotyrosine; by CSK By similarity
Modified residue6381Phosphoserine; by STK4/MST1 By similarity
Modified residue9031Phosphotyrosine; by CSK By similarity
Cross-link389Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link508Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link833Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link835Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Sequence conflict1231T → A in AAQ84563. Ref.2
Sequence conflict1831R → Q in AAQ84563. Ref.2
Sequence conflict2021Q → QQ in AAQ84563. Ref.2
Sequence conflict8231I → V in AAQ84563. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9TT90 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: C8619F78DD2338AF

FASTA90798,727
        10         20         30         40         50         60 
MEVQLGLGRV YPRPPSKTYR GAFQNLFQSV REVIQNPGPR HPEAVSAAPP GAHLQQQQQQ 

        70         80         90        100        110        120 
QQQQETSPRQ QQQQQQGDDG SPQAQSRGPT GYLALDEEQQ PSQQRSASKG HPESACVPEP 

       130        140        150        160        170        180 
GVTSATGKGL QQQQPAPPDE NDSAAPSTLS LLGPTFPGLS SCSTDLKDIL SEAGTMQLLQ 

       190        200        210        220        230        240 
QQRQQQQQQQ QQQQQQQQQQ QQEVVSEGSS SGRAREAAGA STSSKDSYLG GSSTISDSAK 

       250        260        270        280        290        300 
ELCKAVSVSM GLGVEALEHL SPGEQLRGDC MYAPLLGGPP AVRPCAPLAE CKGSLLDDGP 

       310        320        330        340        350        360 
GKGTEETAEY SPFKAGYAKG LDGDSLGCSS SSEAGGSGTL EMPSTLSLYK SGALDEAAAY 

       370        380        390        400        410        420 
QSRDYYNFPL SLGGPPPHPP PPHPHTRIKL ENPLDYGSAW AAAAAQCRYG DLASLHGAGA 

       430        440        450        460        470        480 
AGPSSGSPSA TTSSSWHTLF TAEEGQLYGP CGGSGGGSAG DGGSVAPYGY TRPPQGLAGQ 

       490        500        510        520        530        540 
EGDFPPPDVW YPGGVVSRVP FPSPSCVKSE MGSWMESYSG PYGDMRLETA RDHVLPIDYY 

       550        560        570        580        590        600 
FPPQKTCLIC GDEASGCHYG ALTCGSCKVF FKRAAEGKQK YLCASRNDCT IDKFRRKNCP 

       610        620        630        640        650        660 
SCRLRKCYEA GMTLGARKLK KLGNLKLQEE GEASNVTSPT EEPTQKLTVS HIEGYECQPI 

       670        680        690        700        710        720 
FLNVLEAIEP GVVCAGHDNN QPDSFAALLS SLNELGERQL VHVVKWAKAL PGFRNLHVDD 

       730        740        750        760        770        780 
QMAVIQYSWM GLMVFAMGWR SFTNVNSRML YFAPDLVFNE YRMHKSRMYS QCVRMRHLSQ 

       790        800        810        820        830        840 
EFGWLQITPQ EFLCMKALLL FSIIPVDGLK NQKFFDELRM NYIKELDRII ACKRKNPTSC 

       850        860        870        880        890        900 
SRRFYQLTKL LDSVQPIARE LHQFTFDLLI KSHMVSVDFP EMMAEIISVQ VPKILSGKVK 


PIYFHTQ 

« Hide

References

[1]"Molecular cloning and functional characterization of the canine androgen receptor."
Lu B., Smock S.L., Castleberry T.A., Owen T.A.
Mol. Cell. Biochem. 226:129-140(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Comparision of rat, dog and human androgen receptors."
Duan W.R., Kelce W.R., Levin S., Blomme E.A.G.
Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF197950 mRNA. Translation: AAF18084.1.
AY271347 mRNA. Translation: AAQ84563.1.
RefSeqNP_001003053.1. NM_001003053.1.
UniGeneCfa.141.

3D structure databases

ProteinModelPortalQ9TT90.
SMRQ9TT90. Positions 543-616, 651-906.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID403588.
KEGGcfa:403588.

Organism-specific databases

CTD367.

Phylogenomic databases

eggNOGNOG245477.
HOGENOMHOG000254783.
HOVERGENHBG007583.
InParanoidQ9TT90.
KOK08557.

Family and domain databases

Gene3D1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProIPR001103. Andrgn_rcpt.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF02166. Androgen_recep. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR00521. ANDROGENR.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio20817094.

Entry information

Entry nameANDR_CANFA
AccessionPrimary (citable) accession number: Q9TT90
Secondary accession number(s): Q6WSP7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families