Q9TT90 (ANDR_CANFA) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 112. History...
Names and origin
|Protein names||Recommended name:|
Nuclear receptor subfamily 3 group C member 4
|Organism||Canis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]|
|Taxonomic identifier||9615 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis ›|
|Sequence length||907 AA.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
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.
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.
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.
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.
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.
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.
Contains 1 nuclear receptor DNA-binding domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 907||907||Androgen receptor||PRO_0000053701|
|DNA binding||546 – 619||74||Nuclear receptor|
|Zinc finger||547 – 567||21||NR C4-type|
|Zinc finger||583 – 607||25||NR C4-type|
|Region||1 – 545||545||Modulating By similarity|
|Region||539 – 907||369||Interaction with LPXN By similarity|
|Region||559 – 649||91||Interaction with HIPK3 By similarity|
|Region||612 – 907||296||Interaction with KAT7 By similarity|
|Region||678 – 907||230||Ligand-binding|
|Compositional bias||55 – 64||10||Poly-Gln|
|Compositional bias||70 – 76||7||Poly-Gln|
|Compositional bias||131 – 134||4||Poly-Gln|
|Compositional bias||180 – 202||23||Poly-Gln|
|Compositional bias||329 – 332||4||Poly-Ser|
|Compositional bias||375 – 384||10||Poly-Pro|
|Compositional bias||399 – 405||7||Poly-Ala|
|Binding site||693||1||Androgen By similarity|
|Binding site||740||1||Androgen By similarity|
|Binding site||865||1||Androgen By similarity|
|Site||708||1||Interaction with coactivator LXXL motif By similarity|
|Site||885||1||Interaction with coactivator FXXLF motif By similarity|
Amino acid modifications
|Modified residue||67||1||Phosphoserine; by CDK9 By similarity|
|Modified residue||81||1||Phosphoserine By similarity|
|Modified residue||228||1||Phosphotyrosine; by CSK By similarity|
|Modified residue||272||1||Phosphotyrosine; by CSK and TNK2 By similarity|
|Modified residue||310||1||Phosphotyrosine; by CSK By similarity|
|Modified residue||349||1||Phosphotyrosine; by CSK By similarity|
|Modified residue||360||1||Phosphotyrosine; by CSK By similarity|
|Modified residue||365||1||Phosphotyrosine; by CSK By similarity|
|Modified residue||366||1||Phosphotyrosine; by CSK and TNK2 By similarity|
|Modified residue||396||1||Phosphotyrosine; by CSK By similarity|
|Modified residue||522||1||Phosphotyrosine; by CSK By similarity|
|Modified residue||539||1||Phosphotyrosine; by CSK By similarity|
|Modified residue||638||1||Phosphoserine; by STK4/MST1 By similarity|
|Modified residue||903||1||Phosphotyrosine; by CSK By similarity|
|Cross-link||389||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
|Cross-link||508||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
|Cross-link||833||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|Cross-link||835||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|Sequence conflict||123||1||T → A in AAQ84563. Ref.2|
|Sequence conflict||183||1||R → Q in AAQ84563. Ref.2|
|Sequence conflict||202||1||Q → QQ in AAQ84563. Ref.2|
|Sequence conflict||823||1||I → V in AAQ84563. Ref.2|
|||"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].
|||"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].
|AF197950 mRNA. Translation: AAF18084.1.|
AY271347 mRNA. Translation: AAQ84563.1.
|RefSeq||NP_001003053.1. NM_001003053.1. |
3D structure databases
|SMR||Q9TT90. Positions 543-616, 651-906. |
Protocols and materials databases
Genome annotation databases
Family and domain databases
|Gene3D||1.10.565.10. 2 hits. |
184.108.40.206. 1 hit.
|InterPro||IPR001103. Andrgn_rcpt. |
|Pfam||PF02166. Androgen_recep. 1 hit. |
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
|PRINTS||PR00521. ANDROGENR. |
|SMART||SM00430. HOLI. 1 hit. |
SM00399. ZnF_C4. 1 hit.
|SUPFAM||SSF48508. SSF48508. 1 hit. |
|PROSITE||PS00031. NUCLEAR_REC_DBD_1. 1 hit. |
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
|Accession||Primary (citable) accession number: Q9TT90|
Secondary accession number(s): Q6WSP7
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families