UniProt functional annotation for P15207



	UniProt functional annotation for P15207

UniProt code: P15207.

Organism: Rattus norvegicus (Rat).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.

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 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). {ECO:0000250|UniProtKB:P10275, ECO:0000269|PubMed:17008401, ECO:0000269|PubMed:17181141}.

Subunit: 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, 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 with MACROD1 (via macro domain) (By similarity). 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). Interacts with BUD31 (By similarity). Interacts with ARID4A (By similarity). Interacts with ARID4B (By similarity). 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). Interacts with CRY2 in a ligand-dependent manner (By similarity). {ECO:0000250|UniProtKB:P10275, ECO:0000250|UniProtKB:P19091, ECO:0000269|PubMed:11320241, ECO:0000269|PubMed:12350225, ECO:0000269|PubMed:15037741, ECO:0000269|PubMed:15603938, ECO:0000269|PubMed:17008401, ECO:0000269|PubMed:17181141, ECO:0000269|PubMed:9725910}.

Subcellular location: Nucleus {ECO:0000269|PubMed:9725910}. Cytoplasm {ECO:0000250|UniProtKB:P10275}. Note=Detected at the promoter of target genes. 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. {ECO:0000250|UniProtKB:P10275}.

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

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). {ECO:0000250}.

Ptm: 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). {ECO:0000250|UniProtKB:P10275}.

Ptm: 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). {ECO:0000250|UniProtKB:P10275}.

Ptm: 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). {ECO:0000250|UniProtKB:P10275}.

Disease: Note=Defects in Ar are a cause of androgen insensitivity. Rats with this syndrome are called testicular feminized (TFM). {ECO:0000269|PubMed:2341409}.

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.

Miscellaneous: Transcriptional activity is enhanced by binding to RANBP9.

Similarity: Belongs to the nuclear hormone receptor family. NR3 subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



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 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). {ECO:0000250\|UniProtKB:P10275, ECO:0000269\|PubMed:17008401, ECO:0000269\|PubMed:17181141}.


Subunit:		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, 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 with MACROD1 (via macro domain) (By similarity). 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). Interacts with BUD31 (By similarity). Interacts with ARID4A (By similarity). Interacts with ARID4B (By similarity). 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). Interacts with CRY2 in a ligand-dependent manner (By similarity). {ECO:0000250\|UniProtKB:P10275, ECO:0000250\|UniProtKB:P19091, ECO:0000269\|PubMed:11320241, ECO:0000269\|PubMed:12350225, ECO:0000269\|PubMed:15037741, ECO:0000269\|PubMed:15603938, ECO:0000269\|PubMed:17008401, ECO:0000269\|PubMed:17181141, ECO:0000269\|PubMed:9725910}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:9725910}. Cytoplasm {ECO:0000250\|UniProtKB:P10275}. Note=Detected at the promoter of target genes. 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. {ECO:0000250\|UniProtKB:P10275}.
Tissue specificity:		Highest levels in the seminal vesicle, ventral prostate and coagulating gland with lower levels in the kidney and levator ani muscle.
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). {ECO:0000250}.
Ptm:		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). {ECO:0000250\|UniProtKB:P10275}.
Ptm:		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). {ECO:0000250\|UniProtKB:P10275}.
Ptm:		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). {ECO:0000250\|UniProtKB:P10275}.
Disease:		Note=Defects in Ar are a cause of androgen insensitivity. Rats with this syndrome are called testicular feminized (TFM). {ECO:0000269\|PubMed:2341409}.
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.
Miscellaneous:		Transcriptional activity is enhanced by binding to RANBP9.
Similarity:		Belongs to the nuclear hormone receptor family. NR3 subfamily. {ECO:0000305}.