ANDR_RABIT
ID ANDR_RABIT Reviewed; 709 AA.
AC P49699;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Androgen receptor;
DE AltName: Full=Dihydrotestosterone receptor;
DE AltName: Full=Nuclear receptor subfamily 3 group C member 4;
DE Flags: Fragment;
GN Name=AR; Synonyms=NR3C4;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Prostate;
RX PubMed=7559153;
RA Krongrad A., Wilson J.D., McPhaul M.J.;
RT "Cloning and partial sequence of the rabbit androgen receptor: expression
RT in fetal urogenital tissues.";
RL J. Androl. 16:209-212(1995).
CC -!- FUNCTION: Steroid hormone receptors are ligand-activated transcription
CC factors that regulate eukaryotic gene expression and affect cellular
CC proliferation and differentiation in target tissues. Transcription
CC factor activity is modulated by bound coactivator and corepressor
CC proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen
CC response elements/ARE on target genes, negatively regulating androgen
CC receptor signaling and androgen-induced cell proliferation.
CC Transcription activation is also down-regulated by NR0B2. Activated,
CC but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
CC {ECO:0000250|UniProtKB:P10275, ECO:0000250|UniProtKB:P15207}.
CC -!- SUBUNIT: Binds DNA as a homodimer. Part of a ternary complex containing
CC AR, EFCAB6/DJBP and PARK7. Interacts with HIPK3 and NR0B2 in the
CC presence of androgen. The ligand binding domain interacts with
CC KAT7/HBO1 in the presence of dihydrotestosterone. Interacts with
CC EFCAB6/DJBP, PQBP1, RANBP9, RBAK, SPDEF, SRA1, TGFB1I1 and RREB1.
CC Interacts with ZMIZ1/ZIMP10 and ZMIZ2/ZMIP7 which both enhance its
CC transactivation activity. Interacts with SLC30A9 and RAD54L2/ARIP4.
CC Interacts with MACROD1 (via macro domain) (By similarity). Interacts
CC via the ligand-binding domain with LXXLL and FXXLF motifs from NCOA1,
CC NCOA2, NCOA3, NCOA4 and MAGEA11. The AR N-terminal poly-Gln region
CC binds Ran resulting in enhancement of AR-mediated transactivation. Ran-
CC binding decreases as the poly-Gln length increases. Interacts with HIP1
CC (via coiled coil domain). Interacts (via ligand-binding domain) with
CC TRIM68. Interacts with TNK2. Interacts with USP26. Interacts with RNF6.
CC Interacts (regulated by RNF6 probably through polyubiquitination) with
CC RNF14; regulates AR transcriptional activity. Interacts with PRMT2 and
CC TRIM24. Interacts with RACK1. Interacts with RANBP10; this interaction
CC enhances dihydrotestosterone-induced AR transcriptional activity.
CC Interacts with PRPF6 in a hormone-independent way; this interaction
CC enhances dihydrotestosterone-induced AR transcriptional activity.
CC Interacts with STK4/MST1. Interacts with ZIPK/DAPK3. Interacts with
CC LPXN. Interacts with MAK. Part of a complex containing AR, MAK and
CC NCOA3. Interacts with CRY1. Interacts with CCAR1 and GATA2. Interacts
CC with ZNF318. Interacts with BUD31. Interacts with ARID4A. Interacts
CC with ARID4B. Interacts (via NR LBD domain) with ZBTB7A; the interaction
CC is direct and androgen-dependent (By similarity). Interacts with NCOR1
CC (By similarity). Interacts with NCOR2 (By similarity). Interacts with
CC CRY2 in a ligand-dependent manner (By similarity).
CC {ECO:0000250|UniProtKB:P10275, ECO:0000250|UniProtKB:P19091}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P10275}. Cytoplasm
CC {ECO:0000250|UniProtKB:P10275}. Note=Detected at the promoter of target
CC genes. Predominantly cytoplasmic in unligated form but translocates to
CC the nucleus upon ligand-binding. Can also translocate to the nucleus in
CC unligated form in the presence of RACK1.
CC {ECO:0000250|UniProtKB:P10275}.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC DNA-binding domain and a C-terminal ligand-binding domain. In the
CC presence of bound steroid the ligand-binding domain interacts with the
CC N-terminal modulating domain, and thereby activates AR transcription
CC factor activity. Agonist binding is required for dimerization and
CC binding to target DNA. The transcription factor activity of the complex
CC formed by ligand-activated AR and DNA is modulated by interactions with
CC coactivator and corepressor proteins. Interaction with RANBP9 is
CC mediated by both the N-terminal domain and the DNA-binding domain.
CC Interaction with EFCAB6/DJBP is mediated by the DNA-binding domain (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated in prostate cancer cells in response to several
CC growth factors including EGF. Phosphorylation is induced by c-Src
CC kinase (CSK). Tyr-324 is one of the major phosphorylation sites and an
CC increase in phosphorylation and Src kinase activity is associated with
CC prostate cancer progression (By similarity). Phosphorylation by TNK2
CC enhances the DNA-binding and transcriptional activity. Phosphorylation
CC by CDK9 regulates AR promoter selectivity and cell growth (By
CC similarity). {ECO:0000250|UniProtKB:P10275}.
CC -!- PTM: Sumoylated on Lys-191 (major) and Lys-310 (By similarity).
CC Ubiquitinated. Deubiquitinated by USP26 (By similarity). 'Lys-6' and
CC 'Lys-27'-linked polyubiquitination by RNF6 modulates AR transcriptional
CC activity and specificity (By similarity).
CC {ECO:0000250|UniProtKB:P10275}.
CC -!- PTM: Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required
CC for plasma membrane targeting and for rapid intracellular signaling via
CC ERK and AKT kinases and cAMP generation (By similarity).
CC {ECO:0000250|UniProtKB:P10275}.
CC -!- MISCELLANEOUS: In the absence of ligand, steroid hormone receptors are
CC thought to be weakly associated with nuclear components; hormone
CC binding greatly increases receptor affinity. The hormone-receptor
CC complex appears to recognize discrete DNA sequences upstream of
CC transcriptional start sites.
CC -!- MISCELLANEOUS: Transcriptional activity is enhanced by binding to
CC RANBP9.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
CC subfamily. {ECO:0000305}.
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DR EMBL; U16366; AAC48469.1; -; mRNA.
DR AlphaFoldDB; P49699; -.
DR SMR; P49699; -.
DR STRING; 9986.ENSOCUP00000020480; -.
DR PRIDE; P49699; -.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; P49699; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005497; F:androgen binding; ISS:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0004879; F:nuclear receptor activity; ISS:UniProtKB.
DR GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030521; P:androgen receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030522; P:intracellular receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0045720; P:negative regulation of integrin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; ISS:UniProtKB.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR001103; Andrgn_rcpt.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF02166; Androgen_recep; 1.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00521; ANDROGENR.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; DNA-binding; Isopeptide bond; Lipid-binding; Lipoprotein;
KW Metal-binding; Nucleus; Palmitate; Phosphoprotein; Receptor;
KW Reference proteome; Steroid-binding; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN <1..709
FT /note="Androgen receptor"
FT /id="PRO_0000053711"
FT DOMAIN 458..689
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 348..421
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 349..369
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 385..409
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION <1..376
FT /note="Interaction with ZNF318"
FT /evidence="ECO:0000250|UniProtKB:P19091"
FT REGION <1..347
FT /note="Modulating"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 341..708
FT /note="Interaction with LPXN"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT REGION 361..451
FT /note="Interaction with HIPK3"
FT /evidence="ECO:0000250|UniProtKB:P15207"
FT REGION 381..708
FT /note="Interaction with CCAR1"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT REGION 414..708
FT /note="Interaction with KAT7"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT BINDING 495
FT /ligand="17beta-hydroxy-5alpha-androstan-3-one"
FT /ligand_id="ChEBI:CHEBI:16330"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT BINDING 542
FT /ligand="17beta-hydroxy-5alpha-androstan-3-one"
FT /ligand_id="ChEBI:CHEBI:16330"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT BINDING 667
FT /ligand="17beta-hydroxy-5alpha-androstan-3-one"
FT /ligand_id="ChEBI:CHEBI:16330"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT SITE 510
FT /note="Interaction with coactivator LXXL and FXXFY motifs"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT SITE 687
FT /note="Interaction with coactivator FXXLF and FXXFY motifs"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 32
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 76
FT /note="Phosphotyrosine; by CSK and TNK2"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 116
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 155
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 166
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 171
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 172
FT /note="Phosphotyrosine; by CSK and TNK2"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 198
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 324
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 341
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 440
FT /note="Phosphoserine; by STK4/MST1"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 705
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT CROSSLNK 191
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 310
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 635
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT CROSSLNK 637
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT NON_TER 1
SQ SEQUENCE 709 AA; 77392 MW; 40E7666137E97B6B CRC64;
HHQQQQDAAT EGSSSGRARR PSGASTSSKD SYLGSTSVIS DSAKELCKAV SVSLGLGVEA
LEHLSSGEQL RGDCMYAPLL GGPPVVRPTP CLPLVECKGS LLDDGPGKGT EETAEYTPFK
GGYNKGLEAE SLGCSGSGEA GSSGTLELPS TLSLYKSGTL DEAAAYQTRD YYNFPLALAG
QPPPPHPRRI KLENPLDYGS AWAAAAAQCR YGDLASLHGG GAAGPGSGSP STAASSSWHT
LFTTEEGQLY GLCGGGGGSG PGEAGAVAPY GYTRPPQGLT GQEGDFPAPE VWYPGGVVSR
VPYPNPSCVK SEMGPWMESY SGPYGDMRLE TARDHVLPID YYFPPQKTCL ICGDEASGCH
YGALTCGSCK VFFKRAAEGK QKYLCASRND CTIDKFRRKN CPSCRLRKCY EAGMTLGARK
LKKLGNLKLQ EEGESSSASS PTEDTTQKLT VSHIEGYECQ PIFLNVLEAI EPGVVCAGHD
NNQPDSFAAL LSSLNELGER QLVHVVKWAK ALPGFRNLHV DDQMAVIQYS WMGLMVFAMG
WRSFTNVNSR MLYFAPDLVF NEYRMHKSRM YSQCVRMRHL SQEFGWLQIT PQEFLCMKAL
LLFSIIPVDG LKNQKFFDEL RMNYIKELDR IIACKRKNPT SCSRRFYQLT KLLDSVQPIA
RELHQFTFDL LIKSHMVSVD FPEMMAEIIS VQVPKILSGK VKPIYFHTQ
