ANDR_CANLF
ID ANDR_CANLF Reviewed; 907 AA.
AC Q9TT90; Q6WSP7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Androgen receptor;
DE AltName: Full=Dihydrotestosterone receptor;
DE AltName: Full=Nuclear receptor subfamily 3 group C member 4;
GN Name=AR; Synonyms=NR3C4;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11768233; DOI=10.1023/a:1012752107129;
RA Lu B., Smock S.L., Castleberry T.A., Owen T.A.;
RT "Molecular cloning and functional characterization of the canine androgen
RT receptor.";
RL Mol. Cell. Biochem. 226:129-140(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Duan W.R., Kelce W.R., Levin S., Blomme E.A.G.;
RT "Comparision of rat, dog and human androgen receptors.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
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:P15207,
CC 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-522 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 at Ser-67 by CDK9 regulates AR promoter selectivity and cell growth (By
CC similarity). {ECO:0000250|UniProtKB:P10275}.
CC -!- PTM: Sumoylated on Lys-389 (major) and Lys-508 (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; AF197950; AAF18084.1; -; mRNA.
DR EMBL; AY271347; AAQ84563.1; -; mRNA.
DR RefSeq; NP_001003053.1; NM_001003053.1.
DR AlphaFoldDB; Q9TT90; -.
DR SMR; Q9TT90; -.
DR STRING; 9615.ENSCAFP00000024499; -.
DR PaxDb; Q9TT90; -.
DR GeneID; 403588; -.
DR CTD; 367; -.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; Q9TT90; -.
DR OrthoDB; 615449at2759; -.
DR Proteomes; UP000002254; 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:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
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:0030518; P:intracellular steroid hormone receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0008584; P:male gonad development; IBA:GO_Central.
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 GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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..907
FT /note="Androgen receptor"
FT /id="PRO_0000053701"
FT DOMAIN 656..887
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 546..619
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 547..567
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 583..607
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..574
FT /note="Interaction with ZNF318"
FT /evidence="ECO:0000250|UniProtKB:P19091"
FT REGION 1..545
FT /note="Modulating"
FT /evidence="ECO:0000250"
FT REGION 36..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 200..231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 539..906
FT /note="Interaction with LPXN"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT REGION 559..649
FT /note="Interaction with HIPK3"
FT /evidence="ECO:0000250|UniProtKB:P15207"
FT REGION 579..906
FT /note="Interaction with CCAR1"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT REGION 612..906
FT /note="Interaction with KAT7"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT COMPBIAS 51..88
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..110
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 125..152
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 693
FT /ligand="17beta-hydroxy-5alpha-androstan-3-one"
FT /ligand_id="ChEBI:CHEBI:16330"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT BINDING 740
FT /ligand="17beta-hydroxy-5alpha-androstan-3-one"
FT /ligand_id="ChEBI:CHEBI:16330"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT BINDING 865
FT /ligand="17beta-hydroxy-5alpha-androstan-3-one"
FT /ligand_id="ChEBI:CHEBI:16330"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT SITE 708
FT /note="Interaction with coactivator LXXL and FXXFY motifs"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT SITE 885
FT /note="Interaction with coactivator FXXLF and FXXFY motifs"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 67
FT /note="Phosphoserine; by CDK9"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 81
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 228
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 272
FT /note="Phosphotyrosine; by CSK and TNK2"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 310
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 349
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 360
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 365
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 366
FT /note="Phosphotyrosine; by CSK and TNK2"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 396
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 522
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 539
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 638
FT /note="Phosphoserine; by STK4/MST1"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 903
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT CROSSLNK 389
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 508
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 833
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT CROSSLNK 835
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT CONFLICT 123
FT /note="T -> A (in Ref. 2; AAQ84563)"
FT /evidence="ECO:0000305"
FT CONFLICT 183
FT /note="R -> Q (in Ref. 2; AAQ84563)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="Q -> QQ (in Ref. 2; AAQ84563)"
FT /evidence="ECO:0000305"
FT CONFLICT 823
FT /note="I -> V (in Ref. 2; AAQ84563)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 907 AA; 98727 MW; C8619F78DD2338AF CRC64;
MEVQLGLGRV YPRPPSKTYR GAFQNLFQSV REVIQNPGPR HPEAVSAAPP GAHLQQQQQQ
QQQQETSPRQ QQQQQQGDDG SPQAQSRGPT GYLALDEEQQ PSQQRSASKG HPESACVPEP
GVTSATGKGL QQQQPAPPDE NDSAAPSTLS LLGPTFPGLS SCSTDLKDIL SEAGTMQLLQ
QQRQQQQQQQ QQQQQQQQQQ QQEVVSEGSS SGRAREAAGA STSSKDSYLG GSSTISDSAK
ELCKAVSVSM GLGVEALEHL SPGEQLRGDC MYAPLLGGPP AVRPCAPLAE CKGSLLDDGP
GKGTEETAEY SPFKAGYAKG LDGDSLGCSS SSEAGGSGTL EMPSTLSLYK SGALDEAAAY
QSRDYYNFPL SLGGPPPHPP PPHPHTRIKL ENPLDYGSAW AAAAAQCRYG DLASLHGAGA
AGPSSGSPSA TTSSSWHTLF TAEEGQLYGP CGGSGGGSAG DGGSVAPYGY TRPPQGLAGQ
EGDFPPPDVW YPGGVVSRVP FPSPSCVKSE MGSWMESYSG PYGDMRLETA RDHVLPIDYY
FPPQKTCLIC GDEASGCHYG ALTCGSCKVF FKRAAEGKQK YLCASRNDCT IDKFRRKNCP
SCRLRKCYEA GMTLGARKLK KLGNLKLQEE GEASNVTSPT EEPTQKLTVS HIEGYECQPI
FLNVLEAIEP GVVCAGHDNN QPDSFAALLS SLNELGERQL VHVVKWAKAL PGFRNLHVDD
QMAVIQYSWM GLMVFAMGWR SFTNVNSRML YFAPDLVFNE YRMHKSRMYS QCVRMRHLSQ
EFGWLQITPQ EFLCMKALLL FSIIPVDGLK NQKFFDELRM NYIKELDRII ACKRKNPTSC
SRRFYQLTKL LDSVQPIARE LHQFTFDLLI KSHMVSVDFP EMMAEIISVQ VPKILSGKVK
PIYFHTQ
