ANDR_PIG
ID ANDR_PIG Reviewed; 896 AA.
AC Q9GKL7; Q9GKN9;
DT 21-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 3.
DT 03-AUG-2022, entry version 146.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pituitary;
RA Song J.H., Fahrenkrug S.C., Rohrer G.A., Wise T.H., Ford J.J.;
RT "Sus scrofa androgen receptor (AR) coding sequence.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11086548; DOI=10.1046/j.1365-2052.2000.00654.x;
RA Trakooljul N., Ponsuksili S., Schellander K., Wimmers K.;
RT "A highly polymorphic repetitive polypyrimidine/polypurine (CCTTT)n
RT sequence in the 5' untranslated sequence of the porcine androgen receptor
RT gene.";
RL Anim. Genet. 31:288-289(2000).
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-511 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-65 by CDK9 regulates AR promoter selectivity and cell growth (By
CC similarity). {ECO:0000250|UniProtKB:P10275}.
CC -!- PTM: Sumoylated on Lys-378 (major) and Lys-497 (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; AF202775; AAG37994.1; -; mRNA.
DR EMBL; AF161717; AAG40566.1; -; mRNA.
DR RefSeq; NP_999479.2; NM_214314.2.
DR AlphaFoldDB; Q9GKL7; -.
DR SMR; Q9GKL7; -.
DR STRING; 9823.ENSSSCP00000013166; -.
DR PaxDb; Q9GKL7; -.
DR GeneID; 397582; -.
DR KEGG; ssc:397582; -.
DR CTD; 367; -.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; Q9GKL7; -.
DR OrthoDB; 615449at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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..896
FT /note="Androgen receptor"
FT /id="PRO_0000053710"
FT DOMAIN 645..876
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 535..608
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 536..556
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 572..596
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..563
FT /note="Interaction with ZNF318"
FT /evidence="ECO:0000250|UniProtKB:P19091"
FT REGION 1..534
FT /note="Modulating"
FT /evidence="ECO:0000250"
FT REGION 35..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 178..218
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 528..895
FT /note="Interaction with LPXN"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT REGION 548..638
FT /note="Interaction with HIPK3"
FT /evidence="ECO:0000250|UniProtKB:P15207"
FT REGION 568..895
FT /note="Interaction with CCAR1"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT REGION 601..895
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..111
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 178..204
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 682
FT /ligand="17beta-hydroxy-5alpha-androstan-3-one"
FT /ligand_id="ChEBI:CHEBI:16330"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT BINDING 729
FT /ligand="17beta-hydroxy-5alpha-androstan-3-one"
FT /ligand_id="ChEBI:CHEBI:16330"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT BINDING 854
FT /ligand="17beta-hydroxy-5alpha-androstan-3-one"
FT /ligand_id="ChEBI:CHEBI:16330"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT SITE 697
FT /note="Interaction with coactivator LXXL and FXXFY motifs"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT SITE 874
FT /note="Interaction with coactivator FXXLF and FXXFY motifs"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 65
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 215
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 248
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 259
FT /note="Phosphotyrosine; by CSK and TNK2"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 299
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 338
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 354
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 355
FT /note="Phosphotyrosine; by CSK and TNK2"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 385
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 511
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 528
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 627
FT /note="Phosphoserine; by STK4/MST1"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT MOD_RES 892
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT CROSSLNK 378
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 497
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 822
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT CROSSLNK 824
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10275"
FT CONFLICT 13
FT /note="R -> W (in Ref. 2; AAG40566)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="Missing (in Ref. 2; AAG40566)"
FT /evidence="ECO:0000305"
FT CONFLICT 256
FT /note="D -> G (in Ref. 2; AAG40566)"
FT /evidence="ECO:0000305"
FT CONFLICT 323
FT /note="A -> E (in Ref. 2; AAG40566)"
FT /evidence="ECO:0000305"
FT CONFLICT 352
FT /note="R -> N (in Ref. 1; AAG37994)"
FT /evidence="ECO:0000305"
FT CONFLICT 363
FT /note="G -> R (in Ref. 2; AAG40566)"
FT /evidence="ECO:0000305"
FT CONFLICT 410
FT /note="P -> S (in Ref. 2; AAG40566)"
FT /evidence="ECO:0000305"
FT CONFLICT 820..823
FT /note="ACKR -> VMQE (in Ref. 2; AAG40566)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 896 AA; 97137 MW; 43DD668E3FFDC796 CRC64;
MEVQLGLGRV YPRPPSKTFR GAFQNLFQSV REVIQNPGPR HPEAASAAPP GARLQQQQLQ
QQETSPRRQQ QQQQQPSEDG SPQVQSRGPT GYLALDEKQQ PSQQQSAPEC HPESGCTPEP
GAASAASKGL QQQPPAPPDE DDSAAPSTLS LLGPTFPGLS SCSTDLKDIL SEAGTMQLLQ
QQQQQQQQQE AVSEGNSSGR AREATGAPIS SKDSYLGGSS TISDSAKELC KAVSVSMGLG
VEALEHLSPG EQLRGDCMYA PLLTGPPSVR PTPCAPLAEC KGSLLDDGPG KSNEETAEYS
PFKAGYTKGL DSESLGCSSG GEAGGSGTLE LPSALSLYKS GALDDVAAYP SRDYYNFPLA
LAGPPPPPPP PHPHARIKLE NPLDYGSAWA AAAAQCRYGD LASLHGGGAP GPGSGSPSAT
SSSSWHTLFT AEESQLYGPC GGGGGGSAGE AGAVAPYGYT RPPQGLAGQE GDLAIPDIWY
PGGVVSRVPY PSPSCVKSEM GPWMESYSGP YGDMRLEPTR DHVLPIDYYF PPQKTCLICG
DEASGCHYGA LTCGSCKVFF KRAAEGKQKY LCASRNDCTI DKFRRKNCPS CRLRKCYEAG
MTLGARKLKK LGNLKLQEEG EASSATSPTE EPAQKLTVSH IEGYECQPIF LNVLEAIEPG
VVCAGHDNNQ PDSFAALLSS LNELGERQLV HVVKWAKALP GFRNLHVDDQ MAVIQYSWMG
LMVFAMGWRS FTNVNSRMLY FAPDLVFNEY RMHKSRMYSQ CVRMRHLSQE FGWLQITPQE
FLCMKALLLF SIIPVDGLKN QKFFDELRMN YIKELDRIIA CKRKNPTSCS RRFYQLTKLL
DSVQPIAREL HQFTFDLLIK SHMVSVDFPE MMAEIISVQV PKILSGKVKP IYFHTQ
