ID PRGR_CANFA Reviewed; 939 AA.
AC Q9GLW0;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-APR-2013, entry version 92.
DE RecName: Full=Progesterone receptor;
DE Short=PR;
DE AltName: Full=Nuclear receptor subfamily 3 group C member 3;
GN Name=PGR; Synonyms=NR3C3;
OS Canis familiaris (Dog) (Canis lupus familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae;
OC Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Mammary gland, and Uterus;
RX PubMed=11282275; DOI=10.1016/S0960-0760(00)00173-4;
RA Lantinga-van Leeuwen I.S., van Garderen E., Rutteman G.R., Mol J.A.;
RT "Cloning and cellular localization of the canine progesterone
RT receptor: co-localization with growth hormone in the mammary gland.";
RL J. Steroid Biochem. Mol. Biol. 75:219-228(2000).
CC -!- FUNCTION: The steroid hormones and their receptors are involved in
CC the regulation of eukaryotic gene expression and affect cellular
CC proliferation and differentiation in target tissues. Progesterone
CC receptor isoform B (PRB) is involved in activation of c-SRC/MAPK
CC signaling on hormone stimulation (By similarity).
CC -!- SUBUNIT: Interacts with SMARD1 and UNC45A. Interacts with CUEDC2;
CC the interaction promotes ubiquitination, decreases sumoylation,
CC and repesses transcriptional activity. Interacts with PIAS3; the
CC interaction promotes sumoylation of PR in a hormone-dependent
CC manner, inhibits DNA-binding, and alters nuclear export. Interacts
CC with SP1; the interaction requires ligand-induced phosphorylation
CC on Ser-349 by ERK1/2-MAPK. Interacts with PRMT2 (By similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nucleoplasmic
CC shuttling is both homone- and cell cycle-dependent. On hormone
CC stimulation, retained in the cytoplasm in the G(1) and G(2)/M
CC phases (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B;
CC IsoId=Q9GLW0-1; Sequence=Displayed;
CC Name=A;
CC IsoId=Q9GLW0-2; Sequence=VSP_050763;
CC -!- TISSUE SPECIFICITY: Expressed in mammary gland and uterus.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain,
CC a DNA-binding domain and a C-terminal ligand-binding domain.
CC -!- PTM: Phosphorylated on multiple serine sites. Several of these
CC sites are hormone-dependent. Phosphorylation on Ser-303 occurs
CC preferentially on isoform B, is highly hormone-dependent and
CC modulates ubiquitination and sumoylation on Lys-392.
CC Phosphorylation on Ser-303 and Ser-349 also requires induction by
CC hormone. Basal phosphorylation on Ser-200 and Ser-404 is increased
CC in response to progesterone and can be phosphorylated in vitro by
CC the CDK2-A1 complex. Increased levels of phosphorylation on Ser-
CC 404 also in the presence of EGF, heregulin, IGF, PMA and FBS.
CC Phosphorylation at this site by CDK2 is ligand-independent, and
CC increases nuclear translocation and transcriptional activity.
CC Phosphorylation at Ser-303, but not at Ser-200, is impaired during
CC the G(2)/M phase of the cell cycle. Phosphorylation on Ser-349 by
CC ERK1/2 MAPK is required for interaction with SP1 (By similarity).
CC -!- PTM: Sumoylation is hormone-dependent and represses
CC transcriptional activity. Sumoylation on all three sites is
CC enhanced by PIAS3. Desumoylated by SENP1. Sumoylation on Lys-392,
CC the main site of sumoylation, is repressed by ubiquitination on
CC the same site, and modulated by phosphorylation at Ser-303 (By
CC similarity).
CC -!- PTM: Ubiquitination is hormone-dependent and represses sumoylation
CC on the same site. Promoted by MAPK-mediated phosphorylation on
CC Ser-303 (By similarity).
CC -!- PTM: Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is
CC required for plasma membrane targeting and for rapid intracellular
CC signaling via ERK and AKT kinases and cAMP generation (By
CC similarity).
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
CC subfamily.
CC -!- SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.
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DR EMBL; AF177470; AAG09282.1; -; mRNA.
DR RefSeq; NP_001003074.1; NM_001003074.1.
DR UniGene; Cfa.3484; -.
DR ProteinModelPortal; Q9GLW0; -.
DR SMR; Q9GLW0; 569-646, 688-938.
DR STRING; 9615.ENSCAFP00000005906; -.
DR PRIDE; Q9GLW0; -.
DR GeneID; 403621; -.
DR KEGG; cfa:403621; -.
DR CTD; 5241; -.
DR eggNOG; NOG273252; -.
DR HOGENOM; HOG000290653; -.
DR HOVERGEN; HBG007583; -.
DR InParanoid; Q9GLW0; -.
DR KO; K08556; -.
DR OrthoDB; EOG4TQM93; -.
DR NextBio; 20817126; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IC:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro.
DR GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
DR GO; GO:0003707; F:steroid hormone receptor activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR008946; Nucl_hormone_rcpt_ligand-bd.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd_core.
DR InterPro; IPR000128; Progest_rcpt.
DR InterPro; IPR001723; Str_hrmn_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF02161; Prog_receptor; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00544; PROGESTRONER.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; Str_ncl_receptor; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Complete proteome; Cytoplasm; DNA-binding;
KW Isopeptide bond; Lipid-binding; Lipoprotein; Metal-binding; Nucleus;
KW Palmitate; Phosphoprotein; Receptor; Reference proteome;
KW Steroid-binding; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1 939 Progesterone receptor.
FT /FTId=PRO_0000053692.
FT DNA_BIND 573 645 Nuclear receptor.
FT ZN_FING 573 593 NR C4-type.
FT ZN_FING 609 633 NR C4-type.
FT REGION 1 572 Modulating, Ala/Pro-rich.
FT REGION 687 939 Steroid-binding.
FT MOTIF 193 197 Nuclear localization signal (Potential).
FT COMPBIAS 49 59 Poly-Ala.
FT MOD_RES 20 20 Phosphoserine (By similarity).
FT MOD_RES 141 141 Phosphoserine (By similarity).
FT MOD_RES 200 200 Phosphoserine (By similarity).
FT MOD_RES 303 303 Phosphoserine; by MAPK1 (By similarity).
FT MOD_RES 349 349 Phosphoserine; by MAPK (By similarity).
FT MOD_RES 404 404 Phosphoserine; by CDK2 (By similarity).
FT MOD_RES 682 682 Phosphoserine (By similarity).
FT CROSSLNK 7 7 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO) (By
FT similarity).
FT CROSSLNK 392 392 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO);
FT alternate (By similarity).
FT CROSSLNK 392 392 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate (By similarity).
FT CROSSLNK 537 537 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO) (By
FT similarity).
FT VAR_SEQ 1 174 Missing (in isoform A).
FT /FTId=VSP_050763.
SQ SEQUENCE 939 AA; 98418 MW; 14AB8E535A64F239 CRC64;
MTERTGKDAR APHVAGGAPS PAPAAEPESR RRDGGRLRAS QTSDAPRVAA AAAAAAAAAS
AAPSAPSDRL LFSRRGQGAD PGGKAQDAQP RPDVARADPR LEAASGAGAD SPGPPRQDRG
PLHGAPSTAL RPAGPGQGRS SPAWEPRSPR CPSGPEPPED PRGARSSQGA ACPLMSRPEG
KAGDGCGTAG AHKGPPRGLS PSRQPLPLCP GAHAWPGAAG KAATQPAALG VEDEGGFAAE
GSPGPLLKGK PRPPAGPAAA AGAAPAAPGT APGGTAPVPK EDSRLPAPKG SLAEQDAPAP
GCSPLATTMM DFIHVPILPL GSAFLAARTR QLLEAETYDA GAFAPPRGSP SAPCAPLAAG
DFPDCAYPSD AEPKDDAFPL YGDFQPPALK IKEEEEGAEA AARSPRPYLA AGPHSCVFAD
APPALPALPP LPPRAPSSRP GEGAPAAAAA AGCSASSASS PGPALECVLY KAEGAPPPQG
PFAAAPCRVP GAGACLLPRD GAAAAASAGA AGASPALYQP LGLGALPQLG YQAAVLKEGL
PQVYQPYLNY LRPDSDASQS PQYSFESLPQ KICLICGDEA SGCHYGVLTC GSCKVFFKRA
MEGQHNYLCA GRNDCIVDKI RRKNCPACRL RKCCQAGMVL GGRKFKKFNK VRVMRTLDAV
ALPQPVGIPN ESQALSQRIS FSPSQDIQLI PPLINLLMSI EPDVIYAGHD NTKPDTSSSL
LTSLNQLGER QLLSVVKWSK SLPGFRNLHI DDQITLIQYS WMSLMVFGLG WRSYKHVSGQ
MLYFAPDLIL NEQRMKESSF YSLCLTMWQI PQEFVKLQVS QEEFLCMKVL LLLNTIPLEG
LRSQNQFEEM RSSYIRELIK AIGLRQKGVV SSSQRFYQLT KLLDNLHDLV KQLHLYCLNT
FIQSRALSVE FPEMMSEVIA AQLPKILAGM VKPLLFHKK
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