PRGR_CANLF
ID PRGR_CANLF Reviewed; 939 AA.
AC Q9GLW0;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 133.
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 lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615 {ECO:0000312|EMBL:AAG09282.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Mammary gland {ECO:0000269|PubMed:11282275}, and
RC Uterus {ECO:0000269|PubMed:11282275};
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 receptor: co-
RT 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 the
CC regulation of eukaryotic gene expression and affect cellular
CC proliferation and differentiation in target tissues. Depending on the
CC isoform, progesterone receptor functions as transcriptional activator
CC or repressor (By similarity). {ECO:0000250|UniProtKB:P06401}.
CC -!- FUNCTION: [Isoform A]: Ligand-dependent transdominant repressor of
CC steroid hormone receptor transcriptional activity including repression
CC of its isoform B, MR and ER. Transrepressional activity may involve
CC recruitment of corepressor NCOR2. {ECO:0000250|UniProtKB:P06401}.
CC -!- FUNCTION: [Isoform B]: Transcriptional activator of several
CC progesteron-dependent promoters in a variety of cell types. Involved in
CC activation of SRC-dependent MAPK signaling on hormone stimulation.
CC {ECO:0000250|UniProtKB:P06401}.
CC -!- SUBUNIT: Interacts with SMARD1 and UNC45A. Interacts with CUEDC2; the
CC interaction promotes ubiquitination, decreases sumoylation, and
CC represses transcriptional activity. Interacts with PIAS3; the
CC interaction promotes sumoylation of PR in a hormone-dependent manner,
CC inhibits DNA-binding, and alters nuclear export. Interacts with SP1;
CC the interaction requires ligand-induced phosphorylation on Ser-349 by
CC ERK1/2-MAPK. Interacts with PRMT2. Isoform A interacts with NCOR2.
CC Isoform B (but not isoform A) interacts with NCOA2 and NCOA1. Isoform B
CC (but not isoform A) interacts with KLF9. Interacts with GTF2B (By
CC similarity). {ECO:0000250|UniProtKB:P06401,
CC ECO:0000250|UniProtKB:Q00175}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407,
CC ECO:0000269|PubMed:11282275}. Cytoplasm {ECO:0000269|PubMed:11282275}.
CC Note=Nucleoplasmic shuttling is both hormone- and cell cycle-dependent.
CC On hormone stimulation, retained in the cytoplasm in the G(1) and
CC G(2)/M phases (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B {ECO:0000269|PubMed:11282275};
CC IsoId=Q9GLW0-1; Sequence=Displayed;
CC Name=A {ECO:0000269|PubMed:11282275};
CC IsoId=Q9GLW0-2; Sequence=VSP_050763;
CC -!- TISSUE SPECIFICITY: Expressed in mammary gland and uterus.
CC {ECO:0000269|PubMed:11282275}.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC DNA-binding domain and a C-terminal ligand-binding domain.
CC -!- PTM: Phosphorylated on multiple serine sites. Several of these sites
CC are hormone-dependent. Phosphorylation on Ser-303 occurs preferentially
CC on isoform B, is highly hormone-dependent and modulates ubiquitination
CC and sumoylation on Lys-392. Phosphorylation on Ser-303 and Ser-349 also
CC requires induction by hormone. Basal phosphorylation on Ser-200 and
CC Ser-404 is increased in response to progesterone and can be
CC phosphorylated in vitro by the CDK2-A1 complex. Increased levels of
CC phosphorylation on Ser-404 also in the presence of EGF, heregulin, IGF,
CC PMA and FBS. Phosphorylation at this site by CDK2 is ligand-
CC independent, and increases nuclear translocation and transcriptional
CC activity. Phosphorylation at Ser-303, but not at Ser-200, is impaired
CC during the G(2)/M phase of the cell cycle. Phosphorylation on Ser-349
CC by ERK1/2 MAPK is required for interaction with SP1 (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Sumoylation is hormone-dependent and represses transcriptional
CC activity. Sumoylation on all three sites is enhanced by PIAS3.
CC Desumoylated by SENP1. Sumoylation on Lys-392, the main site of
CC sumoylation, is repressed by ubiquitination on the same site, and
CC modulated by phosphorylation at Ser-303 (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitination is hormone-dependent and represses sumoylation on
CC the same site. Promoted by MAPK-mediated phosphorylation on Ser-303 (By
CC similarity). {ECO:0000250}.
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). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
CC subfamily. {ECO:0000305}.
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DR EMBL; AF177470; AAG09282.1; -; mRNA.
DR RefSeq; NP_001003074.1; NM_001003074.1. [Q9GLW0-1]
DR AlphaFoldDB; Q9GLW0; -.
DR SMR; Q9GLW0; -.
DR STRING; 9612.ENSCAFP00000005906; -.
DR PaxDb; Q9GLW0; -.
DR Ensembl; ENSCAFT00000006379; ENSCAFP00000005906; ENSCAFG00000003978. [Q9GLW0-1]
DR GeneID; 403621; -.
DR KEGG; cfa:403621; -.
DR CTD; 5241; -.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; Q9GLW0; -.
DR OrthoDB; 615449at2759; -.
DR Proteomes; UP000002254; Unplaced.
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:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0003707; F:nuclear steroid receptor activity; IEA:InterPro.
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:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; IBA:GO_Central.
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; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR000128; Progest_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; 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 Alternative splicing; Cytoplasm; DNA-binding; Isopeptide bond;
KW Lipid-binding; Lipoprotein; Metal-binding; Nucleus; Palmitate;
KW Phosphoprotein; Receptor; Reference proteome; Steroid-binding;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..939
FT /note="Progesterone receptor"
FT /id="PRO_0000053692"
FT DOMAIN 685..919
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 573..645
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 573..593
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 609..633
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..572
FT /note="Modulating, Ala/Pro-rich"
FT REGION 1..302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..174
FT /note="AF3; mediates transcriptional activation (in isoform
FT B)"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT REGION 175..314
FT /note="Mediates transcriptional transrepression (in isoform
FT A)"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT REGION 463..552
FT /note="AF1; mediates transcriptional activation"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT REGION 693..939
FT /note="AF2; mediates transcriptional activation"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOTIF 193..197
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 141
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 303
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 349
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 404
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 682
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT CROSSLNK 7
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 392
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 392
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT CROSSLNK 537
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..174
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:11282275"
FT /id="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
