ID PRGR_RAT Reviewed; 923 AA.
AC Q63449;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 24-JAN-2024, entry version 177.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Placenta;
RX PubMed=8299566; DOI=10.1210/endo.134.2.8299566;
RA Park-Sarge O.K., Mayo K.E.;
RT "Regulation of the progesterone receptor gene by gonadotropins and cyclic
RT adenosine 3',5'-monophosphate in rat granulosa cells.";
RL Endocrinology 134:709-718(1994).
RN [2]
RP INDUCTION.
RX PubMed=1840636; DOI=10.1210/mend-5-7-967;
RA Park-Sarge O.K., Mayo K.E.;
RT "Transient expression of progesterone receptor messenger RNA in ovarian
RT granulosa cells after the preovulatory luteinizing hormone surge.";
RL Mol. Endocrinol. 5:967-978(1991).
RN [3]
RP ALTERNATIVE PROMOTER USAGE.
RX PubMed=8145766; DOI=10.1210/mend.7.12.8145766;
RA Kraus W.L., Montano M.M., Katzenellenbogen B.S.;
RT "Cloning of the rat progesterone receptor gene 5'-region and identification
RT of two functionally distinct promoters.";
RL Mol. Endocrinol. 7:1603-1616(1993).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=17003284; DOI=10.1677/joe.1.06923;
RA Turgeon J.L., Waring D.W.;
RT "Differential expression and regulation of progesterone receptor isoforms
RT in rat and mouse pituitary cells and LbetaT2 gonadotropes.";
RL J. Endocrinol. 190:837-846(2006).
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 a 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-344.
CC Interacts with PRMT2 (By similarity). Isoform A interacts with NCOR2.
CC Isoform B (but not isoform A) interacts with NCOA2 and NCOA1 (By
CC similarity). Isoform B (but not isoform A) interacts with KLF9.
CC Interacts with GTF2B (By similarity). {ECO:0000250|UniProtKB:P06401,
CC ECO:0000250|UniProtKB:Q00175}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nucleoplasmic shuttling
CC is both hormone- and cell cycle-dependent. On hormone stimulation,
CC retained in the cytoplasm in the G(1) and G(2)/M phases (By
CC similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=B; Synonyms=PRB, PR-B;
CC IsoId=Q63449-1; Sequence=Displayed;
CC Name=A; Synonyms=PRA, PR-A;
CC IsoId=Q63449-2; Sequence=VSP_058744;
CC -!- TISSUE SPECIFICITY: Isoform A and isoform B are expressed in the
CC pituitary. {ECO:0000269|PubMed:17003284}.
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-293 is highly hormone-
CC dependent and modulates ubiquitination and sumoylation on Lys-387.
CC Phosphorylation on Ser-344 also requires induction by hormone. Basal
CC phosphorylation on Ser-82, Ser-190 and Ser-399 is increased in response
CC to progesterone and can be phosphorylated in vitro by the CDK2-A1
CC complex. Increased levels of phosphorylation on Ser-399 also in the
CC presence of EGF, heregulin, IGF, PMA and FBS. Phosphorylation at this
CC site by CDK2 is ligand-independent, and increases nuclear translocation
CC and transcriptional activity. Phosphorylation at Ser-293, but not at
CC Ser-190, is impaired during the G(2)/M phase of the cell cycle.
CC Phosphorylation on Ser-344 by ERK1/2 MAPK is required for interaction
CC with SP1 (By similarity). {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-387, the main site of
CC sumoylation, is repressed by ubiquitination on the same site, and
CC modulated by phosphorylation at Ser-293 (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-293 (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; L16922; AAA19916.1; -; mRNA.
DR PIR; I53280; I53280.
DR RefSeq; NP_074038.1; NM_022847.1.
DR AlphaFoldDB; Q63449; -.
DR SMR; Q63449; -.
DR STRING; 10116.ENSRNOP00000032053; -.
DR BindingDB; Q63449; -.
DR ChEMBL; CHEMBL2596; -.
DR DrugCentral; Q63449; -.
DR iPTMnet; Q63449; -.
DR PhosphoSitePlus; Q63449; -.
DR PaxDb; 10116-ENSRNOP00000032053; -.
DR GeneID; 25154; -.
DR KEGG; rno:25154; -.
DR UCSC; RGD:3317; rat. [Q63449-1]
DR AGR; RGD:3317; -.
DR CTD; 5241; -.
DR RGD; 3317; Pgr.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; Q63449; -.
DR OrthoDB; 5347911at2759; -.
DR PhylomeDB; Q63449; -.
DR Reactome; R-RNO-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-RNO-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-RNO-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-RNO-9018519; Estrogen-dependent gene expression.
DR PRO; PR:Q63449; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0051117; F:ATPase binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0034056; F:estrogen response element binding; IBA:GO_Central.
DR GO; GO:0042562; F:hormone binding; IMP:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004879; F:nuclear receptor activity; ISO:RGD.
DR GO; GO:0003707; F:nuclear steroid receptor activity; IMP:RGD.
DR GO; GO:0003676; F:nucleic acid binding; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0005496; F:steroid binding; IMP:RGD.
DR GO; GO:0001223; F:transcription coactivator binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0071391; P:cellular response to estrogen stimulus; IEP:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEP:RGD.
DR GO; GO:0071371; P:cellular response to gonadotropin stimulus; IEP:RGD.
DR GO; GO:0071373; P:cellular response to luteinizing hormone stimulus; IEP:RGD.
DR GO; GO:1904568; P:cellular response to wortmannin; IEP:RGD.
DR GO; GO:0016101; P:diterpenoid metabolic process; IEP:RGD.
DR GO; GO:0002070; P:epithelial cell maturation; ISO:RGD.
DR GO; GO:0044849; P:estrous cycle; IEP:RGD.
DR GO; GO:0060180; P:female mating behavior; IMP:RGD.
DR GO; GO:0002071; P:glandular epithelial cell maturation; ISO:RGD.
DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0048286; P:lung alveolus development; ISO:RGD.
DR GO; GO:0001553; P:luteinization; IEP:RGD.
DR GO; GO:0030879; P:mammary gland development; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IEP:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:1904709; P:negative regulation of granulosa cell apoptotic process; IMP:RGD.
DR GO; GO:0001542; P:ovulation from ovarian follicle; ISO:RGD.
DR GO; GO:0038001; P:paracrine signaling; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0050847; P:progesterone receptor signaling pathway; ISO:RGD.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:RGD.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0042220; P:response to cocaine; IDA:RGD.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0032570; P:response to progesterone; IEP:RGD.
DR GO; GO:0060748; P:tertiary branching involved in mammary gland duct morphogenesis; ISO:RGD.
DR CDD; cd07172; NR_DBD_GR_PR; 1.
DR CDD; cd07074; NR_LBD_PR; 1.
DR Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1.
DR Gene3D; 1.10.565.10; Retinoid X Receptor; 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 PANTHER; PTHR48092; KNIRPS-RELATED PROTEIN-RELATED; 1.
DR PANTHER; PTHR48092:SF6; PROGESTERONE RECEPTOR; 1.
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; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1.
DR SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 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 promoter usage; 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..923
FT /note="Progesterone receptor"
FT /id="PRO_0000053697"
FT DOMAIN 669..903
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 557..629
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 557..577
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 593..617
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..556
FT /note="Modulating, Pro-Rich"
FT REGION 1..164
FT /note="AF3; mediates transcriptional activation (in isoform
FT B)"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 67..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 152..239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 165..304
FT /note="Mediates transcriptional transrepression (in isoform
FT A)"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT REGION 333..371
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 412..435
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 450..536
FT /note="AF1; mediates transcriptional activation"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT REGION 677..923
FT /note="AF2; mediates transcriptional activation"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOTIF 56..60
FT /note="LXXL motif 1"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOTIF 115..119
FT /note="LXXL motif 2"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOTIF 184..188
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 68..85
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 90..111
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 341..358
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 415..429
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 190
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 293
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 344
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 399
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 666
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 387
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 387
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT CROSSLNK 521
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..164
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000305"
FT /id="VSP_058744"
SQ SEQUENCE 923 AA; 99408 MW; 05384B9656BF22DC CRC64;
MTELQAKDPR TLHTSGAAPS PTHVGSPLLA RLDPDPFQGS QHSDASSVVS PIPISLDRLL
FSRSCQAQEL PDEKTQNQQS LSDVEGAFSG VEASRRRSRN PRAPEKDSRL LDSVLDTLLA
PSGPEQSQTS PPACEAITSW CLFGPELPED PRSVPATKGL LSPLMSRPES KAGDSSGTGA
GQKVLPKAVS PPRQLLLPTS GSAHWPGAGV KPSQQPATVE VEEDGGLETE GSAGPLLKSK
PRALEGMCSG GGVTANAPGA APGGVTLVPK EDSRFSAPRV SLEQDAPVAP GRSPLATTVV
DFIHVPILPL NHALLAARTR QLLEGDSYDG GAAAQVPFAP PRGSPSAPSP PVPCGDFPDC
TYPPEGDPKE DGFPVYGEFQ PPGLKIKEEE EGTEAASRSP RPYLLAGASA ATFPDFPLPP
RPPRAPPSRP GEAAVAAPSA AVSPVSSSGS ALECILYKAE GAPPTQGSFA PLPCKPPAAS
SCLLPRDSLP AAPTSSAAPA IYPPLGLNGL PQLGYQAAVL KDSLPQVYPP YLNYLRPDSE
ASQSPQYGFD SLPQKICLIC GDEASGCHYG VLTCGSCKVF FKRAMEGQHN YLCAGRNDCI
VDKIRRKNCP ACRLRKCCQA GMVLGGRKFK KFNKVRVMRA LDGVALPQSV AFPNESQTLG
QRITFSPNQE IQLVPPLINL LMSIEPDVVY AGHDNTKPDT SSSLLTSLNQ LGERQLLSVV
KWSKSLPGFR NLHIDDQITL IQYSWMSLMV FGLGWRSYKH VSGQMLYFAP DLILNEQRMK
ELSFYSLCLT MWQIPQEFVK LQVTHEEFLC MKVLLLLNTI PLEGLRSQSQ FEEMRSSYIR
ELIKAIGLRQ KGVVPSSQRF YQLTKLLDSL HDLVKQLHLY CLNTFIQSRA LAVEFPEMMS
EVIAAQLPKI LAGMVKPLLF HKK
//
