PRGR_RABIT
ID PRGR_RABIT Reviewed; 930 AA.
AC P06186;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 171.
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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3538016; DOI=10.1073/pnas.83.23.9045;
RA Loosfelt H., Atger M., Misrahi M., Guiochon-Mantel A., Meriel C.,
RA Logeat F., Benarous R., Milgrom E.;
RT "Cloning and sequence analysis of rabbit progesterone-receptor
RT complementary DNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:9045-9049(1986).
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. Transcriptional
CC activator of several progesteron-dependent promoters in a variety of
CC cell types. Involved in activation of SRC-dependent MAPK signaling on
CC hormone stimulation. {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 by
CC ERK1/2-MAPK. Interacts with PRMT2. Interacts with NCOA2 and NCOA1.
CC Interacts with KLF9. Interacts with GTF2B (By similarity).
CC {ECO:0000250|UniProtKB:P06401, 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 -!- 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-102 and Ser-344 also requires induction by
CC hormone. Basal phosphorylation on Ser-82, Ser-191 and Ser-399 is
CC increased in response to progesterone and can be phosphorylated in
CC vitro by the CDK2-A1 complex. Increased levels of phosphorylation on
CC Ser-399 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-293, but not at Ser-191, is impaired during the
CC G(2)/M phase of the cell cycle. Phosphorylation on Ser-344 by ERK1/2
CC 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-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; M14547; AAA31443.1; -; mRNA.
DR PIR; A25923; A25923.
DR RefSeq; NP_001075736.1; NM_001082267.1.
DR AlphaFoldDB; P06186; -.
DR SMR; P06186; -.
DR STRING; 9986.ENSOCUP00000012634; -.
DR BindingDB; P06186; -.
DR ChEMBL; CHEMBL3456; -.
DR DrugCentral; P06186; -.
DR PRIDE; P06186; -.
DR Ensembl; ENSOCUT00000014695; ENSOCUP00000012634; ENSOCUG00000014693.
DR GeneID; 100009094; -.
DR KEGG; ocu:100009094; -.
DR CTD; 5241; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000159713; -.
DR HOGENOM; CLU_014081_0_0_1; -.
DR InParanoid; P06186; -.
DR OMA; YPKSSDE; -.
DR OrthoDB; 615449at2759; -.
DR PRO; PR:P06186; -.
DR Proteomes; UP000001811; Chromosome 1.
DR Bgee; ENSOCUG00000014693; Expressed in uterus and 13 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0051117; F:ATPase binding; IEA:Ensembl.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0004879; F:nuclear receptor activity; IEA:Ensembl.
DR GO; GO:0003707; F:nuclear steroid receptor activity; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
DR GO; GO:0001223; F:transcription coactivator binding; IEA:Ensembl.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002071; P:glandular epithelial cell maturation; IEA:Ensembl.
DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0001542; P:ovulation from ovarian follicle; IEA:Ensembl.
DR GO; GO:0038001; P:paracrine signaling; IEA:Ensembl.
DR GO; GO:0050847; P:progesterone receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0060748; P:tertiary branching involved in mammary gland duct morphogenesis; IEA:Ensembl.
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 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..930
FT /note="Progesterone receptor"
FT /id="PRO_0000053696"
FT DOMAIN 676..910
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 566..640
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 568..588
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 604..628
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..565
FT /note="Modulating, Pro-Rich"
FT REGION 1..165
FT /note="AF3; mediates transcriptional activation"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT REGION 1..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 148..260
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 166..304
FT /note="Mediates transcriptional transrepression"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT REGION 334..356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 415..454
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 457..547
FT /note="AF1; mediates transcriptional activation"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT REGION 684..930
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 116..120
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 36..50
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 416..431
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 131
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 191
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT MOD_RES 212
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 673
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 532
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 930 AA; 98667 MW; 644FF4C13BF2F883 CRC64;
MTELKAKEPR APHVAGGAPS PTEVGSQLLG RPDPGPFQGS QTSEASSVVS AIPISLDGLL
FPRPCQGQNP PDGKTQDPPS LSDVEGAFPG VEAPEGAGDS SSRPPEKDSG LLDSVLDTLL
APSGPGQSHA SPATCEAISP WCLFGPDLPE DPRAAPATKG VLAPLMSRPE DKAGDSSGTA
AAHKVLPRGL SPSRQLLLPS SGSPHWPAVK PSPQPAAVQV DEEDSSESEG TVGPLLKGQP
RALGGTAAGG GAAPVASGAA AGGVALVPKE DSRFSAPRVS LAEQDAPVAP GRSPLATSVV
DFIHVPILPL NHAFLATRTR QLLEGESYDG GAAAASPFVP QRGSPSASST PVAGGDFPDC
TYPPDAEPKD DAFPLYGDFQ PPALKIKEEE EAAEAAARSP RTYLVAGANP AAFPDFQLAA
PPPPSLPPRV PSSRPGEAAV AASPGSASVS SSSSSGSTLE CILYKAEGAP PQQGPFAPLP
CKPPGAGACL LPRDGLPSTS ASGAAAGAAP ALYPTLGLNG LPQLGYQAAV LKEGLPQVYT
PYLNYLRPDS EASQSPQYSF ESLPQKICLI CGDEASGCHY GVLTCGSCKV FFKRAMEGQH
NYLCAGRNDC IVDKIRRKNC PACRLRKCCQ AGMVLGGRKF KKFNKVRVMR ALDAVALPQP
VGIPNESQRI TFSPSQEIQL IPPLINLLMS IEPDVIYAGH DNTKPDTSSS LLTSLNQLGE
RQLLSVVKWS KSLPGFRNLH IDDQITLIQY SWMSLMVFGL GWRSYKHVSG QMLYFAPDLI
LNEQRMKESS FYSLCLTMWQ IPQEFVKLQV SQEEFLCMKV LLLLNTIPLE GLRSQSQFEE
MRSSYIRELI KAIGLRQKGV VSSSQRFYQL TKLLDNLHDL VKQLHLYCLN TFIQSRALSV
EFPEMMSEVI AAQLPKILAG MVKPLLFHKK