ID   PRGR_PANTR              Reviewed;         933 AA.
AC   A7X8B3;
DT   26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT   23-OCT-2007, sequence version 1.
DT   08-NOV-2023, entry version 80.
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   Pan troglodytes (Chimpanzee).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pan.
OX   NCBI_TaxID=9598;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=18375150; DOI=10.1016/j.ympev.2007.12.026;
RA   Chen C., Opazo J.C., Erez O., Uddin M., Santolaya-Forgas J., Goodman M.,
RA   Grossman L.I., Romero R., Wildman D.E.;
RT   "The human progesterone receptor shows evidence of adaptive evolution
RT   associated with its ability to act as a transcription factor.";
RL   Mol. Phylogenet. Evol. 47:637-649(2008).
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-345 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-294 is highly hormone-
CC       dependent and modulates ubiquitination and sumoylation on Lys-388.
CC       Phosphorylation on Ser-102 and Ser-345 requires induction by hormone.
CC       Basal phosphorylation on Ser-81, Ser-162, Ser-190 and Ser-400 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-400 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-162 and Ser-294, but not at Ser-190, is impaired
CC       during the G(2)/M phase of the cell cycle. Phosphorylation on Ser-345
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-388, the main site of
CC       sumoylation, is repressed by ubiquitination on the same site, and
CC       modulated by phosphorylation at Ser-294 (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-294 (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.
CC       {ECO:0000305}.
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DR   EMBL; DQ234980; ABB72140.1; -; Genomic_DNA.
DR   RefSeq; NP_001129085.1; NM_001135613.1.
DR   STRING; 9598.ENSPTRP00000007237; -.
DR   PaxDb; 9598-ENSPTRP00000007237; -.
DR   GeneID; 451502; -.
DR   KEGG; ptr:451502; -.
DR   CTD; 5241; -.
DR   eggNOG; KOG3575; Eukaryota.
DR   InParanoid; A7X8B3; -.
DR   OrthoDB; 5347911at2759; -.
DR   Proteomes; UP000002277; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005654; C:nucleoplasm; IEA:UniProt.
DR   GO; GO:0034056; F:estrogen response element binding; IBA:GO_Central.
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: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   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   3: Inferred from homology;
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..933
FT                   /note="Progesterone receptor"
FT                   /id="PRO_0000375858"
FT   DOMAIN          679..913
FT                   /note="NR LBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT   DNA_BIND        567..639
FT                   /note="Nuclear receptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         567..587
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         603..627
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   REGION          1..566
FT                   /note="Modulating, Pro-Rich"
FT   REGION          1..260
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1..164
FT                   /note="AF3; mediates transcriptional activation"
FT                   /evidence="ECO:0000250|UniProtKB:P06401"
FT   REGION          165..305
FT                   /note="Mediates transcriptional transrepression"
FT                   /evidence="ECO:0000250|UniProtKB:P06401"
FT   REGION          329..443
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          456..546
FT                   /note="AF1; mediates transcriptional activation"
FT                   /evidence="ECO:0000250|UniProtKB:P06401"
FT   REGION          687..933
FT                   /note="AF2; mediates transcriptional activation"
FT                   /evidence="ECO:0000250|UniProtKB:P06401"
FT   MOTIF           55..59
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           183..187
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        67..84
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        120..135
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        415..433
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         81
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         294
FT                   /note="Phosphoserine; by MAPK1"
FT                   /evidence="ECO:0000250|UniProtKB:P06401"
FT   MOD_RES         345
FT                   /note="Phosphoserine; by MAPK"
FT                   /evidence="ECO:0000250|UniProtKB:P06401"
FT   MOD_RES         400
FT                   /note="Phosphoserine; by CDK2"
FT                   /evidence="ECO:0000250|UniProtKB:P06401"
FT   MOD_RES         676
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P06401"
FT   CROSSLNK        388
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO); alternate"
FT                   /evidence="ECO:0000250"
FT   CROSSLNK        388
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin); alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P06401"
FT   CROSSLNK        531
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO)"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   933 AA;  98944 MW;  9886EEAA06B2F61F CRC64;
     MTELKAKGPR APHVAGGPPS PEVGSPLLCR PAAGPFPGSQ TSDTLPEVSA IPISLDGLLF
     PRPCQGQDPS NEKTQDQQSL SDVEGAYSRA EATRGAGGSS SSPPEKDSGL LDSVLDTLLA
     PSGPGQSQPS PPACEVTSSW CLFGPELPED PPAAPATQGV LSPLMSRSGC KAGDSSGTAA
     AHKVLPRGLS PSRQLLLPAS GSPHWSGAPV KPSPQPAAVE VEEEDGSESE ESAGPLLKGK
     PRALGGAAAG GGAAAVPPGA AAGGVALVPK EDSRFSAPRV ALVEQDAPMA PXRSPLATTM
     MDFIHVPILP LNHALLAART RQLLEDESYD GGAGAXSAFA PPRSSPSASS TPVAVGDFPD
     CAYPPDAEPK DDAYPLYSDF QPPALKIKEE EEGAEASARS PRSYLVAGAN PAAFPDFPLG
     PPPPLPPRAP PSRPGEAAVT AAPASASVSS ASSSGSTLEC ILYKAEGAPP QQGPFAPPPC
     KAPGASGCLL PRDGLPSTSA SAAAAGAAPA LYPALGLNGL PQLGYQAAVL KEGLPQVYPP
     YLNYLRPDSE ASQSPQYSFE SLPQKICLIC GDEASGCHYG VLTCGSCKVF FKRAMEGQHN
     YLCAGRNDCI VDKIRRKNCP ACRLRKCCQA GMVLGGRKFK KFNKVRVVRA LDAVALPQPV
     GIPNESQALS QRFTFSPGQD IQLIPPLINL LMSIEPDVIY AGHDNTKPDT SSSLLTSLNQ
     LGERQLLSVV KWSKSLPGFR NLHIDDQITL IQYSWMSLMV FGLGWRSYKH VSGQMLYFAP
     DLILNEQRMK ESSFYSLCLT MWQIPQEFVK LQVSQEEFLC MKVLLLLNTI PLEGLRSQTQ
     FEEMRSSYIR ELIKAIGLRQ KGVVSSSQRF YQLTKLLDNL HDLVKQLHLY CLNTFIQSRA
     LSVEFPEMMS EVIAAQLPKI LAGMVKPLLF HKK
//