ID   PRGR_ATEPA              Reviewed;         935 AA.
AC   A7XW25;
DT   26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT   23-OCT-2007, sequence version 1.
DT   22-FEB-2023, entry version 60.
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   Ateles paniscus (Black spider monkey) (Red-faced black spider monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Atelidae;
OC   Atelinae; Ateles.
OX   NCBI_TaxID=9510;
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-345 also requires induction by hormone. Basal
CC       phosphorylation on Ser-81, Ser-162, Ser-190 and Ser-400 is increased in
CC       response to progesterone and can be phosphorylated in vitro by the
CC       CDK2-A1 complex. Increased levels of phosphorylation on Ser-400 also in
CC       the presence of EGF, heregulin, IGF, PMA and FBS. Phosphorylation at
CC       this site by CDK2 is ligand-independent, and increases nuclear
CC       translocation and transcriptional activity. Phosphorylation at Ser-162
CC       and Ser-294, but not at Ser-190, is impaired during the G(2)/M phase of
CC       the cell cycle. Phosphorylation on Ser-345 by ERK1/2 MAPK is required
CC       for interaction 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-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; DQ485135; ABE73086.1; -; Genomic_DNA.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005654; C:nucleoplasm; IEA:UniProt.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR   GO; GO:0003707; F:nuclear steroid receptor activity; IEA:InterPro.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR   GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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   Steroid-binding; Transcription; Transcription regulation; Ubl conjugation;
KW   Zinc; Zinc-finger.
FT   CHAIN           1..935
FT                   /note="Progesterone receptor"
FT                   /id="PRO_0000375850"
FT   DOMAIN          681..915
FT                   /note="NR LBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT   DNA_BIND        569..641
FT                   /note="Nuclear receptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         569..589
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         605..629
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   REGION          1..568
FT                   /note="Modulating, Pro-Rich"
FT   REGION          1..263
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          331..443
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          456..548
FT                   /note="AF1; mediates transcriptional activation"
FT                   /evidence="ECO:0000250|UniProtKB:P06401"
FT   REGION          689..935
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        70..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         678
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        533
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO)"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   935 AA;  99487 MW;  52104511E82515BF CRC64;
     MTELKAKGXR APHVAGSPSS PKVXSPLPCR QAAXPFPGSQ TSDTLPEVSA LPISLDGLLF
     PRICQGQDPP DEKTQDQQSL SDVEGAYSRV EATRGAGGSS SRPPEKDSGL LDSVLDTLWA
     PSGPGQSQPS PPACEVTSSW CLFGPELPED PPGTSATQRV LSRLMSRSGG KAGDSSGMAA
     AHKVLPRGLS PSRQLLLPTT GSPHWSGAPV KPSPQSAALE VEEEDGSESE DSAGPLLKGK
     PRALGGAAAG GGAAAVPPGA XAGGIALVPK EDSCFSAPRV ALVEQDAPMA PGRSPLATTV
     TDFIHVPILP LSHALLAART RQLLEDESYD GGAGAASAFA PPRSSPSASS TPVPGGDFPD
     CAYAPDAEPK DDAYPVYGDF QPPALKIKEE EEGAEASARS PRSYLVAGAS PAAFPDFPLG
     PPPPLPPRAP PSRPGEAAVT AAPASASVSS ASSSGSTLEC ILYKAEGAPP QQGPFAPPPC
     KAPGAGGCLL PRDSLPSTSA SAAATAAGAA PALYPALGLN GLPQLGYQAA VLKEGLPQVY
     PPYLNYLRPD SEASQSPQYS FESLPQKICL ICGDEASGCH YGVLTCGSCK VFFKRAMEGQ
     HNYLCAGRND CIVDKIRRKN CPACRLRKCC QAGMVLGGRK FKKFNKVRVM RALDAVALPQ
     PVGIPNENQA LSQRFTFSPN QDIQLIPPLI NLLLSIEPDV IYAGHDHTKP DTSSSLLTSL
     NQLGERQLLS VVKWSKSLPG FRNLHIDDQI TLIQYSWMSL MVFGLGWRSY KHVSGQMLYF
     APDLILNEQR MKESSFYSLC LTMWQIPQEF VKLQVSQEEF LCMKVLLLLN TIPLEGLRSQ
     TQFEEMRSSY IRELIKAIGL RQKGVVPSSQ RFYQLTKLLD NLHDLVKQLH LYCLNTFIQS
     RALSVEFPEM MSEVIAAQLP KILAGMVKPL LFHKK
//