PRGR_GORGO
ID PRGR_GORGO Reviewed; 933 AA.
AC A7X8B7;
DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 1.
DT 03-AUG-2022, entry version 91.
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 Gorilla gorilla gorilla (Western lowland gorilla).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Gorilla.
OX NCBI_TaxID=9595;
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 also requires induction by
CC hormone. Basal phosphorylation on Ser-81, Ser-162, Ser-190 and Ser-400
CC is 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; DQ234982; ABB72142.1; -; Genomic_DNA.
DR RefSeq; XP_004052058.1; XM_004052010.2.
DR AlphaFoldDB; A7X8B7; -.
DR SMR; A7X8B7; -.
DR STRING; 9593.ENSGGOP00000024814; -.
DR Ensembl; ENSGGOT00000027848; ENSGGOP00000024814; ENSGGOG00000016358.
DR GeneID; 101152212; -.
DR KEGG; ggo:101152212; -.
DR CTD; 5241; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000159713; -.
DR InParanoid; A7X8B7; -.
DR OMA; YPKSSDE; -.
DR OrthoDB; 615449at2759; -.
DR Proteomes; UP000001519; Chromosome 11.
DR Bgee; ENSGGOG00000016358; Expressed in heart and 1 other tissue.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProt.
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; IBA:GO_Central.
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; IBA:GO_Central.
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:0030518; P:intracellular steroid hormone receptor signaling pathway; IBA:GO_Central.
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:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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 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_0000375854"
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..256
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..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 415..452
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 68..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; 98830 MW; 9C1080538291E6E6 CRC64;
MTELKAKGPR APHVAGGPPS PEVGSPLLCR PAAGPYPGSQ TSDTLPEVSA IPISLDGLLF
PRPCQGQDPS DEKTQDQQSL SDVEGAYSRA EATRGAGGSS SSPPEKDSGL LDSVLETLLA
PSGPGQSQPS PPACEVTSSW CLFGPELPED PPAAPATQGV LSPLMSRSGG KAGDSSGTAA
AHKVLPRGLS PSRQLLLPVS GSPHWSGAPV KPSPQPAAVE VEEEDGSESE ESAGPLLKGK
PRALGGAAAG GGAAAVPPGA AAGGVALVPK EDSRFSAPRV ALVEQDAPMA PGRSPLATTV
MDFIHVPILP LNHALLAART RQLLEDESYD GGAGAASAFA 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
