PRGR_HYLLA
ID PRGR_HYLLA Reviewed; 932 AA.
AC A7X8C2;
DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 1.
DT 03-AUG-2022, entry version 62.
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 Hylobates lar (Common gibbon) (White-handed gibbon).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hylobatidae;
OC Hylobates.
OX NCBI_TaxID=9580;
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-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-81, Ser-162 and Ser-190 is
CC increased in response to progesterone and can be phosphorylated in
CC vitro by the CDK2-A1 complex. Phosphorylation at Ser-162 and Ser-293,
CC but not at Ser-190, is impaired during the G(2)/M phase of the cell
CC cycle. Phosphorylation on Ser-344 by ERK1/2 MAPK is required for
CC 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-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.
CC {ECO:0000305}.
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DR EMBL; DQ234984; ABB72144.1; -; Genomic_DNA.
DR AlphaFoldDB; A7X8C2; -.
DR SMR; A7X8C2; -.
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 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 Steroid-binding; Transcription; Transcription regulation; Ubl conjugation;
KW Zinc; Zinc-finger.
FT CHAIN 1..932
FT /note="Progesterone receptor"
FT /id="PRO_0000375855"
FT DOMAIN 678..912
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 566..638
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 566..586
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 602..626
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..565
FT /note="Modulating, Pro-Rich"
FT REGION 1..254
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..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 414..451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 455..545
FT /note="AF1; mediates transcriptional activation"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT REGION 468..499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 686..932
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..137
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 414..432
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 470..484
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 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 675
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06401"
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 530
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 932 AA; 98903 MW; 93845B89631D5DCB CRC64;
MTELKAKGPR APHVAGGPPS PEVGSPLLCR PAAGQFPGSQ TSDTLPEVSA IPISLDGLLF
PRPCQGQDPS YEKTQDQQSL SDVEGAYSRA EATRGAGGSS SSPPEKESGL LDSVLDTLLA
PSGPRQSQPS PPACEVTSSW SLFGPELPED PPAAPATQGV LSPLMSRSGG KAGDSSGTAA
AHKVLPQGLS PSRQLLLPAS GSPHWSGAPV KPSPQPAAVE VEEEDGSESE DSAGPLLKGK
PRALGGAAAG GAAAVPPGAA AGGVALVPKE DSRFSAPRVA LVEQDAPMAP GRSPLATTVM
DFIHVPILPL NHALLAARTR QLLEDENYDG GAGAASAFAP PRSSPSASST PVAVGDFPDC
AYPPDVEPKD DAYPLYGDFQ PPALKIKEEE EGAEASARTP RSYLVAGANP AAFPDFPLGP
PPPLPPRAPP SRPGEAAVTA APASASVSSA SSSGSTLECI LYKAEGAPPQ QGPFAPPPSK
APGAGGCLPP RDGLPSTAAS ASAAGAAPAL YPALRLNGLP QLGYQAAVLK EGLPQVYPPY
LNYLRPDSEA SQSPQYSFES LPQKICLICG DEASGCHYGV LTCGSCKVFF KRAMEGQHNY
LCAGRNDCIV DKIRRKNCPA CRLRKCCQAG MVLGGRKFKK FNKVRVVRAL DAVALPQPVG
IPNESQVLSQ RITFSPGQDI QLIPPLINLL MSIEPDVIYA GHDNTKPDTS SSLLTSLNQL
GERQLLSVVK WSKSLPGFRN LHIDDQITLI QYSWMSLMVF GLGWRSYKHV SGQMLYFAPD
LILNEQRMKE SSFYSLCLTM WQIPQEFVKL QVSQEEFLCM KVLLLLNTIP LEGLRSQTQF
EEMRASYIRE LIKAIGLRQK GVVSSSQRFY QLTKLLDNLH DLVKQLHLYC LNTFIQSRAL
SVEFPEMMSE VIAAQLPKIL AGMVKPLLFH KK
