PRGR_SAPAP
ID PRGR_SAPAP Reviewed; 935 AA.
AC A7XW16;
DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 1.
DT 03-AUG-2022, 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 Sapajus apella (Brown-capped capuchin) (Cebus apella).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae;
OC Cebinae; Sapajus.
OX NCBI_TaxID=9515;
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; DQ485133; ABE73084.1; -; Genomic_DNA.
DR AlphaFoldDB; A7XW16; -.
DR SMR; A7XW16; -.
DR Proteomes; UP000504640; Unplaced.
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 Reference proteome; Steroid-binding; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..935
FT /note="Progesterone receptor"
FT /id="PRO_0000375851"
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..164
FT /note="AF3; mediates transcriptional activation"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 62..158
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 165..305
FT /note="Mediates transcriptional transrepression"
FT /evidence="ECO:0000250|UniProtKB:P06401"
FT REGION 187..233
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 328..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 390..452
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 32..48
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 340..354
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; 99627 MW; 89B3472FC07E7C64 CRC64;
MTELKAKGLR APHVAGSPSS PKVGSPLPCR QATGQFPGSQ TSDTLPEVSA LPISLDGLLF
PRICQAQDPP DEKTQDQQSL SDVEGAYSRV EATRGAGGSS SRPPEKDSGL LDSVLDTLWA
PSGPGQSQPS PPACEVTSSW CLFGPELPED PPAAPATQRV LSPLMSRSGG KAGDSSGMAA
AHKVLPRGLS PSRQLLLPTS GSPHWSGAPV KPSPQPAAVE VEEEDGSESE DSAGLLLKGK
PRALGGAAAG GGAPAVTPGT AAGGIALVPK EDSRFSAPRV ALVEQDAPMA PGRSPLATTV
TDFIHVPILP LSHALLAART RQLLEDESYD GGSGAASAFA PPRSSPSASS TPVPGSDFPD
CAYAPDAEPK DDVYPLYGDF QPPALKIKEE EEGAEASTRS PRSYLVAGAS PTTFPDFPLG
PPPPLPPRAP PSRPGEAAVT AAPASASVSS ASSSGSTLEC ILYKAEGAQP QQGPFAPPPC
KAPGAGGCLL PRDSLPSTSA SAGATAAGAA PALYPALGLN GLPQLGYQAA VIKEGLPQVY
PPYLNYLRPD SETSQSPQYS FESLPQKICL ICGDEASGCH YGVLTCGSCK VFFKRAMEGQ
HNYLCAGRND CIVDKIRRKN CPACRLRKCC QAGMVLGGRK FKKFNKVRVM RALDAVALPQ
PVGIPNENQA LSQRFTFSPS QDIQLIPPLI NLLLSIEPDV IYAGHDNTKP DTSSSLLTSL
NQLGERQLLS VVKWSKSLPG FRNLHIDDQI TLIQYSWMSL MVFGLGWRSY KHVSGQMLYF
APDLILNEQR MKESSFYSLC LTMWQIPQEF VKLQVSQEEF LCMKVLLLLN TIPLEGLRSQ
TQFEEMRSSY IRELIKAIGL RQKGVVSSSQ RFYQLTKLLD NLHDLVKQLH LYCLNTFIQS
RALSVEFPEM MSEVIAAQLP KILAGMVKPL LFHKK
