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Protein

Progesterone receptor

Gene

Pgr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor.By similarity
Isoform A: Ligand-dependent transdominant repressor of steroid hormone receptor transcriptional activity including repression of its isoform B, MR and ER. Transrepressional activity may involve recruitment of corepressor NCOR2.By similarity
Isoform B: Transcriptional activator of several progesteron-dependent promoters in a variety of cell types. Involved in activation of SRC-dependent MAPK signaling on hormone stimulation.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi557 – 632Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri560 – 580NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri596 – 615NR C4-typePROSITE-ProRule annotationAdd BLAST20

GO - Molecular functioni

GO - Biological processi

  • epithelial cell maturation Source: MGI
  • lung alveolus development Source: MGI
  • mammary gland development Source: MGI
  • ovulation from ovarian follicle Source: MGI
  • paracrine signaling Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • progesterone receptor signaling pathway Source: MGI
  • regulation of epithelial cell proliferation Source: MGI
  • regulation of transcription, DNA-templated Source: MGI
  • tertiary branching involved in mammary gland duct morphogenesis Source: MGI

Keywordsi

Molecular functionDNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandLipid-binding, Metal-binding, Steroid-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-3371497. HSP90 chaperone cycle for steroid hormone receptors (SHR).
R-MMU-383280. Nuclear Receptor transcription pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Progesterone receptor
Short name:
PR
Alternative name(s):
Nuclear receptor subfamily 3 group C member 3
Gene namesi
Name:Pgr
Synonyms:Nr3c3, Pr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:97567. Pgr.

Subcellular locationi

  • Nucleus
  • Cytoplasm

  • Note: Nucleoplasmic shuttling is both homone- and cell cycle-dependent. On hormone stimulation, retained in the cytoplasm in the G1 and G2/M phases (By similarity).By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • nucleus Source: MGI

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Infertile. Inability to ovulate, uterine hyperplasia and inflammation, severely limited mammary gland development and an impairment in the induction of a sexual behavioral response (PubMed:8603049). In isoform A-defective mice less oocytes are produced, only a subset of implantation-specific uterine epithelial target genes is regulated, and an increased progesterone-dependent proliferative activity of isoform B in the uterine epithelium is observed. Isoform B-defective mice showed unaffected ovulation (PubMed:10976068).2 Publications

Chemistry databases

ChEMBLiCHEMBL4969.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000536951 – 926Progesterone receptorAdd BLAST926

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki7Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei20PhosphoserineBy similarity1
Modified residuei82PhosphoserineBy similarity1
Modified residuei131PhosphoserineBy similarity1
Modified residuei163PhosphoserineBy similarity1
Modified residuei191PhosphoserineBy similarity1
Modified residuei214PhosphoserineBy similarity1
Modified residuei294Phosphoserine; by MAPK1By similarity1
Modified residuei345Phosphoserine; by MAPKBy similarity1
Cross-linki388Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki388Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei400Phosphoserine; by CDK2By similarity1
Cross-linki524Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei669PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on multiple serine sites. Several of these sites are hormone-dependent. Phosphorylation on Ser-294 is highly hormone-dependent and modulates ubiquitination and sumoylation on Lys-388. Phosphorylation on Ser-345 also requires induction by hormone. Basal phosphorylation on Ser-82, Ser-163, Ser-191 and Ser-400 is increased in response to progesterone and can be phosphorylated in vitro by the CDK2-A1 complex. Increased levels of phosphorylation on Ser-400 also in the presence of EGF, heregulin, IGF, PMA and FBS. Phosphorylation at this site by CDK2 is ligand-independent, and increases nuclear translocation and transcriptional activity. Phosphorylation at Ser-163 and Ser-294, but not at Ser-191, is impaired during the G2/M phase of the cell cycle. Phosphorylation on Ser-345 by ERK1/2 MAPK is required for interaction with SP1 (By similarity).By similarity
Sumoylation is hormone-dependent and represses transcriptional activity. Sumoylation on all three sites is enhanced by PIAS3. Desumoylated by SENP1. Sumoylation on Lys-388, the main site of sumoylation, is repressed by ubiquitination on the same site, and modulated by phosphorylation at Ser-294 (By similarity).By similarity
Ubiquitination is hormone-dependent and represses sumoylation on the same site. Promoted by MAPK-mediated phosphorylation on Ser-294 (By similarity).By similarity
Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ00175.
PRIDEiQ00175.

PTM databases

iPTMnetiQ00175.
PhosphoSitePlusiQ00175.

Expressioni

Tissue specificityi

Expression of isoform A and isoform B in mammary epithelial cells is temporally and spatially separated during normal mammary gland development. Isoform A and isoform B are expressed in the pituitary. Isoform A and isoform B are differentially expressed in the ovary and oviduct, and the level of expression is dependent on both the cell type and estrous cycle stage.3 Publications

Gene expression databases

BgeeiENSMUSG00000031870.
CleanExiMM_PGR.

Interactioni

Subunit structurei

Interacts with SMARD1 and UNC45A. Interacts with CUEDC2; the interaction promotes ubiquitination, decreases sumoylation, and repesses transcriptional activity. Interacts with PIAS3; the interaction promotes sumoylation of PR in a hormone-dependent manner, inhibits DNA-binding, and alters nuclear export. Interacts with SP1; the interaction requires ligand-induced phosphorylation on Ser-294 by ERK1/2 MAPK. Interacts with PRMT2 (By similarity). Isoform A interacts with NCOR2. Isoform B (but not isoform A) interacts with NCOA2 and NCOA1. Isoform B (but not isoform A) interacts with KLF9.By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ00175. 4 interactors.
STRINGi10090.ENSMUSP00000063562.

Structurei

3D structure databases

ProteinModelPortaliQ00175.
SMRiQ00175.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 559Modulating, Pro-RichAdd BLAST559
Regioni1 – 165AF3; mediates transcriptional activation (in isoform B)By similarityAdd BLAST165
Regioni166 – 305Mediates transcriptional transrepression (in isoform A)By similarityAdd BLAST140
Regioni453 – 539AF1; mediates transcriptional activationBy similarityAdd BLAST87
Regioni673 – 926AF2; mediates transcriptional activationBy similarityAdd BLAST254
Regioni674 – 926Steroid-bindingAdd BLAST253

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi56 – 60LXXL motif 1By similarity5
Motifi116 – 120LXXL motif 1By similarity5
Motifi184 – 188Nuclear localization signalSequence analysis5

Domaini

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri560 – 580NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri596 – 615NR C4-typePROSITE-ProRule annotationAdd BLAST20

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00760000118887.
HOGENOMiHOG000290653.
HOVERGENiHBG007583.
InParanoidiQ00175.
KOiK08556.
OMAiCAYPPDA.
OrthoDBiEOG091G04YC.
TreeFamiTF106510.

Family and domain databases

Gene3Di3.30.50.10. 1 hit.
InterProiView protein in InterPro
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR000128. Progest_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
PfamiView protein in Pfam
PF00104. Hormone_recep. 1 hit.
PF02161. Prog_receptor. 1 hit.
PF00105. zf-C4. 1 hit.
PRINTSiPR00544. PROGESTRONER.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiView protein in SMART
SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
SUPFAMiSSF48508. SSF48508. 2 hits.
PROSITEiView protein in PROSITE
PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative promoter usage. AlignAdd to basket

Isoform B (identifier: Q00175-1) [UniParc]FASTAAdd to basket
Also known as: PRB, PR-B

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTELQAKDPQ VLHTSGASPS PPHIGSPLLA RLDSGPFQGS QHSDVSSVVS
60 70 80 90 100
PIPISLDGLL FPRSCRGPEL PDGKTGDQQS LSDVEGAFSG VEATHREGGR
110 120 130 140 150
NSRAPEKDSR LLDSVLDSLL TPSGTEQSHA SPPACEAITS WCLFGPELPE
160 170 180 190 200
DPRSVPATKG LLSPLMSRPE IKAGDSSGTG AGQKVLPKGL SPPRQLLLPT
210 220 230 240 250
SGSAHWPGAG VKPSPQPAAG EVEEDSGLET EGSAAPLLKS KPRALEGTGS
260 270 280 290 300
GGGVAANAAS AAPGGVTLVP KEDSRFSAPR VSLEQDSPIA PGRSPLATTV
310 320 330 340 350
VDFIHVPILP LNHALLAART RQLLEGDSYD GGATAQGPFA PPRGSPSAPS
360 370 380 390 400
PPVPCGDFPD CTYPLEGDPK EDVFPLYGDF QTPGLKIKEE EEGADAAVRS
410 420 430 440 450
PRPYLSAGAS SSTFPDFPLA PAPQRAPSSR PGEAAVAGGP SSAAVSPASS
460 470 480 490 500
SGSALECILY KAEGAPPTQG SFAPLPCKPP AAGSCLLPRD SLPAAPATAA
510 520 530 540 550
APAIYQPLGL NGLPQLGYQA AVLKDSLPQV YPPYLNYLRP DSEASQSPQY
560 570 580 590 600
GFDSLPQKIC LICGDEASGC HYGVLTCGSC KVFFKRAMEG QHNYLCAGRN
610 620 630 640 650
DCIVDKIRRK NCPACRLRKC CQAGMVLGGR KFKKFNKVRV MRTLDGVALP
660 670 680 690 700
QSVGLPNESQ ALGQRITFSP NQEIQLVPPL INLLMSIEPD VVYAGHDNTK
710 720 730 740 750
PDTSSSLLTS LNQLGERQLL SVVKWSKSLP GFRNLHIDDQ ITLIQYSWMS
760 770 780 790 800
LMVFGLGWRS YKHVSGQMLY FAPDLILNEQ RMKELSFYSL CLTMWQIPQE
810 820 830 840 850
FVKLQVTHEE FLCMKVLLLL NTIPLEGLRS QSQFEEMRSS YIRELIKAIG
860 870 880 890 900
LRQKGVVPSS QRFYQLTKLL DSLHDLVKQL HLYCLNTFIQ SRTLAVEFPE
910 920
MMSEVIAAQL PKILAGMVKP LLFHKK
Length:926
Mass (Da):98,981
Last modified:January 18, 2017 - v2
Checksum:iE26DDDE9529996A7
GO
Isoform A (identifier: Q00175-2) [UniParc]FASTAAdd to basket
Also known as: PRA, PR-A

The sequence of this isoform differs from the canonical sequence as follows:
     1-165: Missing.

Show »
Length:761
Mass (Da):81,746
Checksum:i0C457B06AE0BA0BA
GO

Sequence cautioni

The sequence AAA39971 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti104A → P in AAA39971 (PubMed:2069958).Curated1
Sequence conflicti125T → P in AAA39971 (PubMed:2069958).Curated1
Sequence conflicti173 – 181AGDSSGTGA → VGDQSGTGR in AAA39971 (PubMed:2069958).Curated9
Sequence conflicti235A → S in AAA39971 (PubMed:2069958).Curated1
Sequence conflicti250S → Q in AAA39971 (PubMed:2069958).Curated1
Sequence conflicti259A → P in AAA39971 (PubMed:2069958).Curated1
Sequence conflicti327D → E in AAA39971 (PubMed:2069958).Curated1
Sequence conflicti351 – 355PPVPC → TPVPR in AAA39971 (PubMed:2069958).Curated5
Sequence conflicti425R → A in AAA39971 (PubMed:2069958).Curated1
Sequence conflicti464Missing in AAA39971 (PubMed:2069958).Curated1
Sequence conflicti483G → A in AAA39971 (PubMed:2069958).Curated1
Sequence conflicti497A → G in AAA39971 (PubMed:2069958).Curated1
Sequence conflicti663G → S in AAA39971 (PubMed:2069958).Curated1
Sequence conflicti692V → I in AAA39971 (PubMed:2069958).Curated1
Sequence conflicti859S → T in AAA39971 (PubMed:2069958).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0587431 – 165Missing in isoform A. CuratedAdd BLAST165

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M68915 mRNA. Translation: AAA39971.1. Sequence problems.
AC113506 Genomic DNA. No translation available.
AC160964 Genomic DNA. No translation available.
CH466522 Genomic DNA. Translation: EDL24960.1.
BC145807 mRNA. Translation: AAI45808.1.
U12644 Genomic DNA. Translation: AAA66067.1.
CCDSiCCDS22816.1. [Q00175-1]
PIRiA39596.
RefSeqiNP_032855.2. NM_008829.2. [Q00175-1]
UniGeneiMm.12798.
Mm.437703.

Genome annotation databases

EnsembliENSMUST00000070463; ENSMUSP00000063562; ENSMUSG00000031870. [Q00175-1]
ENSMUST00000098986; ENSMUSP00000096584; ENSMUSG00000031870. [Q00175-2]
ENSMUST00000189181; ENSMUSP00000140124; ENSMUSG00000031870. [Q00175-1]
GeneIDi18667.
KEGGimmu:18667.
UCSCiuc009odo.1. mouse.

Keywords - Coding sequence diversityi

Alternative promoter usage

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M68915 mRNA. Translation: AAA39971.1. Sequence problems.
AC113506 Genomic DNA. No translation available.
AC160964 Genomic DNA. No translation available.
CH466522 Genomic DNA. Translation: EDL24960.1.
BC145807 mRNA. Translation: AAI45808.1.
U12644 Genomic DNA. Translation: AAA66067.1.
CCDSiCCDS22816.1. [Q00175-1]
PIRiA39596.
RefSeqiNP_032855.2. NM_008829.2. [Q00175-1]
UniGeneiMm.12798.
Mm.437703.

3D structure databases

ProteinModelPortaliQ00175.
SMRiQ00175.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ00175. 4 interactors.
STRINGi10090.ENSMUSP00000063562.

Chemistry databases

ChEMBLiCHEMBL4969.

PTM databases

iPTMnetiQ00175.
PhosphoSitePlusiQ00175.

Proteomic databases

PaxDbiQ00175.
PRIDEiQ00175.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000070463; ENSMUSP00000063562; ENSMUSG00000031870. [Q00175-1]
ENSMUST00000098986; ENSMUSP00000096584; ENSMUSG00000031870. [Q00175-2]
ENSMUST00000189181; ENSMUSP00000140124; ENSMUSG00000031870. [Q00175-1]
GeneIDi18667.
KEGGimmu:18667.
UCSCiuc009odo.1. mouse.

Organism-specific databases

MGIiMGI:97567. Pgr.

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00760000118887.
HOGENOMiHOG000290653.
HOVERGENiHBG007583.
InParanoidiQ00175.
KOiK08556.
OMAiCAYPPDA.
OrthoDBiEOG091G04YC.
TreeFamiTF106510.

Enzyme and pathway databases

ReactomeiR-MMU-3371497. HSP90 chaperone cycle for steroid hormone receptors (SHR).
R-MMU-383280. Nuclear Receptor transcription pathway.

Miscellaneous databases

PROiPR:Q00175.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031870.
CleanExiMM_PGR.

Family and domain databases

Gene3Di3.30.50.10. 1 hit.
InterProiView protein in InterPro
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR000128. Progest_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
PfamiView protein in Pfam
PF00104. Hormone_recep. 1 hit.
PF02161. Prog_receptor. 1 hit.
PF00105. zf-C4. 1 hit.
PRINTSiPR00544. PROGESTRONER.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiView protein in SMART
SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
SUPFAMiSSF48508. SSF48508. 2 hits.
PROSITEiView protein in PROSITE
PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiPRGR_MOUSE
AccessioniPrimary (citable) accession number: Q00175
Secondary accession number(s): A6H6A5, E9QPW3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: January 18, 2017
Last modified: June 7, 2017
This is version 155 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.