Q00175 · PRGR_MOUSE
- ProteinProgesterone receptor
- GenePgr
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids926 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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 a transcriptional activator or repressor.
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.
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.
Features
Showing features for dna binding, binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProgesterone receptor
- Short namesPR
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ00175
- Secondary accessions
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
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).
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).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 36 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, cross-link, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000053695 | 1-926 | Progesterone receptor | |||
Sequence: MTELQAKDPQVLHTSGASPSPPHIGSPLLARLDSGPFQGSQHSDVSSVVSPIPISLDGLLFPRSCRGPELPDGKTGDQQSLSDVEGAFSGVEATHREGGRNSRAPEKDSRLLDSVLDSLLTPSGTEQSHASPPACEAITSWCLFGPELPEDPRSVPATKGLLSPLMSRPEIKAGDSSGTGAGQKVLPKGLSPPRQLLLPTSGSAHWPGAGVKPSPQPAAGEVEEDSGLETEGSAAPLLKSKPRALEGTGSGGGVAANAASAAPGGVTLVPKEDSRFSAPRVSLEQDSPIAPGRSPLATTVVDFIHVPILPLNHALLAARTRQLLEGDSYDGGATAQGPFAPPRGSPSAPSPPVPCGDFPDCTYPLEGDPKEDVFPLYGDFQTPGLKIKEEEEGADAAVRSPRPYLSAGASSSTFPDFPLAPAPQRAPSSRPGEAAVAGGPSSAAVSPASSSGSALECILYKAEGAPPTQGSFAPLPCKPPAAGSCLLPRDSLPAAPATAAAPAIYQPLGLNGLPQLGYQAAVLKDSLPQVYPPYLNYLRPDSEASQSPQYGFDSLPQKICLICGDEASGCHYGVLTCGSCKVFFKRAMEGQHNYLCAGRNDCIVDKIRRKNCPACRLRKCCQAGMVLGGRKFKKFNKVRVMRTLDGVALPQSVGLPNESQALGQRITFSPNQEIQLVPPLINLLMSIEPDVVYAGHDNTKPDTSSSLLTSLNQLGERQLLSVVKWSKSLPGFRNLHIDDQITLIQYSWMSLMVFGLGWRSYKHVSGQMLYFAPDLILNEQRMKELSFYSLCLTMWQIPQEFVKLQVTHEEFLCMKVLLLLNTIPLEGLRSQSQFEEMRSSYIRELIKAIGLRQKGVVPSSQRFYQLTKLLDSLHDLVKQLHLYCLNTFIQSRTLAVEFPEMMSEVIAAQLPKILAGMVKPLLFHKK | ||||||
Cross-link | 7 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | ||||||
Modified residue | 20 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 82 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 131 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 163 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 191 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 214 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 294 | Phosphoserine; by MAPK1 | ||||
Sequence: S | ||||||
Modified residue | 345 | Phosphoserine; by MAPK | ||||
Sequence: S | ||||||
Cross-link | 388 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||||
Sequence: K | ||||||
Cross-link | 388 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate | ||||
Sequence: K | ||||||
Modified residue | 400 | Phosphoserine; by CDK2 | ||||
Sequence: S | ||||||
Cross-link | 524 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | ||||||
Modified residue | 669 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
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).
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).
Ubiquitination is hormone-dependent and represses sumoylation on the same site (By similarity).
Promoted by MAPK-mediated phosphorylation on Ser-294 (By similarity).
Ubiquitinated by UBR5, leading to its degradation: UBR5 specifically recognizes and binds ligand-bound PGR when it is not associated with coactivators (NCOAs) (By similarity).
In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation (By similarity).
Promoted by MAPK-mediated phosphorylation on Ser-294 (By similarity).
Ubiquitinated by UBR5, leading to its degradation: UBR5 specifically recognizes and binds ligand-bound PGR when it is not associated with coactivators (NCOAs) (By similarity).
In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation (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).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
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.
Gene expression databases
Interaction
Subunit
Interacts with SMARD1 and UNC45A. Interacts with CUEDC2; the interaction promotes ubiquitination, decreases sumoylation, and represses 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.
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.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q00175 | Esr1 P19785 | 5 | EBI-346821, EBI-346765 | |
BINARY | Q00175 | Stat3 P42227 | 4 | EBI-346821, EBI-602878 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region, motif, zinc finger, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-21 | Polar residues | ||||
Sequence: MTELQAKDPQVLHTSGASPSP | ||||||
Region | 1-48 | Disordered | ||||
Sequence: MTELQAKDPQVLHTSGASPSPPHIGSPLLARLDSGPFQGSQHSDVSSV | ||||||
Region | 1-165 | AF3; mediates transcriptional activation (in isoform B) | ||||
Sequence: MTELQAKDPQVLHTSGASPSPPHIGSPLLARLDSGPFQGSQHSDVSSVVSPIPISLDGLLFPRSCRGPELPDGKTGDQQSLSDVEGAFSGVEATHREGGRNSRAPEKDSRLLDSVLDSLLTPSGTEQSHASPPACEAITSWCLFGPELPEDPRSVPATKGLLSPL | ||||||
Region | 1-559 | Modulating, Pro-Rich | ||||
Sequence: MTELQAKDPQVLHTSGASPSPPHIGSPLLARLDSGPFQGSQHSDVSSVVSPIPISLDGLLFPRSCRGPELPDGKTGDQQSLSDVEGAFSGVEATHREGGRNSRAPEKDSRLLDSVLDSLLTPSGTEQSHASPPACEAITSWCLFGPELPEDPRSVPATKGLLSPLMSRPEIKAGDSSGTGAGQKVLPKGLSPPRQLLLPTSGSAHWPGAGVKPSPQPAAGEVEEDSGLETEGSAAPLLKSKPRALEGTGSGGGVAANAASAAPGGVTLVPKEDSRFSAPRVSLEQDSPIAPGRSPLATTVVDFIHVPILPLNHALLAARTRQLLEGDSYDGGATAQGPFAPPRGSPSAPSPPVPCGDFPDCTYPLEGDPKEDVFPLYGDFQTPGLKIKEEEEGADAAVRSPRPYLSAGASSSTFPDFPLAPAPQRAPSSRPGEAAVAGGPSSAAVSPASSSGSALECILYKAEGAPPTQGSFAPLPCKPPAAGSCLLPRDSLPAAPATAAAPAIYQPLGLNGLPQLGYQAAVLKDSLPQVYPPYLNYLRPDSEASQSPQYGFDSLPQKI | ||||||
Motif | 56-60 | LXXL motif 1 | ||||
Sequence: LDGLL | ||||||
Motif | 116-120 | LXXL motif 1 | ||||
Sequence: LDSLL | ||||||
Region | 166-305 | Mediates transcriptional transrepression (in isoform A) | ||||
Sequence: MSRPEIKAGDSSGTGAGQKVLPKGLSPPRQLLLPTSGSAHWPGAGVKPSPQPAAGEVEEDSGLETEGSAAPLLKSKPRALEGTGSGGGVAANAASAAPGGVTLVPKEDSRFSAPRVSLEQDSPIAPGRSPLATTVVDFIH | ||||||
Region | 168-256 | Disordered | ||||
Sequence: RPEIKAGDSSGTGAGQKVLPKGLSPPRQLLLPTSGSAHWPGAGVKPSPQPAAGEVEEDSGLETEGSAAPLLKSKPRALEGTGSGGGVAA | ||||||
Motif | 184-188 | Nuclear localization signal | ||||
Sequence: KVLPK | ||||||
Region | 327-364 | Disordered | ||||
Sequence: DSYDGGATAQGPFAPPRGSPSAPSPPVPCGDFPDCTYP | ||||||
Compositional bias | 342-358 | Pro residues | ||||
Sequence: PRGSPSAPSPPVPCGDF | ||||||
Region | 391-447 | Disordered | ||||
Sequence: EEGADAAVRSPRPYLSAGASSSTFPDFPLAPAPQRAPSSRPGEAAVAGGPSSAAVSP | ||||||
Region | 453-539 | AF1; mediates transcriptional activation | ||||
Sequence: SALECILYKAEGAPPTQGSFAPLPCKPPAAGSCLLPRDSLPAAPATAAAPAIYQPLGLNGLPQLGYQAAVLKDSLPQVYPPYLNYLR | ||||||
Zinc finger | 560-580 | NR C4-type | ||||
Sequence: CLICGDEASGCHYGVLTCGSC | ||||||
Zinc finger | 596-615 | NR C4-type | ||||
Sequence: CAGRNDCIVDKIRRKNCPAC | ||||||
Domain | 672-906 | NR LBD | ||||
Sequence: QEIQLVPPLINLLMSIEPDVVYAGHDNTKPDTSSSLLTSLNQLGERQLLSVVKWSKSLPGFRNLHIDDQITLIQYSWMSLMVFGLGWRSYKHVSGQMLYFAPDLILNEQRMKELSFYSLCLTMWQIPQEFVKLQVTHEEFLCMKVLLLLNTIPLEGLRSQSQFEEMRSSYIRELIKAIGLRQKGVVPSSQRFYQLTKLLDSLHDLVKQLHLYCLNTFIQSRTLAVEFPEMMSEVI | ||||||
Region | 673-926 | AF2; mediates transcriptional activation | ||||
Sequence: EIQLVPPLINLLMSIEPDVVYAGHDNTKPDTSSSLLTSLNQLGERQLLSVVKWSKSLPGFRNLHIDDQITLIQYSWMSLMVFGLGWRSYKHVSGQMLYFAPDLILNEQRMKELSFYSLCLTMWQIPQEFVKLQVTHEEFLCMKVLLLLNTIPLEGLRSQSQFEEMRSSYIRELIKAIGLRQKGVVPSSQRFYQLTKLLDSLHDLVKQLHLYCLNTFIQSRTLAVEFPEMMSEVIAAQLPKILAGMVKPLLFHKK |
Domain
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Sequence similarities
Belongs to the nuclear hormone receptor family. NR3 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative promoter usage.
Q00175-1
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.
- NameB
- SynonymsPRB, PR-B
- Length926
- Mass (Da)98,981
- Last updated2017-01-18 v2
- ChecksumE26DDDE9529996A7
Q00175-2
- NameA
- SynonymsPRA, PR-A
- Differences from canonical
- 1-165: Missing
Sequence caution
Features
Showing features for compositional bias, alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-21 | Polar residues | ||||
Sequence: MTELQAKDPQVLHTSGASPSP | ||||||
Alternative sequence | VSP_058743 | 1-165 | in isoform A | |||
Sequence: Missing | ||||||
Sequence conflict | 104 | in Ref. 1; AAA39971 | ||||
Sequence: A → P | ||||||
Sequence conflict | 125 | in Ref. 1; AAA39971 | ||||
Sequence: T → P | ||||||
Sequence conflict | 173-181 | in Ref. 1; AAA39971 | ||||
Sequence: AGDSSGTGA → VGDQSGTGR | ||||||
Sequence conflict | 235 | in Ref. 1; AAA39971 | ||||
Sequence: A → S | ||||||
Sequence conflict | 250 | in Ref. 1; AAA39971 | ||||
Sequence: S → Q | ||||||
Sequence conflict | 259 | in Ref. 1; AAA39971 | ||||
Sequence: A → P | ||||||
Sequence conflict | 327 | in Ref. 1; AAA39971 | ||||
Sequence: D → E | ||||||
Compositional bias | 342-358 | Pro residues | ||||
Sequence: PRGSPSAPSPPVPCGDF | ||||||
Sequence conflict | 351-355 | in Ref. 1; AAA39971 | ||||
Sequence: PPVPC → TPVPR | ||||||
Sequence conflict | 425 | in Ref. 1; AAA39971 | ||||
Sequence: R → A | ||||||
Sequence conflict | 464 | in Ref. 1; AAA39971 | ||||
Sequence: Missing | ||||||
Sequence conflict | 483 | in Ref. 1; AAA39971 | ||||
Sequence: G → A | ||||||
Sequence conflict | 497 | in Ref. 1; AAA39971 | ||||
Sequence: A → G | ||||||
Sequence conflict | 663 | in Ref. 1; AAA39971 | ||||
Sequence: G → S | ||||||
Sequence conflict | 692 | in Ref. 1; AAA39971 | ||||
Sequence: V → I | ||||||
Sequence conflict | 859 | in Ref. 1; AAA39971 | ||||
Sequence: S → T |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M68915 EMBL· GenBank· DDBJ | AAA39971.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
AC113506 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC160964 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH466522 EMBL· GenBank· DDBJ | EDL24960.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC145807 EMBL· GenBank· DDBJ | AAI45808.1 EMBL· GenBank· DDBJ | mRNA | ||
U12644 EMBL· GenBank· DDBJ | AAA66067.1 EMBL· GenBank· DDBJ | Genomic DNA |