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A7X8B7 (PRGR_GORGO) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 45. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Progesterone receptor

Short name=PR
Alternative name(s):
Nuclear receptor subfamily 3 group C member 3
Gene names
Name:PGR
Synonyms:NR3C3
OrganismGorilla gorilla gorilla (Lowland gorilla) [Reference proteome]
Taxonomic identifier9595 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeGorilla

Protein attributes

Sequence length933 AA.
Sequence statusComplete.
Protein existenceInferred from homology

General annotation (Comments)

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. Progesterone receptor is involved in activation of c-SRC/MAPK signaling on hormone stimulation By similarity.

Subunit structure

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-345 by ERK1/2 MAPK. Interacts with PRMT2 By similarity.

Subcellular location

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.

Domain

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

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-102 and Ser-345 also requires induction by hormone. Basal phosphorylation on Ser-81, Ser-162, Ser-190 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-162 and Ser-294, but not at Ser-190, 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. Promoted by MAPK-mediated phosphorylation on Ser-294 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.

Sequence similarities

Belongs to the nuclear hormone receptor family.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DomainZinc-finger
   LigandDNA-binding
Lipid-binding
Metal-binding
Steroid-binding
Zinc
   Molecular functionReceptor
   PTMIsopeptide bond
Lipoprotein
Palmitate
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processepithelial cell maturation

Inferred from electronic annotation. Source: Ensembl

negative regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

ovulation from ovarian follicle

Inferred from electronic annotation. Source: Ensembl

progesterone receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

tertiary branching involved in mammary gland duct morphogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

steroid binding

Inferred from electronic annotation. Source: UniProtKB-KW

steroid hormone receptor activity

Inferred from electronic annotation. Source: Ensembl

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 933933Progesterone receptor
PRO_0000375854

Regions

DNA binding567 – 63973Nuclear receptor
Zinc finger567 – 58721NR C4-type
Zinc finger603 – 62725NR C4-type
Region1 – 566566Modulating, Pro-Rich
Region681 – 933253Steroid-binding
Motif183 – 1875Nuclear localization signal Potential

Amino acid modifications

Modified residue201Phosphoserine By similarity
Modified residue811Phosphoserine By similarity
Modified residue1301Phosphoserine By similarity
Modified residue1621Phosphoserine By similarity
Modified residue1901Phosphoserine By similarity
Modified residue2131Phosphoserine By similarity
Modified residue2941Phosphoserine; by MAPK1 By similarity
Modified residue3451Phosphoserine; by MAPK By similarity
Modified residue4001Phosphoserine; by CDK2 By similarity
Modified residue6761Phosphoserine By similarity
Cross-link7Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link388Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity
Cross-link388Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity
Cross-link531Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Sequences

Sequence LengthMass (Da)Tools
A7X8B7 [UniParc].

Last modified October 23, 2007. Version 1.
Checksum: 9C1080538291E6E6

FASTA93398,830
        10         20         30         40         50         60 
MTELKAKGPR APHVAGGPPS PEVGSPLLCR PAAGPYPGSQ TSDTLPEVSA IPISLDGLLF 

        70         80         90        100        110        120 
PRPCQGQDPS DEKTQDQQSL SDVEGAYSRA EATRGAGGSS SSPPEKDSGL LDSVLETLLA 

       130        140        150        160        170        180 
PSGPGQSQPS PPACEVTSSW CLFGPELPED PPAAPATQGV LSPLMSRSGG KAGDSSGTAA 

       190        200        210        220        230        240 
AHKVLPRGLS PSRQLLLPVS GSPHWSGAPV KPSPQPAAVE VEEEDGSESE ESAGPLLKGK 

       250        260        270        280        290        300 
PRALGGAAAG GGAAAVPPGA AAGGVALVPK EDSRFSAPRV ALVEQDAPMA PGRSPLATTV 

       310        320        330        340        350        360 
MDFIHVPILP LNHALLAART RQLLEDESYD GGAGAASAFA PPRSSPSASS TPVAVGDFPD 

       370        380        390        400        410        420 
CAYPPDAEPK DDAYPLYSDF QPPALKIKEE EEGAEASARS PRSYLVAGAN PAAFPDFPLG 

       430        440        450        460        470        480 
PPPPLPPRAP PSRPGEAAVT AAPASASVSS ASSSGSTLEC ILYKAEGAPP QQGPFAPPPC 

       490        500        510        520        530        540 
KAPGASGCLL PRDGLPSTSA SAAAAGAAPA LYPALGLNGL PQLGYQAAVL KEGLPQVYPP 

       550        560        570        580        590        600 
YLNYLRPDSE ASQSPQYSFE SLPQKICLIC GDEASGCHYG VLTCGSCKVF FKRAMEGQHN 

       610        620        630        640        650        660 
YLCAGRNDCI VDKIRRKNCP ACRLRKCCQA GMVLGGRKFK KFNKVRVVRA LDAVALPQPV 

       670        680        690        700        710        720 
GIPNESQALS QRFTFSPGQD IQLIPPLINL LMSIEPDVIY AGHDNTKPDT SSSLLTSLNQ 

       730        740        750        760        770        780 
LGERQLLSVV KWSKSLPGFR NLHIDDQITL IQYSWMSLMV FGLGWRSYKH VSGQMLYFAP 

       790        800        810        820        830        840 
DLILNEQRMK ESSFYSLCLT MWQIPQEFVK LQVSQEEFLC MKVLLLLNTI PLEGLRSQTQ 

       850        860        870        880        890        900 
FEEMRSSYIR ELIKAIGLRQ KGVVSSSQRF YQLTKLLDNL HDLVKQLHLY CLNTFIQSRA 

       910        920        930 
LSVEFPEMMS EVIAAQLPKI LAGMVKPLLF HKK 

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References

[1]"The human progesterone receptor shows evidence of adaptive evolution associated with its ability to act as a transcription factor."
Chen C., Opazo J.C., Erez O., Uddin M., Santolaya-Forgas J., Goodman M., Grossman L.I., Romero R., Wildman D.E.
Mol. Phylogenet. Evol. 47:637-649(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
DQ234982 Genomic DNA. Translation: ABB72142.1.
RefSeqXP_004052058.1. XM_004052010.1.

3D structure databases

ProteinModelPortalA7X8B7.
SMRA7X8B7. Positions 563-640, 682-932.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PRIDEA7X8B7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSGGOT00000027848; ENSGGOP00000024814; ENSGGOG00000016358.
GeneID101152212.
KEGGggo:101152212.

Organism-specific databases

CTD5241.

Phylogenomic databases

GeneTreeENSGT00730000110451.
KOK08556.
OMARPCQGQD.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProIPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR000128. Progest_rcpt.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF00104. Hormone_recep. 1 hit.
PF02161. Prog_receptor. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR00544. PROGESTRONER.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 2 hits.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry namePRGR_GORGO
AccessionPrimary (citable) accession number: A7X8B7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 26, 2009
Last sequence update: October 23, 2007
Last modified: April 16, 2014
This is version 45 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families