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Protein

Progesterone receptor

Gene

Pgr

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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).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 – 629Nuclear receptorPROSITE-ProRule annotationAdd BLAST73
Zinc fingeri557 – 577NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri593 – 617NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

  • hormone binding Source: RGD
  • sequence-specific DNA binding Source: RGD
  • steroid binding Source: RGD
  • steroid hormone receptor activity Source: RGD
  • transcription factor activity, sequence-specific DNA binding Source: InterPro
  • zinc ion binding Source: InterPro

GO - Biological processi

  • cellular response to follicle-stimulating hormone stimulus Source: RGD
  • cellular response to gonadotropin stimulus Source: RGD
  • cellular response to luteinizing hormone stimulus Source: RGD
  • diterpenoid metabolic process Source: RGD
  • estrous cycle Source: RGD
  • female mating behavior Source: RGD
  • luteinization Source: RGD
  • negative regulation of apoptotic process Source: RGD
  • negative regulation of granulosa cell apoptotic process Source: RGD
  • negative regulation of transcription, DNA-templated Source: RGD
  • positive regulation of cell proliferation Source: RGD
  • positive regulation of smooth muscle cell migration Source: RGD
  • positive regulation of transcription, DNA-templated Source: RGD
  • response to cocaine Source: RGD
  • response to estrogen Source: RGD
  • response to progesterone Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

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

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3317. Pgr.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2596.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000536971 – 923Progesterone receptorAdd BLAST923

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 residuei130PhosphoserineBy similarity1
Modified residuei162PhosphoserineBy similarity1
Modified residuei190PhosphoserineBy similarity1
Modified residuei213PhosphoserineBy similarity1
Modified residuei293Phosphoserine; by MAPK1By similarity1
Modified residuei344Phosphoserine; by MAPKBy similarity1
Cross-linki387Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki387Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei399Phosphoserine; by CDK2By similarity1
Cross-linki521Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei666PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on multiple serine sites. Several of these sites are hormone-dependent. Phosphorylation on Ser-293 is highly hormone-dependent and modulates ubiquitination and sumoylation on Lys-387. Phosphorylation on Ser-344 also requires induction by hormone. Basal phosphorylation on Ser-82, Ser-190 and Ser-399 is increased in response to progesterone and can be phosphorylated in vitro by the CDK2-A1 complex. Increased levels of phosphorylation on Ser-399 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-293, but not at Ser-190, is impaired during the G2/M phase of the cell cycle. Phosphorylation on Ser-344 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-387, the main site of sumoylation, is repressed by ubiquitination on the same site, and modulated by phosphorylation at Ser-293 (By similarity).By similarity
Ubiquitination is hormone-dependent and represses sumoylation on the same site. Promoted by MAPK-mediated phosphorylation on Ser-293 (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

PaxDbiQ63449.
PRIDEiQ63449.

PTM databases

iPTMnetiQ63449.
PhosphoSitePlusiQ63449.

Expressioni

Tissue specificityi

Isoform A and isoform B are expressed in the pituitary.1 Publication

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-344. Interacts with PRMT2 (By similarity). Isoform A interacts with NCOR2. Isoform B (but not isoform A) interacts with NCOA2 and NCOA1 (By similarity). Isoform B (but not isoform A) interacts with KLF9.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000032053.

Chemistry databases

BindingDBiQ63449.

Structurei

3D structure databases

ProteinModelPortaliQ63449.
SMRiQ63449.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 556Modulating, Pro-RichAdd BLAST556
Regioni1 – 164AF3; mediates transcriptional activation (in isoform B)By similarityAdd BLAST164
Regioni165 – 304Mediates transcriptional transrepression (in isoform A)By similarityAdd BLAST140
Regioni450 – 536AF1; mediates transcriptional activationBy similarityAdd BLAST87
Regioni671 – 923Steroid-bindingAdd BLAST253
Regioni677 – 923AF2; mediates transcriptional activationBy similarityAdd BLAST247

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi56 – 60LXXL motif 1By similarity5
Motifi115 – 119LXXL motif 2By 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 fingeri557 – 577NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri593 – 617NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
HOGENOMiHOG000290653.
HOVERGENiHBG007583.
InParanoidiQ63449.
KOiK08556.
PhylomeDBiQ63449.

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: Q63449-1) [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
MTELQAKDPR TLHTSGAAPS PTHVGSPLLA RLDPDPFQGS QHSDASSVVS
60 70 80 90 100
PIPISLDRLL FSRSCQAQEL PDEKTQNQQS LSDVEGAFSG VEASRRRSRN
110 120 130 140 150
PRAPEKDSRL LDSVLDTLLA PSGPEQSQTS PPACEAITSW CLFGPELPED
160 170 180 190 200
PRSVPATKGL LSPLMSRPES KAGDSSGTGA GQKVLPKAVS PPRQLLLPTS
210 220 230 240 250
GSAHWPGAGV KPSQQPATVE VEEDGGLETE GSAGPLLKSK PRALEGMCSG
260 270 280 290 300
GGVTANAPGA APGGVTLVPK EDSRFSAPRV SLEQDAPVAP GRSPLATTVV
310 320 330 340 350
DFIHVPILPL NHALLAARTR QLLEGDSYDG GAAAQVPFAP PRGSPSAPSP
360 370 380 390 400
PVPCGDFPDC TYPPEGDPKE DGFPVYGEFQ PPGLKIKEEE EGTEAASRSP
410 420 430 440 450
RPYLLAGASA ATFPDFPLPP RPPRAPPSRP GEAAVAAPSA AVSPVSSSGS
460 470 480 490 500
ALECILYKAE GAPPTQGSFA PLPCKPPAAS SCLLPRDSLP AAPTSSAAPA
510 520 530 540 550
IYPPLGLNGL PQLGYQAAVL KDSLPQVYPP YLNYLRPDSE ASQSPQYGFD
560 570 580 590 600
SLPQKICLIC GDEASGCHYG VLTCGSCKVF FKRAMEGQHN YLCAGRNDCI
610 620 630 640 650
VDKIRRKNCP ACRLRKCCQA GMVLGGRKFK KFNKVRVMRA LDGVALPQSV
660 670 680 690 700
AFPNESQTLG QRITFSPNQE IQLVPPLINL LMSIEPDVVY AGHDNTKPDT
710 720 730 740 750
SSSLLTSLNQ LGERQLLSVV KWSKSLPGFR NLHIDDQITL IQYSWMSLMV
760 770 780 790 800
FGLGWRSYKH VSGQMLYFAP DLILNEQRMK ELSFYSLCLT MWQIPQEFVK
810 820 830 840 850
LQVTHEEFLC MKVLLLLNTI PLEGLRSQSQ FEEMRSSYIR ELIKAIGLRQ
860 870 880 890 900
KGVVPSSQRF YQLTKLLDSL HDLVKQLHLY CLNTFIQSRA LAVEFPEMMS
910 920
EVIAAQLPKI LAGMVKPLLF HKK
Length:923
Mass (Da):99,408
Last modified:November 1, 1996 - v1
Checksum:i05384B9656BF22DC
GO
Isoform A (identifier: Q63449-2) [UniParc]FASTAAdd to basket
Also known as: PRA, PR-A

The sequence of this isoform differs from the canonical sequence as follows:
     1-164: Missing.

Show »
Length:759
Mass (Da):81,864
Checksum:iEB0F4957FAF6FA64
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0587441 – 164Missing in isoform A. CuratedAdd BLAST164

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L16922 mRNA. Translation: AAA19916.1.
PIRiI53280.
RefSeqiNP_074038.1. NM_022847.1. [Q63449-1]
UniGeneiRn.10303.

Genome annotation databases

GeneIDi25154.
KEGGirno:25154.
UCSCiRGD:3317. rat. [Q63449-1]

Keywords - Coding sequence diversityi

Alternative promoter usage

Similar proteinsi

Entry informationi

Entry nameiPRGR_RAT
AccessioniPrimary (citable) accession number: Q63449
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: August 30, 2017
This is version 143 of the entry and version 1 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. SIMILARITY comments
    Index of protein domains and families