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A7X8B3

- PRGR_PANTR

UniProt

A7X8B3 - PRGR_PANTR

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Protein

Progesterone receptor

Gene

PGR

Organism
Pan troglodytes (Chimpanzee)
Status
Reviewed - Annotation score: 4 out of 5- Protein inferred from homologyi

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

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi567 – 63973Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri567 – 58721NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri603 – 62725NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. sequence-specific DNA binding Source: InterPro
  2. sequence-specific DNA binding transcription factor activity Source: InterPro
  3. steroid binding Source: UniProtKB-KW
  4. steroid hormone receptor activity Source: InterPro
  5. zinc ion binding Source: InterPro

GO - Biological processi

  1. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Lipid-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
OrganismiPan troglodytes (Chimpanzee)
Taxonomic identifieri9598 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePan
ProteomesiUP000002277: Unplaced

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

  1. cytoplasm Source: UniProtKB-KW
  2. nucleus Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 933933Progesterone receptorPRO_0000375858Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki7 – 7Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei20 – 201PhosphoserineBy similarity
Modified residuei81 – 811PhosphoserineBy similarity
Modified residuei130 – 1301PhosphoserineBy similarity
Modified residuei162 – 1621PhosphoserineBy similarity
Modified residuei190 – 1901PhosphoserineBy similarity
Modified residuei213 – 2131PhosphoserineBy similarity
Modified residuei294 – 2941Phosphoserine; by MAPK1By similarity
Modified residuei345 – 3451Phosphoserine; by MAPKBy similarity
Cross-linki388 – 388Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki388 – 388Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei400 – 4001Phosphoserine; by CDK2By similarity
Cross-linki531 – 531Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei676 – 6761PhosphoserineBy similarity

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-102 and Ser-345 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).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

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

Structurei

3D structure databases

ProteinModelPortaliA7X8B3.
SMRiA7X8B3. Positions 563-640, 682-932.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 566566Modulating, Pro-RichAdd
BLAST
Regioni681 – 933253Steroid-bindingAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi183 – 1875Nuclear localization signalSequence Analysis

Domaini

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

Sequence similaritiesi

Belongs to the nuclear hormone receptor family.Curated
Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri567 – 58721NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri603 – 62725NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG273252.
InParanoidiA7X8B3.
KOiK08556.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR008946. 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]
PfamiPF00104. Hormone_recep. 1 hit.
PF02161. Prog_receptor. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00544. PROGESTRONER.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 2 hits.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

A7X8B3 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MTELKAKGPR APHVAGGPPS PEVGSPLLCR PAAGPFPGSQ TSDTLPEVSA
60 70 80 90 100
IPISLDGLLF PRPCQGQDPS NEKTQDQQSL SDVEGAYSRA EATRGAGGSS
110 120 130 140 150
SSPPEKDSGL LDSVLDTLLA PSGPGQSQPS PPACEVTSSW CLFGPELPED
160 170 180 190 200
PPAAPATQGV LSPLMSRSGC KAGDSSGTAA AHKVLPRGLS PSRQLLLPAS
210 220 230 240 250
GSPHWSGAPV KPSPQPAAVE VEEEDGSESE ESAGPLLKGK PRALGGAAAG
260 270 280 290 300
GGAAAVPPGA AAGGVALVPK EDSRFSAPRV ALVEQDAPMA PXRSPLATTM
310 320 330 340 350
MDFIHVPILP LNHALLAART RQLLEDESYD GGAGAXSAFA PPRSSPSASS
360 370 380 390 400
TPVAVGDFPD CAYPPDAEPK DDAYPLYSDF QPPALKIKEE EEGAEASARS
410 420 430 440 450
PRSYLVAGAN PAAFPDFPLG PPPPLPPRAP PSRPGEAAVT AAPASASVSS
460 470 480 490 500
ASSSGSTLEC ILYKAEGAPP QQGPFAPPPC KAPGASGCLL PRDGLPSTSA
510 520 530 540 550
SAAAAGAAPA LYPALGLNGL PQLGYQAAVL KEGLPQVYPP YLNYLRPDSE
560 570 580 590 600
ASQSPQYSFE SLPQKICLIC GDEASGCHYG VLTCGSCKVF FKRAMEGQHN
610 620 630 640 650
YLCAGRNDCI VDKIRRKNCP ACRLRKCCQA GMVLGGRKFK KFNKVRVVRA
660 670 680 690 700
LDAVALPQPV GIPNESQALS QRFTFSPGQD IQLIPPLINL LMSIEPDVIY
710 720 730 740 750
AGHDNTKPDT SSSLLTSLNQ LGERQLLSVV KWSKSLPGFR NLHIDDQITL
760 770 780 790 800
IQYSWMSLMV FGLGWRSYKH VSGQMLYFAP DLILNEQRMK ESSFYSLCLT
810 820 830 840 850
MWQIPQEFVK LQVSQEEFLC MKVLLLLNTI PLEGLRSQTQ FEEMRSSYIR
860 870 880 890 900
ELIKAIGLRQ KGVVSSSQRF YQLTKLLDNL HDLVKQLHLY CLNTFIQSRA
910 920 930
LSVEFPEMMS EVIAAQLPKI LAGMVKPLLF HKK
Length:933
Mass (Da):98,944
Last modified:October 23, 2007 - v1
Checksum:i9886EEAA06B2F61F
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
DQ234980 Genomic DNA. Translation: ABB72140.1.
RefSeqiNP_001129085.1. NM_001135613.1.
UniGeneiPtr.6317.

Genome annotation databases

GeneIDi451502.
KEGGiptr:451502.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
DQ234980 Genomic DNA. Translation: ABB72140.1 .
RefSeqi NP_001129085.1. NM_001135613.1.
UniGenei Ptr.6317.

3D structure databases

ProteinModelPortali A7X8B3.
SMRi A7X8B3. Positions 563-640, 682-932.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 451502.
KEGGi ptr:451502.

Organism-specific databases

CTDi 5241.

Phylogenomic databases

eggNOGi NOG273252.
InParanoidi A7X8B3.
KOi K08556.

Miscellaneous databases

NextBioi 20834047.

Family and domain databases

Gene3Di 1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProi IPR008946. 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 ]
Pfami PF00104. Hormone_recep. 1 hit.
PF02161. Prog_receptor. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view ]
PRINTSi PR00544. PROGESTRONER.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTi SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view ]
SUPFAMi SSF48508. SSF48508. 2 hits.
PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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].

Entry informationi

Entry nameiPRGR_PANTR
AccessioniPrimary (citable) accession number: A7X8B3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 26, 2009
Last sequence update: October 23, 2007
Last modified: October 29, 2014
This is version 42 of the entry and version 1 of the sequence. [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

External Data

Dasty 3