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A7X8B3

- PRGR_PANTR

UniProt

A7X8B3 - PRGR_PANTR

Protein

Progesterone receptor

Gene

PGR

Organism
Pan troglodytes (Chimpanzee)
Status
Reviewed - Annotation score: 4 out of 5- Protein inferred from homologyi
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    • History
      Entry version 41 (01 Oct 2014)
      Sequence version 1 (23 Oct 2007)
      Previous versions | rss
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    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

    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-SubCell
    2. nucleus Source: UniProtKB-SubCell

    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.
    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.

    A7X8B3-1 [UniParc]FASTAAdd to Basket

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    MTELKAKGPR APHVAGGPPS PEVGSPLLCR PAAGPFPGSQ TSDTLPEVSA    50
    IPISLDGLLF PRPCQGQDPS NEKTQDQQSL SDVEGAYSRA EATRGAGGSS 100
    SSPPEKDSGL LDSVLDTLLA PSGPGQSQPS PPACEVTSSW CLFGPELPED 150
    PPAAPATQGV LSPLMSRSGC KAGDSSGTAA AHKVLPRGLS PSRQLLLPAS 200
    GSPHWSGAPV KPSPQPAAVE VEEEDGSESE ESAGPLLKGK PRALGGAAAG 250
    GGAAAVPPGA AAGGVALVPK EDSRFSAPRV ALVEQDAPMA PXRSPLATTM 300
    MDFIHVPILP LNHALLAART RQLLEDESYD GGAGAXSAFA PPRSSPSASS 350
    TPVAVGDFPD CAYPPDAEPK DDAYPLYSDF QPPALKIKEE EEGAEASARS 400
    PRSYLVAGAN PAAFPDFPLG PPPPLPPRAP PSRPGEAAVT AAPASASVSS 450
    ASSSGSTLEC ILYKAEGAPP QQGPFAPPPC KAPGASGCLL PRDGLPSTSA 500
    SAAAAGAAPA LYPALGLNGL PQLGYQAAVL KEGLPQVYPP YLNYLRPDSE 550
    ASQSPQYSFE SLPQKICLIC GDEASGCHYG VLTCGSCKVF FKRAMEGQHN 600
    YLCAGRNDCI VDKIRRKNCP ACRLRKCCQA GMVLGGRKFK KFNKVRVVRA 650
    LDAVALPQPV GIPNESQALS QRFTFSPGQD IQLIPPLINL LMSIEPDVIY 700
    AGHDNTKPDT SSSLLTSLNQ LGERQLLSVV KWSKSLPGFR NLHIDDQITL 750
    IQYSWMSLMV FGLGWRSYKH VSGQMLYFAP DLILNEQRMK ESSFYSLCLT 800
    MWQIPQEFVK LQVSQEEFLC MKVLLLLNTI PLEGLRSQTQ FEEMRSSYIR 850
    ELIKAIGLRQ KGVVSSSQRF YQLTKLLDNL HDLVKQLHLY CLNTFIQSRA 900
    LSVEFPEMMS EVIAAQLPKI LAGMVKPLLF HKK 933
    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.
    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 1, 2014
    This is version 41 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