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P52631

- STAT3_RAT

UniProt

P52631 - STAT3_RAT

Protein

Signal transducer and activator of transcription 3

Gene

Stat3

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 129 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    Functioni

    Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF and other growth factors. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA By similarity. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity By similarity. Plays an important role in host defense in methicillin-resistant S.aureus lung infection by regulating the expression of the antimicrobial lectin REG3G By similarity.By similarity

    GO - Molecular functioni

    1. calcium ion binding Source: InterPro
    2. CCR5 chemokine receptor binding Source: RGD
    3. DNA binding Source: UniProtKB
    4. glucocorticoid receptor binding Source: RGD
    5. ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Source: Ensembl
    6. protein dimerization activity Source: UniProtKB
    7. protein kinase binding Source: UniProtKB
    8. sequence-specific DNA binding Source: RGD
    9. sequence-specific DNA binding transcription factor activity Source: RGD
    10. signal transducer activity Source: InterPro
    11. transcription factor binding Source: RGD
    12. transcription regulatory region DNA binding Source: Ensembl

    GO - Biological processi

    1. acute-phase response Source: RGD
    2. astrocyte differentiation Source: UniProtKB
    3. cell proliferation Source: Ensembl
    4. eating behavior Source: UniProtKB
    5. eye photoreceptor cell differentiation Source: UniProtKB
    6. glucose homeostasis Source: UniProtKB
    7. interleukin-6-mediated signaling pathway Source: UniProtKB
    8. JAK-STAT cascade Source: RGD
    9. JAK-STAT cascade involved in growth hormone signaling pathway Source: UniProtKB
    10. negative regulation of cell death Source: RGD
    11. negative regulation of neuron migration Source: Ensembl
    12. phosphorylation Source: UniProtKB
    13. positive regulation of Notch signaling pathway Source: UniProtKB
    14. positive regulation of transcription, DNA-templated Source: UniProtKB
    15. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    16. protein import into nucleus Source: UniProtKB
    17. radial glial cell differentiation Source: UniProtKB
    18. regulation of multicellular organism growth Source: Ensembl
    19. regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    20. response to cytokine Source: RGD
    21. response to drug Source: RGD
    22. response to estradiol Source: RGD
    23. response to ethanol Source: RGD
    24. response to organic cyclic compound Source: RGD
    25. response to organic substance Source: RGD
    26. response to peptide hormone Source: RGD
    27. sexual reproduction Source: UniProtKB
    28. stem cell maintenance Source: Ensembl
    29. temperature homeostasis Source: UniProtKB

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_195025. Signaling by SCF-KIT.
    REACT_195204. Signaling by Leptin.
    REACT_196425. Growth hormone receptor signaling.
    REACT_198628. Signaling by FGFR1 fusion mutants.
    REACT_199244. Interleukin-6 signaling.
    REACT_206819. Downstream signal transduction.
    REACT_212185. POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.
    REACT_228003. Transcriptional regulation of pluripotent stem cells.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Signal transducer and activator of transcription 3
    Gene namesi
    Name:Stat3
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 10

    Organism-specific databases

    RGDi3772. Stat3.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity
    Note: Shuttles between the nucleus and the cytoplasm. Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4. Constitutive nuclear presence is independent of tyrosine phosphorylation. Predominantly present in the cytoplasm without stimuli. Upon leukemia inhibitory factor (LIF) stimulation, accumulates in the nucleus. The complex composed of BART and ARL2 plays an important role in the nuclear translocation and retention of STAT3 By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: Reactome
    3. mitochondrial inner membrane Source: UniProtKB
    4. nucleus Source: UniProtKB
    5. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 770769Signal transducer and activator of transcription 3PRO_0000182419Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei705 – 7051Phosphotyrosine; by FER and PTK6By similarity
    Modified residuei727 – 7271Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5, ZIPK/DAPK3 and PKC/PRKCEBy similarity

    Post-translational modificationi

    Activated through tyrosine phosphorylation by BMX. Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated on serine upon DNA damage, probably by ATM or ATR. Serine phosphorylation is important for the formation of stable DNA-binding STAT3 homodimers and maximal transcriptional activity. ARL2BP may participate in keeping the phosphorylated state of STAT3 within the nucleus. Tyrosine phosphorylated upon stimulation with EGF. Upon LPS challenge, phosphorylated within the nucleus by IRAK1. Phosphorylated on Ser-727 by RPS6KA5 By similarity. Phosphoryation at Tyr-705 by FER or PTK6 leads to an increase of its transcriptional activity. Dephosphorylation on tyrosine residues by PTPN2 negatively regulates IL6/interleukin-6 signaling By similarity.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PaxDbiP52631.
    PRIDEiP52631.

    PTM databases

    PhosphoSiteiP52631.

    Expressioni

    Tissue specificityi

    Detected in lung, heart, oviduct, ovary, uterus and kidney (at protein level). Detected in ovary, oviduct, and at lower levels in uterus and lung.

    Gene expression databases

    GenevestigatoriP52631.

    Interactioni

    Subunit structurei

    Forms a homodimer or a heterodimer with a related family member (at least STAT1). Interacts with IL31RA, NCOA1, PELP1, SIPAR, SOCS7, STATIP1 and TMF1. Interacts with IL23R in presence of IL23. Interacts (via SH2 domain) with NLK. Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of nuclear import By similarity. Interacts with ARL2BP; interaction is enhanced with ARL2. Interacts with ARL2BP; the interaction is enhanced by LIF and JAK1 expression By similarity. Interacts with CAV2; the interaction is increased on insulin-induced tyrosine phosphorylation of CAV2 and leads to STAT3 activation. Interacts with NEK6. Binds to CDK9 when activated and nuclear By similarity. Interacts with BMX By similarity. Interacts with ZIPK/DAPK3 By similarity. Interacts with STMN3, antagonizing its microtubule-destabilizing activity By similarity. Interacts with the 'Lys-129' acetylated form of BIRC5/survivin. Interacts with FER By similarity. Interacts (via SH2 domain) with EIF2AK2/PKR (via the kinase catalytic domain) By similarity.By similarity

    Protein-protein interaction databases

    BioGridi247196. 2 interactions.
    DIPiDIP-44909N.
    MINTiMINT-1529438.
    STRINGi10116.ENSRNOP00000026760.

    Structurei

    3D structure databases

    ProteinModelPortaliP52631.
    SMRiP52631. Positions 136-715.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini580 – 67091SH2PROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi150 – 16213Essential for nuclear importBy similarityAdd
    BLAST

    Sequence similaritiesi

    Belongs to the transcription factor STAT family.Curated
    Contains 1 SH2 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH2 domain

    Phylogenomic databases

    eggNOGiNOG303257.
    GeneTreeiENSGT00750000117596.
    HOGENOMiHOG000220792.
    HOVERGENiHBG055669.
    InParanoidiP52631.
    KOiK04692.
    OMAiNKESHAT.
    OrthoDBiEOG73JKTT.
    PhylomeDBiP52631.
    TreeFamiTF318648.

    Family and domain databases

    Gene3Di1.10.238.10. 1 hit.
    1.10.532.10. 1 hit.
    1.20.1050.20. 1 hit.
    2.60.40.630. 1 hit.
    3.30.505.10. 1 hit.
    InterProiIPR011992. EF-hand-dom_pair.
    IPR008967. p53-like_TF_DNA-bd.
    IPR000980. SH2.
    IPR001217. STAT.
    IPR013800. STAT_TF_alpha.
    IPR015988. STAT_TF_coiled-coil.
    IPR013801. STAT_TF_DNA-bd.
    IPR012345. STAT_TF_DNA-bd_sub.
    IPR013799. STAT_TF_prot_interaction.
    [Graphical view]
    PANTHERiPTHR11801. PTHR11801. 1 hit.
    PfamiPF00017. SH2. 1 hit.
    PF01017. STAT_alpha. 1 hit.
    PF02864. STAT_bind. 1 hit.
    PF02865. STAT_int. 1 hit.
    [Graphical view]
    SMARTiSM00252. SH2. 1 hit.
    SM00964. STAT_int. 1 hit.
    [Graphical view]
    SUPFAMiSSF47655. SSF47655. 1 hit.
    SSF48092. SSF48092. 1 hit.
    SSF49417. SSF49417. 1 hit.
    SSF55550. SSF55550. 1 hit.
    PROSITEiPS50001. SH2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P52631-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQFLAPWIES QDWAYAASKE    50
    SHATLVFHNL LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME 100
    IARIVARCLW EESRLLQTAA TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD 150
    VRKRVQDLEQ KMKVVENLQD DFDFNYKTLK SQGDMQDLNG NNQSVTRQKM 200
    QQLEQMLTAL DQMRRSIVSE LAGLLSAMEY VQKTLTDEEL ADWKRRQQIA 250
    CIGGPPNICL DRLENWITSL AESQLQTRQQ IKKLEELQQK VSYKGDPIVQ 300
    HRPMLEERIV DLFRNLMKSA FVVERQPCMP MHPDRPLVIK TGVQFTTKVR 350
    LLVKFPELNY QLKIKVCIDK DSGDVAALRG SRKFNILGTN TKVMNMEESN 400
    NGSLSAEFKH LTLREQRCGN GGRANCDASL IVTEELHLIT FETEVYHQGL 450
    KIDLETHSLP VVVISNICQM PNAWASILWY NMLTNNPKNV NFFTKPPIGT 500
    WDQVAEVLSW QFSSTTKRGL SIEQLTTLAE KLLGPGVNYS GCQITWAKFC 550
    KENMAGKGFS FWVWLDNIID LVKKYILALW NEGYIMGFIS KERERAILST 600
    KPPGTFLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF 650
    AEIIMGYKIM DATNILVSPL VYLYPDIPKE EAFGKYCRPE SQEHPEADPG 700
    SAAPYLKTKF ICVTPTTCSN TIDLPMSPRT LDSLMQFGNN GEGAEPSAGG 750
    QFESLTFDMD LTSECATSPM 770
    Length:770
    Mass (Da):88,040
    Last modified:October 1, 1996 - v1
    Checksum:iD74A0C76954754ED
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X91810 mRNA. Translation: CAA62920.1.
    BC087025 mRNA. Translation: AAH87025.1.
    RefSeqiNP_036879.1. NM_012747.2.
    UniGeneiRn.10247.

    Genome annotation databases

    EnsembliENSRNOT00000026760; ENSRNOP00000026760; ENSRNOG00000019742.
    GeneIDi25125.
    KEGGirno:25125.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X91810 mRNA. Translation: CAA62920.1 .
    BC087025 mRNA. Translation: AAH87025.1 .
    RefSeqi NP_036879.1. NM_012747.2.
    UniGenei Rn.10247.

    3D structure databases

    ProteinModelPortali P52631.
    SMRi P52631. Positions 136-715.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 247196. 2 interactions.
    DIPi DIP-44909N.
    MINTi MINT-1529438.
    STRINGi 10116.ENSRNOP00000026760.

    Chemistry

    ChEMBLi CHEMBL1764933.

    PTM databases

    PhosphoSitei P52631.

    Proteomic databases

    PaxDbi P52631.
    PRIDEi P52631.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000026760 ; ENSRNOP00000026760 ; ENSRNOG00000019742 .
    GeneIDi 25125.
    KEGGi rno:25125.

    Organism-specific databases

    CTDi 6774.
    RGDi 3772. Stat3.

    Phylogenomic databases

    eggNOGi NOG303257.
    GeneTreei ENSGT00750000117596.
    HOGENOMi HOG000220792.
    HOVERGENi HBG055669.
    InParanoidi P52631.
    KOi K04692.
    OMAi NKESHAT.
    OrthoDBi EOG73JKTT.
    PhylomeDBi P52631.
    TreeFami TF318648.

    Enzyme and pathway databases

    Reactomei REACT_195025. Signaling by SCF-KIT.
    REACT_195204. Signaling by Leptin.
    REACT_196425. Growth hormone receptor signaling.
    REACT_198628. Signaling by FGFR1 fusion mutants.
    REACT_199244. Interleukin-6 signaling.
    REACT_206819. Downstream signal transduction.
    REACT_212185. POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.
    REACT_228003. Transcriptional regulation of pluripotent stem cells.

    Miscellaneous databases

    NextBioi 605521.
    PROi P52631.

    Gene expression databases

    Genevestigatori P52631.

    Family and domain databases

    Gene3Di 1.10.238.10. 1 hit.
    1.10.532.10. 1 hit.
    1.20.1050.20. 1 hit.
    2.60.40.630. 1 hit.
    3.30.505.10. 1 hit.
    InterProi IPR011992. EF-hand-dom_pair.
    IPR008967. p53-like_TF_DNA-bd.
    IPR000980. SH2.
    IPR001217. STAT.
    IPR013800. STAT_TF_alpha.
    IPR015988. STAT_TF_coiled-coil.
    IPR013801. STAT_TF_DNA-bd.
    IPR012345. STAT_TF_DNA-bd_sub.
    IPR013799. STAT_TF_prot_interaction.
    [Graphical view ]
    PANTHERi PTHR11801. PTHR11801. 1 hit.
    Pfami PF00017. SH2. 1 hit.
    PF01017. STAT_alpha. 1 hit.
    PF02864. STAT_bind. 1 hit.
    PF02865. STAT_int. 1 hit.
    [Graphical view ]
    SMARTi SM00252. SH2. 1 hit.
    SM00964. STAT_int. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47655. SSF47655. 1 hit.
    SSF48092. SSF48092. 1 hit.
    SSF49417. SSF49417. 1 hit.
    SSF55550. SSF55550. 1 hit.
    PROSITEi PS50001. SH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements."
      Ripperger J.A., Fritz S., Richter K., Hocke G.M., Lottspeich F., Fey G.H.
      J. Biol. Chem. 270:29998-30006(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Liver.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Kidney.
    3. "Caveolin-2 regulation of STAT3 transcriptional activation in response to insulin."
      Kwon H., Jeong K., Hwang E.M., Park J.-Y., Hong S.-G., Choi W.-S., Pak Y.
      Biochim. Biophys. Acta 1793:1325-1333(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CAV2.

    Entry informationi

    Entry nameiSTAT3_RAT
    AccessioniPrimary (citable) accession number: P52631
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 129 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Involved in the gp130-mediated signaling pathway.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3