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P42225

- STAT1_MOUSE

UniProt

P42225 - STAT1_MOUSE

Protein

Signal transducer and activator of transcription 1

Gene

Stat1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
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    Functioni

    Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors. Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of IFN-stimulated genes (ISG), which drive the cell in an antiviral state. In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated. It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state. Becomes activated in response to KITLG/SCF and KIT signaling. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4.4 Publications

    GO - Molecular functioni

    1. calcium ion binding Source: InterPro
    2. DNA binding Source: UniProtKB-KW
    3. protein binding Source: IntAct
    4. sequence-specific DNA binding transcription factor activity Source: MGI
    5. signal transducer activity Source: InterPro

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    2. apoptotic process Source: UniProtKB
    3. blood circulation Source: UniProtKB
    4. cytokine-mediated signaling pathway Source: MGI
    5. interferon-gamma-mediated signaling pathway Source: UniProtKB
    6. lipopolysaccharide-mediated signaling pathway Source: MGI
    7. metanephric mesenchymal cell differentiation Source: UniProtKB
    8. metanephric mesenchymal cell proliferation involved in metanephros development Source: UniProtKB
    9. negative regulation of macrophage fusion Source: MGI
    10. negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis Source: UniProtKB
    11. negative regulation of metanephric nephron tubule epithelial cell differentiation Source: UniProtKB
    12. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    13. positive regulation of mesenchymal cell proliferation Source: UniProtKB
    14. positive regulation of smooth muscle cell proliferation Source: UniProtKB
    15. renal tubule development Source: UniProtKB
    16. response to bacterium Source: MGI
    17. response to cAMP Source: UniProtKB
    18. response to cytokine Source: UniProtKB
    19. response to exogenous dsRNA Source: MGI
    20. response to lipopolysaccharide Source: MGI
    21. response to peptide hormone Source: UniProtKB
    22. transcription, DNA-templated Source: MGI
    23. type I interferon signaling pathway Source: UniProtKB

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_198614. Growth hormone receptor signaling.
    SABIO-RKP42225.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Signal transducer and activator of transcription 1
    Gene namesi
    Name:Stat1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:103063. Stat1.

    Subcellular locationi

    Cytoplasm 1 Publication. Nucleus 1 Publication
    Note: Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to IFN-gamma and signaling by activated FGFR1; FGFR2; FGFR3 or FGFR4.By similarity

    GO - Cellular componenti

    1. axon Source: UniProtKB
    2. cytoplasm Source: MGI
    3. cytosol Source: Reactome
    4. dendrite Source: UniProtKB
    5. nucleus Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi708 – 7081Missing: Strongly decreases ISGF3 binding to the ISRE of IKBKE-dependent genes but noo effect on ISGF3 binding to the ISRE of IKBKE-independent genes. 1 Publication
    Mutagenesisi744 – 7474SMMS → MM: No effect on ISGF3 binding to ISREs.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 749748Signal transducer and activator of transcription 1PRO_0000182411Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserineBy similarity
    Modified residuei701 – 7011Phosphotyrosine; by JAK1, JAK2 or TYK22 Publications
    Cross-linki703 – 703Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
    Modified residuei708 – 7081Phosphoserine; by IKKE2 Publications
    Modified residuei727 – 7271Phosphoserine; by MAPK14By similarity
    Modified residuei744 – 7441Phosphoserine; by IKKE1 Publication

    Post-translational modificationi

    Phosphorylated on tyrosine and serine residues in response to a variety of cytokines/growth hormones including IFN-alpha, IFN-gamma, PDGF and EGF. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. Upon EGF stimulation, phosphorylation on Tyr-701 (lacking in beta form) by JAK1, JAK2 or TYK2 promotes dimerization and subsequent translocation to the nucleus. Growth hormone (GH) activates STAT1 signaling only via JAK2. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylation on Ser-727 by several kinases including MAPK14, ERK1/2 and CAMKII on IFN-gamma stimulation, regulates STAT1 transcriptional activity. Phosphorylation on Ser-727 promotes sumoylation though increasing interaction with PIAS. Phosphorylation on Ser-727 by PRKCD induces apoptosis in response to DNA-damaging agents. Phosphorylated on tyrosine residues when PTK2/FAK1 is activated; most likely this is catalyzed by a SRC family kinase. Dephosphorylation on tyrosine residues by PTPN2 negatively regulates interferon-mediated signaling. Upon viral infection or IFN induction, phosphorylation on Ser-708 occurs much later than phosphorylation on Tyr-701 and is required for the binding of ISGF3 on the ISREs of a subset of IFN-stimulated genes IKBKE-dependent. Phosphorylation at Tyr-701 and Ser-708 are mutually exclusive, phosphorylation at Ser-708 requires previous dephosphorylation of Tyr-701.7 Publications
    Sumoylated with SUMO1, SUMO2 and SUMO3. Sumoylation is enhanced by IFN-gamma-induced phosphorylation on Ser-727, and by interaction with PIAS proteins. Enhances the transactivation activity By similarity.By similarity
    ISGylated.1 Publication

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP42225.
    PaxDbiP42225.
    PRIDEiP42225.

    PTM databases

    PhosphoSiteiP42225.

    Expressioni

    Inductioni

    By IFN and EGF.

    Gene expression databases

    GenevestigatoriP42225.

    Interactioni

    Subunit structurei

    Homodimerizes upon IFN-gamma induced phosphorylation. Heterodimer with STAT2 upon IFN-alpha/beta induced phosphorylation. The heterodimer STAT1:STAT2 forms the interferon-stimulated gene factor 3 complex (ISGF3) with IRF9. Interacts (phosphorylated at Ser-727) with PIAS1 (dimethylated on arginine); the interaction results in release of STAT1 from its target gene. Interacts with IFNAR1, IFNAR2, NMI, PTK2/FAK1 and SRC. Interacts with ERBB4 (phosphorylated).2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Ptpn6P293512EBI-647118,EBI-2620699
    Stat4P422282EBI-647118,EBI-6253572
    Usf1Q610692EBI-647118,EBI-2325635
    Usf2Q647053EBI-647118,EBI-647583

    Protein-protein interaction databases

    DIPiDIP-38739N.
    IntActiP42225. 14 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP42225.
    SMRiP42225. Positions 2-749.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini573 – 67098SH2PROSITE-ProRule annotationAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili136 – 317182By similarityAdd
    BLAST

    Sequence similaritiesi

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

    Keywords - Domaini

    Coiled coil, SH2 domain

    Phylogenomic databases

    eggNOGiNOG310130.
    HOVERGENiHBG055669.
    InParanoidiP42225.
    PhylomeDBiP42225.

    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.
    IPR022752. STAT1_TAZ2-bd_C.
    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.
    PF12162. STAT1_TAZ2bind. 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.

    P42225-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSQWFELQQL DSKFLEQVHQ LYDDSFPMEI RQYLAQWLEK QDWEHAAYDV    50
    SFATIRFHDL LSQLDDQYSR FSLENNFLLQ HNIRKSKRNL QDNFQEDPVQ 100
    MSMIIYNCLK EERKILENAQ RFNQAQEGNI QNTVMLDKQK ELDSKVRNVK 150
    DQVMCIEQEI KTLEELQDEY DFKCKTSQNR EGEANGVAKS DQKQEQLLLH 200
    KMFLMLDNKR KEIIHKIREL LNSIELTQNT LINDELVEWK RRQQSACIGG 250
    PPNACLDQLQ TWFTIVAETL QQIRQQLKKL EELEQKFTYE PDPITKNKQV 300
    LSDRTFLLFQ QLIQSSFVVE RQPCMPTHPQ RPLVLKTGVQ FTVKSRLLVK 350
    LQESNLLTKV KCHFDKDVNE KNTVKGFRKF NILGTHTKVM NMEESTNGSL 400
    AAELRHLQLK EQKNAGNRTN EGPLIVTEEL HSLSFETQLC QPGLVIDLET 450
    TSLPVVVISN VSQLPSGWAS ILWYNMLVTE PRNLSFFLNP PCAWWSQLSE 500
    VLSWQFSSVT KRGLNADQLS MLGEKLLGPN AGPDGLIPWT RFCKENINDK 550
    NFSFWPWIDT ILELIKNDLL CLWNDGCIMG FISKERERAL LKDQQPGTFL 600
    LRFSESSREG AITFTWVERS QNGGEPDFHA VEPYTKKELS AVTFPDIIRN 650
    YKVMAAENIP ENPLKYLYPN IDKDHAFGKY YSRPKEAPEP MELDDPKRTG 700
    YIKTELISVS EVHPSRLQTT DNLLPMSPEE FDEMSRIVGP EFDSMMSTV 749
    Length:749
    Mass (Da):87,197
    Last modified:November 1, 1995 - v1
    Checksum:i249D919952BE65F1
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U06924 mRNA. Translation: AAA19454.1.
    CCDSiCCDS56628.1.
    UniGeneiMm.277406.
    Mm.487336.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U06924 mRNA. Translation: AAA19454.1 .
    CCDSi CCDS56628.1.
    UniGenei Mm.277406.
    Mm.487336.

    3D structure databases

    ProteinModelPortali P42225.
    SMRi P42225. Positions 2-749.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-38739N.
    IntActi P42225. 14 interactions.

    Chemistry

    BindingDBi P42225.
    ChEMBLi CHEMBL1667670.

    PTM databases

    PhosphoSitei P42225.

    Proteomic databases

    MaxQBi P42225.
    PaxDbi P42225.
    PRIDEi P42225.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    MGIi MGI:103063. Stat1.

    Phylogenomic databases

    eggNOGi NOG310130.
    HOVERGENi HBG055669.
    InParanoidi P42225.
    PhylomeDBi P42225.

    Enzyme and pathway databases

    Reactomei REACT_198614. Growth hormone receptor signaling.
    SABIO-RK P42225.

    Miscellaneous databases

    ChiTaRSi STAT1. mouse.
    PROi P42225.
    SOURCEi Search...

    Gene expression databases

    Genevestigatori P42225.

    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.
    IPR022752. STAT1_TAZ2-bd_C.
    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.
    PF12162. STAT1_TAZ2bind. 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. "Stat3 and Stat4: members of the family of signal transducers and activators of transcription."
      Zhong Z., Wen Z., Darnell J.E. Jr.
      Proc. Natl. Acad. Sci. U.S.A. 91:4806-4810(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Thymus.
    2. "c-Src activates both STAT1 and STAT3 in PDGF-stimulated NIH3T3 cells."
      Cirri P., Chiarugi P., Marra F., Raugei G., Camici G., Manao G., Ramponi G.
      Biochem. Biophys. Res. Commun. 239:493-497(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, FUNCTION, INTERACTION WITH SRC.
    3. "Identification of tyrosine residues in constitutively activated fibroblast growth factor receptor 3 involved in mitogenesis, Stat activation, and phosphatidylinositol 3-kinase activation."
      Hart K.C., Robertson S.C., Donoghue D.J.
      Mol. Biol. Cell 12:931-942(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION.
    4. Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN2.
    5. Cited for: ISGYLATION.
    6. "Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity."
      Tenoever B.R., Ng S.L., Chua M.A., McWhirter S.M., Garcia-Sastre A., Maniatis T.
      Science 315:1274-1278(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN THE ISGF3 COMPLEX, PHOSPHORYLATION AT SER-708 AND SER-744, MUTAGENESIS OF SER-708 AND 744-SER--SER-747.
    7. "Analysis of STAT1 activation by six FGFR3 mutants associated with skeletal dysplasia undermines dominant role of STAT1 in FGFR3 signaling in cartilage."
      Krejci P., Salazar L., Kashiwada T.A., Chlebova K., Salasova A., Thompson L.M., Bryja V., Kozubik A., Wilcox W.R.
      PLoS ONE 3:E3961-E3961(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION AT TYR-701 IN RESPONSE TO CONSTITUTIVELY ACTIVATED FGFR3.
    8. "Mechanisms of STAT protein activation by oncogenic KIT mutants in neoplastic mast cells."
      Chaix A., Lopez S., Voisset E., Gros L., Dubreuil P., De Sepulveda P.
      J. Biol. Chem. 286:5956-5966(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION IN RESPONSE TO KIT SIGNALING.
    9. "Inhibitor of kappaB kinase epsilon (IKK(epsilon)), STAT1, and IFIT2 proteins define novel innate immune effector pathway against West Nile virus infection."
      Perwitasari O., Cho H., Diamond M.S., Gale M. Jr.
      J. Biol. Chem. 286:44412-44423(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION AT TYR-701; SER-708 AND SER-727.

    Entry informationi

    Entry nameiSTAT1_MOUSE
    AccessioniPrimary (citable) accession number: P42225
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 127 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3