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Q14765

- STAT4_HUMAN

UniProt

Q14765 - STAT4_HUMAN

Protein

Signal transducer and activator of transcription 4

Gene

STAT4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 144 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    Carries out a dual function: signal transduction and activation of transcription. Involved in IL12 signaling.

    GO - Molecular functioni

    1. calcium ion binding Source: InterPro
    2. sequence-specific DNA binding Source: Ensembl
    3. sequence-specific DNA binding transcription factor activity Source: ProtInc
    4. signal transducer activity Source: InterPro

    GO - Biological processi

    1. cell proliferation Source: Ensembl
    2. cytokine-mediated signaling pathway Source: Ensembl
    3. JAK-STAT cascade Source: ProtInc
    4. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    5. protein phosphorylation Source: Ensembl
    6. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    SignaLinkiQ14765.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Signal transducer and activator of transcription 4
    Gene namesi
    Name:STAT4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:11365. STAT4.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Translocated into the nucleus in response to phosphorylation.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: HPA

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Systemic lupus erythematosus 11 (SLEB11) [MIM:612253]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.1 Publication
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures.1 Publication
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

    Keywords - Diseasei

    Systemic lupus erythematosus

    Organism-specific databases

    MIMi180300. phenotype.
    612253. phenotype.
    Orphaneti117. Behcet disease.
    85408. Juvenile rheumatoid factor-negative polyarthritis.
    85410. Oligoarticular juvenile arthritis.
    93552. Pediatric systemic lupus erythematosus.
    536. Systemic lupus erythematosus.
    PharmGKBiPA36185.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 748748Signal transducer and activator of transcription 4PRO_0000182420Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei693 – 6931Phosphotyrosine; by JAKBy similarity

    Post-translational modificationi

    Tyrosine phosphorylated. Serine phosphorylation is also required for maximal transcriptional activity By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ14765.
    PRIDEiQ14765.

    PTM databases

    PhosphoSiteiQ14765.

    Expressioni

    Gene expression databases

    ArrayExpressiQ14765.
    BgeeiQ14765.
    CleanExiHS_STAT4.
    GenevestigatoriQ14765.

    Organism-specific databases

    HPAiCAB013108.
    HPA001860.

    Interactioni

    Subunit structurei

    Forms a homodimer or a heterodimer with a related family member. Interacts with ARL2BP By similarity. The SH2 domain interacts, in vitro, with IL12RB2 via a short cytoplasmic domain.By similarity2 Publications

    Protein-protein interaction databases

    BioGridi112652. 7 interactions.
    DIPiDIP-39854N.
    IntActiQ14765. 4 interactions.
    MINTiMINT-8020311.
    STRINGi9606.ENSP00000351255.

    Structurei

    3D structure databases

    ProteinModelPortaliQ14765.
    SMRiQ14765. Positions 2-702.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini569 – 66496SH2PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

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

    Keywords - Domaini

    SH2 domain

    Phylogenomic databases

    eggNOGiNOG267627.
    HOGENOMiHOG000220792.
    HOVERGENiHBG055669.
    InParanoidiQ14765.
    KOiK11222.
    OMAiGNEGCHM.
    OrthoDBiEOG73JKTT.
    PhylomeDBiQ14765.
    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.

    Q14765-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSQWNQVQQL EIKFLEQVDQ FYDDNFPMEI RHLLAQWIEN QDWEAASNNE    50
    TMATILLQNL LIQLDEQLGR VSKEKNLLLI HNLKRIRKVL QGKFHGNPMH 100
    VAVVISNCLR EERRILAAAN MPVQGPLEKS LQSSSVSERQ RNVEHKVAAI 150
    KNSVQMTEQD TKYLEDLQDE FDYRYKTIQT MDQSDKNSAM VNQEVLTLQE 200
    MLNSLDFKRK EALSKMTQII HETDLLMNTM LIEELQDWKR RQQIACIGGP 250
    LHNGLDQLQN CFTLLAESLF QLRRQLEKLE EQSTKMTYEG DPIPMQRTHM 300
    LERVTFLIYN LFKNSFVVER QPCMPTHPQR PLVLKTLIQF TVKLRLLIKL 350
    PELNYQVKVK ASIDKNVSTL SNRRFVLCGT NVKAMSIEES SNGSLSVEFR 400
    HLQPKEMKSS AGGKGNEGCH MVTEELHSIT FETQICLYGL TIDLETSSLP 450
    VVMISNVSQL PNAWASIIWY NVSTNDSQNL VFFNNPPPAT LSQLLEVMSW 500
    QFSSYVGRGL NSDQLHMLAE KLTVQSSYSD GHLTWAKFCK EHLPGKSFTF 550
    WTWLEAILDL IKKHILPLWI DGYVMGFVSK EKERLLLKDK MPGTFLLRFS 600
    ESHLGGITFT WVDHSESGEV RFHSVEPYNK GRLSALPFAD ILRDYKVIMA 650
    ENIPENPLKY LYPDIPKDKA FGKHYSSQPC EVSRPTERGD KGYVPSVFIP 700
    ISTIRSDSTE PHSPSDLLPM SPSVYAVLRE NLSPTTIETA MKSPYSAE 748
    Length:748
    Mass (Da):85,941
    Last modified:November 1, 1996 - v1
    Checksum:i11E43803A9AF4FFA
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti365 – 3717KNVSTLS → N in AAL12164. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti112 – 1121E → Q in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036002
    Natural varianti115 – 1151I → V.
    Corresponds to variant rs3024839 [ dbSNP | Ensembl ].
    VAR_020190
    Natural varianti584 – 5841R → W.
    Corresponds to variant rs3024933 [ dbSNP | Ensembl ].
    VAR_047939

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L78440 mRNA. Translation: AAB05605.1.
    BC031212 mRNA. Translation: AAH31212.1.
    AF423072 Genomic DNA. Translation: AAL12164.1.
    CCDSiCCDS2310.1.
    RefSeqiNP_001230764.1. NM_001243835.1.
    NP_003142.1. NM_003151.3.
    XP_006712782.1. XM_006712719.1.
    UniGeneiHs.735572.
    Hs.80642.

    Genome annotation databases

    EnsembliENST00000358470; ENSP00000351255; ENSG00000138378.
    ENST00000392320; ENSP00000376134; ENSG00000138378.
    GeneIDi6775.
    KEGGihsa:6775.
    UCSCiuc002usm.2. human.

    Polymorphism databases

    DMDMi6226158.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L78440 mRNA. Translation: AAB05605.1 .
    BC031212 mRNA. Translation: AAH31212.1 .
    AF423072 Genomic DNA. Translation: AAL12164.1 .
    CCDSi CCDS2310.1.
    RefSeqi NP_001230764.1. NM_001243835.1.
    NP_003142.1. NM_003151.3.
    XP_006712782.1. XM_006712719.1.
    UniGenei Hs.735572.
    Hs.80642.

    3D structure databases

    ProteinModelPortali Q14765.
    SMRi Q14765. Positions 2-702.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112652. 7 interactions.
    DIPi DIP-39854N.
    IntActi Q14765. 4 interactions.
    MINTi MINT-8020311.
    STRINGi 9606.ENSP00000351255.

    PTM databases

    PhosphoSitei Q14765.

    Polymorphism databases

    DMDMi 6226158.

    Proteomic databases

    PaxDbi Q14765.
    PRIDEi Q14765.

    Protocols and materials databases

    DNASUi 6775.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000358470 ; ENSP00000351255 ; ENSG00000138378 .
    ENST00000392320 ; ENSP00000376134 ; ENSG00000138378 .
    GeneIDi 6775.
    KEGGi hsa:6775.
    UCSCi uc002usm.2. human.

    Organism-specific databases

    CTDi 6775.
    GeneCardsi GC02M191894.
    HGNCi HGNC:11365. STAT4.
    HPAi CAB013108.
    HPA001860.
    MIMi 180300. phenotype.
    600558. gene.
    612253. phenotype.
    neXtProti NX_Q14765.
    Orphaneti 117. Behcet disease.
    85408. Juvenile rheumatoid factor-negative polyarthritis.
    85410. Oligoarticular juvenile arthritis.
    93552. Pediatric systemic lupus erythematosus.
    536. Systemic lupus erythematosus.
    PharmGKBi PA36185.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG267627.
    HOGENOMi HOG000220792.
    HOVERGENi HBG055669.
    InParanoidi Q14765.
    KOi K11222.
    OMAi GNEGCHM.
    OrthoDBi EOG73JKTT.
    PhylomeDBi Q14765.
    TreeFami TF318648.

    Enzyme and pathway databases

    SignaLinki Q14765.

    Miscellaneous databases

    GeneWikii STAT4.
    GenomeRNAii 6775.
    NextBioi 26446.
    PROi Q14765.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q14765.
    Bgeei Q14765.
    CleanExi HS_STAT4.
    Genevestigatori Q14765.

    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. "The STAT amino-terminal domain mediates cooperative DNA binding and confers selective sequence recognition."
      Xu X., Sun Y.L., Hoey T.
      Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    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: Testis.
    3. SeattleSNPs variation discovery resource
      Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 91-748.
    4. "Direct interaction of STAT4 with the IL-12 receptor."
      Yao B.B., Niu P., Surowy C.S., Faltynek C.R.
      Arch. Biochem. Biophys. 368:147-155(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IL12RB2.
    5. "Identification of a STAT4 binding site in the interleukin-12 receptor required for signaling."
      Naeger L.K., McKinney J., Salvekar A., Hoey T.
      J. Biol. Chem. 274:1875-1878(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IL12RB2.
    6. "Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo."
      Kariuki S.N., Kirou K.A., MacDermott E.J., Barillas-Arias L., Crow M.K., Niewold T.B.
      J. Immunol. 182:34-38(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN SLEB11.
    7. Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-112.
    8. Cited for: INVOLVEMENT IN SLEB11 AND RA.

    Entry informationi

    Entry nameiSTAT4_HUMAN
    AccessioniPrimary (citable) accession number: Q14765
    Secondary accession number(s): Q96NZ6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 144 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3