Homo sapiens Gene: STAT1
Summary
InnateDB Gene IDBG-77617.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol STAT1
Gene Name signal transducer and activator of transcription 1, 91kDa
Synonyms CANDF7; IMD31A; IMD31B; IMD31C; ISGF-3; STAT91;
Species Homo sapiens
Ensembl Gene ENSG00000115415
Encoded Proteins
signal transducer and activator of transcription 1, 91kDa
signal transducer and activator of transcription 1, 91kDa
signal transducer and activator of transcription 1, 91kDa
signal transducer and activator of transcription 1, 91kDa
signal transducer and activator of transcription 1, 91kDa
signal transducer and activator of transcription 1, 91kDa
signal transducer and activator of transcription 1, 91kDa
signal transducer and activator of transcription 1, 91kDa
signal transducer and activator of transcription 1, 91kDa
signal transducer and activator of transcription 1, 91kDa
signal transducer and activator of transcription 1, 91kDa
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
STAT1 mediates IFNG cytokine signalling, and as a member of the STAT family protein, STAT1 has a significant impact on the innate immunity during sepsis.
STAT1 serine phosphorylation is induced by TNF-alpha and PGE2 and this activates expression of the STAT1 and NF-kappaB target gene IFN regulatory factor 1 (IRF1), which contributes to IFN responses.
STAT1 phosphorylation and DNA binding activity is under the control of Janus protein-tyrosine kinases (JAKs) and the epidermal growth factor receptor (EGFR).
Acetylation of STAT1 modulates NF-kappaB activity and thus ultimately apoptosis where, as a result, RELA DNA binding, nuclear localization, and expression of anti-apoptotic NF-kappaB target genes decrease.
STAT1 is part of the interferon-stimulated gene factor 3 (ISGF3) transcription complex which is composed of a STAT1:2 heterodimer and a weak DNA-binding protein, IRF9.
STAT1 transcription factor enhances TLR8 functionality by binding of to GAS elements on the TLR8 promoter in an IFN-gamma-dependent manner.
STAT1 phosphorylation at Ser708 is a key event in the IFN signalling pathway that imparts anti-viral immunity to restrict West Nile virus infection. (Demonstrated in mice)
Histone deacetylase inhibitors prevent IFNG-mediated phosphorylation of STAT1.
TNK1 is a component of the IFN-JAK-STAT signalling cascade and is a critical antiviral host factor where its abundance is inversely correlated to viral replication and contributes to the hepatocytic response to antiviral treatment.
STAT1 is directly recruited to TRAF6, demonstrating cross-talk between the TLR and JAK/STAT signalling pathways, and this direct activation of STAT1 by TLR signalling suggests a crucial role for STAT1 in TLR-induced inflammation. Demonstrated in mice.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Stat1 phosphorylation at Ser708 is a key event in the IFN signalling pathway that imparts anti-viral immunity to restrict West Nile virus infection.
[Mus musculus] Histone deacetylase inhibitors prevent Ifng-mediated phosphorylation of Stat1. (Demonstrated in human)
[Mus musculus] Il28ra (Ifnlr1), Stat1 and Irf3 are required for antibiotics to prevent persistent murine norovirus infection.
[Mus musculus] Cd81 inhibits Rac1/Stat1 activation and negatively regulates the defence mechanisms to Listeria monocytogenes infection.
[Mus musculus] Treml4 is an essential positive regulator of Tlr7 signalling. Treml4(-/-) macrophages are hyporesponsive to Tlr7 agonists and fail to produce type I interferons due to impaired phosphorylation of Stat1 by Mapk14 and decreased recruitment of Myd88 to Tlr7.
[Mus musculus] Transcriptional activation of Adar by IFN occurs in the absence of Stat1 by a non-canonical Stat2-dependent pathway.
Entrez Gene
Summary The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein can be activated by various ligands including interferon-alpha, interferon-gamma, EGF, PDGF and IL6. This protein mediates the expression of a variety of genes, which is thought to be important for cell viability in response to different cell stimuli and pathogens. Two alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
Gene Information
Type Protein coding
Genomic Location Chromosome 2:190964358-191020960
Strand Reverse strand
Band q32.2
Transcripts
ENST00000361099 ENSP00000354394
ENST00000392323 ENSP00000376137
ENST00000392322 ENSP00000376136
ENST00000409465 ENSP00000386244
ENST00000415035 ENSP00000388240
ENST00000423282 ENSP00000388772
ENST00000452281 ENSP00000394512
ENST00000424722 ENSP00000402548
ENST00000454414 ENSP00000411398
ENST00000432058 ENSP00000416019
ENST00000464072
ENST00000540176 ENSP00000438703
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 332 experimentally validated interaction(s) in this database.
They are also associated with 31 interaction(s) predicted by orthology.
Experimentally validated
Total 332 [view]
Protein-Protein 235 [view]
Protein-DNA 95 [view]
Protein-RNA 0
DNA-DNA 1 [view]
RNA-RNA 1 [view]
DNA-RNA 0
Predicted by orthology
Total 31 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding
GO:0000983 RNA polymerase II core promoter sequence-specific DNA binding transcription factor activity
GO:0003677 DNA binding
GO:0003690 double-stranded DNA binding
GO:0003700 sequence-specific DNA binding transcription factor activity
GO:0004871 signal transducer activity
GO:0005164 tumor necrosis factor receptor binding
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0019899 enzyme binding
GO:0031730 CCR5 chemokine receptor binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0043565 sequence-specific DNA binding
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001937 negative regulation of endothelial cell proliferation
GO:0002053 positive regulation of mesenchymal cell proliferation
GO:0003340 negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006366 transcription from RNA polymerase II promoter
GO:0006915 apoptotic process
GO:0007165 signal transduction
GO:0007259 JAK-STAT cascade
GO:0007584 response to nutrient
GO:0008015 blood circulation
GO:0008284 positive regulation of cell proliferation
GO:0009612 response to mechanical stimulus
GO:0009617 response to bacterium
GO:0014070 response to organic cyclic compound
GO:0016032 viral process
GO:0016525 negative regulation of angiogenesis
GO:0019221 cytokine-mediated signaling pathway
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032496 response to lipopolysaccharide
GO:0032869 cellular response to insulin stimulus
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0034097 response to cytokine
GO:0034240 negative regulation of macrophage fusion
GO:0035458 cellular response to interferon-beta
GO:0042493 response to drug
GO:0042542 response to hydrogen peroxide
GO:0042981 regulation of apoptotic process
GO:0043124 negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043330 response to exogenous dsRNA
GO:0043434 response to peptide hormone
GO:0045087 innate immune response (InnateDB)
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0051591 response to cAMP
GO:0051607 defense response to virus
GO:0060333 interferon-gamma-mediated signaling pathway
GO:0060334 regulation of interferon-gamma-mediated signaling pathway
GO:0060337 type I interferon signaling pathway
GO:0060338 regulation of type I interferon-mediated signaling pathway
GO:0060397 JAK-STAT cascade involved in growth hormone signaling pathway
GO:0061326 renal tubule development
GO:0072136 metanephric mesenchymal cell proliferation involved in metanephros development
GO:0072162 metanephric mesenchymal cell differentiation
GO:0072308 negative regulation of metanephric nephron tubule epithelial cell differentiation
Cellular Component
GO:0000790 nuclear chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0030424 axon
GO:0030425 dendrite
Orthologs
Species
Mus musculus
Gene ID
Gene Order
Method
Confidence
Comments
Low
Tentative data, uncurated. RBBH derived.
Pathways
NETPATH
EGFR1 pathway
KitReceptor pathway
TNFalpha pathway
TCR pathway
BCR pathway
IL2 pathway
IL4 pathway
IL5 pathway
IL6 pathway
IL-7 pathway
IL9 pathway
RANKL pathway
Leptin pathway
TSH pathway
TSLP pathway
Prolactin pathway
IL11 pathway
Oncostatin_M pathway
REACTOME
Signaling by FGFR in disease pathway
Signaling by FGFR mutants pathway
Antiviral mechanism by IFN-stimulated genes pathway
Cytokine Signaling in Immune system pathway
Signaling by FGFR1 mutants pathway
Signaling by SCF-KIT pathway
Signal Transduction pathway
Interferon Signaling pathway
Immune System pathway
Downstream signal transduction pathway
ISG15 antiviral mechanism pathway
Signaling by PDGF pathway
Signaling by FGFR1 fusion mutants pathway
Disease pathway
KEGG
Chemokine signaling pathway pathway
Osteoclast differentiation pathway
Toll-like receptor signaling pathway pathway
Jak-STAT signaling pathway pathway
Leishmaniasis pathway
Toxoplasmosis pathway
Hepatitis C pathway
Pathways in cancer pathway
Pancreatic cancer pathway
INOH
IFN gamma signaling pathway
IFN alpha signaling pathway
JAK STAT pathway and regulation pathway
EPO signaling pathway pathway
IL-5 signaling pathway
PID BIOCARTA
Inhibition of cellular proliferation by gleevec [Biocarta view]
Ifn alpha signaling pathway [Biocarta view]
Pdgf signaling pathway [Biocarta view]
P38 mapk signaling pathway [Biocarta view]
Il22 soluble receptor signaling pathway [Biocarta view]
Tpo signaling pathway [Biocarta view]
Bioactive peptide induced signaling pathway [Biocarta view]
Mapkinase signaling pathway [Biocarta view]
Egf signaling pathway [Biocarta view]
Ifn gamma signaling pathway [Biocarta view]
PID NCI
IL2-mediated signaling events
IL27-mediated signaling events
TNF receptor signaling pathway
IL12-mediated signaling events
ErbB1 downstream signaling
EPO signaling pathway
Glucocorticoid receptor regulatory network
FGF signaling pathway
Signaling events mediated by Stem cell factor receptor (c-Kit)
Signaling events mediated by TCPTP
IL23-mediated signaling events
SHP2 signaling
PDGFR-beta signaling pathway
IL6-mediated signaling events
IFN-gamma pathway
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.627802 Hs.743244
RefSeq NM_007315 NM_139266 XM_006712718
HUGO
OMIM
CCDS CCDS2309 CCDS42793
HPRD 02777
IMGT
EMBL
GenPept
RNA Seq Atlas