InnateDB: Systems Biology of the Innate Immune Response

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

IDBP-77619

signal transducer and activator of transcription 1, 91kDa

IDBP-245890

signal transducer and activator of transcription 1, 91kDa

IDBP-245892

signal transducer and activator of transcription 1, 91kDa

IDBP-293291

signal transducer and activator of transcription 1, 91kDa

IDBP-388063

signal transducer and activator of transcription 1, 91kDa

IDBP-388067

signal transducer and activator of transcription 1, 91kDa

IDBP-388068

signal transducer and activator of transcription 1, 91kDa

IDBP-388069

signal transducer and activator of transcription 1, 91kDa

IDBP-388070

signal transducer and activator of transcription 1, 91kDa

IDBP-388071

signal transducer and activator of transcription 1, 91kDa

IDBP-596000

signal transducer and activator of transcription 1, 91kDa

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 17971840

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.

PMID 18678606

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.

PMID 7657660

STAT1 phosphorylation and DNA binding activity is under the control of Janus protein-tyrosine kinases (JAKs) and the epidermal growth factor receptor (EGFR).

PMID 16481475

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.

PMID 8943351

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.

PMID 20829351

STAT1 transcription factor enhances TLR8 functionality by binding of to GAS elements on the TLR8 promoter in an IFN-gamma-dependent manner.

PMID 22065572

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)

PMID 22425562

Histone deacetylase inhibitors prevent IFNG-mediated phosphorylation of STAT1.

PMID 24449862

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.

PMID 25027037

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

PMID 22065572

[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.

PMID 22425562

[Mus musculus] Histone deacetylase inhibitors prevent Ifng-mediated phosphorylation of Stat1. (Demonstrated in human)

PMID 25431490

[Mus musculus] Il28ra (Ifnlr1), Stat1 and Irf3 are required for antibiotics to prevent persistent murine norovirus infection.

PMID 25972472

[Mus musculus] Cd81 inhibits Rac1/Stat1 activation and negatively regulates the defence mechanisms to Listeria monocytogenes infection.

PMID 25848864

[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.

PMID 26335850

[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