InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: STAT1

Summary

InnateDB Protein

IDBP-77619.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

STAT1

Protein Name

signal transducer and activator of transcription 1, 91kDa

Synonyms

CANDF7; IMD31A; IMD31B; IMD31C; ISGF-3; STAT91;

Species

Homo sapiens

Ensembl Protein

ENSP00000354394

InnateDB Gene

IDBG-77617 (STAT1)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:12764129, ECO:0000269PubMed:12855578, ECO:0000269PubMed:15322115, ECO:0000269PubMed:19088846, ECO:0000269PubMed:9724754}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:15322115}. Nucleus {ECO:0000269PubMed:15322115}. Note=Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to IFN-gamma and signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4.

Disease Associations

STAT1 deficiency complete (STAT1D) [MIM:613796]: A disorder characterized by susceptibility to severe mycobacterial and viral infections. Affected individuals can develop disseminated infections and die of viral illness. {ECO:0000269PubMed:12590259, ECO:0000269PubMed:20841510}. Note=The disease is caused by mutations affecting the gene represented in this entry.Mendelian susceptibility to mycobacterial disease (MSMD) [MIM:209950]: This rare condition confers predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine and environmental non- tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. The pathogenic mechanism underlying MSMD is the impairment of interferon-gamma mediated immunity, whose severity determines the clinical outcome. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance. {ECO:0000269PubMed:11452125, ECO:0000269PubMed:16934001, ECO:0000269PubMed:22573496}. Note=The disease is caused by mutations affecting the gene represented in this entry.Candidiasis, familial, 7 (CANDF7) [MIM:614162]: A primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans. {ECO:0000269PubMed:21714643, ECO:0000269PubMed:21727188}. Note=The disease is caused by mutations affecting the gene represented in this entry. STAT1 mutations in patients with autosomal dominant candidiasis lead to defective responses of type 1 and type 17 helper T-cells, characterized by reduced production of interferon-alpha, interleukin-17, and interleukin-22. These cytokines are crucial for the antifungal defense of skin and mucosa (PubMed:21714643). {ECO:0000269PubMed:21714643}.

Tissue Specificity

Comments

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

Protein Structure and Domains

PDB ID

InterPro

IPR000980 SH2 domain
IPR008967 p53-like transcription factor, DNA-binding
IPR013799 STAT transcription factor, protein interaction
IPR013800 STAT transcription factor, all-alpha
IPR013801 STAT transcription factor, DNA-binding
IPR015988 STAT transcription factor, coiled coil
IPR022752 Signal transducer and activation of transcription 1, TAZ2 binding domain, C-terminal

PFAM

PF00017
PF14633
PF02865
PF01017
PF02864
PF12162

PRINTS

PR00401

PIRSF

SMART

SM00252
SM00964

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt