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STAT1

GeneName

STAT1

Summary

STAT1, also known as STAT-1 or STAT1 alpha, is an 87 kDa transcription factor that plays a pivotal role in mediating cellular responses to various cytokines, particularly interferons. It is predominantly expressed in the nucleus and cytoplasm, and is involved in the regulation of gene expression through its DNA-binding activity. STAT1 is a critical component of the JAK-STAT signalling pathway, facilitating the transcription of genes associated with immune responses, cell differentiation, and apoptosis. It localises to several cellular compartments, including the nucleus, cytoplasm, and chromatin, and forms part of the ISGF3 complex, which is essential for the transcriptional response to type I interferons. Additionally, STAT1 interacts with various proteins, including histones and other transcription factors, to modulate transcriptional activity.

Importance

STAT1 is relevant to: - Immune response regulation, particularly in the context of viral infections, through its role in interferon signalling - Cancer biology, as it influences tumour microenvironment and immune evasion mechanisms - Autoimmune diseases, given its involvement in inflammatory responses and regulation of immune cell activity - Developmental processes, including renal development, due to its role in cell differentiation and proliferation

Top Products

For researchers investigating STAT1, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the well-cited polyclonal antibody, Anti-STAT1 antibody (ab31369), which has garnered 34 citations and is particularly effective in Western blotting (WB) and immunohistochemistry (IHC). In addition, we offer the top-selling recombinant antibody, Anti-STAT1 antibody [EPR4407] (ab109320). This monoclonal antibody has been validated in knockout models and is suitable for a broader range of applications, including WB, IHC, immunocytochemistry (ICC), flow cytometry (FC), and immunoprecipitation (IP). With 65 citations, it demonstrates strong reliability and is an excellent choice for researchers seeking consistent performance in their experiments. The Anti-STAT1 antibody [1/Stat1] ELISA Kit (ab281999), supported by 3 citations, is an excellent option for researchers looking to accurately measure STAT1 levels in their samples.

Abcam Product Citation Summary

The data indicates that STAT1 is frequently studied in the context of various human cell types, including primary cortical neurons, peripheral blood mononuclear cells, and lung epithelial cells. The applications primarily involve Western blotting and immunofluorescence, highlighting its role in pathways related to viral infections, chronic hepatitis, and immune responses. Additionally, studies involving rat models suggest its significance in understanding the effects of treatments like ICH.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab2071
Human
WB
Primary cortical neurons
29531801
ab2071
Human
WB
Effects of metformin
29531801
ab31369
Human
WB
Chronic hepatitis B
29181338
ab31369
Human
WB
Regulatory role of interleukin-35
29181338
ab31369
Rat
WB
ICH treatment
28196545
ab3987
Human
WB
Activation of JAK/STAT pathways
31217935
ab92506
Human
WB
Influenza infection responses
23139774
ab92506
Human
WB
Macrophage activation
31997535

Function

Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:12764129, PubMed:12855578, PubMed:15322115, PubMed:23940278, PubMed:34508746, PubMed:35568036, PubMed:9724754). 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 (PubMed:28753426, PubMed:35568036). 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 (PubMed:28753426, PubMed:35568036). In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated (PubMed:26479788). 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 (PubMed:8156998). Becomes activated in response to KITLG/SCF and KIT signaling (PubMed:15526160). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:19088846). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylated at Thr-749 by IKBKB which promotes binding of STAT1 to the 5'-TTTGAGGC-3' sequence in the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). Phosphorylation at Thr-749 also promotes binding of STAT1 to the 5'-TTTGAGTC-3' sequence in the IL12B promoter and activation of IL12B transcription (PubMed:32209697). Involved in food tolerance in small intestine: associates with the Gasdermin-D, p13 cleavage product (13 kDa GSDMD) and promotes transcription of CIITA, inducing type 1 regulatory T (Tr1) cells in upper small intestine (By similarity).

Involvement in disease

Immunodeficiency 31B

IMD31B

A disorder characterized by susceptibility to severe mycobacterial and viral infections. Affected individuals can develop disseminated infections and die of viral illness.

None

The disease is caused by variants affecting the gene represented in this entry.

Immunodeficiency 31A

IMD31A

A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, 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. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. 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. IMD31A has low penetrance, and affected individuals have relatively mild disease and good prognosis. IMD31A confers a predisposition to mycobacterial infections only, with no increased susceptibility to viral infections.

None

The disease is caused by variants affecting the gene represented in this entry.

Immunodeficiency 31C

IMD31C

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.

None

The disease is caused by variants 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).

Post-translational modifications

Deubiquitinated by USP13; leading to STAT1 stabilization and positive regulation of type I and type II IFN signalings.

Phosphorylated on tyrosine and serine residues in response to a variety of cytokines/growth hormones including IFN-alpha, IFN-gamma, PDGF and EGF (PubMed:26479788, PubMed:28753426). Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus (PubMed:21135090). Upon EGF stimulation, phosphorylation on Tyr-701 (lacking in beta form) by JAK1, JAK2 or TYK2 promotes dimerization and subsequent translocation to the nucleus (PubMed:28753426, PubMed:7657660). Growth hormone (GH) activates STAT1 signaling only via JAK2 (PubMed:7657660). Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:17561467, PubMed:19088846). Phosphorylation on Ser-727 by several kinases including MAPK14, ERK1/2, CAMK2/CAMKII and CK2 in response to IFN-gamma stimulation, is required for maximal transcriptional activity (PubMed:15322115, PubMed:16799645, PubMed:17897103, PubMed:7543024). Phosphorylated on Ser-727 by CAMK2/CAMKII in response to IFN-gamma stimulation and calcium mobilization, promoting activity (PubMed:11972023, PubMed:16257975). Phosphorylated by CAMK2/CAMKII in response to IFN-beta stimulation and calcium mobilization in epithelial cells, promoting activity (PubMed:35568036). Phosphorylation on Ser-727 promotes sumoylation though increasing interaction with PIAS (PubMed:17897103). Phosphorylation on Ser-727 by PRKCD induces apoptosis in response to DNA-damaging agents (PubMed:15322115). Phosphorylated on tyrosine residues when PTK2/FAK1 is activated; most likely this is catalyzed by a SRC family kinase (PubMed:11278462). Dephosphorylation on tyrosine residues by PTPN2 negatively regulates interferon-mediated signaling (PubMed:12138178). 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 (PubMed:22065572). Phosphorylation at Tyr-701 and Ser-708 are mutually exclusive, phosphorylation at Ser-708 requires previous dephosphorylation of Tyr-701 (PubMed:22065572). Phosphorylation at Thr-749 by IKBKB/IKKB promotes transcriptional activation of ARID5A and IL12B by STAT1 (PubMed:32209697). Phosphorylation at Thr-749 restricts interferon signaling and anti-inflammatory responses and promotes innate inflammatory responses (By similarity).

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.

ISGylated.

Mono-ADP-ribosylated at Glu-657 and Glu-705 by PARP14; ADP-ribosylation prevents phosphorylation at Tyr-701 (PubMed:27796300). However, the role of ADP-ribosylation in the prevention of phosphorylation has been called into question and the lack of phosphorylation may be due to sumoylation of Lys-703 (PubMed:29858569).

Monomethylated at Lys-525 by SETD2; monomethylation is necessary for phosphorylation at Tyr-701, translocation into the nucleus and activation of the antiviral defense.

(Microbial infection) Ubiquitinated by Herpes simplex virus 2 E3 ubiquitin ligase ICP22.

Sequence Similarities

Belongs to the transcription factor STAT family.

Cellular localization

Alternative names

Signal transducer and activator of transcription 1-alpha/beta, Transcription factor ISGF-3 components p91/p84, STAT1

swissprot:P42224 omim:600555 entrezGene:6772

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