STAT2
STAT2 (signal transducer and activator of transcription 2, also known as STAT113) is a member of the STAT transcription factor family that mediates signalling by type I interferons, IFN-alpha and IFN-beta. It acts as a transactivator within the ISGF3 complex to drive innate antiviral responses. Browse Assay Genie's current range of STAT2 research reagents below, or read on for the biology behind the target.
STAT2 transmits the signal from type I interferons (IFN-alpha and IFN-beta) to the nucleus. When type I IFN binds its cell surface receptors, the Jak kinases TYK2 and JAK1 are activated and phosphorylate STAT1 and STAT2 on tyrosine. The phosphorylated STATs dimerise and associate with IRF9 (also called ISGF3G, or p48) to form the ISGF3 transcription factor complex. ISGF3 enters the nucleus and binds the IFN stimulated response element (ISRE), activating interferon stimulated genes that place the cell in an antiviral state.
Within this complex STAT2 acts as a transactivator but lacks the ability to bind DNA directly. It also has a negative feedback role in type I interferon signalling: by recruiting USP18 to the receptor subunit IFNAR2, it mitigates the response to type I IFNs. In addition, STAT2 regulates mitochondrial fission by modulating the phosphorylation of DNM1L at Ser-616 and Ser-637, which activate and inactivate its GTPase activity respectively.
The STAT2 gene encodes a member of the STAT family, which is classed in HGNC as an SH2 domain containing group. Family members are phosphorylated by receptor-associated kinases in response to cytokines and growth factors, then form homo- or heterodimers that translocate to the nucleus and activate transcription. The STAT2 protein is found in the cytoplasm and the nucleus. Mutations in the gene result in Immunodeficiency 44. The mouse ortholog is Stat2. Earlier HGNC names referred to the protein by its approximate size, 113 kDa.
STAT2 is a core component of the type I interferon pathway, linking IFN-alpha and IFN-beta receptor activation to interferon stimulated gene transcription.
The protein mediates innate antiviral activity as part of the ISGF3 complex, which drives cells into an antiviral state.
Mutations in the STAT2 gene result in Immunodeficiency 44, making the protein relevant to studies of inherited immune disorders.
STAT2 modulates DNM1L phosphorylation at Ser-616 and Ser-637, giving it a role in the regulation of mitochondrial fission.
STAT2 mediates type I interferon signalling. After phosphorylation by TYK2 and JAK1, it joins STAT1 and IRF9 to form ISGF3, which binds the ISRE and activates interferon stimulated genes. It also provides negative feedback by recruiting USP18 to IFNAR2 and regulates mitochondrial fission.
Not by itself. In the ISGF3 complex with STAT1 and IRF9 (ISGF3G, p48), STAT2 acts as a transactivator but lacks the ability to bind DNA directly. The complex as a whole binds the interferon stimulated response element in target gene promoters.
Mutations in the STAT2 gene result in Immunodeficiency 44. A mouse ortholog, Stat2, is annotated, so mouse models are available for study. Check the datasheet of any product for its validated reactivity.
Other STAT family transcription factors, including STAT1, the ISGF3 partner of STAT2, with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P52630; product specifications from Assay Genie datasheets.