Signal transducer and activator of transcription 2 phospho Y689
Function
Signal transducer and activator of transcription that mediates signaling by type I interferons (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with IRF9/ISGF3G 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 interferon stimulated genes, which drive the cell in an antiviral state (PubMed:23391734, PubMed:9020188). In addition, has also a negative feedback regulatory role in the type I interferon signaling by recruiting USP18 to the type I IFN receptor subunit IFNAR2 thereby mitigating the response to type I IFNs (PubMed:28165510). Acts as a regulator of mitochondrial fission by modulating the phosphorylation of DNM1L at 'Ser-616' and 'Ser-637' which activate and inactivate the GTPase activity of DNM1L respectively (PubMed:23391734, PubMed:26122121, PubMed:9020188).
Involvement in disease
Immunodeficiency 44
IMD44
An autosomal recessive disorder characterized by increased susceptibility to viral infection, resulting in some patients in encephalopathy and infection-associated neurologic decompensation.
None
The disease is caused by variants affecting the gene represented in this entry.
Pseudo-TORCH syndrome 3
PTORCH3
An autosomal recessive disorder characterized by developmental delay with acute episodes of fever and multisystemic organ involvement, including coagulopathy, elevated liver enzymes, and proteinuria, often associated with thrombotic microangiopathy. Brain imaging shows progressive intracranial calcifications, white matter abnormalities, and sometimes cerebral or cerebellar atrophy. Disease onset is in the neonatal period, and death in early childhood is common.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Tyrosine phosphorylated in response to IFN-alpha. Phosphorylation at Ser-287 negatively regulates the transcriptional response.
'Lys-48'-linked ubiquitination by DCST1 leads to STAT2 proteasomal degradation.
(Microbial infection) Ubiquitinated by Herpes simplex virus 2 E3 ubiquitin ligase ICP22.
Sequence Similarities
Belongs to the transcription factor STAT family.
Cellular localization
- Cytoplasm
- Nucleus
- Translocated into the nucleus upon activation by IFN-alpha/beta.
Alternative names
Signal transducer and activator of transcription 2, p113, STAT2