Phospho-STAT2 (Tyr690)

Full Name

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:9020188, PubMed:23391734).
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:26122121, PubMed:23391734, PubMed:9020188).

Biological Process

Cytokine-mediated signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Defense responseManual Assertion Based On ExperimentIBA:GO_Central
Defense response to virusManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of type I interferon-mediated signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:ComplexPortal
Receptor signaling pathway via JAK-STATManual Assertion Based On ExperimentIBA:GO_Central
Regulation of cell population proliferationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of mitochondrial fissionManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of protein phosphorylationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Response to peptide hormoneManual Assertion Based On ExperimentIBA:GO_Central
Type I interferon signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB

Cellular Location

Cytoplasm
Nucleus
Translocated into the nucleus upon activation by IFN-alpha/beta.

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.
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.

PTM

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.