ECSIT gene

The ECSIT gene (ECSIT stands for: Signaling Integrator) is a protein-coding gene located on chromosome 19p13.2.

This encoded a 49 kDa protein consisting of 431 amino acids, a cytosolic adaptor protein involved in inflammatory responses, embryonic development and the assembly and stabilization of mitochondrial NADH:ubiquinone oxidoreductase (complex I). The protein is thus localized in mitochondria (Vogel et al., 2007), where it regulates the production of reactive oxygen species (mROS) following the activation of Toll-like receptors (TLRs).

In addition, ECSIT appears to contribute to bactericidal activity in TLR signaling through its interaction with tumor necrosis factor receptor-associated factor 6 (TRAF6).

ESCIT plays a role in the activation of NF-kappa-B by forming a signaling complex with TRAF6 and TAK1/MAP3K7 to activate TAK1/MAP3K7, leading to the activation of IKKs (Mi Wi S et al. (2015). Once ubiquitinated, it interacts with dissociated RELA and NFKB1 proteins and translocates to the nucleus, where it induces NF-kappa B-dependent gene expression (Mi Wi S et al. 2015).

Plays a role in the innate antiviral immune response by linking the pattern recognition receptors RIGI and MDA5/IFIT1(MDA5 = Melanoma Differentiation-Associated Gene 5 a cytoplasmic sensor for viral nucleic acid RNA) to the MAVS complex in the mitochondrion (Lei CQ et al. 2015)

Promotes proteolytic activation of MAP3K1.

ESCIT is involved in the BMP signaling pathway and is required for normal embryonic development.

Diseases associated with ECSIT include Mitochondrial Complex I Deficiency, Nuclear Type 20.

1. Lei CQ et al. (2015) ECSIT bridges RIG-I-like receptors to VISA in signaling events of innate antiviral responses. J Innate Immun 7:153-64.
2. Mi Wi S et al. (2015) Ubiquitination of ECSIT is crucial for the activation of p65/p50 NF-κBs in Toll-like receptor 4 signaling. Mol Biol Cell 26:151-60