ECSIT

Description

The ECSIT (ECSIT signaling integrator) is a protein-coding gene located on chromosome 19.

Evolutionarily conserved signaling intermediate in Toll pathway, mitochondrial (ECSIT), also known as SITPEC, is a protein that in humans is encoded by the ECSIT gene. ECSIT is a cytosolic adaptor protein involved in inflammatory responses, embryonic development, and the assembly and stabilization of mitochondrial NADH:ubiquinone oxidoreductase (complex I).

== Structure == ECSIT is located on the p arm of chromosome 19 in position 13.2 and has 9 exons. The ECSIT gene produces a 49 kDa protein composed of 431 amino acids. ECSIT's interactions with p65/p50 NF-κB proteins is dependent on lysine 372 ubiquitination. ECSIT also contains an N-terminal targeting signal that causes it to localize to mitochondria where only the 45 kDa mitochondrial ECSIT is found to interact.

== Function == ECSIT has been found to play multiple roles in cell-signaling, including those that utilize Toll-like receptors (TLRs), TGF-β, and BMP. ECSIT plays a regulatory role as part of the TAK1-ECSIT-TRAF6 complex that is involved in the activation of NF-κB by the TLR4 signal and through its interactions with TRIM59 to negatively regulate NF-κB, IRF-3, and IRF-7-mediated signal pathways. Additionally, ECSIT appears to contribute to bactericidal activity in TLR signaling through its interaction with tumor necrosis factor receptor-associated factor 6 (TRAF6). Importantly, ubiquitination of ECSIT has shown itself to be necessary for the activation of p65/p50 NF-κBs in TLR4 signaling. Functioning as a scaffold protein, ECSIT is also essential for the association of RIG-I-like receptors (RIG-I or MDA5) to VISA. The bridging of these receptors to VISA is an important signaling event used in innate antiviral responses.

ECSIT is an adapter protein involved in various signaling pathways, including TLRs, IL-1 pathways, and innate antiviral induction signaling. It plays a role in activating NF-κB by forming a complex with TRAF6 and TAK1/MAP3K7, leading to TAK1/MAP3K7 activation and subsequent activation of IKKs. Once ubiquitinated, ECSIT interacts with the dissociated RELA and NFKB1 proteins, translocating to the nucleus where it induces NF-κB-dependent gene expression. ECSIT contributes to innate antiviral immune response by bridging pattern recognition receptors RIGI and MDA5/IFIT1 to the MAVS complex at the mitochondrion. It promotes proteolytic activation of MAP3K1 and is involved in the BMP signaling pathway. ECSIT is essential for normal embryonic development.

ECSIT is also known as SITPEC.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing