TIGIT

Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.

Inhibitory receptor that plays a role in the modulation of immune responses. Suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells (PubMed:19011627). Upon binding to its ligands PVR/CD155 or NECTIN2/CD112, which are expressed on antigen-presenting cells, sends inhibitory signals to the T-cell or NK cell. Mechanistically, interaction with ligand leads to phosphorylation of the cytoplasmic tail by Src family tyrosine kinases such as FYN or LCK, allowing subsequent binding to adapter GRB2 and SHIP1/INPP5D. In turn, inhibits PI3K and MAPK signaling cascades (PubMed:23154388). In addition, associates with beta-arrestin-2/ARRB2 to recruit SHIP1/INPP5D that suppresses autoubiquitination of TRAF6 and subsequently inhibits NF-kappa-B signaling pathway (PubMed:24817116). Acts also as a receptor for NECTIN4 to inhibit NK cell cytotoxicity (PubMed:32503945).

Expressed at low levels on peripheral memory and regulatory CD4+ T-cells and NK cells and is up-regulated following activation of these cells (at protein level).

• Cell membrane
• Single-pass type I membrane protein
• Clustered to the immunological synapse where it disrupts granule polarization and cytotoxicity of NK cells once engaged with PVR.

VSIG9, VSTM3, TIGIT, T-cell immunoreceptor with Ig and ITIM domains, V-set and immunoglobulin domain-containing protein 9, V-set and transmembrane domain-containing protein 3

• entrezGene:201633
• omim:612859
• swissprot:Q495A1

Proteins

Immuno-oncology

• Immunology & Infectious Disease

26319Da