TELO2-interacting protein 1 (TTI1)

TELO2-interacting protein 1 (TTI1) is a large scaffold protein that forms the TTT complex together with TELO2 and TTI2[1][2][3]. This complex is essential for the stabilization and maturation of members of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, including mTOR, ATM, and SMG1, by delivering them to the R2TP (RUVBL1-RUVBL2-RPAP3-PIH1D1) Hsp90 co-chaperone complex[1][2][3][4]. TTI1 is mainly located in the cytoplasm and functions in the positive regulation of the DNA damage checkpoint and regulation of TOR signaling, crucial for cellular response to growth and stress signals[2][4]. Structural studies reveal TTI1 as an α-solenoid repeat protein acting as a platform for interactions within the TTT complex and with PIKKs[2][3]. Mutations in TTI1 disrupt its function and are associated with autosomal-recessive neurodevelopmental disorders with microcephaly and abnormal movements, underlining its importance in human brain development[2][4]. Currently, TTI1 itself is not a direct therapeutic target for drugs, and there are no known drugs that specifically interact with it[4].

Other names

TELO2 interacting protein 1KIAA0406SMG10smg-10Protein SMG10smg-10 homolog, nonsense mediated mRNA decay factor (C. elegans)NEDMIMTel two interacting protein 1nonsense mediated mRNA decay factor