| Structural highlights
Disease
TTI1_HUMAN The disease is caused by variants affecting the gene represented in this entry.
Function
TTI1_HUMAN Regulator of the DNA damage response (DDR). Part of the TTT complex that is required to stabilize protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. The TTT complex is involved in the cellular resistance to DNA damage stresses, like ionizing radiation (IR), ultraviolet (UV) and mitomycin C (MMC). Together with the TTT complex and HSP90 may participate in the proper folding of newly synthesized PIKKs. Promotes assembly, stabilizes and maintains the activity of mTORC1 and mTORC2 complexes, which regulate cell growth and survival in response to nutrient and hormonal signals.[1] [2] [3] [4]
References
- ↑ Kaizuka T, Hara T, Oshiro N, Kikkawa U, Yonezawa K, Takehana K, Iemura S, Natsume T, Mizushima N. Tti1 and Tel2 are critical factors in mammalian target of rapamycin complex assembly. J Biol Chem. 2010 Jun 25;285(26):20109-16. doi: 10.1074/jbc.M110.121699. Epub , 2010 Apr 28. PMID:20427287 doi:https://dx.doi.org/10.1074/jbc.M110.121699
- ↑ Takai H, Xie Y, de Lange T, Pavletich NP. Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes. Genes Dev. 2010 Aug 27. PMID:20801936 doi:10.1101/gad.1956410
- ↑ Hurov KE, Cotta-Ramusino C, Elledge SJ. A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability. Genes Dev. 2010 Sep 1;24(17):1939-50. doi: 10.1101/gad.1934210. PMID:20810650 doi:https://dx.doi.org/10.1101/gad.1934210
- ↑ Serey-Gaut M, Cortes M, Makrythanasis P, Suri M, Taylor AMR, Sullivan JA, Asleh AN, Mitra J, Dar MA, McNamara A, Shashi V, Dugan S, Song X, Rosenfeld JA, Cabrol C, Iwaszkiewicz J, Zoete V, Pehlivan D, Akdemir ZC, Roeder ER, Littlejohn RO, Dibra HK, Byrd PJ, Stewart GS, Geckinli BB, Posey J, Westman R, Jungbluth C, Eason J, Sachdev R, Evans CA, Lemire G, VanNoy GE, O'Donnell-Luria A, Mau-Them FT, Juven A, Piard J, Nixon CY, Zhu Y, Ha T, Buckley MF, Thauvin C, Essien Umanah GK, Van Maldergem L, Lupski JR, Roscioli T, Dawson VL, Dawson TM, Antonarakis SE. Bi-allelic TTI1 variants cause an autosomal-recessive neurodevelopmental disorder with microcephaly. Am J Hum Genet. 2023 Mar 2;110(3):499-515. doi: 10.1016/j.ajhg.2023.01.006. Epub , 2023 Jan 31. PMID:36724785 doi:https://dx.doi.org/10.1016/j.ajhg.2023.01.006
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