Phosphatase Subfamily TIMM50
Phosphatase Classification: FCP: TIMM50
TIMM50 (or TIM50) is named after translocase of inner mitochondrial membrane 50 homolog (S. cerevisiae) [1] [2]. It is a subunit of the TIM23 complex that translocates proteins across the outer and inner mitochondrial membranes. It lacks the DxDx[T|V] motif at catalytic site, and so is a predicted pseudophosphatase, but has been reported to have catalytic activity.
Evolution
TIMM50 is found in most eukaryotes other than those with reduced or absent mitochondria. The single human member is TIMM50.
Domain Structure
Catalytic activity
TIMM50 has been show to possess a phosphatase activity toward both phospho-serine/threonine and phospho-tyrosine in an in vitro assay [3].
Related Kinases
1) Raf. High throughput yeast two-hybrid assay show Raf kinase can interact with TIMM50, as well as FCP1. The paper also guessed Raf is the substrate of TIMM50 [4], but actually TIMM50 lacks the catalytic motif. (Note: Raf also interacts with FCP1 in the paper).
References
- Yamamoto H, Esaki M, Kanamori T, Tamura Y, Nishikawa Si, and Endo T. Tim50 is a subunit of the TIM23 complex that links protein translocation across the outer and inner mitochondrial membranes. Cell. 2002 Nov 15;111(4):519-28. DOI:10.1016/s0092-8674(02)01053-x |
- Meinecke M, Wagner R, Kovermann P, Guiard B, Mick DU, Hutu DP, Voos W, Truscott KN, Chacinska A, Pfanner N, and Rehling P. Tim50 maintains the permeability barrier of the mitochondrial inner membrane. Science. 2006 Jun 9;312(5779):1523-6. DOI:10.1126/science.1127628 |
- Guo Y, Cheong N, Zhang Z, De Rose R, Deng Y, Farber SA, Fernandes-Alnemri T, and Alnemri ES. Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death. J Biol Chem. 2004 Jun 4;279(23):24813-25. DOI:10.1074/jbc.M402049200 |
- Yuryev A and Wennogle LP. Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis. Genomics. 2003 Feb;81(2):112-25. DOI:10.1016/s0888-7543(02)00008-3 |
