Alternative titles; symbols
HGNC Approved Gene Symbol: TOMM22
Cytogenetic location: 22q13.1 Genomic coordinates (GRCh38): 22:38,681,957-38,685,421 (from NCBI)
The translocase of outer mitochondrial membrane (TOM) complex is a multisubunit complex involved in the recognition, unfolding, and translocation of preproteins from the cytosol into the mitochondria.
By EST database searching with yeast Tom22 as the probe, followed by PCR on a liver cDNA library, Yano et al. (2000) obtained cDNAs encoding mouse and human TOMM22. The deduced 142-amino acid human protein, which is approximately 33% similar to the yeast proteins, contains an N-terminal negatively charged region, an internal hydrophobic transmembrane region, and a C-terminal region with a glutamine-rich segment. Immunoblot analysis and fluorescence microscopy showed expression of a 21-kD mitochondrial membrane protein with its N and C termini exposed to the cytosol and intermembrane space of the mitochondrial outer membrane, respectively.
Saeki et al. (2000) also cloned and characterized TOMM22, which they termed 1C9-2. Western blot analysis showed ubiquitous expression in tissues and cell lines. An association between the rat Tomm22 protein, which is 94% identical to the human protein, and Tomm40 (608061) was observed. Saeki et al. (2000) concluded that the components of the mitochondrial import machinery are evolutionarily conserved.
Functional analysis by Yano et al. (2000) indicated that the N terminus of TOMM22 mediates import of preproteins. Immunoprecipitation and pulse-chase analysis pointed to an association of the cytosolic domain of TOMM22 and TOMM20 (601848) and their cooperation in protein import.
Using sequence analysis, Saeki et al. (2000) determined that the TOMM22 gene contains 4 exons.
Crystal Structure
Shiota et al. (2015) used a crosslinking approach to map the active TOM complex down to single amino acid residues, revealing different transport paths for preproteins through the Tom40 channel. An N-terminal segment of Tom40 passes from the cytosol through the channel to recruit chaperones from the intermembrane space that guide the transfer of hydrophobic preproteins. The translocator contains 3 Tom40 beta-barrel channels sandwiched between a central alpha-helical Tom22 receptor cluster and external regulatory Tom proteins. The preprotein-translocating trimeric complex exchanges with a dimeric isoform to assemble new TOM complexes. Dynamic coupling of alpha-helical receptors, beta-barrel channels, and chaperones generates a versatile machinery that transports about 1,000 different proteins.
By genomic sequence analysis, Saeki et al. (2000) mapped the TOMM22 gene to chromosome 22q12-q13.
Saeki, K., Suzuki, H., Tsuneoka, M., Maeda, M., Iwamoto, R., Hasuwa, H., Shida, S., Takahashi, T., Sakaguchi, M., Endo, T., Miura, Y., Mekada, E., Mihara, K. Identification of mammalian TOM22 as a subunit of the preprotein translocase of the mitochondrial outer membrane. J. Biol. Chem. 275: 31996-32002, 2000. [PubMed: 10900208] [Full Text: https://doi.org/10.1074/jbc.M004794200]
Shiota, T., Imai, K., Qiu, J., Hewitt, V. L., Tan, K., Shen, H.-H., Sakiyama, N., Fukasawa, Y., Hayat, S., Kamiya, M., Elofsson, A., Tomii, K., Horton, P., Wiedemann, N., Pfanner, N., Lithgow, T., Endo, T. Molecular architecture of the active mitochondrial protein gate. Science 349: 1544-1548, 2015. [PubMed: 26404837] [Full Text: https://doi.org/10.1126/science.aac6428]
Yano, M., Hoogenraad, N., Terada, K., Mori, M. Identification and functional analysis of human Tom22 for protein import into mitochondria. Molec. Cell. Biol. 20: 7205-7213, 2000. [PubMed: 10982837] [Full Text: https://doi.org/10.1128/MCB.20.19.7205-7213.2000]