Alternative titles; symbols
HGNC Approved Gene Symbol: TOMM20
Cytogenetic location: 1q42.3 Genomic coordinates (GRCh38): 1:235,109,341-235,128,837 (from NCBI)
TOMM20 is a nuclear-encoded subunit of the mitochondrial translocation complex, which imports other nuclear-encoded proteins. TOMM20 is expressed on the outer mitochondrial membrane, and its globular cytosolic domain functions as a receptor that recognizes mitochondrial targeting signals on nuclear-encoded mitochondrial proteins (summary by Hernandez et al., 1999).
By sequencing clones obtained from a size-fractionated human immature myeloid cell line KG-1 cDNA library, Nomura et al. (1994) cloned TOMM20, which they designated KIAA0016. The deduced 145-amino acid protein has a possible transmembrane region. Northern blot analysis detected variable TOMM20 expression in all human tissues and cell lines examined, with highest expression in brain, lung, skeletal muscle, kidney, spleen, peripheral blood leukocytes, KG-1 cells, and HeLa cells.
The protein import machinery of the mitochondrial outer membrane is composed of a dynamic complex of proteins that mediates translocation of cytosolic precursor proteins into or across the membrane. Several proteins within this complex have been identified, such as Mas20 in yeast (Ramage et al., 1993) and MOM19 in Neurospora crassa (Sollner et al., 1989). Goping et al. (1995) cloned and characterized the human homolog of Mas20/MOM19. The 145-amino acid human polypeptide shares high similarity with Mas20 and MOM19 within the N-terminal region, but exhibits only weak homology to the tetratricopeptide-repeat B domain that is found in the other 2 proteins. Goping et al. (1995) showed that human MAS20 is targeted and inserted into the outer membrane of isolated rat heart mitochondria in the N(in)-to-C(cyto) orientation. Goping et al. (1995) also showed that the expression of the human gene complemented the respiratory defect of delta-mas20 yeast cells, which lack the endogenous gene.
Hernandez et al. (1999) stated that TOMM20 has a short N-terminal hydrophobic region that faces the intermembrane space, followed by a transmembrane domain and a globular region that faces the cytosol. The globular region contains a domain that recognizes N-terminal mitochondrial targeting signals and another that recognizes internal mitochondrial targeting signals, and these domains are separated by a 34-amino acid tetratricopeptide repeat.
Abe et al. (2000) reported the NMR structure of rat Tom20 in a complex with a prepeptide derived from rat aldehyde dehydrogenase (see 100640). The cytosolic domain of Tom20 forms an all alpha-helical structure with a groove to accommodate the prepeptide. The bound prepeptide forms an amphiphilic helical structure with hydrophobic leucines aligned on 1 side to interact with a hydrophobic patch in the Tom20 groove. Although the positive charges of the prepeptide are essential for import ability, prepeptide binding to Tom20 is mediated mainly by hydrophobic rather than ionic interactions.
Using import assays with yeast mitochondria, Mukhopadhyay et al. (2002) found that rat Tom20 bound only to mitochondrial proteins that retained their N-terminal leader sequences. In contrast, human TOM34 (616049) bound to mature portions of mitochondrial proteins.
Using chromatin immunoprecipitation, reporter gene assays, and ELISA, Blesa et al. (2007) found that NRF1 (600879) and NRF2 (600492) bound the proximal promoter region of the human TOMM20 gene and activated its transcription. They identified 2 functional NRF1 sites and 1 functional NRF2 site.
Hernandez et al. (1999) determined that the TOMM20 gene contains 5 exons and spans 20 kb. The 5-prime UTR lacks consensus TATA and CCAAT boxes, but it has an NRF2-binding site and a CpG island that begins at position -300 and extends into the initial 200 nucleotides of intron 1. The 3-prime UTR is unusually long and has 4 polyadenylation signals.
By PCR of a human-rodent hybrid panel, Nomura et al. (1994) mapped the TOMM20 gene to chromosome 1.
Hartz (2014) mapped the TOMM20 gene to chromosome 1q42.3 based on an alignment of the TOMM20 sequence (GenBank D13641) with the genomic sequence (GRCh37).
Abe, Y., Shodai, T., Muto, T., Mihara, K., Torii, H., Nishikawa, S., Endo, T., Kohda, D. Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20. Cell 100: 551-560, 2000. [PubMed: 10721992] [Full Text: https://doi.org/10.1016/s0092-8674(00)80691-1]
Blesa, J. R., Prieto-Ruiz, J. A., Hernandez, J. M., Hernandez-Yago, J. NRF-2 transcription factor is required for human TOMM20 gene expression. Gene 391: 198-208, 2007. [PubMed: 17300881] [Full Text: https://doi.org/10.1016/j.gene.2006.12.024]
Goping, I. S., Millar, D. G., Shore, G. C. Identification of the human mitochondrial protein import receptor, huMas20p: complementation of delta-mas20 in yeast. FEBS Lett. 373: 45-50, 1995. [PubMed: 7589431] [Full Text: https://doi.org/10.1016/0014-5793(95)01010-c]
Hartz, P. A. Personal Communication. Baltimore, Md. 4/18/2014.
Hernandez, J. M., Giner, P., Hernandez-Yago, J. Gene structure of the human mitochondrial outer membrane receptor Tom20 and evolutionary study of its family of processed pseudogenes. Gene 239: 283-291, 1999. [PubMed: 10548729] [Full Text: https://doi.org/10.1016/s0378-1119(99)00409-6]
Mukhopadhyay, A., Avramova, L. V., Weiner, H. Tom34 unlike Tom20 does not interact with the leader sequences of mitochondrial precursor proteins. Arch. Biochem. Biophys. 400: 97-104, 2002. [PubMed: 11913975] [Full Text: https://doi.org/10.1006/abbi.2002.2777]
Nomura, N., Miyajima, N., Sazuka, T., Tanaka, A., Kawarabayasi, Y., Sato, S., Nagase, T., Seki, N., Ishikawa, K., Tabata, S. Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly samples cDNA clones from human immature myeloid cell line KG-1. DNA Res. 1: 27-35, 1994. Note: Erratum: DNA Res. 2: 210 only, 1995. [PubMed: 7584026] [Full Text: https://doi.org/10.1093/dnares/1.1.27]
Ramage, L., Junne, T., Hahne, K., Lithgow, T., Schatz, G. Functional cooperation of mitochondrial protein import receptors in yeast. EMBO J. 12: 4115-4123, 1993. [PubMed: 8223428] [Full Text: https://doi.org/10.1002/j.1460-2075.1993.tb06095.x]
Sollner, T., Griffiths, G., Pfaller, R., Pfanner, N., Neupert, W. MOM19, an import receptor for mitochondrial precursor proteins. Cell 59: 1061-1070, 1989. [PubMed: 2557158] [Full Text: https://doi.org/10.1016/0092-8674(89)90762-9]