Biology:MTCH1
 Generic protein structure example |
Mitochondrial carrier homolog 1 (MTCH1), also referred to as presenilin 1-associated protein (PSAP), is a protein that in humans is encoded by the MTCH1 gene on chromosome 6.[1][2][3] MTCH1 is a proapoptotic mitochondrial protein potentially involved in Alzheimer’s disease (AD).[2][3][4]
Structure
The protein encoded by this gene is named for its structural resemblance to the members of the mitochondrial carrier protein family.[1][3] The MTCH1 gene contains 12 exons and produces four isoforms. These isoforms arise from alternative splicing of exon 8 and two potential start codons, which results in the deletion of 17 amino acid residues in the hydrophilic loop between two transmembrane domains of some isoforms.[5][6] Though they differ in sequence and length, the four isoforms still share a similar topological structure, including six transmembrane domains, one of which is responsible for localization to the outer mitochondrial membrane (OMM), and two N-terminal apoptotic domains. As a result, all four isoforms retain these apoptotic domains and mitochondrial localization, both of which are required for the protein’s proapoptotic function.[3][5][6]
Function
MTCH1 is a proapoptotic protein that localizes to the OMM and induces apoptosis independently of BAX and BAK.[2][3] One possible mechanism proposes that its interactions with the mitochondrial permeability transition pore (MPTP) complex leads to depolarization of the mitochondrial membrane, release of cytochrome C, and activation of caspase-3.[1][3] Expression of this protein is observed in 16 different tissue types, indicating that the protein may serve a housekeeping function.[6]
Clinical Significance
MTCH1 may be associated with AD and other neurodegenerative and neuroinflammatory diseases through its close interaction with presenilin.[1][4] However, more research is required to confirm its clinical involvement.[4]
Interactions
MTCH1 has been shown to interact with PS1.[1]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 "The novel presenilin-1-associated protein is a proapoptotic mitochondrial protein". J Biol Chem 277 (50): 48913–48922. Dec 2002. doi:10.1074/jbc.M209613200. PMID 12377771.
- ↑ 2.0 2.1 2.2 "Entrez Gene: MTCH1 mitochondrial carrier homolog 1 (C. elegans)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23787.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Lamarca, V; Marzo, I; Sanz-Clemente, A; Carrodeguas, JA (May 2008). "Exposure of any of two proapoptotic domains of presenilin 1-associated protein/mitochondrial carrier homolog 1 on the surface of mitochondria is sufficient for induction of apoptosis in a Bax/Bak-independent manner.". European Journal of Cell Biology 87 (5): 325–34. doi:10.1016/j.ejcb.2008.02.004. PMID 18375015.
- ↑ 4.0 4.1 4.2 Vural, B; Sehitoğlu, E; Cavuş, F; Yalçınkaya, N; Haytural, H; Küçükerden, M; Ulusoy, C; Uğurel, E et al. (15 October 2013). "Mitochondrial carrier homolog 1 (Mtch1) antibodies in neuro-Behçet's disease.". Journal of Neuroimmunology 263 (1–2): 139–44. doi:10.1016/j.jneuroim.2013.08.007. PMID 24035008.
- ↑ 5.0 5.1 Mao, G; Tan, J; Gao, W; Shi, Y; Cui, MZ; Xu, X (April 2008). "Both the N-terminal fragment and the protein-protein interaction domain (PDZ domain) are required for the pro-apoptotic activity of presenilin-associated protein PSAP.". Biochimica et Biophysica Acta (BBA) - General Subjects 1780 (4): 696–708. doi:10.1016/j.bbagen.2008.01.013. PMID 18291114.
- ↑ 6.0 6.1 6.2 Lamarca, V; Sanz-Clemente, A; Pérez-Pé, R; Martínez-Lorenzo, MJ; Halaihel, N; Muniesa, P; Carrodeguas, JA (October 2007). "Two isoforms of PSAP/MTCH1 share two proapoptotic domains and multiple internal signals for import into the mitochondrial outer membrane.". American Journal of Physiology. Cell Physiology 293 (4): C1347–61. doi:10.1152/ajpcell.00431.2006. PMID 17670888.
Further reading
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–174. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Suzuki Y; Yoshitomo-Nakagawa K; Maruyama K et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Xu X; Shi Y; Wu X et al. (2000). "Identification of a novel PSD-95/Dlg/ZO-1 (PDZ)-like protein interacting with the C terminus of presenilin-1". J. Biol. Chem. 274 (46): 32543–32546. doi:10.1074/jbc.274.46.32543. PMID 10551805.
- Lai CH; Chou CY; Ch'ang LY et al. (2000). "Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics". Genome Res. 10 (5): 703–713. doi:10.1101/gr.10.5.703. PMID 10810093.
- Strausberg RL; Feingold EA; Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- Clark HF; Gurney AL; Abaya E et al. (2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Res. 13 (10): 2265–2270. doi:10.1101/gr.1293003. PMID 12975309.
- Mungall AJ; Palmer SA; Sims SK et al. (2003). "The DNA sequence and analysis of human chromosome 6". Nature 425 (6960): 805–811. doi:10.1038/nature02055. PMID 14574404. Bibcode: 2003Natur.425..805M.
- Ota T; Suzuki Y; Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–45. doi:10.1038/ng1285. PMID 14702039.
- Gerhard DS; Wagner L; Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMID 15489334.
- Lamarca V; Sanz-Clemente A; Pérez-Pé R et al. (2007). "Two isoforms of PSAP/MTCH1 share two proapoptotic domains and multiple internal signals for import into the mitochondrial outer membrane". Am. J. Physiol., Cell Physiol. 293 (4): C1347–C1361. doi:10.1152/ajpcell.00431.2006. PMID 17670888.
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