MTCH1

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MTCH1
Identifiers
AliasesMTCH1, CGI-64, PIG60, PSAP, SLC25A49, mitochondrial carrier 1
External IDsOMIM: 610449 MGI: 1929261 HomoloGene: 22807 GeneCards: MTCH1
Gene location (Human)
Chromosome 6 (human)
Chr.Chromosome 6 (human)[1]
Chromosome 6 (human)
Genomic location for MTCH1
Genomic location for MTCH1
Band6p21.2Start36,968,141 bp[1]
End36,986,298 bp[1]
RNA expression pattern
PBB GE MTCH1 221619 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001271641
NM_014341

NM_019880
NM_001347335
NM_001357762
NM_001357763

RefSeq (protein)

NP_001258570
NP_055156

NP_001334264
NP_063933
NP_001344691
NP_001344692

Location (UCSC)Chr 6: 36.97 – 36.99 MbChr 17: 29.33 – 29.35 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5][6][7] MTCH1 is a proapoptotic mitochondrial protein potentially involved in Alzheimer’s disease (AD).[6][7][8]

Structure[edit]

The protein encoded by this gene is named for its structural resemblance to the members of the mitochondrial carrier protein family.[5][7] 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.[9][10] 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.[7][9][10]

Function[edit]

MTCH1 is a proapoptotic protein that localizes to the OMM and induces apoptosis independently of BAX and BAK.[6][7] 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.[5][7] Expression of this protein is observed in 16 different tissue types, indicating that the protein may serve a housekeeping function.[10]

Clinical Significance[edit]

MTCH1 may be associated with AD and other neurodegenerative and neuroinflammatory diseases through its close interaction with presenilin.[5][8] However, more research is required to confirm its clinical involvement.[8]

Interactions[edit]

MTCH1 has been shown to interact with PS1.[5]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000137409 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024012 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d e Xu X, Shi YC, Gao W, Mao G, Zhao G, Agrawal S, Chisolm GM, Sui D, Cui MZ (Dec 2002). "The novel presenilin-1-associated protein is a proapoptotic mitochondrial protein". J Biol Chem. 277 (50): 48913–48922. doi:10.1074/jbc.M209613200. PMID 12377771.
  6. ^ a b c "Entrez Gene: MTCH1 mitochondrial carrier homolog 1 (C. elegans)".
  7. ^ a b c d e f 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.
  8. ^ a b c Vural, B; Sehitoğlu, E; Cavuş, F; Yalçınkaya, N; Haytural, H; Küçükerden, M; Ulusoy, C; Uğurel, E; Turan, S; Bulut, L; Türkoğlu, R; Shugaiv, E; Kürtüncü, M; Atakan, S; Güre, AO; Gül, A; Eraksoy, M; Akman-Demir, G; Tüzün, E (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. hdl:11693/12552. PMID 24035008.
  9. ^ a b 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. 1780 (4): 696–708. doi:10.1016/j.bbagen.2008.01.013. PMC 3509497. PMID 18291114.
  10. ^ a b c 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[edit]