| MTCH1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | MTCH1 , CGI-64, PIG60, PSAP, SLC25A49, mitochondrial carrier 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 610449 MGI: 1929261 HomoloGene: 22807 GeneCards: MTCH1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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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]
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]
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]
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]
Apoptosis regulator BAX, also known as bcl-2-like protein 4, is a protein that in humans is encoded by the BAX gene. BAX is a member of the Bcl-2 gene family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and has been shown to be involved in P53-mediated apoptosis.
The BCL2 associated agonist of cell death (BAD) protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in initiating apoptosis. BAD is a member of the BH3-only family, a subfamily of the Bcl-2 family. It does not contain a C-terminal transmembrane domain for outer mitochondrial membrane and nuclear envelope targeting, unlike most other members of the Bcl-2 family. After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.
Bcl-2-like protein 1 is a protein encoded in humans by the BCL2L1 gene. Through alternative splicing, the gene encodes both of the human proteins Bcl-xL and Bcl-xS.
DnaJ homolog subfamily A member 3, mitochondrial, also known as Tumorous imaginal disc 1 (TID1), is a protein that in humans is encoded by the DNAJA3 gene on chromosome 16. This protein belongs to the DNAJ/Hsp40 protein family, which is known for binding and activating Hsp70 chaperone proteins to perform protein folding, degradation, and complex assembly. As a mitochondrial protein, it is involved in maintaining membrane potential and mitochondrial DNA (mtDNA) integrity, as well as cellular processes such as cell movement, growth, and death. Furthermore, it is associated with a broad range of diseases, including neurodegenerative diseases, inflammatory diseases, and cancers.
Bcl-2-like protein 11, commonly called BIM, is a protein that in humans is encoded by the BCL2L11 gene.
Cadherin EGF LAG seven-pass G-type receptor 1 also known as flamingo homolog 2 or cadherin family member 9 is a protein that in humans is encoded by the CELSR1 gene.
MAP kinase-activating death domain protein is an enzyme that in humans is encoded by the MADD gene.
Apoptosis regulatory protein Siva is a protein that in humans is encoded by the SIVA1 gene. This gene encodes a protein with an important role in the apoptotic pathway induced by the CD27 antigen, a member of the tumor necrosis factor receptor (TFNR) superfamily. The CD27 antigen cytoplasmic tail binds to the N-terminus of this protein. Two alternatively spliced transcript variants encoding distinct proteins have been described.
Mitochondrial import receptor subunit TOM22 homolog(hTom22) is a protein that in humans is encoded by the TOMM22 gene.
Phosphate carrier protein, mitochondrial is a protein that in humans is encoded by the SLC25A3 gene. The encoded protein is a transmembrane protein located in the mitochondrial inner membrane and catalyzes the transport of phosphate ions across it for the purpose of oxidative phosphorylation. There are two significant isoforms of this gene expressed in human cells, which differ slightly in structure and function. Mutations in this gene can cause mitochondrial phosphate carrier deficiency (MPCD), a fatal disorder of oxidative phosphorylation symptomized by lactic acidosis, neonatal hypotonia, hypertrophic cardiomyopathy, and death within the first year of life.
Mitofusin-1 is a protein that in humans is encoded by the MFN1 gene.
Bcl-2-modifying factor is a protein that in humans is encoded by the BMF gene.
Growth hormone-inducible transmembrane protein (GHITM), also known as transmembrane BAX inhibitor motif containing protein 5 (TMBIM5), is a protein that in humans is encoded by the GHITM gene on chromosome 10. It is a member of the BAX inhibitor motif containing (TMBIM) family and localizes to the inner mitochondrial membrane (IMM), as well as the endoplasmic reticulum (ER), where it plays a role in apoptosis through mediating mitochondrial morphology and cytochrome c release. Through its apoptotic function, GHITM may be involved in tumor metastasis and innate antiviral responses.
Mitochondrial uncoupling protein 4 is a protein that in humans is encoded by the SLC25A27 gene.
Etoposide-induced protein 2.4 homolog is a protein that in humans is encoded by the EI24 gene.
Presenilins-associated rhomboid-like protein, mitochondrial (PSARL), also known as PINK1/PGAM5-associated rhomboid-like protease (PARL), is an inner mitochondrial membrane protein that in humans is encoded by the PARL gene on chromosome 3. It is a member of the rhomboid family of intramembrane serine proteases. This protein is involved in signal transduction and apoptosis, as well as neurodegenerative diseases and type 2 diabetes.
ADP/ATP translocase 4 (ANT4) is an enzyme that in humans is encoded by the SLC25A31 gene on chromosome 4. This enzyme inhibits apoptosis by catalyzing ADP/ATP exchange across the mitochondrial membranes and regulating membrane potential. In particular, ANT4 is essential to spermatogenesis, as it imports ATP into sperm mitochondria to support their development and survival. Outside this role, the SLC25AC31 gene has not been implicated in any human disease.
Voltage-dependent anion-selective channel protein 2 is a protein that in humans is encoded by the VDAC2 gene on chromosome 10. This protein is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms. VDACs are generally involved in the regulation of cell metabolism, mitochondrial apoptosis, and spermatogenesis. Additionally, VDAC2 participates in cardiac contractions and pulmonary circulation, which implicate it in cardiopulmonary diseases. VDAC2 also mediates immune response to infectious bursal disease (IBD).
Ubiquinone biosynthesis protein COQ9, mitochondrial, also known as coenzyme Q9 homolog (COQ9), is a protein that in humans is encoded by the COQ9 gene.
ADP/ATP translocase 2 is a protein that in humans is encoded by the SLC25A5 gene on the X chromosome.
