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Coiled-coil-helix-coiled-coil-helix domain containing 2 is a protein that in humans is encoded by the CHCHD2 gene.
[5]
Function
The protein encoded by this gene belongs to a class of eukaryotic CX(9)C proteins characterized by four cysteine residues spaced ten amino acids apart from one another. These residues form disulfide linkages that define a CHCH fold. In response to stress, the protein translocates from the mitochondrial intermembrane space to the nucleus where it binds to a highly conserved 13 nucleotide oxygen responsive element in the promoter of cytochrome oxidase 4I2, a subunit of the terminal enzyme of the electron transport chain.
In concert with recombination signal sequence-binding protein J, binding of this protein activates the oxygen responsive element at four percent oxygen. In addition, it has been shown that this protein is a negative regulator of mitochondria-mediated apoptosis. In response to apoptotic stimuli, mitochondrial levels of this protein decrease, allowing BCL2-associated X protein to oligomerize and activate the Caspase Cascade. Pseudogenes of this gene are found on multiple chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016].
Aras S, Bai M, Lee I, Springett R, Hüttemann M, Grossman LI (January 2015). "MNRR1 (formerly CHCHD2) is a bi-organellar regulator of mitochondrial metabolism". Mitochondrion. 20: 43–51. doi:10.1016/j.mito.2014.10.003. PMID25315652.
Funayama M, Ohe K, Amo T, Furuya N, Yamaguchi J, Saiki S, Li Y, Ogaki K, Ando M, Yoshino H, Tomiyama H, Nishioka K, Hasegawa K, Saiki H, Satake W, Mogushi K, Sasaki R, Kokubo Y, Kuzuhara S, Toda T, Mizuno Y, Uchiyama Y, Ohno K, Hattori N (March 2015). "CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a genome-wide linkage and sequencing study". Lancet Neurol. 14 (3): 274–82. doi:10.1016/S1474-4422(14)70266-2. PMID25662902. S2CID35183690.
Liu Z, Guo J, Li K, Qin L, Kang J, Shu L, Zhang Y, Wei Y, Yang N, Luo Y, Sun Q, Xu Q, Yan X, Tang B (November 2015). "Mutation analysis of CHCHD2 gene in Chinese familial Parkinson's disease". Neurobiol. Aging. 36 (11): 3117.e7–3117.e8. doi:10.1016/j.neurobiolaging.2015.08.010. PMID26343503. S2CID21297237.
Ogaki K, Koga S, Heckman MG, Fiesel FC, Ando M, Labbé C, Lorenzo-Betancor O, Moussaud-Lamodière EL, Soto-Ortolaza AI, Walton RL, Strongosky AJ, Uitti RJ, McCarthy A, Lynch T, Siuda J, Opala G, Rudzinska M, Krygowska-Wajs A, Barcikowska M, Czyzewski K, Puschmann A, Nishioka K, Funayama M, Hattori N, Parisi JE, Petersen RC, Graff-Radford NR, Boeve BF, Springer W, Wszolek ZK, Dickson DW, Ross OA (December 2015). "Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders". Neurology. 85 (23): 2016–25. doi:10.1212/WNL.0000000000002170. PMC4676755. PMID26561290.