The HCCS gene is located on the Xp22 region of chromosome X and encodes a protein that is ~30 kDa in size. The HCCS protein is localized to the inner mitochondrial membrane and is expressed in multiple tissue including prominently in the cardiovascular system and the central nervous system.[6]
Function[]
The HCCS protein functions as a lyase to covalently attach the heme group to the apoprotein of cytochrome c on the inner mitochondrial membrane of the mitochondrion.[7] The heme group is required for cytochrome c to transport electrons from complex III to complex IV of the electron transport chain during respiration. Heme attachment to cytochrome c takes place in the intermembrane space and requires conserved heme-interacting residues on HCCS on one of the two heme-binding domains on HCCS, including His154.[8] The HCCS protein may function to regulate mitochondrial lipid and total mitochondrial mass in response to mitochondrial dysfunctions.[9]
Clinical Significance[]
Mutations in the MCCS gene cause Microphthalmia with linear skin defects (MLS) syndrome,[10] also known as MIDAS syndrome, microphthalmia, syndromic 7 (MCOPS7), or microphthalmia, dermal aplasia, and sclerocornea.[11][12] MLS is a rare X-linked dominant male-lethal disease characterized by unilateral or bilateral microphthalmia and linear skin defects in affected females, and in utero lethality for affected males.[11]
^Wimplinger I, Shaw GM, Kutsche K (2007). "HCCS loss-of-function missense mutation in a female with bilateral microphthalmia and sclerocornea: a novel gene for severe ocular malformations?". Mol. Vis. 13: 1475–82. PMID17893649.
Further reading[]
Wapenaar MC, Bassi MT, Schaefer L, et al. (1993). "The genes for X-linked ocular albinism (OA1) and microphthalmia with linear skin defects (MLS): cloning and characterization of the critical regions". Hum. Mol. Genet. 2 (7): 947–52. doi:10.1093/hmg/2.7.947. PMID8364577.
Schaefer L, Ballabio A, Zoghbi HY (1997). "Cloning and characterization of a putative human holocytochrome c-type synthetase gene (HCCS) isolated from the critical region for microphthalmia with linear skin defects (MLS)". Genomics. 34 (2): 166–72. doi:10.1006/geno.1996.0261. PMID8661044.
Van den Veyver IB, Subramanian S, Zoghbi HY (1998). "Genomic structure of a human holocytochrome c-type synthetase gene in Xp22.3 and mutation analysis in patients with Rett syndrome". Am. J. Med. Genet. 78 (2): 179–81. doi:10.1002/(SICI)1096-8628(19980630)78:2<179::AID-AJMG17>3.0.CO;2-K. PMID9674913.
Schwarz QP, Cox TC (2002). "Complementation of a yeast CYC3 deficiency identifies an X-linked mammalian activator of apocytochrome c". Genomics. 79 (1): 51–7. doi:10.1006/geno.2001.6677. PMID11827457.
Wimplinger I, Shaw GM, Kutsche K (2007). "HCCS loss-of-function missense mutation in a female with bilateral microphthalmia and sclerocornea: a novel gene for severe ocular malformations?". Mol. Vis. 13: 1475–82. PMID17893649.