Biology:HCCS (gene)
 Generic protein structure example |
Cytochrome c-type heme lyase is an enzyme that in humans is encoded by the HCCS gene on chromosome X.[1]
Structure
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.[2]
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.[3] 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.[4] The HCCS protein may function to regulate mitochondrial lipid and total mitochondrial mass in response to mitochondrial dysfunctions.[5]
Clinical Significance
Mutations in the HCCS gene cause Microphthalmia with linear skin defects (MLS) syndrome,[6] also known as MIDAS syndrome, microphthalmia, syndromic 7 (MCOPS7), or microphthalmia, dermal aplasia, and sclerocornea.[7][8] 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.[7]
References
- ↑ "Entrez Gene: HCCS holocytochrome c synthase (cytochrome c heme-lyase)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3052.
- ↑ "Search results < Expression Atlas < EMBL-EBI". http://www.ebi.ac.uk/gxa/genes/ENSG00000004961.
- ↑ "Mechanisms of mitochondrial holocytochrome c synthase and the key roles played by cysteines and histidine of the heme attachment site, Cys-XX-Cys-His". J. Biol. Chem. 289 (42): 28795–807. 2014. doi:10.1074/jbc.M114.593509. PMID 25170082.
- ↑ "Conserved residues of the human mitochondrial holocytochrome c synthase mediate interactions with heme". Biochemistry 53 (32): 5261–71. 2014. doi:10.1021/bi500704p. PMID 25054239.
- ↑ "MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction". J. Cell Sci. 118 (Pt 22): 5357–67. 2005. doi:10.1242/jcs.02645. PMID 16263763.
- ↑ "Mutations of the mitochondrial holocytochrome c-type synthase in X-linked dominant microphthalmia with linear skin defects syndrome". Am. J. Hum. Genet. 79 (5): 878–89. 2006. doi:10.1086/508474. PMID 17033964.
- ↑ 7.0 7.1 "OMIM Entry - # 309801 - LINEAR SKIN DEFECTS WITH MULTIPLE CONGENITAL ANOMALIES 1; LSDMCA1". http://www.omim.org/entry/309801.
- ↑ "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. 2007. PMID 17893649.
Further reading
- "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. 1993. doi:10.1093/hmg/2.7.947. PMID 8364577.
- "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. 1997. doi:10.1006/geno.1996.0261. PMID 8661044.
- "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. 1998. doi:10.1002/(SICI)1096-8628(19980630)78:2<179::AID-AJMG17>3.0.CO;2-K. PMID 9674913.
- "Complementation of a yeast CYC3 deficiency identifies an X-linked mammalian activator of apocytochrome c". Genomics 79 (1): 51–7. 2002. doi:10.1006/geno.2001.6677. PMID 11827457.
- "Loss of holocytochrome c-type synthetase causes the male lethality of X-linked dominant microphthalmia with linear skin defects (MLS) syndrome". Hum. Mol. Genet. 11 (25): 3237–48. 2003. doi:10.1093/hmg/11.25.3237. PMID 12444108.
- "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): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039.
- "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction". J. Cell Sci. 118 (Pt 22): 5357–67. 2006. doi:10.1242/jcs.02645. PMID 16263763.
- "Mutations of the mitochondrial holocytochrome c-type synthase in X-linked dominant microphthalmia with linear skin defects syndrome". Am. J. Hum. Genet. 79 (5): 878–89. 2006. doi:10.1086/508474. PMID 17033964.
- "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. 2007. PMID 17893649.
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