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HCCS
Identifiers
Aliases	HCCS, CCHL, MCOPS7, MLS, LSDMCA1, holocytochrome c synthase
External IDs	OMIM: 300056; MGI: 106911; HomoloGene: 3897; GeneCards: HCCS; OMA:HCCS - orthologs
Gene location (Human) Chr. X chromosome (human) Band Xp22.2 Start 11,111,301 bp End 11,123,086 bp
Gene location (Mouse) Chr. X chromosome (mouse) Band X|X F5 Start 168,033,189 bp End 168,103,368 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Skeletal muscle tissue of biceps brachii gastrocnemius muscle muscle of thigh right ventricle mucosa of transverse colon Skeletal muscle tissue of rectus abdominis vastus lateralis muscle left ventricle deltoid muscle gonad Top expressed in right ventricle digastric muscle atrioventricular valve myocardium of ventricle sternocleidomastoid muscle interventricular septum temporal muscle soleus muscle intercostal muscle cumulus cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function metal ion binding lyase activity holocytochrome-c synthase activity Cellular component mitochondrion mitochondrial inner membrane membrane Biological process animal organ morphogenesis cytochrome c-heme linkage Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3052 15159 Ensembl ENSG00000004961 ENSMUSG00000031352 UniProt P53701 P53702 RefSeq (mRNA) NM_005333 NM_001122608 NM_001171991 NM_008222 NM_001331049 NM_001331050 RefSeq (protein) NP_001116080 NP_001165462 NP_005324 NP_001317978 NP_001317979 NP_032248 Location (UCSC) Chr X: 11.11 – 11.12 Mb Chr X: 168.03 – 168.1 Mb PubMed search
Wikidata
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Cytochrome c-type heme lyase is an enzyme that in humans is encoded by the HCCS gene on chromosome X.

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.

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. 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. The HCCS protein may function to regulate mitochondrial lipid and total mitochondrial mass in response to mitochondrial dysfunctions.

Clinical significance

Mutations in the HCCS gene cause microphthalmia with linear skin defects (MLS) syndrome, also known as MIDAS syndrome, microphthalmia, syndromic 7 (MCOPS7), or microphthalmia, dermal aplasia, and sclerocornea. 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.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000004961 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000031352 – 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. "Entrez Gene: HCCS holocytochrome c synthase (cytochrome c heme-lyase)".
6. "Search results < Expression Atlas < EMBL-EBI".
7. Babbitt SE, San Francisco B, Mendez DL, Lukat-Rodgers GS, Rodgers KR, Bretsnyder EC, Kranz RG (2014). "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. doi:10.1074/jbc.M114.593509. PMC 4200240. PMID 25170082.
8. Babbitt SE, San Francisco B, Bretsnyder EC, Kranz RG (2014). "Conserved residues of the human mitochondrial holocytochrome c synthase mediate interactions with heme". Biochemistry. 53 (32): 5261–71. doi:10.1021/bi500704p. PMC 4139152. PMID 25054239.
9. Nakashima-Kamimura N, Asoh S, Ishibashi Y, Mukai Y, Shidara Y, Oda H, Munakata K, Goto Y, Ohta S (2005). "MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction". J. Cell Sci. 118 (Pt 22): 5357–67. doi:10.1242/jcs.02645. PMID 16263763.
10. Wimplinger I, Morleo M, Rosenberger G, Iaconis D, Orth U, Meinecke P, Lerer I, Ballabio A, Gal A, Franco B, Kutsche K (2006). "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. doi:10.1086/508474. PMC 1698567. PMID 17033964.
11. ^ "OMIM Entry - # 309801 - LINEAR SKIN DEFECTS WITH MULTIPLE CONGENITAL ANOMALIES 1; LSDMCA1".
12. 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. PMID 17893649.

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. PMID 8364577.
• 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. PMID 8661044.
• 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. PMID 9674913.
• 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. PMID 11827457.
• Prakash SK, Cormier TA, McCall AE, et al. (2003). "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. doi:10.1093/hmg/11.25.3237. PMID 12444108.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Nakashima-Kamimura N, Asoh S, Ishibashi Y, et al. (2006). "MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction". J. Cell Sci. 118 (Pt 22): 5357–67. doi:10.1242/jcs.02645. PMID 16263763.
• Wimplinger I, Morleo M, Rosenberger G, et al. (2006). "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. doi:10.1086/508474. PMC 1698567. PMID 17033964.
• 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. PMID 17893649.

External links

• GeneReview/NIH/UW entry on Microphthalmia with Linear Skin Defects Syndrome

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