HCCS
Identifiers
AliasesHCCS, CCHL, MCOPS7, MLS, LSDMCA1, holocytochrome c synthase
External IDsOMIM: 300056 MGI: 106911 HomoloGene: 3897 GeneCards: HCCS
Orthologs
SpeciesHumanMouse
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 MbChr X: 168.03 – 168.1 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Cytochrome c-type heme lyase is an enzyme that in humans is encoded by the HCCS gene on chromosome X.[5]

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.[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 HCCS 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]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000004961 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 "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


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