Cytochrome c oxidase assembly factor 6 is a protein that in humans is encoded by the COA6gene.[3]Mitochondrial respiratory chainComplex IV, or cytochrome c oxidase, is the component of the respiratory chain that catalyzes the transfer of electrons from intermembrane spacecytochrome c to molecular oxygen in the matrix and as a consequence contributes to the proton gradient involved in mitochondrial ATP synthesis.[4][5] The COA6 gene encodes an assembly factor for mitochondrial complex IV and is a member of the cytochrome c oxidase subunit 6B family.[3][6] This protein is located in the intermembrane space, associating with SCO2 and COX2. It stabilizes newly formed COX2 and is part of the mitochondrial copper relay system.[7]Mutations in this gene result in fatal infantile cardioencephalomyopathy.[6]
The COA6 gene is located on the q arm of chromosome 1 in position 42.2 and spans 10,612 base pairs.[3] The gene produces a 14.1 kDa protein composed of 125 amino acids.[8][9] The COA6 protein is found a complex with TMEM177, COX20, MT-CO2/COX2, COX18, SCO1 and SCO2.[4][5] The protein has a CX9CXnCX10C motif and a CHCH domain, which hints that the protein is most likely a redox protein rather than a copper metallochaperone.[10][11]
Functionedit
The COA6 encodes a protein which is an assembly factor for Complex IV.[3] This protein is specifically required for COX2 biogenesis and stability; the absence of this protein will cause fast turnover of newly synthesized COX2.The presence of a CHCH domain facilitates its function as a thiol-disulfide reductant as it facilitates the transfer of copper from SCO1 to COX2.[10]
This protein interacts transiently with the copper-containing catalytic domain of newly synthesized COX2 via its C-terminal tail exposed to the intermembrane space. It also interacts selectively with the copper metallochaperone SCO2 in a COX2-dependent manner and with COX20 in a COX2- and COX18-dependent manner.[7] Additionally, this protein interacts with COA1, SCO1, COX16, TTC19, DTX2, NADSYN1, GABARAP, AIFM1, COX4I1, CD81, COX14, SFXN1, and PLGRKT.[4][5][12]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000168275 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ abcde"COA6 - Cytochrome c oxidase assembly factor 6 homolog - Homo sapiens (Human) - COA6 gene & protein". www.uniprot.org. Retrieved 2018-08-07. This article incorporates text available under the CC BY 4.0 license.
^ abcde"UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC5210571. PMID 27899622.
^ abPacheu-Grau D, Bareth B, Dudek J, Juris L, Vögtle FN, Wissel M, et al. (June 2015). "Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies". Cell Metabolism. 21 (6): 823–33. doi:10.1016/j.cmet.2015.04.012. PMID 25959673.
^Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC4076475. PMID 23965338.
^. Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 2018-08-09. Retrieved 2018-08-09.
^ abSoma, S.; Morgada, M. N.; Naik, M. T.; Boulet, A.; Roesler, A. A.; Dziuba, N.; Ghosh, A.; Yu, Q.; Lindahl, P. A.; Ames, J. B.; Leary, S. C.; Vila, A. J.; Gohil, V. M. (2019). "COA6 is Structurally Tuned to Function as a Thiol-Disulfide Oxidoreductase in Copper Delivery to Mitochondrial Cytochrome c Oxidase". Cell Reports. 29 (12): 4114–4126.e5. doi:10.1016/j.celrep.2019.11.054. PMC6946597. PMID 31851937.
^Maghool, S.; Cooray NDG; Stroud, D. A.; Aragão, D.; Ryan, M. T.; Maher, M. J. (2019). "Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6". Life Science Alliance. 2 (5): e201900458. doi:10.26508/lsa.201900458. PMC6743065. PMID 31515291.
Calvo SE, Compton AG, Hershman SG, Lim SC, Lieber DS, Tucker EJ, Laskowski A, Garone C, Liu S, Jaffe DB, Christodoulou J, Fletcher JM, Bruno DL, Goldblatt J, Dimauro S, Thorburn DR, Mootha VK (January 2012). "Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing". Science Translational Medicine. 4 (118): 118ra10. doi:10.1126/scitranslmed.3003310. PMC3523805. PMID 22277967.
Szklarczyk R, Wanschers BF, Cuypers TD, Esseling JJ, Riemersma M, van den Brand MA, Gloerich J, Lasonder E, van den Heuvel LP, Nijtmans LG, Huynen MA (February 2012). "Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14, a protein involved in the assembly of cytochrome c oxidase". Genome Biology. 13 (2): R12. doi:10.1186/gb-2012-13-2-r12. PMC3334569. PMID 22356826.
Szklarczyk R, Wanschers BF, Cuypers TD, Esseling JJ, Riemersma M, van den Brand MA, Gloerich J, Lasonder E, van den Heuvel LP, Nijtmans LG, Huynen MA (February 2012). "Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14, a protein involved in the assembly of cytochrome c oxidase". Genome Biology. 13 (2): R12. doi:10.1186/gb-2012-13-2-r12. PMC3334569. PMID 22356826.
Shivatheja Soma; Marcos N Morgada; Mandar T Naik; Aren Boulet; Anna A Roesler; Nathaniel Dziuba; Alok Ghosh; Qinhong Yu; Paul A Lindahl; James B Ames; Scot C Leary; Alejandro J Vila; Vishal M Gohil (December 2019). "COA6 Is Structurally Tuned to Function as a Thiol-Disulfide Oxidoreductase in Copper Delivery to Mitochondrial Cytochrome C Oxidase". Cell Reports. 29 (12): 4114–26. doi:10.1016/j.celrep.2019.11.054. PMC6946597. PMID 31851937.
Shadi Maghool; N Dinesha G Cooray; David A Stroud; David Aragão; Michael T Ryan; Megan J Maher (September 2019). "Structural and Functional Characterization of the Mitochondrial Complex IV Assembly Factor Coa6". Life Sci Alliance. 2 (5): e201900458. doi:10.26508/lsa.201900458. PMC6743065. PMID 31515291.
Pacheu-Grau D, Bareth B, Dudek J, Juris L, Vögtle FN, Wissel M, Leary SC, Dennerlein S, Rehling P, Deckers M (June 2015). "Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies". Cell Metabolism. 21 (6): 823–33. doi:10.1016/j.cmet.2015.04.012. PMID 25959673.
coa6, cytochrome, oxidase, assembly, factor, protein, that, humans, encoded, gene, mitochondrial, respiratory, chain, complex, cytochrome, oxidase, component, respiratory, chain, that, catalyzes, transfer, electrons, from, intermembrane, space, cytochrome, mol. Cytochrome c oxidase assembly factor 6 is a protein that in humans is encoded by the COA6 gene 3 Mitochondrial respiratory chain Complex IV or cytochrome c oxidase is the component of the respiratory chain that catalyzes the transfer of electrons from intermembrane space cytochrome c to molecular oxygen in the matrix and as a consequence contributes to the proton gradient involved in mitochondrial ATP synthesis 4 5 The COA6 gene encodes an assembly factor for mitochondrial complex IV and is a member of the cytochrome c oxidase subunit 6B family 3 6 This protein is located in the intermembrane space associating with SCO2 and COX2 It stabilizes newly formed COX2 and is part of the mitochondrial copper relay system 7 Mutations in this gene result in fatal infantile cardioencephalomyopathy 6 COA6IdentifiersAliasesCOA6 C1orf31 CEMCOX4 cytochrome c oxidase assembly factor 6 MC4DN13External IDsOMIM 614772 GeneCards COA6Gene location Human Chr Chromosome 1 human 1 Band1q42 2Start234 373 456 bp 1 End234 385 080 bp 1 RNA expression patternBgeeHumanMouse ortholog Top expressed ingastrocnemius muscleputamendeltoid musclecaudate nucleusquadriceps femoris musclevastus lateralis musclenucleus accumbensBrodmann area 9cingulate gyrusprefrontal cortexn aMore reference expression dataBioGPSn aGene ontologyMolecular functioncopper ion binding protein binding RNA bindingCellular componentmitochondrial intermembrane space mitochondrion plasma membraneBiological processplasma membrane ATP synthesis coupled electron transport respiratory chain complex IV assemblySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez388753n aEnsemblENSG00000168275n aUniProtQ5JTJ3n aRefSeq mRNA NM 001301733NM 001012985NM 001206641n aRefSeq protein NP 001013003NP 001193570NP 001288662n aLocation UCSC Chr 1 234 37 234 39 Mbn aPubMed search 2 n aWikidataView Edit Human Contents 1 Structure 2 Function 3 Clinical Significance 4 Interactions 5 References 6 Further readingStructure editThe COA6 gene is located on the q arm of chromosome 1 in position 42 2 and spans 10 612 base pairs 3 The gene produces a 14 1 kDa protein composed of 125 amino acids 8 9 The COA6 protein is found a complex with TMEM177 COX20 MT CO2 COX2 COX18 SCO1 and SCO2 4 5 The protein has a CX9CXnCX10C motif and a CHCH domain which hints that the protein is most likely a redox protein rather than a copper metallochaperone 10 11 Function editThe COA6 encodes a protein which is an assembly factor for Complex IV 3 This protein is specifically required for COX2 biogenesis and stability the absence of this protein will cause fast turnover of newly synthesized COX2 The presence of a CHCH domain facilitates its function as a thiol disulfide reductant as it facilitates the transfer of copper from SCO1 to COX2 10 Clinical Significance editTwo mutations have been identified in this protein W66R and W59C The latter mutation results in the protein being mistargeted to the mitochondrial matrix resulting in the loss of interaction with SCO2 and COX2 4 5 Inheritance of this mutation is autosomal recessive and results in a phenotype of fatal infantile cardioencephalomyopathy due to Complex IV deficiency 6 Symptoms include hypertrophic cardiomyopathy left ventricular non compaction lactic acidosis and metabolic hypotonia 4 5 Interactions editThis protein interacts transiently with the copper containing catalytic domain of newly synthesized COX2 via its C terminal tail exposed to the intermembrane space It also interacts selectively with the copper metallochaperone SCO2 in a COX2 dependent manner and with COX20 in a COX2 and COX18 dependent manner 7 Additionally this protein interacts with COA1 SCO1 COX16 TTC19 DTX2 NADSYN1 GABARAP AIFM1 COX4I1 CD81 COX14 SFXN1 and PLGRKT 4 5 12 References edit a b c GRCh38 Ensembl release 89 ENSG00000168275 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b c d Entrez Gene Cytochrome c oxidase assembly factor 6 Retrieved 2018 08 08 a b c d e COA6 Cytochrome c oxidase assembly factor 6 homolog Homo sapiens Human COA6 gene amp protein www uniprot org Retrieved 2018 08 07 nbsp This article incorporates text available under the CC BY 4 0 license a b c d e UniProt the universal protein knowledgebase Nucleic Acids Research 45 D1 D158 D169 January 2017 doi 10 1093 nar gkw1099 PMC 5210571 PMID 27899622 a b c Online Mendelian Inheritance in Man OMIM 614772 a b Pacheu Grau D Bareth B Dudek J Juris L Vogtle FN Wissel M et al June 2015 Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies Cell Metabolism 21 6 823 33 doi 10 1016 j cmet 2015 04 012 PMID 25959673 Zong NC Li H Li H Lam MP Jimenez RC Kim CS Deng N Kim AK Choi JH Zelaya I Liem D Meyer D Odeberg J Fang C Lu HJ Xu T Weiss J Duan H Uhlen M Yates JR Apweiler R Ge J Hermjakob H Ping P October 2013 Integration of cardiac proteome biology and medicine by a specialized knowledgebase Circulation Research 113 9 1043 53 doi 10 1161 CIRCRESAHA 113 301151 PMC 4076475 PMID 23965338 COA6 Cytochrome c oxidase assembly factor 6 homolog Cardiac Organellar Protein Atlas Knowledgebase COPaKB Archived from the original on 2018 08 09 Retrieved 2018 08 09 a b Soma S Morgada M N Naik M T Boulet A Roesler A A Dziuba N Ghosh A Yu Q Lindahl P A Ames J B Leary S C Vila A J Gohil V M 2019 COA6 is Structurally Tuned to Function as a Thiol Disulfide Oxidoreductase in Copper Delivery to Mitochondrial Cytochrome c Oxidase Cell Reports 29 12 4114 4126 e5 doi 10 1016 j celrep 2019 11 054 PMC 6946597 PMID 31851937 Maghool S Cooray NDG Stroud D A Aragao D Ryan M T Maher M J 2019 Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6 Life Science Alliance 2 5 e201900458 doi 10 26508 lsa 201900458 PMC 6743065 PMID 31515291 IntAct COA6 interactions www ebi ac uk Retrieved 2018 08 08 Further reading editHendrickson SL Lautenberger JA Chinn LW Malasky M Sezgin E Kingsley LA Goedert JJ Kirk GD Gomperts ED Buchbinder SP Troyer JL O Brien SJ September 2010 Genetic variants in nuclear encoded mitochondrial genes influence AIDS progression PLOS ONE 5 9 e12862 Bibcode 2010PLoSO 512862H doi 10 1371 journal pone 0012862 PMC 2943476 PMID 20877624 Calvo SE Compton AG Hershman SG Lim SC Lieber DS Tucker EJ Laskowski A Garone C Liu S Jaffe DB Christodoulou J Fletcher JM Bruno DL Goldblatt J Dimauro S Thorburn DR Mootha VK January 2012 Molecular diagnosis of infantile mitochondrial disease with targeted next generation sequencing Science Translational Medicine 4 118 118ra10 doi 10 1126 scitranslmed 3003310 PMC 3523805 PMID 22277967 Szklarczyk R Wanschers BF Cuypers TD Esseling JJ Riemersma M van den Brand MA Gloerich J Lasonder E van den Heuvel LP Nijtmans LG Huynen MA February 2012 Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14 a protein involved in the assembly of cytochrome c oxidase Genome Biology 13 2 R12 doi 10 1186 gb 2012 13 2 r12 PMC 3334569 PMID 22356826 Szklarczyk R Wanschers BF Cuypers TD Esseling JJ Riemersma M van den Brand MA Gloerich J Lasonder E van den Heuvel LP Nijtmans LG Huynen MA February 2012 Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14 a protein involved in the assembly of cytochrome c oxidase Genome Biology 13 2 R12 doi 10 1186 gb 2012 13 2 r12 PMC 3334569 PMID 22356826 Shivatheja Soma Marcos N Morgada Mandar T Naik Aren Boulet Anna A Roesler Nathaniel Dziuba Alok Ghosh Qinhong Yu Paul A Lindahl James B Ames Scot C Leary Alejandro J Vila Vishal M Gohil December 2019 COA6 Is Structurally Tuned to Function as a Thiol Disulfide Oxidoreductase in Copper Delivery to Mitochondrial Cytochrome C Oxidase Cell Reports 29 12 4114 26 doi 10 1016 j celrep 2019 11 054 PMC 6946597 PMID 31851937 Shadi Maghool N Dinesha G Cooray David A Stroud David Aragao Michael T Ryan Megan J Maher September 2019 Structural and Functional Characterization of the Mitochondrial Complex IV Assembly Factor Coa6 Life Sci Alliance 2 5 e201900458 doi 10 26508 lsa 201900458 PMC 6743065 PMID 31515291 Pacheu Grau D Bareth B Dudek J Juris L Vogtle FN Wissel M Leary SC Dennerlein S Rehling P Deckers M June 2015 Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies Cell Metabolism 21 6 823 33 doi 10 1016 j cmet 2015 04 012 PMID 25959673 This article incorporates text from the United States National Library of Medicine which is in the public domain Retrieved from https en wikipedia org w index php title COA6 amp oldid 1188090084, wikipedia, wiki, book, books, library,
