PET100 homolog is a protein that in humans is encoded by the PET100 gene . Mitochondrial complex IV , or cytochrome c oxidase, is a large transmembrane protein complex that is part of the respiratory electron transport chain of mitochondria. The small protein encoded by the PET100 gene plays a role in the biogenesis of mitochondrial complex IV. This protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space . Mutations in this gene are associated with mitochondrial complex IV deficiency. This gene has a pseudogene on chromosome 3 . Alternative splicing results in multiple transcript variants.[1]
Structure The PET100 gene is located on the p arm of chromosome 19 in position 13.2 and spans 1,839 base pairs.[1] amino acids .[2] [3] N-terminus is essential for mitochondrial localization. It assembles into a 300 kDA complex which is dependent on the mitochondrial membrane potential , accumulating over time.[4] [5]
Function The protein encoded by PET100 is involved in Complex IV biogenesis as a COX chaperone ; it is required for interaction between MR-1S , PET117 , and Complex IV.[1] [6]
Clinical significance In 8 patients of Lebanese origin living in Australia, a c.3G>C mutation in the PET100 gene caused Complex IV deficiency and Leigh syndrome . Symptoms included delayed psychomotor development , seizures , hypotonia , brain abnormalities, and elevated blood and cerebrospinal fluid lactate levels.[5] intrauterine growth retardation , metabolic and lactic acidosis , hypoglycemia , coagulopathy , elevated serum creatine kinase levels, seizures , and intraventricular cysts .[7] [4]
Interactions The encoded protein interacts with MR-1S and COX7A2 .[8] [9]
References
↑ 1.0 1.1 1.2 "Entrez Gene: PET100 homolog" . Retrieved 2018-08-09 .This article incorporates text from this source, which is in the public domain . ↑ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (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 . ↑ "PET100 - Protein PET100 homolog, mitochondrial" . Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) .↑ 4.0 4.1 Online Mendelian Inheritance in Man (OMIM) 614770 ↑ 5.0 5.1 Lim SC, Smith KR, Stroud DA, Compton AG, Tucker EJ, Dasvarma A, et al. (February 2014). "A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese individuals with Leigh syndrome" . American Journal of Human Genetics . 94 (2): 209–22. doi :10.1016/j.ajhg.2013.12.015 . PMC 3928654 PMID 24462369 . ↑ Vidoni S, Harbour ME, Guerrero-Castillo S, Signes A, Ding S, Fearnley IM, Taylor RW, Tiranti V, Arnold S, Fernandez-Vizarra E, Zeviani M (February 2017). "MR-1S Interacts with PET100 and PET117 in Module-Based Assembly of Human Cytochrome c Oxidase". Cell Reports . 18 (7): 1727–1738. doi :10.1016/j.celrep.2017.01.044 . PMID 28199844 . ↑ Oláhová M, Haack TB, Alston CL, Houghton JA, He L, Morris AA, Brown GK, McFarland R, Chrzanowska-Lightowlers ZM, Lightowlers RN, Prokisch H, Taylor RW (July 2015). "A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency" . European Journal of Human Genetics . 23 (7): 935–9. doi :10.1038/ejhg.2014.214 . PMC 4305338 PMID 25293719 . ↑ "COA6 - Cytochrome c oxidase assembly factor 6 homolog - Homo sapiens (Human) - COA6 gene & protein" . www.uniprot.org . Retrieved 2018-08-07 .File:CC-BY-icon-80x15.png CC BY 4.0 license.↑ "UniProt: the universal protein knowledgebase" . Nucleic Acids Research . 45 (D1): D158–D169. January 2017. doi :10.1093/nar/gkw1099 . PMC 5210571 PMID 27899622 .
Further reading
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 . Lim SC, Smith KR, Stroud DA, Compton AG, Tucker EJ, Dasvarma A, Gandolfo LC, Marum JE, McKenzie M, Peters HL, Mowat D, Procopis PG, Wilcken B, Christodoulou J, Brown GK, Ryan MT, Bahlo M, Thorburn DR (February 2014). "A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese individuals with Leigh syndrome" . American Journal of Human Genetics . 94 (2): 209–22. doi :10.1016/j.ajhg.2013.12.015 . PMC 3928654 PMID 24462369 .
This article incorporates text from the United States National Library of Medicine , which is in the public domain .
This article incorporates text from this source, which is in the public domain.
