Biology:PET100
 Generic protein structure example |
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] The gene produces a 9.1 kDa protein composed of 73 amino acids.[2][3] The encoded protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. This protein's 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] In another patient of Pakistani origin, a homozygous c.142C>T mutation resulted in Complex IV deficiency with 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] This protein is required for MR-1S, PET117, and Complex IV to interact.
References
- ↑ 1.0 1.1 1.2 "Entrez Gene: PET100 homolog". https://www.ncbi.nlm.nih.gov/gene/100131801.
This article incorporates text from this source, which is in the public domain.
- ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. October 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338.
- ↑ "PET100 - Protein PET100 homolog, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). https://amino.heartproteome.org/web/protein/P0DJ07.
- ↑ 4.0 4.1 Online Mendelian Inheritance in Man (OMIM) 614770
- ↑ 5.0 5.1 "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. February 2014. doi:10.1016/j.ajhg.2013.12.015. PMID 24462369.
- ↑ "MR-1S Interacts with PET100 and PET117 in Module-Based Assembly of Human Cytochrome c Oxidase". Cell Reports 18 (7): 1727–1738. February 2017. doi:10.1016/j.celrep.2017.01.044. PMID 28199844.
- ↑ "A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency" (in En). European Journal of Human Genetics 23 (7): 935–9. July 2015. doi:10.1038/ejhg.2014.214. PMID 25293719.
- ↑ "COA6 - Cytochrome c oxidase assembly factor 6 homolog - Homo sapiens (Human) - COA6 gene & protein" (in en). https://www.uniprot.org/uniprot/Q5JTJ3.
This article incorporates text available under the CC BY 4.0 license.
- ↑ "UniProt: the universal protein knowledgebase". Nucleic Acids Research 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMID 27899622.
Further reading
- "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. February 2012. doi:10.1186/gb-2012-13-2-r12. PMID 22356826.
- "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. February 2012. doi:10.1186/gb-2012-13-2-r12. PMID 22356826.
- "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. February 2014. doi:10.1016/j.ajhg.2013.12.015. PMID 24462369.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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