PET100

{{Short description|Protein-coding gene in the species Homo sapiens}}

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.{{cite web|url=https://www.ncbi.nlm.nih.gov/gene/100131801|title=Entrez Gene: PET100 homolog|access-date=2018-08-09}}{{PD-notice}}

Structure

The PET100 gene is located on the p arm of chromosome 19 in position 13.2 and spans 1,839 base pairs. The gene produces a 9.1 kDa protein composed of 73 amino acids.{{cite journal | vauthors = 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 | display-authors = 6 | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}{{cite web|url=https://amino.heartproteome.org/web/protein/P0DJ07|title=PET100 - Protein PET100 homolog, mitochondrial|work=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)|access-date=2018-08-09|archive-date=2018-08-10|archive-url=https://web.archive.org/web/20180810011326/https://amino.heartproteome.org/web/protein/P0DJ07|url-status=dead}} 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.{{OMIM|614770}}{{cite journal | vauthors = 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 | display-authors = 6 | title = A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese individuals with Leigh syndrome | journal = American Journal of Human Genetics | volume = 94 | issue = 2 | pages = 209–22 | date = February 2014 | pmid = 24462369 | pmc = 3928654 | doi = 10.1016/j.ajhg.2013.12.015 }}

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.{{cite journal | vauthors = Vidoni S, Harbour ME, Guerrero-Castillo S, Signes A, Ding S, Fearnley IM, Taylor RW, Tiranti V, Arnold S, Fernandez-Vizarra E, Zeviani M | title = MR-1S Interacts with PET100 and PET117 in Module-Based Assembly of Human Cytochrome c Oxidase | journal = Cell Reports | volume = 18 | issue = 7 | pages = 1727–1738 | date = February 2017 | pmid = 28199844 | doi = 10.1016/j.celrep.2017.01.044 | doi-access = free | hdl = 2066/170194 | hdl-access = free }}

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. 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.{{cite journal | vauthors = 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 | title = A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency | language = En | journal = European Journal of Human Genetics | volume = 23 | issue = 7 | pages = 935–9 | date = July 2015 | pmid = 25293719 | pmc = 4305338 | doi = 10.1038/ejhg.2014.214 }}

Interactions

The encoded protein interacts with MR-1S and COX7A2.{{Cite web|url=https://www.uniprot.org/uniprot/Q5JTJ3|title=COA6 - Cytochrome c oxidase assembly factor 6 homolog - Homo sapiens (Human) - COA6 gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-07}}{{CC-notice|cc=by4}}{{cite journal | title = UniProt: the universal protein knowledgebase | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D158–D169 | date = January 2017 | pmid = 27899622 | pmc = 5210571 | doi = 10.1093/nar/gkw1099 }}

This protein is required for MR-1S, PET117, and Complex IV to interact.

PET100

Structure

Function

Clinical significance

Interactions

References

Further reading