From Wikipedia, the free encyclopedia
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.
[5]
Structure
The PET100 gene is located on the p arm of
chromosome 19 in position 13.2 and spans 1,839 base pairs.
[5] The gene produces a 9.1 kDa protein composed of 73
amino acids .
[6]
[7] 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.
[8]
[9]
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.
[5]
[10]
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.
[9] 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 .
[11]
[8]
Interactions
The encoded protein
interacts with MR-1S and
COX7A2 .
[12]
[13]
This protein is required for MR-1S, PET117, and Complex IV to interact.
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000229833 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000087687 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
a
b
c
"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) . Archived from
the original on 2018-08-10. Retrieved 2018-08-09 .
^
a
b
Online Mendelian Inheritance in Man (OMIM):
614770
^
a
b 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 .
hdl :
2066/170194 .
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 .
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 .
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 .