Biology:ATP5MK
ATP synthase membrane subunit k (or ATP5MK) is a protein that in humans is encoded by the ATP5MK gene (previously USMG5).[1][2][3]
Structure
The USMG5 gene is located on the q arm of chromosome 10 at position 24.33 and it spans 7,463 base pairs.[1] The USMG5 gene produces a 6.46 kDa protein composed of 58 amino acids.[4][5] USMG5 is a small subunit of the mitochondrial ATP synthase (complex V), as well as the lysosomal V-ATPase.[6] The protein is associated with the ATP synthase in a stoichiometric manner.[7] The structure of the protein contains a putative transmembrane segment and a single presumed α-helix that spans from amino acid 23 to 45. The structure has been found to be similar to its putative yeast ortholog.[8]
Function
The human USMG5 gene codes for a protein with a role in maintaining and regulating the ATP synthase population in the mitochondria.[2][3][8] The protein is responsible for several minor roles that are expendable for the core function of complex V.[7] A knockdown of the protein has been shown to lead to reduced ATP synthesis rate and CV dimer expression, while the wild type has been shown to boost the dimerization of complex V as well as enhance the ATP synthesis rate.[9]
Clinical Significance
Mutations in USMG5 has been found to result in mitochondrial deficiencies and associated disorders of the mitochondrial ATP synthase (complex V). Homozygous splice-site mutations (c.87 + 1G>C) in the Ashkenazi Jewish population have been associated with cases of leigh syndrome caused by the decrease of Complex V dimerization and ATP synthesis. Leigh syndrome is a heterogeneous mitochondrial oxidative phosphorylation (OXPHOS) disease that is characterized by psychomotor retardation and necrotizing lesions in the brain.[9]
Interactions
USMG5 is a component of the ATP synthase complex, and has co-complex interactions with ATP5F1, ATP5MC1, TP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, and others.[2][3]
References
- ↑ 1.0 1.1
"Entrez Gene: ATP synthase membrane subunit DAPIT". https://www.ncbi.nlm.nih.gov/gene/84833.
This article incorporates text from this source, which is in the public domain.
- ↑ 2.0 2.1 2.2 "USMG5 - Up-regulated during skeletal muscle growth protein 5 - Homo sapiens (Human) - USMG5 gene & protein". https://www.uniprot.org/uniprot/P30049.
This article incorporates text available under the CC BY 4.0 license.
- ↑ 3.0 3.1 3.2 "UniProt: the universal protein knowledgebase". Nucleic Acids Research 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMID 27899622.
- ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–1053. October 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338.
- ↑ "Up-regulated during skeletal muscle growth protein 5". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). https://amino.heartproteome.org/web/protein/Q96IX5.
- ↑ "Cellular and tissue expression of DAPIT, a phylogenetically conserved peptide". European Journal of Histochemistry 56 (2): e18. May 2012. doi:10.4081/ejh.2012.18. PMID 22688299.
- ↑ 7.0 7.1 "Knockdown of DAPIT (diabetes-associated protein in insulin-sensitive tissue) results in loss of ATP synthase in mitochondria". The Journal of Biological Chemistry 286 (23): 20292–20296. June 2011. doi:10.1074/jbc.M110.198523. PMID 21345788.
- ↑ 8.0 8.1 "Cellular and tissue expression of DAPIT, a phylogenetically conserved peptide". European Journal of Histochemistry 56 (2): e18. May 2012. doi:10.4081/ejh.2012.18. PMID 22688299.
- ↑ 9.0 9.1 "USMG5 Ashkenazi Jewish founder mutation impairs mitochondrial complex V dimerization and ATP synthesis". Human Molecular Genetics 27 (19): 3305–3312. October 2018. doi:10.1093/hmg/ddy231. PMID 29917077.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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