ATPAF2

ATP synthase mitochondrial F1 complex assembly factor 2 is an enzyme that in humans is encoded by the ATPAF2 gene.[5][6][7]

ATPAF2
Identifiers
AliasesATPAF2, ATP12, ATP12p, MC5DN1, LP3663, ATP synthase mitochondrial F1 complex assembly factor 2
External IDsOMIM: 608918 MGI: 2180561 HomoloGene: 34602 GeneCards: ATPAF2
Gene location (Human)
Chr.Chromosome 17 (human)[1]
Band17p11.2Start17,977,409 bp[1]
End18,039,209 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

91647

246782

Ensembl

ENSG00000171953

ENSMUSG00000042709

UniProt

Q8N5M1

Q91YY4

RefSeq (mRNA)

NM_145691

NM_145427
NM_001364117
NM_001364118

RefSeq (protein)

NP_663729

NP_663402
NP_001351046
NP_001351047

Location (UCSC)Chr 17: 17.98 – 18.04 MbChr 11: 60.4 – 60.42 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 alpha subunit and is thought to prevent the subunit from forming nonproductive homooligomers during enzyme assembly. This gene is located within the Smith–Magenis syndrome region on chromosome 17. An alternatively spliced transcript variant has been described, but its biological validity has not been determined.[7] A mutation in this gene has caused nuclear type 1 Complex V deficiency, characterized by lactic acidosis, encephalopathy, and developmental delays.[8][9]

Structure

The ATPAF2 gene is located on the p arm of chromosome 17 in position 11.2 and spans 24,110 base pairs.[7] The gene produces a 32.8 kDa protein composed of 289 amino acids.[10][11] This gene has at least 8 exons and is located within the Smith-Magenis syndrome region on chromosome 17.[7]

Function

The ATPAF2 gene encodes an essential housekeeping protein, an assembly factor for the F1 component of mitochondrial ATP synthase. This protein binds specifically to the F1 alpha subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly.[5][7]

Clinical significance

In the only report of a mutation in the ATPAF2 gene, the resulting phenotype was nuclear type 1 Complex V deficiency inherited in an autosomal recessive manner. A homozygous 280T-A transversion caused a W94R amino acid substitution adjacent to a highly conserved glutamine. Symptoms included elevated blood, CSF, and urine lactate levels, developmental delays with failure to thrive and seizures, and a degenerative encephalopathy with cortical and subcortical atrophy.[8][9]

Interactions

The encoded protein interacts with ATP5F1A and FMC1, along with many other proteins.[5][12][13]

Model organisms

Model organisms have been used in the study of ATPAF2 function. A conditional knockout mouse line, called Atpaf2tm1a(KOMP)Wtsi[19][20] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[21][22][23]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[17][24] Twenty six tests were carried out on mutant mice and three significant abnormalities were observed.[17] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; males had abnormal vertebrae morphology.[17]

References
  1. GRCh38: Ensembl release 89: ENSG00000171953 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000042709 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Wang ZG, White PS, Ackerman SH (August 2001). "Atp11p and Atp12p are assembly factors for the F(1)-ATPase in human mitochondria". The Journal of Biological Chemistry. 276 (33): 30773–30778. doi:10.1074/jbc.M104133200. PMID 11410595.
  6. Bi W, Yan J, Stankiewicz P, Park SS, Walz K, Boerkoel CF, Potocki L, Shaffer LG, Devriendt K, Nowaczyk MJ, Inoue K, Lupski JR (May 2002). "Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse". Genome Research. 12 (5): 713–728. doi:10.1101/gr.73702. PMC 186594. PMID 11997338.
  7. "Entrez Gene: ATPAF2 ATP synthase mitochondrial F1 complex assembly factor 2". This article incorporates text from this source, which is in the public domain.
  8. De Meirleir L, Seneca S, Lissens W, De Clercq I, Eyskens F, Gerlo E, Smet J, Van Coster R (February 2004). "Respiratory chain complex V deficiency due to a mutation in the assembly gene ATP12". Journal of Medical Genetics. 41 (2): 120–124. doi:10.1136/jmg.2003.012047. PMC 1735674. PMID 14757859.
  9. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: {608918}: {2017-08-17}: . World Wide Web URL: https://omim.org/
  10. 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): 1043–1053. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  11. "ATPAF2 - ATP synthase mitochondrial F1 complex assembly factor 2". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  12. Li Y, Jourdain AA, Calvo SE, Liu JS, Mootha VK (July 2017). "CLIC, a tool for expanding biological pathways based on co-expression across thousands of datasets". PLOS Computational Biology. 13 (7): e1005653. doi:10.1371/journal.pcbi.1005653. PMC 5546725. PMID 28719601.
  13. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  14. "Radiography data for Atpaf2". Wellcome Trust Sanger Institute.
  15. "Salmonella infection data for Atpaf2". Wellcome Trust Sanger Institute.
  16. "Citrobacter infection data for Atpaf2". Wellcome Trust Sanger Institute.
  17. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–927. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  18. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  19. "International Knockout Mouse Consortium".
  20. "Mouse Genome Informatics".
  21. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  22. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–263. doi:10.1038/474262a. PMID 21677718.
  23. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  24. van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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