ATP synthase mitochondrial F1 complex assembly factor 2 is an enzyme that in humans is encoded by the ATPAF2 gene .[1] [2] [3]
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.[3] mutation in this gene has caused nuclear type 1 Complex V deficiency, characterized by lactic acidosis , encephalopathy , and developmental delays .[4] [5]
Structure The ATPAF2 gene is located on the p arm of chromosome 17 in position 11.2 and spans 24,110 base pairs.[3] amino acids .[6] [7] exons and is located within the Smith-Magenis syndrome region on chromosome 17.[3]
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.[1] [3]
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 .[4] [5]
Interactions The encoded protein interacts with ATP5F1A and FMC1 , along with many other proteins.[1] [8] [9]
Model organisms Model organisms have been used in the study of ATPAF2 function. A conditional knockout mouse line, called Atpaf2tm1a(KOMP)Wtsi [15] [16] International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[17] [18] [19]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[13] [20] mutant mice and three significant abnormalities were observed.[13] 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.[13]
References
↑ 1.0 1.1 1.2 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): 30773–8. doi :10.1074/jbc.M104133200 . PMID 11410595 . ↑ 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): 713–28. doi :10.1101/gr.73702 . PMC 186594 PMID 11997338 . ↑ 3.0 3.1 3.2 3.3 3.4 "Entrez Gene: ATPAF2 ATP synthase mitochondrial F1 complex assembly factor 2" .This article incorporates text from this source, which is in the public domain . ↑ 4.0 4.1 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): 120–4. doi :10.1136/jmg.2003.012047 . PMC 1735674 PMID 14757859 . ↑ 5.0 5.1 Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: {608918}: {08/17/2017}: . World Wide Web URL: https://omim.org/
↑ 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 . ↑ "ATPAF2 - ATP synthase mitochondrial F1 complex assembly factor 2" . Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) .↑ 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 . ↑ "UniProt: the universal protein knowledgebase" . Nucleic Acids Research . 45 (D1): D158–D169. January 2017. doi :10.1093/nar/gkw1099 . PMC 5210571 PMID 27899622 .↑ "Radiography data for Atpaf2" . Wellcome Trust Sanger Institute.↑ "Salmonella infection data for Atpaf2" . Wellcome Trust Sanger Institute.↑ "Citrobacter infection data for Atpaf2" . Wellcome Trust Sanger Institute.↑ 13.0 13.1 13.2 13.3 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica . 88 : 925–7. doi :10.1111/j.1755-3768.2010.4142.x . ↑ Mouse Resources Portal , Wellcome Trust Sanger Institute.↑ "International Knockout Mouse Consortium" .↑ "Mouse Genome Informatics" .↑ 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): 337–42. doi :10.1038/nature10163 . PMC 3572410 PMID 21677750 . ↑ Dolgin E (June 2011). "Mouse library set to be knockout". Nature . 474 (7351): 262–3. doi :10.1038/474262a . PMID 21677718 . ↑ 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 . ↑ 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
Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry . 236 (1): 107–13. doi :10.1006/abio.1996.0138 . PMID 8619474 . Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (April 1997). "Large-scale concatenation cDNA sequencing" . Genome Research . 7 (4): 353–8. doi :10.1101/gr.7.4.353 . PMC 139146 PMID 9110174 . Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination" . Genome Research . 10 (11): 1788–95. doi :10.1101/gr.143000 . PMC 310948 PMID 11076863 . 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): 120–4. doi :10.1136/jmg.2003.012047 . PMC 1735674 PMID 14757859 . Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (October 2004). "From ORFeome to biology: a functional genomics pipeline" . Genome Research . 14 (10B): 2136–44. doi :10.1101/gr.2576704 . PMC 528930 PMID 15489336 . Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (January 2006). "The LIFEdb database in 2006" . Nucleic Acids Research . 34 (Database issue): D415–8. doi :10.1093/nar/gkj139 . PMC 1347501 PMID 16381901 .
External links This article incorporates text from the United States National Library of Medicine , which is in the public domain .
This article incorporates text from this source, which is in the public domain.