Biology:NDUFAF2
 Generic protein structure example |
NADH:ubiquinone oxidoreductase complex assembly factor 2 (NDUFAF2), also known as B17.2L or NDUFA12L is a protein that in humans is encoded by the NDUFAF2, or B17.2L, gene.[1] The NDUFAF2 protein is a chaperone involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[2][3] Mutations in this gene have been associated with progressive encephalopathy and Leigh disease resulting from mitochondrial complex I deficiency.[1]
Structure
NDUFAF2 is located on the q arm of chromosome 5 in position 12.1.[1] The NDUFAF2 gene produces a 20 kDa protein composed of 169 amino acids.[4][5] The protein is a chaperone of the complex I NDUFA12 subunit family.[6][7]
Function
NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. The NDUFAF2 gene encodes a complex I assembly factor, B17.2L, that is important for the correct function of the mitochondrial respiratory chain.[1] Specifically, B17.2L acts as a molecular chaperone, associating with an 830 kDa subassembly in the late stages of complex I assembly.[3]
Clinical significance
Mutations in NDUFAF2 have been associated with complex I deficiency and mitochondrial diseases. These disorders are a result of the dysfunction of the mitochondrial respiratory chain and can cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.[6][7] Clinically, NDUFAF2 mutations have been associated with progressive encephalopathy[3] and Leigh disease.[8][9]
Interactions
In addition to co-complexes, NDUFAF2 has protein-protein interactions with CYB5B SEC22B, TMEM97, TMEM201, SPG21, LPAR3, STX8, OPTN.[10]
References
- ↑ 1.0 1.1 1.2 1.3 "Entrez Gene: NADH:ubiquinone oxidoreductase complex assembly factor 2". https://www.ncbi.nlm.nih.gov/gene/91942.
- ↑ Donald Voet; Judith G. Voet; Charlotte W. Pratt (2013). "18". Fundamentals of biochemistry : life at the molecular level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 9780470547847.
- ↑ 3.0 3.1 3.2 Ogilvie, Isla; Kennaway, Nancy G.; Shoubridge, Eric A. (October 2005). "A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy". The Journal of Clinical Investigation 115 (10): 2784–2792. doi:10.1172/JCI26020. ISSN 0021-9738. PMID 16200211.
- ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. October 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338.
- ↑ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". https://amino.heartproteome.org/web/protein/Q8N183.
- ↑ 6.0 6.1 "NDUFAF2 - NADH dehydrogenase [ubiquinone 1 alpha subcomplex assembly factor 2 precursor - Homo sapiens (Human) - NDUFAF2 gene & protein"] (in en). https://www.uniprot.org/uniprot/Q8N183.
- ↑ 7.0 7.1 "UniProt: the universal protein knowledgebase" (in en). Nucleic Acids Research 45 (D1): D158–D169. 2016-11-29. doi:10.1093/nar/gkw1099. ISSN 0305-1048. PMID 27899622.
- ↑ Herzer, M.; Koch, J.; Prokisch, H.; Rodenburg, R.; Rauscher, C.; Radauer, W.; Forstner, R.; Pilz, P. et al. (February 2010). "Leigh disease with brainstem involvement in complex I deficiency due to assembly factor NDUFAF2 defect". Neuropediatrics 41 (1): 30–34. doi:10.1055/s-0030-1255062. ISSN 1439-1899. PMID 20571988. http://mediatum.ub.tum.de/doc/1073140/document.pdf.
- ↑ Hoefs, Saskia J. G.; Dieteren, Cindy E. J.; Rodenburg, Richard J.; Naess, Karin; Bruhn, Helene; Wibom, Rolf; Wagena, Esther; Willems, Peter H. et al. (July 2009). "Baculovirus complementation restores a novel NDUFAF2 mutation causing complex I deficiency". Human Mutation 30 (7): E728–736. doi:10.1002/humu.21037. ISSN 1098-1004. PMID 19384974.
- ↑ IntAct. "21 Binary interactions for NDUFAF2". https://www.ebi.ac.uk/intact/interactors/id:Q8N183*#.
Further reading
- "A novel Myc-target gene, mimitin, that is involved in cell proliferation of esophageal squamous cell carcinoma". J. Biol. Chem. 280 (20): 19977–85. May 2005. doi:10.1074/jbc.M501231200. PMID 15774466.
- "Investigation of the complex I assembly chaperones B17.2L and NDUFAF1 in a cohort of CI deficient patients". Mol. Genet. Metab. 91 (2): 176–82. June 2007. doi:10.1016/j.ymgme.2007.02.007. PMID 17383918.
- "Polymorphisms in mitochondrial genes and prostate cancer risk". Cancer Epidemiol. Biomarkers Prev. 17 (12): 3558–66. December 2008. doi:10.1158/1055-9965.EPI-08-0434. PMID 19064571.
- "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Mol. Med. 16 (7–8): 247–53. 2010. doi:10.2119/molmed.2009.00159. PMID 20379614.
- "Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression". PLOS ONE 5 (9): e12862. September 2010. doi:10.1371/journal.pone.0012862. PMID 20877624. Bibcode: 2010PLoSO...512862H.
- "Quantitative proteomic analysis of mitochondria from human ovarian cancer cells and their paclitaxel-resistant sublines". Cancer Sci. 106 (8): 1075–83. August 2015. doi:10.1111/cas.12710. PMID 26033570.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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