NDUFAF2

NDUFAF2
Identifiers
Aliases	NDUFAF2 , B17.2L, MMTN, NDUFA12L, mimitin, NADH:ubiquinone oxidoreductase complex assembly factor 2, MC1DN10
External IDs	OMIM: 609653; MGI: 1922847; HomoloGene: 18372; GeneCards: NDUFAF2; OMA:NDUFAF2 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) [1] Band 5q12.1 Start 60,945,177 bp [1] End 61,154,531 bp [1]
Gene location (Mouse) Chr. Chromosome 13 (mouse) [2] Band 13|13 D2.1 Start 108,139,249 bp [2] End 108,295,157 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon gastrocnemius muscle tibial arteries islet of Langerhans left coronary artery left ventricle muscle layer of sigmoid colon right auricle of heart nucleus accumbens ascending aorta Top expressed in hand facial motor nucleus yolk sac maxillary prominence mandibular prominence medial vestibular nucleus deep cerebellar nuclei zygote seminiferous tubule supraoptic nucleus More reference expression data BioGPS n/a
Gene ontology Molecular function electron transfer activity NADH dehydrogenase (ubiquinone) activity Cellular component mitochondrial inner membrane membrane mitochondrion Biological process cellular respiration negative regulation of insulin secretion involved in cellular response to glucose stimulus reactive oxygen species metabolic process mitochondrial respiratory chain complex I assembly respiratory electron transport chain Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 91942 75597 Ensembl ENSG00000164182 ENSMUSG00000068184 UniProt Q8N183 Q59J78 RefSeq (mRNA) NM_174889 NM_001127346 NM_001360140 RefSeq (protein) NP_777549 NP_001120818 NP_001347069 Location (UCSC) Chr 5: 60.95 – 61.15 Mb Chr 13: 108.14 – 108.3 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. ^[5] 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. ^{[6] [7]} Mutations in this gene have been associated with progressive encephalopathy and Leigh disease resulting from mitochondrial complex I deficiency. ^[5]

Structure

NDUFAF2 is located on the q arm of chromosome 5 in position 12.1. ^[5] The NDUFAF2 gene produces a 20 kDa protein composed of 169 amino acids. ^{[8] [9]} The protein is a chaperone of the complex I NDUFA12 subunit family. ^{[10] [11]}

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. ^[5] Specifically, B17.2L acts as a molecular chaperone, associating with an 830 kDa subassembly in the late stages of complex I assembly. ^[7]

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. ^{[10] [11]} Clinically, NDUFAF2 mutations have been associated with progressive encephalopathy ^[7] and Leigh disease. ^{[12] [13]}

Interactions

In addition to co-complexes, NDUFAF2 has protein-protein interactions with CYB5B SEC22B, TMEM97, TMEM201, SPG21, LPAR3, STX8, OPTN. ^[14]

References

1. GRCh38: Ensembl release 89: ENSG00000164182 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000068184 – 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. "Entrez Gene: NADH:ubiquinone oxidoreductase complex assembly factor 2" . Retrieved 2018-07-23.
6. 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.
7. 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. PMC   1236688 . PMID   16200211.
8. Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (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.
9. Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Archived from the original on 2018-07-24. Retrieved 2018-07-23.
10. "NDUFAF2 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 2 precursor - Homo sapiens (Human) - NDUFAF2 gene & protein". www.uniprot.org. Retrieved 2018-07-23.
11. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158 –D169. 2016-11-29. doi:10.1093/nar/gkw1099. ISSN   0305-1048. PMC   5210571 . PMID   27899622.
12. Herzer, M.; Koch, J.; Prokisch, H.; Rodenburg, R.; Rauscher, C.; Radauer, W.; Forstner, R.; Pilz, P.; Rolinski, B. (February 2010). "Leigh disease with brainstem involvement in complex I deficiency due to assembly factor NDUFAF2 defect" (PDF). Neuropediatrics. 41 (1): 30–34. doi:10.1055/s-0030-1255062. hdl: 2066/87232 . ISSN   1439-1899. PMID   20571988. S2CID   46175747.^{[ permanent dead link ]}
13. Hoefs, Saskia J. G.; Dieteren, Cindy E. J.; Rodenburg, Richard J.; Naess, Karin; Bruhn, Helene; Wibom, Rolf; Wagena, Esther; Willems, Peter H.; Smeitink, Jan A. M. (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. S2CID   32746835.
14. IntAct. "21 Binary interactions for NDUFAF2". IntAct. Retrieved 2018-07-23.

Further reading

• Tsuneoka M, Teye K, Arima N, Soejima M, Otera H, Ohashi K, Koga Y, Fujita H, Shirouzu K, Kimura H, Koda Y (May 2005). "A novel Myc-target gene, mimitin, that is involved in cell proliferation of esophageal squamous cell carcinoma". J. Biol. Chem. 280 (20): 19977–85. doi: 10.1074/jbc.M501231200 . PMID   15774466.
• Vogel RO, van den Brand MA, Rodenburg RJ, van den Heuvel LP, Tsuneoka M, Smeitink JA, Nijtmans LG (June 2007). "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. doi:10.1016/j.ymgme.2007.02.007. PMID   17383918.
• Wang L, McDonnell SK, Hebbring SJ, Cunningham JM, St Sauver J, Cerhan JR, Isaya G, Schaid DJ, Thibodeau SN (December 2008). "Polymorphisms in mitochondrial genes and prostate cancer risk". Cancer Epidemiol. Biomarkers Prev. 17 (12): 3558–66. doi:10.1158/1055-9965.EPI-08-0434. PMC   2750891 . PMID   19064571.
• Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR (2010). "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Mol. Med. 16 (7–8): 247–53. doi:10.2119/molmed.2009.00159. PMC   2896464 . PMID   20379614.
• Hendrickson SL, Lautenberger JA, Chinn LW, Malasky M, Sezgin E, Kingsley LA, Goedert JJ, Kirk GD, Gomperts ED, Buchbinder SP, Troyer JL, O'Brien SJ (September 2010). "Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression". PLOS ONE. 5 (9): e12862. Bibcode:2010PLoSO...512862H. doi: 10.1371/journal.pone.0012862 . PMC   2943476 . PMID   20877624.
• Chen M, Huang H, He H, Ying W, Liu X, Dai Z, Yin J, Mao N, Qian X, Pan L (August 2015). "Quantitative proteomic analysis of mitochondria from human ovarian cancer cells and their paclitaxel-resistant sublines". Cancer Sci. 106 (8): 1075–83. doi:10.1111/cas.12710. PMC   4556398 . PMID   26033570.

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