{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox gene}} '''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.<ref name="entrez" /> 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.<ref name="Biochem">{{cite book|title=Fundamentals of biochemistry: life at the molecular level|author=Donald Voet|author2=Judith G. Voet|author3=Charlotte W. Pratt|date=2013|publisher=Wiley|isbn=978-0-470-54784-7|edition=4th|location=Hoboken, NJ|pages=581–620|chapter=18}}</ref><ref name=":0" /> Mutations in this gene have been associated with progressive encephalopathy and Leigh disease resulting from mitochondrial complex I deficiency.<ref name="entrez">{{cite web|url=https://www.ncbi.nlm.nih.gov/gene/91942|title=Entrez Gene: NADH:ubiquinone oxidoreductase complex assembly factor 2|access-date=2018-07-23}}</ref>
== Structure ==
''NDUFAF2'' is located on the q arm of chromosome 5 in position 12.1.<ref name="entrez" /> The ''NDUFAF2'' gene produces a 20 kDa protein composed of 169 amino acids.<ref>{{cite journal|vauthors=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|date=October 2013|title=Integration of cardiac proteome biology and medicine by a specialized knowledgebase|journal=Circulation Research|volume=113|issue=9|pages=1043–53|doi=10.1161/CIRCRESAHA.113.301151|pmc=4076475|pmid=23965338}}</ref><ref>{{Cite web|url=https://amino.heartproteome.org/web/protein/Q8N183|title=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information|last=Yao|first=Daniel|website=amino.heartproteome.org|access-date=2018-07-23|archive-date=2018-07-24|archive-url=https://web.archive.org/web/20180724032346/https://amino.heartproteome.org/web/protein/Q8N183}}</ref> The protein is a chaperone of the complex I NDUFA12 subunit family.<ref name=":3" /><ref name=":4" />
== 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.<ref name="entrez" /> Specifically, B17.2L acts as a molecular chaperone, associating with an 830 kDa subassembly in the late stages of complex I assembly.<ref name=":0">{{Cite journal|last1=Ogilvie|first1=Isla|last2=Kennaway|first2=Nancy G.|last3=Shoubridge|first3=Eric A.|date=October 2005|title=A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy|journal=The Journal of Clinical Investigation|volume=115|issue=10|pages=2784–2792|doi=10.1172/JCI26020|issn=0021-9738|pmc=1236688|pmid=16200211}}</ref>
== 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.<ref name=":3">{{Cite web|url=https://www.uniprot.org/uniprot/Q8N183|title=NDUFAF2 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 2 precursor - Homo sapiens (Human) - NDUFAF2 gene & protein|website=www.uniprot.org|language=en|access-date=2018-07-23}}</ref><ref name=":4">{{Cite journal|date=2016-11-29|title=UniProt: the universal protein knowledgebase|journal=Nucleic Acids Research|language=en|volume=45|issue=D1|pages=D158–D169|doi=10.1093/nar/gkw1099|issn=0305-1048|pmc=5210571|pmid=27899622}}</ref> Clinically, NDUFAF2 mutations have been associated with progressive encephalopathy<ref name=":0" /> and Leigh disease.<ref name=":1">{{Cite journal|last1=Herzer|first1=M.|last2=Koch|first2=J.|last3=Prokisch|first3=H.|last4=Rodenburg|first4=R.|last5=Rauscher|first5=C.|last6=Radauer|first6=W.|last7=Forstner|first7=R.|last8=Pilz|first8=P.|last9=Rolinski|first9=B.|date=February 2010|title=Leigh disease with brainstem involvement in complex I deficiency due to assembly factor NDUFAF2 defect|journal=Neuropediatrics|volume=41|issue=1|pages=30–34|doi=10.1055/s-0030-1255062|issn=1439-1899|pmid=20571988|url=http://mediatum.ub.tum.de/doc/1073140/document.pdf|hdl=2066/87232|s2cid=46175747|hdl-access=free}}{{Dead link|date=July 2025 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref name=":2">{{Cite journal|last1=Hoefs|first1=Saskia J. G.|last2=Dieteren|first2=Cindy E. J.|last3=Rodenburg|first3=Richard J.|last4=Naess|first4=Karin|last5=Bruhn|first5=Helene|last6=Wibom|first6=Rolf|last7=Wagena|first7=Esther|last8=Willems|first8=Peter H.|last9=Smeitink|first9=Jan A. M.|date=July 2009|title=Baculovirus complementation restores a novel NDUFAF2 mutation causing complex I deficiency|journal=Human Mutation|volume=30|issue=7|pages=E728–736|doi=10.1002/humu.21037|issn=1098-1004|pmid=19384974|s2cid=32746835|doi-access=free}}</ref>
== Interactions == In addition to co-complexes, NDUFAF2 has protein-protein interactions with CYB5B SEC22B, TMEM97, TMEM201, SPG21, LPAR3, STX8, OPTN.<ref name = "IntAct">{{Cite web|url=https://www.ebi.ac.uk/intact/interactors/id:Q8N183*#|title=21 Binary interactions for NDUFAF2 |last=IntAct|website= IntAct |access-date=2018-07-23}}</ref>
== References == {{reflist}}
== Further reading == {{refbegin}} *{{cite journal|vauthors=Tsuneoka M, Teye K, Arima N, Soejima M, Otera H, Ohashi K, Koga Y, Fujita H, Shirouzu K, Kimura H, Koda Y|date=May 2005|title=A novel Myc-target gene, mimitin, that is involved in cell proliferation of esophageal squamous cell carcinoma|journal=J. Biol. Chem.|volume=280|issue=20|pages=19977–85|doi=10.1074/jbc.M501231200|pmid=15774466|doi-access=free}} *{{cite journal|vauthors=Vogel RO, van den Brand MA, Rodenburg RJ, van den Heuvel LP, Tsuneoka M, Smeitink JA, Nijtmans LG|date=June 2007|title=Investigation of the complex I assembly chaperones B17.2L and NDUFAF1 in a cohort of CI deficient patients|journal=Mol. Genet. Metab.|volume=91|issue=2|pages=176–82|doi=10.1016/j.ymgme.2007.02.007|pmid=17383918}} *{{cite journal|vauthors=Wang L, McDonnell SK, Hebbring SJ, Cunningham JM, St Sauver J, Cerhan JR, Isaya G, Schaid DJ, Thibodeau SN|date=December 2008|title=Polymorphisms in mitochondrial genes and prostate cancer risk|journal=Cancer Epidemiol. Biomarkers Prev.|volume=17|issue=12|pages=3558–66|doi=10.1158/1055-9965.EPI-08-0434|pmc=2750891|pmid=19064571}} *{{cite journal|vauthors=Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR|date=2010|title=Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score|journal=Mol. Med.|volume=16|issue=7–8|pages=247–53|doi=10.2119/molmed.2009.00159|pmc=2896464|pmid=20379614}} *{{cite journal|vauthors=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|date=September 2010|title=Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression|journal=PLOS ONE|volume=5|issue=9|article-number=e12862|doi=10.1371/journal.pone.0012862|pmc=2943476|pmid=20877624|bibcode=2010PLoSO...512862H|doi-access=free}} *{{cite journal|vauthors=Chen M, Huang H, He H, Ying W, Liu X, Dai Z, Yin J, Mao N, Qian X, Pan L|date=August 2015|title=Quantitative proteomic analysis of mitochondria from human ovarian cancer cells and their paclitaxel-resistant sublines|journal=Cancer Sci.|volume=106|issue=8|pages=1075–83|doi=10.1111/cas.12710|pmc=4556398|pmid=26033570}} {{refend}}
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Category:Genes on human chromosome 5