NDUFAF2

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NDUFAF2
Identifiers
AliasesNDUFAF2, B17.2L, MMTN, NDUFA12L, mimitin, NADH:ubiquinone oxidoreductase complex assembly factor 2, MC1DN10
External IDsMGI: 1922847 HomoloGene: 18372 GeneCards: NDUFAF2
Gene location (Human)
Chromosome 5 (human)
Chr.Chromosome 5 (human)[1]
Chromosome 5 (human)
Genomic location for NDUFAF2
Genomic location for NDUFAF2
Band5q12.1Start60,945,205 bp[1]
End61,153,026 bp[1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_174889

NM_001127346
NM_001360140

RefSeq (protein)

NP_777549

NP_001120818
NP_001347069

Location (UCSC)Chr 5: 60.95 – 61.15 MbChr 13: 108 – 108.16 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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[edit]

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[edit]

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[edit]

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[edit]

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


References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164182 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000068184 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ a b c d "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. ^ a b c 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. Retrieved 2018-07-23.
  10. ^ a b "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. ^ a b "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. ISSN 1439-1899. PMID 20571988.
  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.
  14. ^ IntAct. "21 Binary interactions for NDUFAF2". IntAct. Retrieved 2018-07-23.

Further reading[edit]

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