NDUFA5

NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 5
Identifiers
Symbols NDUFA5 ; B13; CI-13KD-B; CI-13kB; NUFM; UQOR13
External IDs OMIM: 601677 MGI: 1915452 HomoloGene: 3664 GeneCards: NDUFA5 Gene
EC number 1.6.5.3, 1.6.99.3
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 4698 68202
Ensembl ENSG00000128609 ENSMUSG00000023089
UniProt Q16718 Q9CPP6
RefSeq (mRNA) NM_001282419 NM_026614
RefSeq (protein) NP_001269348 NP_080890
Location (UCSC) Chr 7:
123.54 – 123.56 Mb
Chr 6:
24.52 – 24.53 Mb
PubMed search

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 is an enzyme that in humans is encoded by the NDUFA5 gene.[1] The NDUFA5 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[2]

Structure

The NDUFA5 gene is located on the q arm of chromosome 7 and it spans 64,655 base pairs.[1] The gene produces a 13.5 kDa protein composed of 116 amino acids.[3][4] NDUFA5 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[2] It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. NDUFA5 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I. The protein localizes to the inner mitochondrial membrane as part of the 7 component-containing, water-soluble iron-sulfur protein (IP) fraction of complex I, although its specific role is unknown. It is assumed to undergo post-translational removal of the initiator methionine and N-acetylation of the next amino acid. The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal. Related pseudogenes have also been identified on four other chromosomes.[1][5]

Function

The human NDUFA5 gene codes for the B13 subunit of complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone. The NDUFA5 protein localizes to the mitochondrial inner membrane and it is thought to aid in this transfer of electrons.[1] Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[2] The high degree of conservation of NDUFA5 extending to plants and fungi indicates its functional significance in the enzyme complex.[6]

Clinical significance

NDUFA5, ATP5A1 and ATP5A1 all show consistently reduced expression in brains of autism patients. Mitochondrial dysfunction and impaired ATP synthesis can result in oxidative stress, which may play a role in the development of autism.[7][8]

Interactions

NDUFA5 has many protein-protein interactions, such as ubiquitin C and with members of the NADH dehydrogenase [ubiquinone] 1 beta subcomplex, including NDUFB1, NDUFB9 and NDUFB10.[1]

References

  1. 1 2 3 4 5 "Entrez Gene: NDUFA5 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 5".
  2. 1 2 3 Pratt, Donald Voet, Judith G. Voet, Charlotte W. (2013). "18". Fundamentals of biochemistry : life at the molecular level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 9780470547847.
  3. 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 (Oct 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.
  4. "NDUFA5 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  5. Emahazion T, Beskow A, Gyllensten U, Brookes AJ (Nov 1998). "Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain". Cytogenet Cell Genet 82 (1-2): 115–9. doi:10.1159/000015082. PMID 9763677.
  6. Russell MW, du Manoir S, Collins FS, Brody LC (Mar 1997). "Cloning of the human NADH: ubiquinone oxidoreductase subunit B13: localization to chromosome 7q32 and identification of a pseudogene on 11p15". Mamm Genome 8 (1): 60–1. doi:10.1007/s003359900350. PMID 9021153.
  7. Anitha, A; Nakamura, K; Thanseem, I; Matsuzaki, H; Miyachi, T; Tsujii, M; Iwata, Y; Suzuki, K; Sugiyama, T; Mori, N (2013). "Downregulation of the expression of mitochondrial electron transport complex genes in autism brains". Brain Pathology 23 (3): 294–302. doi:10.1111/bpa.12002. PMID 23088660.
  8. Marui, T; Funatogawa, I; Koishi, S; Yamamoto, K; Matsumoto, H; Hashimoto, O; Jinde, S; Nishida, H; Sugiyama, T; Kasai, K; Watanabe, K; Kano, Y; Kato, N (2011). "The NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants are associated with autism". Acta Psychiatrica Scandinavica 123 (2): 118–24. doi:10.1111/j.1600-0447.2010.01600.x. PMID 20825370.

Further reading

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

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