NDUFA3

NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 3, 9kDa
Identifiers
SymbolsNDUFA3 ; B9; CI-B9
External IDsOMIM: 603832 HomoloGene: 3338 GeneCards: NDUFA3 Gene
Orthologs
SpeciesHumanMouse
Entrez469666091
EnsemblENSG00000170906ENSMUSG00000035674
UniProtO95167Q9CQ91
RefSeq (mRNA)NM_004542NM_025348
RefSeq (protein)NP_004533NP_079624
Location (UCSC)Chr 19:
54.1 – 54.11 Mb		Chr 7:
3.62 – 3.62 Mb
PubMed search

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 is a protein that in humans is encoded by the NDUFA3 gene.[1] The NDUFA3 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 NDUFA3 gene is located on the q arm of chromosome 19 at position 13.42, and it has a total span of 4,123 base pairs.[1] The NDUFA3 gene produces an 11 kDa protein composed of 99 amino acids.[3][4] NDUFA3 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] NDUFA3 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I. 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:ubiquinone oxidoreductase complex at the inner mitochondrial membrane.[1]

Function

The human NDUFA3 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[1] However, NDUFA3 is an accessory subunit of the complex that is believed not to be involved in catalysis.[5] 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]

Interactions

NDUFA3 has been shown to interact with ubiquitin C, a polyubiquitin precursor.[1][6]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "Entrez Gene: NDUFA1 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 3, 9kDa".
  2. ↑ 2.0 2.1 2.2 Voet D, Voet JG, Pratt CW (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 et al. (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. ↑ "NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  5. ↑ "NDUFA3 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3". UniProt: a hub for protein information. The UniProt Consortium. Retrieved 24 March 2015.
  6. ↑ Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M et al. (Oct 2011). "A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles". Molecular & Cellular Proteomics 10 (10). doi:10.1074/mcp.M111.013284. PMID 21890473.

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