NDUFB6

NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6, 17kDa
Identifiers
Aliases NDUFB6, B17, CI
External IDs MGI: 2684983 HomoloGene: 1864 GeneCards: 4712
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

4712

230075

Ensembl

ENSG00000165264

ENSMUSG00000071014

UniProt

O95139

Q3UIU2

RefSeq (mRNA)

NM_182739
NM_001199987
NM_002493

NM_001033305

RefSeq (protein)

NP_002484.1
NP_877416.1

NP_001028477.1

Location (UCSC) Chr 9: 32.55 – 32.57 Mb Chr 4: 40.27 – 40.28 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6, also known as complex I-B17, is a protein that in humans is encoded by the NDUFB6 gene.[1][2][3] NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 6, is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.[4]

Gene

The NDUFB6 gene is located on the p arm of chromosome 9 in position 21.1 and is 19,659 base pairs long.[5][6]

Structure

The NDUFB6 protein weighs 17 kDa and is composed of 128 amino acids.[5][6] NDUFB6 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.[4] 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.[3]

Function

The protein encoded by this gene is an accessory subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I) that is not directly involved in catalysis.[3] However, NDUFB6 is required for electron transfer activity.[7] Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein complex has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified.[3] 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.[4]

Clinical significance

Decreased expression of genes involved in oxidative phosphorylation, including NDUFB6, is associated with insulin resistance and type 2 diabetes. A polymorphism in the promoter region of the NDFUB6 gene resulting in an adenine to guanine shift at rs629566 was shown to create a DNA methylation site that is associated with a decline in NDUFB6 expression in muscle of aging patients.[8]

References

  1. ↑ 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". Cytogenetics and Cell Genetics 82 (1-2): 115–9. doi:10.1159/000015082. PMID 9763677.
  2. ↑ Smeitink J, Loeffen J, Smeets R, Triepels R, Ruitenbeek W, Trijbels F, van den Heuvel L (Aug 1998). "Molecular characterization and mutational analysis of the human B17 subunit of the mitochondrial respiratory chain complex I". Human Genetics 103 (2): 245–50. doi:10.1007/s004390050813. PMID 9760212.
  3. 1 2 3 4 "Entrez Gene: NDUFB6 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6, 17kDa".
  4. 1 2 3 Voet D, Voet JG, Pratt CW (2013). "Chapter 18". Fundamentals of biochemistry: life at the molecular level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 978-0-470-54784-7.
  5. 1 2 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.
  6. 1 2 "NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  7. ↑ Loublier S, Bayot A, Rak M, El-Khoury R, Bénit P, Rustin P (Oct 2011). "The NDUFB6 subunit of the mitochondrial respiratory chain complex I is required for electron transfer activity: a proof of principle study on stable and controlled RNA interference in human cell lines". Biochemical and Biophysical Research Communications 414 (2): 367–72. doi:10.1016/j.bbrc.2011.09.078. PMID 21964293.
  8. ↑ Ling C, Poulsen P, Simonsson S, Rönn T, Holmkvist J, Almgren P, Hagert P, Nilsson E, Mabey AG, Nilsson P, Vaag A, Groop L (Nov 2007). "Genetic and epigenetic factors are associated with expression of respiratory chain component NDUFB6 in human skeletal muscle". The Journal of Clinical Investigation 117 (11): 3427–35. doi:10.1172/JCI30938. PMID 17948130.

Further reading

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

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