NDUFB8

NDUFB8
Identifiers
Aliases NDUFB8, ASHI, CI-ASHI, NADH:ubiquinone oxidoreductase subunit B8
External IDs MGI: 1914514 HomoloGene: 3668 GeneCards: NDUFB8
RNA expression pattern




More reference expression data
Orthologs
Species Human Mouse
Entrez

4714

67264

Ensembl

ENSG00000166136

ENSMUSG00000025204

UniProt

O95169

Q9D6J5

RefSeq (mRNA)

NM_005004
NM_001284367
NM_001284368

NM_026061

RefSeq (protein)

NP_001271296.1
NP_001271297.1
NP_004995.1

NP_080337.1

Location (UCSC) Chr 10: 100.52 – 100.53 Mb Chr 19: 44.55 – 44.56 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial is an enzyme that in humans is encoded by the NDUFB8 gene.[3][4] NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8 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.[5]

Gene

The NDUFB8 gene is located on the q arm of chromosome 10 in position 24.31 and is 6,194 base pairs long.[6][7]

Structure

The NDUFB8 protein weighs 22 kDa and is composed of 186 amino acids.[6][7] NDUFB8 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.[5] NDUFB7 and NDUFB8 have been shown to localize at the intermembrane surface of complex I.[8] 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.[4]

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. 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.[4] 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.[5]

Model organisms

Model organisms have been used in the study of NDUFB8 function. A conditional knockout mouse line called Ndufb8tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[9] Male and female animals underwent a standardized phenotypic screen[10] to determine the effects of deletion.[11][12][13][14] Additional screens performed: - In-depth immunological phenotyping[15]

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. ↑ Emahazion T, Brookes AJ (Nov 1998). "Mapping of the NDUFA2, NDUFA6, NDUFA7, NDUFB8, and NDUFS8 electron transport chain genes by intron based radiation hybrid mapping". Cytogenetics and Cell Genetics. 82 (1-2): 114. doi:10.1159/000015081. PMID 9763676.
  4. 1 2 3 "Entrez Gene: NDUFB8 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8, 19kDa".
  5. 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.
  6. 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 4076475Freely accessible. PMID 23965338.
  7. 1 2 "NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  8. ↑ Szklarczyk R, Wanschers BF, Nabuurs SB, Nouws J, Nijtmans LG, Huynen MA (Mar 2011). "NDUFB7 and NDUFA8 are located at the intermembrane surface of complex I". FEBS Letters. 585 (5): 737–43. doi:10.1016/j.febslet.2011.01.046. PMID 21310150.
  9. ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  10. 1 2 "International Mouse Phenotyping Consortium".
  11. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410Freely accessible. PMID 21677750.
  12. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  13. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  14. ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207Freely accessible. PMID 23870131.
  15. 1 2 "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

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