NDUFB9

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 is an enzyme that in humans is encoded by the NDUFB9 gene.[5][6] NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 9 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.[7]

NDUFB9
Identifiers
AliasesNDUFB9, B22, CI-B22, LYRM3, UQOR22, NADH:ubiquinone oxidoreductase subunit B9, MC1DN24
External IDsOMIM: 601445 MGI: 1913468 HomoloGene: 3669 GeneCards: NDUFB9
Gene location (Human)
Chr.Chromosome 8 (human)[1]
Band8q24.13Start124,539,101 bp[1]
End124,580,648 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

4715

66218

Ensembl

ENSG00000147684

ENSMUSG00000022354

UniProt

Q9Y6M9

Q9CQJ8

RefSeq (mRNA)

NM_005005
NM_001278645
NM_001278646
NM_001311168

NM_023172
NM_001364808

RefSeq (protein)

NP_001265574
NP_001265575
NP_001298097
NP_004996

NP_075661
NP_001351737

Location (UCSC)Chr 8: 124.54 – 124.58 MbChr 15: 58.93 – 58.94 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

The NDUFB9 gene is located on the q arm of chromosome 8 in position 13.3 and is 10,884 base pairs long. The NDUFB9 protein weighs 22 kDa and is composed of 179 amino acids.[8][9] NDUFB9 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.[7] 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.[6]

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.[6] 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.[7]

Clinical significance

A mutation in NDUFB9 resulting in reduction in NDUFB9 protein and both amount and activity of complex I has been shown to be a causal mutation leading to Complex I deficiency.[10]

References
  1. GRCh38: Ensembl release 89: ENSG00000147684 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000022354 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Gu JZ, Lin X, Wells DE (Sep 1996). "The human B22 subunit of the NADH-ubiquinone oxidoreductase maps to the region of chromosome 8 involved in branchio-oto-renal syndrome". Genomics. 35 (1): 6–10. doi:10.1006/geno.1996.0316. PMID 8661098.
  6. "Entrez Gene: NDUFB9 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 9, 22kDa".
  7. 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.
  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 (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.
  9. "NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  10. Haack, TB; Madignier, F; Herzer, M; Lamantea, E; Danhauser, K; Invernizzi, F; Koch, J; Freitag, M; Drost, R; Hillier, I; Haberberger, B; Mayr, JA; Ahting, U; Tiranti, V; Rötig, A; Iuso, A; Horvath, R; Tesarova, M; Baric, I; Uziel, G; Rolinski, B; Sperl, W; Meitinger, T; Zeviani, M; Freisinger, P; Prokisch, H (February 2012). "Mutation screening of 75 candidate genes in 152 complex I deficiency cases identifies pathogenic variants in 16 genes including NDUFB9". Journal of Medical Genetics. 49 (2): 83–9. doi:10.1136/jmedgenet-2011-100577. PMID 22200994. S2CID 13907809.

Further reading


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