NDUFB3

NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3, 12kDa is a protein that in humans is encoded by the NDUFB3 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3, 12kDa 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] Mutations in this gene contribute to mitochondrial complex I deficiency.[6]

NDUFB3
Identifiers
AliasesNDUFB3, B12, CI-B12, NADH:ubiquinone oxidoreductase subunit B3, MC1DN25
External IDsOMIM: 603839 MGI: 1913745 HomoloGene: 37630 GeneCards: NDUFB3
Orthologs
SpeciesHumanMouse
Entrez

4709

66495

Ensembl

ENSG00000119013

ENSMUSG00000026032

UniProt

O43676

Q9CQZ6

RefSeq (mRNA)

NM_001257102
NM_002491

NM_025597

RefSeq (protein)

NP_001244031
NP_002482

NP_079873

Location (UCSC)Chr 2: 201.07 – 201.09 MbChr 1: 58.63 – 58.64 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

The NDUFB3 gene, located on the q arm of chromosome 2 in position 31.3, is 14,012 base pairs long. The NDUFB3 protein weighs 11.4 kDa and is composed of 98 amino acids.[7][8] NDUFB3 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] NDUFB3 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I. This protein localizes to the inner membrane of the mitochondrion as a single-pass membrane protein. 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 human NDUFB3 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[6] However, NDUFB3 is an accessory subunit of the complex that is believed not to be involved in catalysis.[9] 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]

Clinical significance

Mutations in the NDUFB3 gene have been implicated in the pathogenicity of human oxidative phosphorylation disease, characterized by a biochemical defect in the respiratory chain.[10]

References
  1. GRCh38: Ensembl release 89: ENSG00000119013 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000026032 - 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. 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. "Entrez Gene: NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3, 12kDa".
  7. 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.
  8. "NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  9. "NDUFB3 - NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3". UniProt: a hub for protein information. The UniProt Consortium. Retrieved 2 April 2015.
  10. Calvo SE, Compton AG, Hershman SG, Lim SC, Lieber DS, Tucker EJ, Laskowski A, Garone C, Liu S, Jaffe DB, Christodoulou J, Fletcher JM, Bruno DL, Goldblatt J, Dimauro S, Thorburn DR, Mootha VK (Jan 2012). "Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing". Science Translational Medicine. 4 (118): 118ra10. doi:10.1126/scitranslmed.3003310. PMC 3523805. PMID 22277967.

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