NDUFB8

NDUFB8
Identifiers
Aliases	NDUFB8 , ASHI, CI-ASHI, NADH:ubiquinone oxidoreductase subunit B8, MC1DN32
External IDs	OMIM: 602140 MGI: 1914514 HomoloGene: 3668 GeneCards: NDUFB8
Gene location (Human) Chr. Chromosome 10 (human) [1] Band 10q24.31 Start 100,523,740 bp [1] End 100,530,000 bp [1]
Gene location (Mouse) Chr. Chromosome 19 (mouse) [2] Band 19|19 C3 Start 44,537,011 bp [2] End 44,543,879 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell Brodmann area 23 pons middle temporal gyrus Brodmann area 9 superior vestibular nucleus prefrontal cortex amygdala cingulate gyrus superior frontal gyrus Top expressed in digastric muscle sternocleidomastoid muscle triceps brachii muscle thoracic diaphragm temporal muscle intercostal muscle myocardium of ventricle soleus muscle extensor digitorum longus muscle motor neuron More reference expression data BioGPS More reference expression data
Gene ontology Molecular function NADH dehydrogenase (ubiquinone) activity NADH dehydrogenase activity Cellular component integral component of membrane mitochondrial inner membrane respirasome endoplasmic reticulum membrane mitochondrion mitochondrial respiratory chain complex I mitochondrial matrix Biological process mitochondrial respiratory chain complex I assembly mitochondrial electron transport, NADH to ubiquinone Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4714 67264 Ensembl ENSG00000166136 ENSMUSG00000025204 UniProt O95169 Q9D6J5 RefSeq (mRNA) NM_005004 NM_001284367 NM_001284368 NM_026061 NM_001347447 RefSeq (protein) NP_001271296 NP_001271297 NP_004995 NP_001334376 NP_080337 Location (UCSC) Chr 10: 100.52 – 100.53 Mb Chr 19: 44.54 – 44.54 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial is an enzyme that in humans is encoded by the NDUFB8 gene. ^{[5] [6]} 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. ^[7]

Gene

The NDUFB8 gene is located on the q arm of chromosome 10 in position 24.31 and is 6,194 base pairs long. ^{[8] [9]}

Structure

The NDUFB8 protein weighs 22 kDa and is composed of 186 amino acids. ^{[8] [9]} 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. ^[7] NDUFB7 and NDUFB8 have been shown to localize at the intermembrane surface of complex I. ^[10] 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]

Model organisms

Model organisms have been used in the study of NDUFB8 function. A conditional knockout mouse line called Ndufb8^{tm1a(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute. ^[11] Male and female animals underwent a standardized phenotypic screen ^[12] to determine the effects of deletion. ^{[13] [14] [15] [16]} Additional screens performed: - In-depth immunological phenotyping ^[17]

Ndufb8 knockout mouse phenotype

Characteristic	Phenotype
All data available at. [12] [17]
Peripheral blood leukocytes 6 Weeks	Normal
Insulin	Normal
Haematology 6 Weeks	Normal
Homozygous viability at P14	Abnormal
Recessive lethal study	Abnormal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Bone Marrow Immunophenotyping	Normal
Epidermal Immune Composition	Normal

References

1. GRCh38: Ensembl release 89: ENSG00000166136 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000025204 - 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. 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. S2CID   46861680.
6. "Entrez Gene: NDUFB8 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8, 19kDa".
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 8". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
10. 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. S2CID   20557524.
11. 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. S2CID   85911512.
12. "International Mouse Phenotyping Consortium".
13. 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   3572410 . PMID   21677750.
14. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi: 10.1038/474262a . PMID   21677718.
15. 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. S2CID   18872015.
16. 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   3717207 . PMID   23870131.
17. "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi: 10.1101/gr.6.9.791 . PMID   8889548.
• Dunbar DR, Shibasaki Y, Dobbie L, Andersson B, Brookes AJ (1997). "In situ hybridisation mapping of genomic clones for five human respiratory chain complex I genes". Cytogenetics and Cell Genetics. 78 (1): 21–4. doi:10.1159/000134618. PMID   9345899.
• Loeffen JL, Triepels RH, van den Heuvel LP, Schuelke M, Buskens CA, Smeets RJ, Trijbels JM, Smeitink JA (Dec 1998). "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed". Biochemical and Biophysical Research Communications. 253 (2): 415–22. doi:10.1006/bbrc.1998.9786. PMID   9878551.
• Emahazion T, Jobs M, Howell WM, Siegfried M, Wyöni PI, Prince JA, Brookes AJ (Oct 1999). "Identification of 167 polymorphisms in 88 genes from candidate neurodegeneration pathways". Gene. 238 (2): 315–24. doi:10.1016/S0378-1119(99)00330-3. PMID   10570959.
• Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (Oct 2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Research. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC   310934 . PMID   11042152.
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (Mar 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC   311072 . PMID   11230166.
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (Sep 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC   1083732 . PMID   11256614.
• Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC (Mar 2007). "Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects". Atherosclerosis. 191 (1): 63–72. doi:10.1016/j.atherosclerosis.2006.05.032. PMID   16806233.
• Hsieh SM, Maguire DJ, Lintell NA, McCabe M, Griffiths LR (2007). "Pten and Ndufb8 Aberrations in Cervical Cancer Tissue". Oxygen Transport to Tissue XXVIII. Advances in Experimental Medicine and Biology. Vol. 599. pp. 31–6. doi:10.1007/978-0-387-71764-7_5. ISBN   978-0-387-71763-0. PMID   17727244.