NDUFB8: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial''' is an [[enzyme]] that in humans is encoded by the ''NDUFB8'' [[gene]].<ref name="pmid9763676">{{cite journal | vauthors = Emahazion T, Brookes AJ | title = Mapping of the NDUFA2, NDUFA6, NDUFA7, NDUFB8, and NDUFS8 electron transport chain genes by intron based radiation hybrid mapping | journal = Cytogenetics and Cell Genetics | volume = 82 | issue = 1-2 | pages = 114 | date = Nov 1998 | pmid = 9763676 | pmc =  | doi = 10.1159/000015081 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: NDUFB8 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8, 19kDa| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4714| accessdate = }}</ref> 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]].<ref name = "Biochem">{{cite book | first1 = Donald | last1 = Voet | first2 = Judith G. | last2 = Voet | first3 = Charlotte W. | last3 = Pratt | name-list-format = vanc | author1-link = Donald Voet | author2-link = Judith G. Voet | title = Fundamentals of biochemistry: life at the molecular level | date = 2013 | publisher = Wiley | location = Hoboken, NJ | isbn = 978-0-470-54784-7 | chapter = Chapter 18 | pages = 581–620 | edition = 4th }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Gene ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8, 19kDa
| HGNCid = 7703
| Symbol = NDUFB8
| AltSymbols =; ASHI; CI-ASHI
| OMIM = 602140
| ECnumber = 
| Homologene = 3668
| MGIid = 1914514
| GeneAtlas_image1 = PBB_GE_NDUFB8_201227_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_NDUFB8_201226_at_tn.png
| GeneAtlas_image3 = PBB_GE_NDUFB8_214241_at_tn.png
| Function = {{GNF_GO|id=GO:0003954 |text = NADH dehydrogenase activity}} {{GNF_GO|id=GO:0008137 |text = NADH dehydrogenase (ubiquinone) activity}} {{GNF_GO|id=GO:0016491 |text = oxidoreductase activity}}
| Component = {{GNF_GO|id=GO:0005624 |text = membrane fraction}} {{GNF_GO|id=GO:0005739 |text = mitochondrion}} {{GNF_GO|id=GO:0005743 |text = mitochondrial inner membrane}} {{GNF_GO|id=GO:0005783 |text = endoplasmic reticulum}}
| Process = {{GNF_GO|id=GO:0006118 |text = electron transport}} {{GNF_GO|id=GO:0006120 |text = mitochondrial electron transport, NADH to ubiquinone}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 4714
    | Hs_Ensembl = ENSG00000166136
    | Hs_RefseqProtein = NP_004995
    | Hs_RefseqmRNA = NM_005004
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 10
    | Hs_GenLoc_start = 102273487
    | Hs_GenLoc_end = 102279747
    | Hs_Uniprot = O95169
    | Mm_EntrezGene = 67264
    | Mm_Ensembl = ENSMUSG00000025204
    | Mm_RefseqmRNA = NM_026061
    | Mm_RefseqProtein = NP_080337
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 19
    | Mm_GenLoc_start = 44603563
    | Mm_GenLoc_end = 44608726
    | Mm_Uniprot = Q3V406
  }}
}}
'''NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8, 19kDa''', also known as '''NDUFB8''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: NDUFB8 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8, 19kDa| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4714| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
The NDUFB8 gene is located on the q arm of [[chromosome 10]] in position 24.31 and is 6,194 base pairs long.<ref name=COPaKB>{{cite journal | vauthors = 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 | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = Oct 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}</ref><ref name="url_COPaKB">{{cite web | url = http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O95169 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8 }}</ref>
{{PBB_Summary
| section_title =  
| summary_text =  
}}


==References==
== Structure ==
{{reflist|2}}
 
==Further reading==
The NDUFB8 protein weighs 22 kDa and is composed of 186 amino acids.<ref name=COPaKB/><ref name="url_COPaKB"/> 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.<ref name = "Biochem"/> [[NDUFB7]] and NDUFB8 have been shown to localize at the intermembrane surface of [[complex I]].<ref>{{cite journal | vauthors = Szklarczyk R, Wanschers BF, Nabuurs SB, Nouws J, Nijtmans LG, Huynen MA | title = NDUFB7 and NDUFA8 are located at the intermembrane surface of complex I | journal = FEBS Letters | volume = 585 | issue = 5 | pages = 737–43 | date = Mar 2011 | pmid = 21310150 | doi = 10.1016/j.febslet.2011.01.046 }}</ref> It has been noted that the [[N-terminus|N-terminal]] hydrophobic domain has the potential to be folded into an [[alpha helix]] spanning the inner [[mitochondrion|mitochondrial membrane]] with a [[C-terminus|C-terminal]] hydrophilic domain interacting with globular subunits of Complex I. The highly [[conserved sequence|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.<ref name = "entrez" />
{{refbegin | 2}}
 
{{PBB_Further_reading
== Function ==
| citations =  
 
*{{cite journal | author=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery. |journal=Genome Res. |volume=6 |issue= 9 |pages= 791-806 |year= 1997 |pmid= 8889548 |doi= }}
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.<ref name="entrez"/> Initially, [[NADH]] binds to Complex I and transfers two electrons to the [[isoalloxazine ring]] of the [[flavin mononucleotide]] (FMN) prosthetic arm to form FMNH<sub>2</sub>. The electrons are transferred through a series of [[iron-sulfur protein|iron-sulfur (Fe-S) clusters]] in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to [[ubiquinol]] (CoQH<sub>2</sub>). The flow of electrons changes the redox state of the protein, resulting in a conformational change and p''K'' shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.<ref name=Biochem />
*{{cite journal | author=Dunbar DR, Shibasaki Y, Dobbie L, ''et al.'' |title=In situ hybridisation mapping of genomic clones for five human respiratory chain complex I genes. |journal=Cytogenet. Cell Genet. |volume=78 |issue= 1 |pages= 21-4 |year= 1997 |pmid= 9345899 |doi= }}
 
*{{cite journal  | author=Emahazion T, Brookes AJ |title=Mapping of the NDUFA2, NDUFA6, NDUFA7, NDUFB8, and NDUFS8 electron transport chain genes by intron based radiation hybrid mapping. |journal=Cytogenet. Cell Genet. |volume=82 |issue= 1-2 |pages= 114 |year= 1998 |pmid= 9763676 |doi=  }}
== Model organisms ==
*{{cite journal | author=Loeffen JL, Triepels RH, van den Heuvel LP, ''et al.'' |title=cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed. |journal=Biochem. Biophys. Res. Commun. |volume=253 |issue= 2 |pages= 415-22 |year= 1999 |pmid= 9878551 |doi= 10.1006/bbrc.1998.9786 }}
 
*{{cite journal | author=Emahazion T, Jobs M, Howell WM, ''et al.'' |title=Identification of 167 polymorphisms in 88 genes from candidate neurodegeneration pathways. |journal=Gene |volume=238 |issue= 2 |pages= 315-24 |year= 1999 |pmid= 10570959 |doi= }}
[[Model organism]]s have been used in the study of NDUFB8 function. A conditional [[knockout mouse]] line called ''Ndufb8<sup>tm1a(EUCOMM)Wtsi</sup>'' was generated at the [[Wellcome Trust Sanger Institute]].<ref name="mgp_reference">{{cite journal |title=The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice |author=Gerdin AK |year=2010 |journal=Acta Ophthalmologica|volume=88 |pages=925–7|doi=10.1111/j.1755-3768.2010.4142.x }}</ref> Male and female animals underwent a standardized [[phenotypic screen]]<ref name="IMPCsearch_ref">{{cite web |url=http://www.mousephenotype.org/data/search?q=Ndufb8#fq=*:*&facet=gene |title=International Mouse Phenotyping Consortium}}</ref> to determine the effects of deletion.<ref name="pmid21677750">{{cite journal | vauthors = 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 | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref><ref name="pmid23870131">{{cite journal | vauthors = 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 | title = Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes | journal = Cell | volume = 154 | issue = 2 | pages = 452–64 | year = 2013 | pmid = 23870131 | doi = 10.1016/j.cell.2013.06.022 | pmc=3717207}}</ref> Additional screens performed:  - In-depth immunological phenotyping<ref name="iii_ref">{{cite web |url= http://www.immunophenotyping.org/data/search?keys=Ndufb8&field_gene_construct_tid=All |title=Infection and Immunity Immunophenotyping (3i) Consortium}}</ref>
*{{cite journal | author=Zhang QH, Ye M, Wu XY, ''et al.'' |title=Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. |journal=Genome Res. |volume=10 |issue= 10 |pages= 1546-60 |year= 2001 |pmid= 11042152 |doi= }}
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: left;" |
*{{cite journal | author=Wiemann S, Weil B, Wellenreuther R, ''et al.'' |title=Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. |journal=Genome Res. |volume=11 |issue= 3 |pages= 422-35 |year= 2001 |pmid= 11230166 |doi= 10.1101/gr.154701 }}
|+ ''Ndufb8'' knockout mouse phenotype
*{{cite journal | author=Simpson JC, Wellenreuther R, Poustka A, ''et al.'' |title=Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing. |journal=EMBO Rep. |volume=1 |issue= 3 |pages= 287-92 |year= 2001 |pmid= 11256614 |doi= 10.1093/embo-reports/kvd058 }}
|-
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
! Characteristic!! Phenotype
*{{cite journal  | author=Deloukas P, Earthrowl ME, Grafham DV, ''et al.'' |title=The DNA sequence and comparative analysis of human chromosome 10. |journal=Nature |volume=429 |issue= 6990 |pages= 375-81 |year= 2004 |pmid= 15164054 |doi= 10.1038/nature02462 }}
|-
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
| colspan=2; style="text-align: center;" | All data available at.<ref name="IMPCsearch_ref"/><ref name="iii_ref" />
*{{cite journal  | author=Ma J, Dempsey AA, Stamatiou D, ''et al.'' |title=Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects. |journal=Atherosclerosis |volume=191 |issue= 1 |pages= 63-72 |year= 2007 |pmid= 16806233 |doi= 10.1016/j.atherosclerosis.2006.05.032 }}
|-
*{{cite journal | author=Hsieh SM, Maguire DJ, Lintell NA, ''et al.'' |title=PTEN and NDUFB8 aberrations in cervical cancer tissue. |journal=Adv. Exp. Med. Biol. |volume=599 |issue=  |pages= 31-6 |year= 2007 |pmid= 17727244 |doi= }}
| Peripheral blood leukocytes 6 Weeks || bgcolor="#488ED3"|Normal
}}
 
|-
| Insulin || bgcolor="#488ED3"|Normal
 
|-
| ''[[Haematology]]'' 6 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Homozygous viability at P14 || bgcolor="#C40000"|Abnormal
 
|-
| [[Recessive]] lethal study || bgcolor="#C40000"|Abnormal
 
|-
| Body weight || bgcolor="#488ED3"|Normal
 
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
 
|-
| Grip strength || bgcolor="#488ED3"|Normal
 
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
 
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| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
 
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
 
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
 
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
 
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
 
|-
| Eye morphology || bgcolor="#488ED3"|Normal
 
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
 
|-
| ''[[Haematology]]'' 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Peripheral blood leukocytes 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Heart weight || bgcolor="#488ED3"|Normal
 
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal
 
|-
| Cytotoxic T Cell Function || bgcolor="#488ED3"|Normal
 
|-
| Spleen Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Mesenteric Lymph Node Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Bone Marrow Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Epidermal Immune Composition || bgcolor="#488ED3"|Normal
 
|-
|}
{{Clear}}
 
== References ==
{{reflist|33em}}
 
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = Sep 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 }}
* {{cite journal | vauthors = Dunbar DR, Shibasaki Y, Dobbie L, Andersson B, Brookes AJ | title = In situ hybridisation mapping of genomic clones for five human respiratory chain complex I genes | journal = Cytogenetics and Cell Genetics | volume = 78 | issue = 1 | pages = 21–4 | year = 1997 | pmid = 9345899 | doi = 10.1159/000134618 }}
* {{cite journal | vauthors = Loeffen JL, Triepels RH, van den Heuvel LP, Schuelke M, Buskens CA, Smeets RJ, Trijbels JM, Smeitink JA | title = cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed | journal = Biochemical and Biophysical Research Communications | volume = 253 | issue = 2 | pages = 415–22 | date = Dec 1998 | pmid = 9878551 | doi = 10.1006/bbrc.1998.9786 }}
* {{cite journal | vauthors = Emahazion T, Jobs M, Howell WM, Siegfried M, Wyöni PI, Prince JA, Brookes AJ | title = Identification of 167 polymorphisms in 88 genes from candidate neurodegeneration pathways | journal = Gene | volume = 238 | issue = 2 | pages = 315–24 | date = Oct 1999 | pmid = 10570959 | doi = 10.1016/S0378-1119(99)00330-3 }}
* {{cite journal | vauthors = 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 | title = Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells | journal = Genome Research | volume = 10 | issue = 10 | pages = 1546–60 | date = Oct 2000 | pmid = 11042152 | pmc = 310934 | doi = 10.1101/gr.140200 }}
* {{cite journal | vauthors = 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 | title = Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs | journal = Genome Research | volume = 11 | issue = 3 | pages = 422–35 | date = Mar 2001 | pmid = 11230166 | pmc = 311072 | doi = 10.1101/gr.GR1547R }}
* {{cite journal | vauthors = Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S | title = Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing | journal = EMBO Reports | volume = 1 | issue = 3 | pages = 287–92 | date = Sep 2000 | pmid = 11256614 | pmc = 1083732 | doi = 10.1093/embo-reports/kvd058 }}
* {{cite journal | vauthors = Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC | title = Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects | journal = Atherosclerosis | volume = 191 | issue = 1 | pages = 63–72 | date = Mar 2007 | pmid = 16806233 | doi = 10.1016/j.atherosclerosis.2006.05.032 }}
* {{cite journal | vauthors = Hsieh SM, Maguire DJ, Lintell NA, McCabe M, Griffiths LR | title = PTEN and NDUFB8 aberrations in cervical cancer tissue | journal = Advances in Experimental Medicine and Biology | volume = 599 | issue =  | pages = 31–6 | year = 2007 | pmid = 17727244 | doi = 10.1007/978-0-387-71764-7_5 }}
{{refend}}
{{refend}}


{{protein-stub}}
[[Category:Human proteins]]
{{WikiDoc Sources}}

Revision as of 12:46, 5 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial is an enzyme that in humans is encoded by the NDUFB8 gene.[1][2] 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.[3]

Gene

The NDUFB8 gene is located on the q arm of chromosome 10 in position 24.31 and is 6,194 base pairs long.[4][5]

Structure

The NDUFB8 protein weighs 22 kDa and is composed of 186 amino acids.[4][5] 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.[3] NDUFB7 and NDUFB8 have been shown to localize at the intermembrane surface of complex I.[6] 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.[2]

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.[2] 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.[3]

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.[7] Male and female animals underwent a standardized phenotypic screen[8] to determine the effects of deletion.[9][10][11][12] Additional screens performed: - In-depth immunological phenotyping[13]

References

  1. ↑ 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.
  2. ↑ 2.0 2.1 2.2 "Entrez Gene: NDUFB8 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8, 19kDa".
  3. ↑ 3.0 3.1 3.2 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.
  4. ↑ 4.0 4.1 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.
  5. ↑ 5.0 5.1 "NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 8.0 8.1 "International Mouse Phenotyping Consortium".
  9. ↑ 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.
  10. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 13.0 13.1 "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

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