NDUFA10: Difference between revisions
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'''NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10''' is an [[enzyme]] that in humans is encoded by the '''NDUFA10''' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: NDUFA10 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 10 | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4705 | |
'''NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10''' is an [[enzyme]] that in humans is encoded by the '''NDUFA10''' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: NDUFA10 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 10 | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4705 | access-date = }}</ref><ref name="pmid9878551">{{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 = December 1998 | pmid = 9878551 | pmc = | doi = 10.1006/bbrc.1998.9786 }}</ref> The NDUFA10 protein is a subunit of [[NADH dehydrogenase (ubiquinone)]], which is located in the [[mitochondrial inner membrane]] 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><ref name="pmid9763677">{{cite journal | vauthors = Emahazion T, Beskow A, Gyllensten U, Brookes AJ | title = Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain | journal = Cytogenetics and Cell Genetics | volume = 82 | issue = 1-2 | pages = 115–9 | date = Nov 1998 | pmid = 9763677 | pmc = | doi = 10.1159/000015082 }}</ref> Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as [[Complex I]], frequently lead to complex neurodegenerative diseases such as [[Leigh's syndrome]].<ref name = "entrez"/> Furthermore, reduced NDUFA10 expression levels due to [[FOXM1]]-directed hypermethylation are associated with human [[squamous cell carcinoma]] and may be related to other forms of cancer.<ref name=pmid22461910>{{cite journal | vauthors = Teh MT, Gemenetzidis E, Patel D, Tariq R, Nadir A, Bahta AW, Waseem A, Hutchison IL | title = FOXM1 induces a global methylation signature that mimics the cancer epigenome in head and neck squamous cell carcinoma | journal = PloS One | volume = 7 | issue = 3 | pages = e34329 | year = 2012 | pmid = 22461910 | pmc = 3312909 | doi = 10.1371/journal.pone.0034329 }}</ref> |
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== Structure == |
== Structure == |
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The NDUFA10 gene is located on the q arm of [[chromosome 2]] in position 37.3 and spans 68,031 base pairs.<ref name = "entrez"/> The gene produces a 41 kDa protein composed of 355 [[amino acids]].<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 = |
The NDUFA10 gene is located on the q arm of [[chromosome 2]] in position 37.3 and spans 68,031 base pairs.<ref name = "entrez"/> The gene produces a 41 kDa protein composed of 355 [[amino acids]].<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 = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}</ref><ref name="url_COPaKB">{{cite web | url = https://amino.heartproteome.org/web/protein/O95299 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = NDUFA10 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10 }}</ref> NDUFA10 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 /> 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. NDUFA10 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis.<ref>{{cite web|title=NDUFA10 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10 |url=https://www.uniprot.org/uniprot/O95299|website=UniProt.org|publisher=The UniProt Consortium}}</ref> The predicted [[secondary structure]] is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.<ref name="entrez"/><ref name="pmid9763677"/><ref name="pmid9425316">{{cite journal | vauthors = Ton C, Hwang DM, Dempsey AA, Liew CC | title = Identification and primary structure of five human NADH-ubiquinone oxidoreductase subunits | journal = Biochemical and Biophysical Research Communications | volume = 241 | issue = 2 | pages = 589–94 | date = December 1997 | pmid = 9425316 | pmc = | doi = 10.1006/bbrc.1997.7707 }}</ref> |
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== Function == |
== Function == |
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== Clinical significance == |
== Clinical significance == |
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NDUFA10 demonstrated significantly downregulated mRNA expression levels in human [[squamous cell carcinoma]], due to [[FOXM1]]-induced hypermethylation. [[FOXM1]] is a known oncogene that has been implicated in all human cancer types. It operates by inhibiting [[tumor suppressor]] genes through promoter hypermethylation, among other mechanisms.<ref name = pmid22461910/> Mutations in ''NDUFA10'' have also been associated with [[Leigh syndrome|Leigh disease]] resulting from complex I deficiency.<ref>{{ |
NDUFA10 demonstrated significantly downregulated mRNA expression levels in human [[squamous cell carcinoma]], due to [[FOXM1]]-induced hypermethylation. [[FOXM1]] is a known oncogene that has been implicated in all human cancer types. It operates by inhibiting [[tumor suppressor]] genes through promoter hypermethylation, among other mechanisms.<ref name = pmid22461910/> Mutations in ''NDUFA10'' have also been associated with [[Leigh syndrome|Leigh disease]] resulting from complex I deficiency.<ref>{{cite journal | vauthors = Hoefs SJ, van Spronsen FJ, Lenssen EW, Nijtmans LG, Rodenburg RJ, Smeitink JA, van den Heuvel LP | title = NDUFA10 mutations cause complex I deficiency in a patient with Leigh disease | journal = European Journal of Human Genetics | volume = 19 | issue = 3 | pages = 270–4 | date = March 2011 | pmid = 21150889 | pmc = 3061993 | doi = 10.1038/ejhg.2010.204 }}</ref> |
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== Interactions == |
== Interactions == |
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== Further reading == |
== Further reading == |
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{{refbegin|33em}} |
{{refbegin|33em}} |
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* {{cite journal | vauthors = Smeitink J, van den Heuvel L | title = Human mitochondrial complex I in health and disease | journal = American Journal of Human Genetics | volume = 64 | issue = 6 | pages = 1505–10 | date = |
* {{cite journal | vauthors = Smeitink J, van den Heuvel L | title = Human mitochondrial complex I in health and disease | journal = American Journal of Human Genetics | volume = 64 | issue = 6 | pages = 1505–10 | date = June 1999 | pmid = 10330338 | pmc = 1377894 | doi = 10.1086/302432 }} |
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* {{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 = |
* {{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 = March 2007 | pmid = 16806233 | doi = 10.1016/j.atherosclerosis.2006.05.032 }} |
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* {{cite journal | vauthors = Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J | title = Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides | journal = Nature Biotechnology | volume = 21 | issue = 5 | pages = 566–9 | date = May 2003 | pmid = 12665801 | doi = 10.1038/nbt810 }} |
* {{cite journal | vauthors = Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J | title = Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides | journal = Nature Biotechnology | volume = 21 | issue = 5 | pages = 566–9 | date = May 2003 | pmid = 12665801 | doi = 10.1038/nbt810 }} |
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* {{cite journal | vauthors = Baens M, Chaffanet M, Aerssens J, Cassiman JJ, Marynen P | title = Assignment of the gene for the human proliferating cell nucleolar protein P120 (NOL1) to chromosome 12p13 by fluorescence in situ hybridization and polymerase chain reaction with somatic cell hybrids | journal = Genomics | volume = 21 | issue = 1 | pages = 296–7 | date = May 1994 | pmid = 8088812 | doi = 10.1006/geno.1994.1267 }} |
* {{cite journal | vauthors = Baens M, Chaffanet M, Aerssens J, Cassiman JJ, Marynen P | title = Assignment of the gene for the human proliferating cell nucleolar protein P120 (NOL1) to chromosome 12p13 by fluorescence in situ hybridization and polymerase chain reaction with somatic cell hybrids | journal = Genomics | volume = 21 | issue = 1 | pages = 296–7 | date = May 1994 | pmid = 8088812 | doi = 10.1006/geno.1994.1267 }} |
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Revision as of 21:06, 23 August 2018
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| Aliases | NDUFA10, CI-42KD, CI-42k, NADH:ubiquinone oxidoreductase subunit A10, MC1DN22 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 603835; MGI: 1914523; HomoloGene: 15342; GeneCards: NDUFA10; OMA:NDUFA10 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10 is an enzyme that in humans is encoded by the NDUFA10 gene.[5][6] The NDUFA10 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[7][8] Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome.[5] Furthermore, reduced NDUFA10 expression levels due to FOXM1-directed hypermethylation are associated with human squamous cell carcinoma and may be related to other forms of cancer.[9]
Structure
The NDUFA10 gene is located on the q arm of chromosome 2 in position 37.3 and spans 68,031 base pairs.[5] The gene produces a 41 kDa protein composed of 355 amino acids.[10][11] NDUFA10 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. NDUFA10 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis.[12] The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.[5][8][13]
Function
The human NDUFA10 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[5] 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
NDUFA10 demonstrated significantly downregulated mRNA expression levels in human squamous cell carcinoma, due to FOXM1-induced hypermethylation. FOXM1 is a known oncogene that has been implicated in all human cancer types. It operates by inhibiting tumor suppressor genes through promoter hypermethylation, among other mechanisms.[9] Mutations in NDUFA10 have also been associated with Leigh disease resulting from complex I deficiency.[14]
Interactions
NDUFA10 has been shown to have 56 binary protein-protein interactions including 55 co-complex interactions. NDUFA10 appears to interact with RAB8A.[15]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000130414 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026260 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d e "Entrez Gene: NDUFA10 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 10".
- ^ Loeffen JL, Triepels RH, van den Heuvel LP, Schuelke M, Buskens CA, Smeets RJ, Trijbels JM, Smeitink JA (December 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.
- ^ a b c Voet, Donald; Voet, Judith G.; Pratt, Charlotte W. (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.
{{cite book}}: Unknown parameter|name-list-format=ignored (|name-list-style=suggested) (help) - ^ a b Emahazion T, Beskow A, Gyllensten U, Brookes AJ (Nov 1998). "Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain". Cytogenetics and Cell Genetics. 82 (1–2): 115–9. doi:10.1159/000015082. PMID 9763677.
- ^ a b Teh MT, Gemenetzidis E, Patel D, Tariq R, Nadir A, Bahta AW, Waseem A, Hutchison IL (2012). "FOXM1 induces a global methylation signature that mimics the cancer epigenome in head and neck squamous cell carcinoma". PloS One. 7 (3): e34329. doi:10.1371/journal.pone.0034329. PMC 3312909. PMID 22461910.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ 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 (October 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.
- ^ "NDUFA10 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
- ^ "NDUFA10 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10". UniProt.org. The UniProt Consortium.
- ^ Ton C, Hwang DM, Dempsey AA, Liew CC (December 1997). "Identification and primary structure of five human NADH-ubiquinone oxidoreductase subunits". Biochemical and Biophysical Research Communications. 241 (2): 589–94. doi:10.1006/bbrc.1997.7707. PMID 9425316.
- ^ Hoefs SJ, van Spronsen FJ, Lenssen EW, Nijtmans LG, Rodenburg RJ, Smeitink JA, van den Heuvel LP (March 2011). "NDUFA10 mutations cause complex I deficiency in a patient with Leigh disease". European Journal of Human Genetics. 19 (3): 270–4. doi:10.1038/ejhg.2010.204. PMC 3061993. PMID 21150889.
- ^ IntAct. "https://www.ebi.ac.uk/intact/interactions?conversationContext=1". www.ebi.ac.uk. Retrieved 2018-08-23.
{{cite web}}: External link in|title=
Further reading
- Smeitink J, van den Heuvel L (June 1999). "Human mitochondrial complex I in health and disease". American Journal of Human Genetics. 64 (6): 1505–10. doi:10.1086/302432. PMC 1377894. PMID 10330338.
- Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC (March 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.
- Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology. 21 (5): 566–9. doi:10.1038/nbt810. PMID 12665801.
- Baens M, Chaffanet M, Aerssens J, Cassiman JJ, Marynen P (May 1994). "Assignment of the gene for the human proliferating cell nucleolar protein P120 (NOL1) to chromosome 12p13 by fluorescence in situ hybridization and polymerase chain reaction with somatic cell hybrids". Genomics. 21 (1): 296–7. doi:10.1006/geno.1994.1267. PMID 8088812.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.