MT-ND2
ND2 | |||
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Identifiers | |||
Gene ontology | |||
Molecular function | |||
Cellular component | |||
Biological process | |||
Sources:Amigo / QuickGO |
Ensembl | |||||||||
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UniProt | |||||||||
RefSeq (mRNA) |
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RefSeq (protein) |
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Location (UCSC) | Chr M: 0 – 0.01 Mb | Chr M: 0 – 0 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
MT-ND2 is a
Leigh's syndrome (LS), Leber's hereditary optic neuropathy (LHON) and increases in adult BMI.[7][8][9]
Structure
MT-ND2 is located in mitochondrial DNA from base pair 4,470 to 5,511.hydrophilic domain for the peripheral arm that includes all the known redox centres and the NADH binding site. The MT-ND2 product and the rest of the mitochondrially encoded subunits are the most hydrophobic of the subunits of Complex I and form the core of the transmembrane region.[6]
Function
The MT-ND2 product is a subunit of the respiratory chain
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.[6]
Clinical significance
Pathogenic variants of the mitochondrial gene MT-ND2 are known to cause mtDNA-associated
MELAS) and the previously mentioned Leigh syndrome.[8]
Mitochondrial dysfunction resulting from variants of MT-ND2, MT-ND1 and MT-ND4L have been linked to BMI in adults and implicated in metabolic disorders including obesity, diabetes and hypertension.[9]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000198763 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000064345 – 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 "Entrez Gene: MT-ND2 NADH dehydrogenase subunit 2".
- ^ ISBN 978-0-47054784-7.
- ^ PMID 20301352.
- ^ PMID 24884847.
- ^ PMID 25153900.
- PMID 23965338.
- ^ "Mitochondrially encoded NADH dehydrogenase 2". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
- ^ "MT-ND2 - NADH-ubiquinone oxidoreductase chain 2 - Homo sapiens (Human)". UniProt.org: a hub for protein information. The UniProt Consortium.
Further reading
- Torroni A, Achilli A, Macaulay V, Richards M, Bandelt HJ (Jun 2006). "Harvesting the fruit of the human mtDNA tree". Trends in Genetics. 22 (6): 339–45. PMID 16678300.
- Bodenteich A, Mitchell LG, Polymeropoulos MH, Merril CR (May 1992). "Dinucleotide repeat in the human mitochondrial D-loop". Human Molecular Genetics. 1 (2): 140. PMID 1301157.
- Lin FH, Lin R, Wisniewski HM, Hwang YW, Grundke-Iqbal I, Healy-Louie G, Iqbal K (Jan 1992). "Detection of point mutations in codon 331 of mitochondrial NADH dehydrogenase subunit 2 in Alzheimer's brains". Biochemical and Biophysical Research Communications. 182 (1): 238–46. PMID 1370613.
- Lu X, Walker T, MacManus JP, Seligy VL (Jul 1992). "Differentiation of HT-29 human colonic adenocarcinoma cells correlates with increased expression of mitochondrial RNA: effects of trehalose on cell growth and maturation". Cancer Research. 52 (13): 3718–25. PMID 1377597.
- Brown MD, Voljavec AS, Lott MT, Torroni A, Yang CC, Wallace DC (Jan 1992). "Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy". Genetics. 130 (1): 163–73. PMID 1732158.
- Marzuki S, Noer AS, Lertrit P, Thyagarajan D, Kapsa R, Utthanaphol P, Byrne E (Dec 1991). "Normal variants of human mitochondrial DNA and translation products: the building of a reference data base". Human Genetics. 88 (2): 139–45. S2CID 28048453.
- Johns DR, Berman J (Feb 1991). "Alternative, simultaneous complex I mitochondrial DNA mutations in Leber's hereditary optic neuropathy". Biochemical and Biophysical Research Communications. 174 (3): 1324–30. PMID 1900003.
- Moraes CT, Andreetta F, Bonilla E, Shanske S, DiMauro S, Schon EA (Mar 1991). "Replication-competent human mitochondrial DNA lacking the heavy-strand promoter region". Molecular and Cellular Biology. 11 (3): 1631–7. PMID 1996112.
- Attardi G, Chomyn A, Doolittle RF, Mariottini P, Ragan CI (1987). "Seven unidentified reading frames of human mitochondrial DNA encode subunits of the respiratory chain NADH dehydrogenase". Cold Spring Harbor Symposia on Quantitative Biology. 51 (1): 103–14. PMID 3472707.
- Chomyn A, Cleeter MW, Ragan CI, Riley M, Doolittle RF, Attardi G (Oct 1986). "URF6, last unidentified reading frame of human mtDNA, codes for an NADH dehydrogenase subunit". Science. 234 (4776): 614–8. PMID 3764430.
- Chomyn A, Mariottini P, Cleeter MW, Ragan CI, Matsuno-Yagi A, Hatefi Y, Doolittle RF, Attardi G (1985). "Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase". Nature. 314 (6012): 592–7. S2CID 32964006.
- Sanger F, Coulson AR, Barrell BG, Smith AJ, Roe BA (Oct 1980). "Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing". Journal of Molecular Biology. 143 (2): 161–78. PMID 6260957.
- Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG (Apr 1981). "Sequence and organization of the human mitochondrial genome". Nature. 290 (5806): 457–65. S2CID 4355527.
- Montoya J, Ojala D, Attardi G (Apr 1981). "Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs". Nature. 290 (5806): 465–70. S2CID 4358928.
- Horai S, Hayasaka K, Kondo R, Tsugane K, Takahata N (Jan 1995). "Recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs". Proceedings of the National Academy of Sciences of the United States of America. 92 (2): 532–6. PMID 7530363.
- Rieder MJ, Taylor SL, Tobe VO, Nickerson DA (Feb 1998). "Automating the identification of DNA variations using quality-based fluorescence re-sequencing: analysis of the human mitochondrial genome". Nucleic Acids Research. 26 (4): 967–73. PMID 9461455.
- Wise CA, Sraml M, Easteal S (Jan 1998). "Departure from neutrality at the mitochondrial NADH dehydrogenase subunit 2 gene in humans, but not in chimpanzees". Genetics. 148 (1): 409–21. PMID 9475751.
- Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N (Oct 1999). "Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA". Nature Genetics. 23 (2): 147. S2CID 32212178.
- Ingman M, Kaessmann H, Pääbo S, Gyllensten U (Dec 2000). "Mitochondrial genome variation and the origin of modern humans". Nature. 408 (6813): 708–13. S2CID 52850476.
- Finnilä S, Lehtonen MS, Majamaa K (Jun 2001). "Phylogenetic network for European mtDNA". American Journal of Human Genetics. 68 (6): 1475–84. PMID 11349229.