MT-ND3

MT-ND3 is located in human mitochondrial DNA from base pair 10,059 to 10,404. The MT-ND3 gene produces a 13 kDa protein composed of 115 amino acids.{{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 }}{{cite web | url = https://amino.heartproteome.org/web/protein/P03897 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = NADH-ubiquinone oxidoreductase chain 3 }} MT-ND3 is one of seven mitochondrial genes encoding subunits of the enzyme NADH dehydrogenase (ubiquinone), together with MT-ND1, MT-ND2, MT-ND4, MT-ND4L, MT-ND5, and MT-ND6. Also known as Complex I, this enzyme is 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 centres and the NADH binding site. The MT-ND3 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.

In the MT-ND3 gene from many species of birds and turtles {{Cite web|url=http://megasun.bch.umontreal.ca/ogmp/projects/other/mt_list.html|title=Complete mitochondrial genome sequences|website=megasun.bch.umontreal.ca|access-date=2017-02-20}} there is an extra nucleotide that is not translated to protein.{{cite journal | vauthors = Mindell DP, Sorenson MD, Dimcheff DE | title = An extra nucleotide is not translated in mitochondrial ND3 of some birds and turtles | journal = Molecular Biology and Evolution | volume = 15 | issue = 11 | pages = 1568–71 | date = November 1998 | pmid = 12572620 | doi = 10.1093/oxfordjournals.molbev.a025884 | doi-access = free }}

Translational frameshifting or RNA editing are alternative explanations for maintenance of the functionality of the ND3 reading frame in birds possessing the one-nucleotide insertion.

This extra nucleotide feature suggests that turtles might be related to Archosauria, as evidenced by molecular phylogeny studies.{{cite journal | vauthors = Chiari Y, Cahais V, Galtier N, Delsuc F | title = Phylogenomic analyses support the position of turtles as the sister group of birds and crocodiles (Archosauria) | journal = BMC Biology | volume = 10 | pages = 65 | date = July 2012 | pmid = 22839781 | pmc = 3473239 | doi = 10.1186/1741-7007-10-65 | doi-access = free }}{{cite journal | vauthors = Crawford NG, Faircloth BC, McCormack JE, Brumfield RT, Winker K, Glenn TC | title = More than 1000 ultraconserved elements provide evidence that turtles are the sister group of archosaurs | journal = Biology Letters | volume = 8 | issue = 5 | pages = 783–6 | date = October 2012 | pmid = 22593086 | pmc = 3440978 | doi = 10.1098/rsbl.2012.0331 }} The absence of the extra nucleotide in crocodilians and some birds and turtles might also indicate that the corresponding taxa have lost this feature.

The MT-ND3 product is a subunit of the respiratory chain Complex I that is believed to belong to the minimal assembly of core proteins required to catalyze NADH dehydrogenation and electron transfer to ubiquinone (coenzyme Q10).{{cite web|title=MT-ND3 - NADH-ubiquinone oxidoreductase chain 3 - Homo sapiens (Human)|url=https://www.uniprot.org/uniprot/P03897|website=UniProt.org: a hub for protein information|publisher=The UniProt Consortium}} 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.

Pathogenic variants of the mitochondrial gene MT-ND3 are known to cause mtDNA-associated Leigh syndrome, as are variants of MT-ATP6, MT-TL1, MT-TK, MT-TW, MT-TV, MT-ND1, MT-ND2, MT-ND4, MT-ND5, MT-ND6 and MT-CO3. Abnormalities in mitochondrial energy generation result in neurodegenerative disorders like Leigh syndrome, which is characterized by an onset of symptoms between 12 months and three years of age. The symptoms frequently present themselves following a viral infection and include movement disorders and peripheral neuropathy, as well as hypotonia, spasticity and cerebellar ataxia. Roughly half of affected patients die of respiratory or cardiac failure by the age of three. Leigh syndrome is a maternally inherited disorder and its diagnosis is established through genetic testing of the aforementioned mitochondrial genes, including MT-ND3. These complex I genes have been associated with a variety of neurodegenerative disorders, including Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and the previously mentioned Leigh syndrome.

MT-ND3 has been shown to have 5 binary protein-protein interactions including 2 co-complex interactions. MT-ND3 appears to interact with APP and NDUFA9.{{Cite web | url = https://www.ebi.ac.uk/intact/interactions?conversationContext=3&query=MT-ND3 | title = 5 binary interactions found for search term MT-ND3 | work = IntAct Molecular Interaction Database | publisher = EMBL-EBI | access-date = 2018-08-25 }}

{{reflist|33em}}

{{refbegin|33em}}

• {{cite journal | vauthors = Leshinsky-Silver E, Lev D, Tzofi-Berman Z, Cohen S, Saada A, Yanoov-Sharav M, Gilad E, Lerman-Sagie T | title = Fulminant neurological deterioration in a neonate with Leigh syndrome due to a maternally transmitted missense mutation in the mitochondrial ND3 gene | journal = Biochemical and Biophysical Research Communications | volume = 334 | issue = 2 | pages = 582–7 | date = August 2005 | pmid = 16023078 | doi = 10.1016/j.bbrc.2005.06.134 }}
• {{cite journal | vauthors = Levy RJ, Ríos PG, Akman HO, Sciacco M, Vivo DC, DiMauro S | title = Long survival in patients with leigh syndrome and the m.10191T>C mutation in MT-ND3 : a case report and review of the literature | journal = Journal of Child Neurology | volume = 29 | issue = 10 | pages = NP105–10 | date = October 2014 | pmid = 24284231 | pmc = 4035473 | doi = 10.1177/0883073813506783 }}
• {{cite journal | vauthors = Grosso S, Carluccio MA, Cardaioli E, Cerase A, Malandrini A, Romano C, Federico A, Dotti MT | title = Complex I deficiency related to T10158C mutation ND3 gene: A further definition of the clinical spectrum | journal = Brain & Development | volume = 39 | issue = 3 | pages = 261–265 | date = March 2017 | pmid = 27742419 | doi = 10.1016/j.braindev.2016.09.013 | s2cid = 6565853 }}
• {{cite journal | vauthors = Torroni A, Achilli A, Macaulay V, Richards M, Bandelt HJ | title = Harvesting the fruit of the human mtDNA tree | journal = Trends in Genetics | volume = 22 | issue = 6 | pages = 339–45 | date = June 2006 | pmid = 16678300 | doi = 10.1016/j.tig.2006.04.001 }}
• {{cite journal | vauthors = Horai S, Hayasaka K, Kondo R, Tsugane K, Takahata N | title = Recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 2 | pages = 532–6 | date = January 1995 | pmid = 7530363 | pmc = 42775 | doi = 10.1073/pnas.92.2.532 | bibcode = 1995PNAS...92..532H | doi-access = free }}
• {{cite journal | vauthors = Ingman M, Kaessmann H, Pääbo S, Gyllensten U | title = Mitochondrial genome variation and the origin of modern humans | journal = Nature | volume = 408 | issue = 6813 | pages = 708–13 | date = December 2000 | pmid = 11130070 | doi = 10.1038/35047064 | bibcode = 2000Natur.408..708I | s2cid = 52850476 }}
• {{cite journal | vauthors = Finnilä S, Lehtonen MS, Majamaa K | title = Phylogenetic network for European mtDNA | journal = American Journal of Human Genetics | volume = 68 | issue = 6 | pages = 1475–84 | date = June 2001 | pmid = 11349229 | pmc = 1226134 | doi = 10.1086/320591 }}
• {{cite journal | vauthors = Maca-Meyer N, González AM, Larruga JM, Flores C, Cabrera VM | title = Major genomic mitochondrial lineages delineate early human expansions | journal = BMC Genetics | volume = 2 | pages = 13 | year = 2003 | pmid = 11553319 | pmc = 55343 | doi = 10.1186/1471-2156-2-13 | doi-access = free }}
• {{cite journal | vauthors = Herrnstadt C, Elson JL, Fahy E, Preston G, Turnbull DM, Anderson C, Ghosh SS, Olefsky JM, Beal MF, Davis RE, Howell N | title = Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups | journal = American Journal of Human Genetics | volume = 70 | issue = 5 | pages = 1152–71 | date = May 2002 | pmid = 11938495 | pmc = 447592 | doi = 10.1086/339933 }}
• {{cite journal | vauthors = Silva WA, Bonatto SL, Holanda AJ, Ribeiro-Dos-Santos AK, Paixão BM, Goldman GH, Abe-Sandes K, Rodriguez-Delfin L, Barbosa M, Paçó-Larson ML, Petzl-Erler ML, Valente V, Santos SE, Zago MA | title = Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America | journal = American Journal of Human Genetics | volume = 71 | issue = 1 | pages = 187–92 | date = July 2002 | pmid = 12022039 | pmc = 384978 | doi = 10.1086/341358 }}
• {{cite journal | vauthors = Sudoyo H, Suryadi H, Lertrit P, Pramoonjago P, Lyrawati D, Marzuki S | title = Asian-specific mtDNA backgrounds associated with the primary G11778A mutation of Leber's hereditary optic neuropathy | journal = Journal of Human Genetics | volume = 47 | issue = 11 | pages = 594–604 | year = 2003 | pmid = 12436196 | doi = 10.1007/s100380200091 | doi-access = free }}
• {{cite journal | vauthors = Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, Brandon M, Easley K, Chen E, Brown MD, Sukernik RI, Olckers A, Wallace DC | title = Natural selection shaped regional mtDNA variation in humans | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 1 | pages = 171–6 | date = January 2003 | pmid = 12509511 | pmc = 140917 | doi = 10.1073/pnas.0136972100 | bibcode = 2003PNAS..100..171M | doi-access = free }}
• {{cite journal | vauthors = Ingman M, Gyllensten U | title = Mitochondrial genome variation and evolutionary history of Australian and New Guinean aborigines | journal = Genome Research | volume = 13 | issue = 7 | pages = 1600–6 | date = July 2003 | pmid = 12840039 | pmc = 403733 | doi = 10.1101/gr.686603 }}
• {{cite journal | vauthors = Kong QP, Yao YG, Sun C, Bandelt HJ, Zhu CL, Zhang YP | title = Phylogeny of east Asian mitochondrial DNA lineages inferred from complete sequences | journal = American Journal of Human Genetics | volume = 73 | issue = 3 | pages = 671–6 | date = September 2003 | pmid = 12870132 | pmc = 1180693 | doi = 10.1086/377718 }}
• {{cite journal | vauthors = Moilanen JS, Finnila S, Majamaa K | title = Lineage-specific selection in human mtDNA: lack of polymorphisms in a segment of MTND5 gene in haplogroup J | journal = Molecular Biology and Evolution | volume = 20 | issue = 12 | pages = 2132–42 | date = December 2003 | pmid = 12949126 | doi = 10.1093/molbev/msg230 | doi-access = free }}
• {{cite journal | vauthors = Coble MD, Just RS, O'Callaghan JE, Letmanyi IH, Peterson CT, Irwin JA, Parsons TJ | title = Single nucleotide polymorphisms over the entire mtDNA genome that increase the power of forensic testing in Caucasians | journal = International Journal of Legal Medicine | volume = 118 | issue = 3 | pages = 137–46 | date = June 2004 | pmid = 14760490 | doi = 10.1007/s00414-004-0427-6 | s2cid = 8413730 }}
• {{cite journal | vauthors = Crimi M, Papadimitriou A, Galbiati S, Palamidou P, Fortunato F, Bordoni A, Papandreou U, Papadimitriou D, Hadjigeorgiou GM, Drogari E, Bresolin N, Comi GP | title = A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethality | journal = Pediatric Research | volume = 55 | issue = 5 | pages = 842–6 | date = May 2004 | pmid = 14764913 | doi = 10.1203/01.PDR.0000117844.73436.68 | doi-access = free }}
• {{cite journal | vauthors = Tanaka M, Cabrera VM, González AM, Larruga JM, Takeyasu T, Fuku N, Guo LJ, Hirose R, Fujita Y, Kurata M, Shinoda K, Umetsu K, Yamada Y, Oshida Y, Sato Y, Hattori N, Mizuno Y, Arai Y, Hirose N, Ohta S, Ogawa O, Tanaka Y, Kawamori R, Shamoto-Nagai M, Maruyama W, Shimokata H, Suzuki R, Shimodaira H | title = Mitochondrial genome variation in eastern Asia and the peopling of Japan | journal = Genome Research | volume = 14 | issue = 10A | pages = 1832–50 | date = October 2004 | pmid = 15466285 | pmc = 524407 | doi = 10.1101/gr.2286304 }}
• {{cite journal | vauthors = Palanichamy MG, Sun C, Agrawal S, Bandelt HJ, Kong QP, Khan F, Wang CY, Chaudhuri TK, Palla V, Zhang YP | title = Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete sequencing: implications for the peopling of South Asia | journal = American Journal of Human Genetics | volume = 75 | issue = 6 | pages = 966–78 | date = December 2004 | pmid = 15467980 | pmc = 1182158 | doi = 10.1086/425871 }}
• {{cite journal | vauthors = Starikovskaya EB, Sukernik RI, Derbeneva OA, Volodko NV, Ruiz-Pesini E, Torroni A, Brown MD, Lott MT, Hosseini SH, Huoponen K, Wallace DC | title = Mitochondrial DNA diversity in indigenous populations of the southern extent of Siberia, and the origins of Native American haplogroups | journal = Annals of Human Genetics | volume = 69 | issue = Pt 1 | pages = 67–89 | date = January 2005 | pmid = 15638829 | pmc = 3905771 | doi = 10.1046/j.1529-8817.2003.00127.x }}
• {{cite journal | vauthors = Achilli A, Rengo C, Battaglia V, Pala M, Olivieri A, Fornarino S, Magri C, Scozzari R, Babudri N, Santachiara-Benerecetti AS, Bandelt HJ, Semino O, Torroni A | title = Saami and Berbers--an unexpected mitochondrial DNA link | journal = American Journal of Human Genetics | volume = 76 | issue = 5 | pages = 883–6 | date = May 2005 | pmid = 15791543 | pmc = 1199377 | doi = 10.1086/430073 }}
• {{cite journal | vauthors = Rajkumar R, Banerjee J, Gunturi HB, Trivedi R, Kashyap VK | title = Phylogeny and antiquity of M macrohaplogroup inferred from complete mt DNA sequence of Indian specific lineages | journal = BMC Evolutionary Biology | volume = 5 | pages = 26 | date = April 2005 | pmid = 15804362 | pmc = 1079809 | doi = 10.1186/1471-2148-5-26 | doi-access = free }}
• {{cite journal | vauthors = Friedlaender J, Schurr T, Gentz F, Koki G, Friedlaender F, Horvat G, Babb P, Cerchio S, Kaestle F, Schanfield M, Deka R, Yanagihara R, Merriwether DA | title = Expanding Southwest Pacific mitochondrial haplogroups P and Q | journal = Molecular Biology and Evolution | volume = 22 | issue = 6 | pages = 1506–17 | date = June 2005 | pmid = 15814828 | doi = 10.1093/molbev/msi142 | doi-access = free }}

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• [http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P03897 Mass spectrometry characterization of MT-ND3 at COPaKB]

{{Mitochondrial enzymes}}

Category:Proteins

Category:Human mitochondrial genes