NADH-ubiquinone oxidoreductase chain 4

NameNADH-ubiquinone oxidoreductase chain 4
Synonyms
  • 1.6.5.3
  • MTND4
  • NADH dehydrogenase subunit 4
  • NADH4
  • ND4
Gene NameMT-ND4
OrganismHuman
Amino acid sequence
>lcl|BSEQ0010383|NADH-ubiquinone oxidoreductase chain 4
MLKLIVPTIMLLPLTWLSKKHMIWINTTTHSLIISIIPLLFFNQINNNLFSCSPTFSSDP
LTTPLLMLTTWLLPLTIMASQRHLSSEPLSRKKLYLSMLISLQISLIMTFTATELIMFYI
FFETTLIPTLAIITRWGNQPERLNAGTYFLFYTLVGSLPLLIALIYTHNTLGSLNILLLT
LTAQELSNSWANNLMWLAYTMAFMVKMPLYGLHLWLPKAHVEAPIAGSMVLAAVLLKLGG
YGMMRLTLILNPLTKHMAYPFLVLSLWGMIMTSSICLRQTDLKSLIAYSSISHMALVVTA
ILIQTPWSFTGAVILMIAHGLTSSLLFCLANSNYERTHSRIMILSQGLQTLLPLMAFWWL
LASLANLALPPTINLLGELSVLVTTFSWSNITLLLTGLNMLVTALYSLYMFTTTQWGSLT
HHINNMKPSFTRENTLMFMHLSPILLLSLNPDIITGFSS
Number of residues459
Molecular Weight51580.26
Theoretical pI9.67
GO Classification
Functions
  • NADH dehydrogenase (ubiquinone) activity
Processes
  • mitochondrial electron transport, NADH to ubiquinone
  • small molecule metabolic process
  • in utero embryonic development
  • cellular metabolic process
  • response to hypoxia
  • respiratory electron transport chain
  • cerebellum development
  • response to ethanol
  • aging
  • response to nicotine
Components
  • mitochondrial inner membrane
  • integral component of membrane
  • mitochondrial respiratory chain complex I
General FunctionNadh dehydrogenase (ubiquinone) activity
Specific FunctionCore subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity).
Pfam Domain Function
Transmembrane Regions22-42 60-80 102-122 145-165 196-216 224-244 257-277 284-303 308-330 351-371 391-411
GenBank Protein IDNot Available
UniProtKB IDP03905
UniProtKB Entry NameNU4M_HUMAN
Cellular LocationMitochondrion membrane
Gene sequence
>lcl|BSEQ0010384|NADH-ubiquinone oxidoreductase chain 4 (MT-ND4)
ATGCTAAAACTAATCGTCCCAACAATTATATTACTACCACTGACATGACTTTCCAAAAAA
CACATAATTTGAATCAACACAACCACCCACAGCCTAATTATTAGCATCATCCCTCTACTA
TTTTTTAACCAAATCAACAACAACCTATTTAGCTGTTCCCCAACCTTTTCCTCCGACCCC
CTAACAACCCCCCTCCTAATACTAACTACCTGACTCCTACCCCTCACAATCATGGCAAGC
CAACGCCACTTATCCAGTGAACCACTATCACGAAAAAAACTCTACCTCTCTATACTAATC
TCCCTACAAATCTCCTTAATTATAACATTCACAGCCACAGAACTAATCATATTTTATATC
TTCTTCGAAACCACACTTATCCCCACCTTGGCTATCATCACCCGATGAGGCAACCAGCCA
GAACGCCTGAACGCAGGCACATACTTCCTATTCTACACCCTAGTAGGCTCCCTTCCCCTA
CTCATCGCACTAATTTACACTCACAACACCCTAGGCTCACTAAACATTCTACTACTCACT
CTCACTGCCCAAGAACTATCAAACTCCTGAGCCAACAACTTAATATGACTAGCTTACACA
ATAGCTTTTATAGTAAAGATACCTCTTTACGGACTCCACTTATGACTCCCTAAAGCCCAT
GTCGAAGCCCCCATCGCTGGGTCAATAGTACTTGCCGCAGTACTCTTAAAACTAGGCGGC
TATGGTATAATACGCCTCACACTCATTCTCAACCCCCTGACAAAACACATAGCCTACCCC
TTCCTTGTACTATCCCTATGAGGCATAATTATAACAAGCTCCATCTGCCTACGACAAACA
GACCTAAAATCGCTCATTGCATACTCTTCAATCAGCCACATAGCCCTCGTAGTAACAGCC
ATTCTCATCCAAACCCCCTGAAGCTTCACCGGCGCAGTCATTCTCATAATCGCCCACGGG
CTTACATCCTCATTACTATTCTGCCTAGCAAACTCAAACTACGAACGCACTCACAGTCGC
ATCATAATCCTCTCTCAAGGACTTCAAACTCTACTCCCACTAATAGCTTTTTGATGACTT
CTAGCAAGCCTCGCTAACCTCGCCTTACCCCCCACTATTAACCTACTGGGAGAACTCTCT
GTGCTAGTAACCACGTTCTCCTGATCAAATATCACTCTCCTACTTACAGGACTCAACATA
CTAGTCACAGCCCTATACTCCCTCTACATATTTACCACAACACAATGGGGCTCACTCACC
CACCACATTAACAACATAAAACCCTCATTCACACGAGAAAACACCCTCATGTTCATACAC
CTATCCCCCATTCTCCTCCTATCCCTCAACCCCGACATCATTACCGGGTTTTCCTCTT
GenBank Gene IDJ01415
GeneCard IDNot Available
GenAtlas IDMT-ND4
HGNC IDHGNC:7459
Chromosome LocationNot Available
Locus-
References
  1. 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: Sequence and organization of the human mitochondrial genome. Nature. 1981 Apr 9;290(5806):457-65. 7219534
  2. Lu X, Walker T, MacManus JP, Seligy VL: Differentiation of HT-29 human colonic adenocarcinoma cells correlates with increased expression of mitochondrial RNA: effects of trehalose on cell growth and maturation. Cancer Res. 1992 Jul 1;52(13):3718-25. 1377597
  3. Silva WA Jr, Bonatto SL, Holanda AJ, Ribeiro-Dos-Santos AK, Paixao BM, Goldman GH, Abe-Sandes K, Rodriguez-Delfin L, Barbosa M, Paco-Larson ML, Petzl-Erler ML, Valente V, Santos SE, Zago MA: Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America. Am J Hum Genet. 2002 Jul;71(1):187-92. Epub 2002 May 17. 12022039
  4. Moilanen JS, Finnila S, Majamaa K: Lineage-specific selection in human mtDNA: lack of polymorphisms in a segment of MTND5 gene in haplogroup J. Mol Biol Evol. 2003 Dec;20(12):2132-42. Epub 2003 Aug 29. 12949126
  5. Ingman M, Kaessmann H, Paabo S, Gyllensten U: Mitochondrial genome variation and the origin of modern humans. Nature. 2000 Dec 7;408(6813):708-13. 11130070
  6. Ingman M, Gyllensten U: Mitochondrial genome variation and evolutionary history of Australian and New Guinean aborigines. Genome Res. 2003 Jul;13(7):1600-6. 12840039
  7. Coble MD, Just RS, O'Callaghan JE, Letmanyi IH, Peterson CT, Irwin JA, Parsons TJ: Single nucleotide polymorphisms over the entire mtDNA genome that increase the power of forensic testing in Caucasians. Int J Legal Med. 2004 Jun;118(3):137-46. Epub 2004 Feb 4. 14760490
  8. Brown WM, Prager EM, Wang A, Wilson AC: Mitochondrial DNA sequences of primates: tempo and mode of evolution. J Mol Evol. 1982;18(4):225-39. 6284948
  9. Chomyn A, Mariottini P, Cleeter MW, Ragan CI, Matsuno-Yagi A, Hatefi Y, Doolittle RF, Attardi G: Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase. Nature. 1985 Apr 18-24;314(6012):592-7. 3921850
  10. Murray J, Zhang B, Taylor SW, Oglesbee D, Fahy E, Marusich MF, Ghosh SS, Capaldi RA: The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification. J Biol Chem. 2003 Apr 18;278(16):13619-22. Epub 2003 Feb 28. 12611891
  11. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  12. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  13. Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AM, Elsas LJ 2nd, Nikoskelainen EK: Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science. 1988 Dec 9;242(4884):1427-30. 3201231
  14. Majander A, Huoponen K, Savontaus ML, Nikoskelainen E, Wikstrom M: Electron transfer properties of NADH:ubiquinone reductase in the ND1/3460 and the ND4/11778 mutations of the Leber hereditary optic neuroretinopathy (LHON). FEBS Lett. 1991 Nov 4;292(1-2):289-92. 1959619
  15. Kormann BA, Schuster H, Berninger TA, Leo-Kottler B: Detection of the G to A mitochondrial DNA mutation at position 11778 in German families with Leber's hereditary optic neuropathy. Hum Genet. 1991 Nov;88(1):98-100. 1959931
  16. Marzuki S, Noer AS, Lertrit P, Thyagarajan D, Kapsa R, Utthanaphol P, Byrne E: Normal variants of human mitochondrial DNA and translation products: the building of a reference data base. Hum Genet. 1991 Dec;88(2):139-45. 1757091
  17. Lertrit P, Noer AS, Jean-Francois MJ, Kapsa R, Dennett X, Thyagarajan D, Lethlean K, Byrne E, Marzuki S: A new disease-related mutation for mitochondrial encephalopathy lactic acidosis and strokelike episodes (MELAS) syndrome affects the ND4 subunit of the respiratory complex I. Am J Hum Genet. 1992 Sep;51(3):457-68. 1323207
  18. De Vries DD, Went LN, Bruyn GW, Scholte HR, Hofstra RM, Bolhuis PA, van Oost BA: Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia. Am J Hum Genet. 1996 Apr;58(4):703-11. 8644732
  19. Sudoyo H, Sitepu M, Malik S, Poesponegoro HD, Marzuki S: Leber's hereditary optic neuropathy in Indonesia: two families with the mtDNA 11778G>A and 14484T>C mutations. Hum Mutat. 1998;Suppl 1:S271-4. 9452107
  20. Calvo SE, Tucker EJ, Compton AG, Kirby DM, Crawford G, Burtt NP, Rivas M, Guiducci C, Bruno DL, Goldberger OA, Redman MC, Wiltshire E, Wilson CJ, Altshuler D, Gabriel SB, Daly MJ, Thorburn DR, Mootha VK: High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency. Nat Genet. 2010 Oct;42(10):851-8. doi: 10.1038/ng.659. Epub 2010 Sep 5. 20818383