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Identification
HMDB Protein ID HMDBP00178
Secondary Accession Numbers
  • 5410
  • HMDBP03446
Name NADH-ubiquinone oxidoreductase chain 4
Synonyms
  1. NADH dehydrogenase subunit 4
Gene Name MT-ND4
Protein Type Unknown
Biological Properties
General Function Involved in NADH dehydrogenase (ubiquinone) activity
Specific Function Core 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).
Pathways
  • Oxidative phosphorylation
  • Parkinson's disease
Reactions
NADH + Coenzyme Q10 → NAD + QH(2) details
QH2 + Acceptor → Ubiquinone-2 + Reduced acceptor details
GO Classification
Biological Process
small molecule metabolic process
mitochondrial electron transport, NADH to ubiquinone
embryo development
cerebellum development
aging
response to hypoxia
Cellular Component
mitochondrial respiratory chain complex I
integral to membrane
Component
mitochondrion
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
Function
catalytic activity
nadh dehydrogenase activity
nadh dehydrogenase (quinone) activity
nadh dehydrogenase (ubiquinone) activity
oxidoreductase activity
oxidoreductase activity, acting on nadh or nadph
Molecular Function
NADH dehydrogenase (ubiquinone) activity
Process
metabolic process
generation of precursor metabolites and energy
electron transport chain
respiratory electron transport chain
atp synthesis coupled electron transport
cellular metabolic process
mitochondrial electron transport, nadh to ubiquinone
oxidation reduction
Cellular Location
  1. Mitochondrion membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs MT-ND4
Gene Sequence
>1378 bp
ATGCTAAAACTAATCGTCCCAACAATTATATTACTACCACTGACATGACTTTCCAAAAAA
CACATAATTTGAATCAACACAACCACCCACAGCCTAATTATTAGCATCATCCCTCTACTA
TTTTTTAACCAAATCAACAACAACCTATTTAGCTGTTCCCCAACCTTTTCCTCCGACCCC
CTAACAACCCCCCTCCTAATACTAACTACCTGACTCCTACCCCTCACAATCATGGCAAGC
CAACGCCACTTATCCAGTGAACCACTATCACGAAAAAAACTCTACCTCTCTATACTAATC
TCCCTACAAATCTCCTTAATTATAACATTCACAGCCACAGAACTAATCATATTTTATATC
TTCTTCGAAACCACACTTATCCCCACCTTGGCTATCATCACCCGATGAGGCAACCAGCCA
GAACGCCTGAACGCAGGCACATACTTCCTATTCTACACCCTAGTAGGCTCCCTTCCCCTA
CTCATCGCACTAATTTACACTCACAACACCCTAGGCTCACTAAACATTCTACTACTCACT
CTCACTGCCCAAGAACTATCAAACTCCTGAGCCAACAACTTAATATGACTAGCTTACACA
ATAGCTTTTATAGTAAAGATACCTCTTTACGGACTCCACTTATGACTCCCTAAAGCCCAT
GTCGAAGCCCCCATCGCTGGGTCAATAGTACTTGCCGCAGTACTCTTAAAACTAGGCGGC
TATGGTATAATACGCCTCACACTCATTCTCAACCCCCTGACAAAACACATAGCCTACCCC
TTCCTTGTACTATCCCTATGAGGCATAATTATAACAAGCTCCATCTGCCTACGACAAACA
GACCTAAAATCGCTCATTGCATACTCTTCAATCAGCCACATAGCCCTCGTAGTAACAGCC
ATTCTCATCCAAACCCCCTGAAGCTTCACCGGCGCAGTCATTCTCATAATCGCCCACGGG
CTTACATCCTCATTACTATTCTGCCTAGCAAACTCAAACTACGAACGCACTCACAGTCGC
ATCATAATCCTCTCTCAAGGACTTCAAACTCTACTCCCACTAATAGCTTTTTGATGACTT
CTAGCAAGCCTCGCTAACCTCGCCTTACCCCCCACTATTAACCTACTGGGAGAACTCTCT
GTGCTAGTAACCACGTTCTCCTGATCAAATATCACTCTCCTACTTACAGGACTCAACATA
CTAGTCACAGCCCTATACTCCCTCTACATATTTACCACAACACAATGGGGCTCACTCACC
CACCACATTAACAACATAAAACCCTCATTCACACGAGAAAACACCCTCATGTTCATACAC
CTATCCCCCATTCTCCTCCTATCCCTCAACCCCGACATCATTACCGGGTTTTCCTCTT
Protein Properties
Number of Residues 459
Molecular Weight 51580.26
Theoretical pI 9.352
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>NADH-ubiquinone oxidoreductase chain 4
MLKLIVPTIMLLPLTWLSKKHMIWINTTTHSLIISIIPLLFFNQINNNLFSCSPTFSSDP
LTTPLLMLTTWLLPLTIMASQRHLSSEPLSRKKLYLSMLISLQISLIMTFTATELIMFYI
FFETTLIPTLAIITRWGNQPERLNAGTYFLFYTLVGSLPLLIALIYTHNTLGSLNILLLT
LTAQELSNSWANNLMWLAYTMAFMVKMPLYGLHLWLPKAHVEAPIAGSMVLAAVLLKLGG
YGMMRLTLILNPLTKHMAYPFLVLSLWGMIMTSSICLRQTDLKSLIAYSSISHMALVVTA
ILIQTPWSFTGAVILMIAHGLTSSLLFCLANSNYERTHSRIMILSQGLQTLLPLMAFWWL
LASLANLALPPTINLLGELSVLVTTFSWSNITLLLTGLNMLVTALYSLYMFTTTQWGSLT
HHINNMKPSFTRENTLMFMHLSPILLLSLNPDIITGFSS
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P03905
UniProtKB/Swiss-Prot Entry Name NU4M_HUMAN
PDB IDs Not Available
GenBank Gene ID J01415
GeneCard ID MT-ND4
GenAtlas ID MT-ND4
HGNC ID HGNC:7459
References
General References
  1. 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. [PubMed:12611891 ]
  2. 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. [PubMed:7219534 ]
  3. 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. [PubMed:12949126 ]
  4. 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. [PubMed:11130070 ]
  5. Ingman M, Gyllensten U: Mitochondrial genome variation and evolutionary history of Australian and New Guinean aborigines. Genome Res. 2003 Jul;13(7):1600-6. [PubMed:12840039 ]
  6. 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. [PubMed:14760490 ]
  7. 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. [PubMed:3921850 ]
  8. 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. [PubMed:1959619 ]
  9. 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. [PubMed:1757091 ]
  10. 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. [PubMed:6284948 ]
  11. 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. [PubMed:1377597 ]
  12. 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. [PubMed:12022039 ]
  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. [PubMed:3201231 ]
  14. 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. [PubMed:1959931 ]
  15. 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. [PubMed:1323207 ]
  16. 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. [PubMed:8644732 ]
  17. 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. [PubMed:9452107 ]