NU4M_HUMAN
ID NU4M_HUMAN Reviewed; 459 AA.
AC P03905; Q6RL39; Q6RQN9; Q8HNR8;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=NADH-ubiquinone oxidoreductase chain 4;
DE EC=7.1.1.2 {ECO:0000269|PubMed:15250827, ECO:0000269|PubMed:8344246, ECO:0000269|PubMed:8644732};
DE AltName: Full=NADH dehydrogenase subunit 4;
GN Name=MT-ND4; Synonyms=MTND4, NADH4, ND4;
OS Homo sapiens (Human).
OG Mitochondrion.
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=7219534; DOI=10.1038/290457a0;
RA Anderson S., Bankier A.T., Barrell B.G., de Bruijn M.H.L., Coulson A.R.,
RA Drouin J., Eperon I.C., Nierlich D.P., Roe B.A., Sanger F., Schreier P.H.,
RA Smith A.J.H., Staden R., Young I.G.;
RT "Sequence and organization of the human mitochondrial genome.";
RL Nature 290:457-465(1981).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1377597;
RA Lu X., Walker T., Macmanus J.P., Seligy V.L.;
RT "Differentiation of HT-29 human colonic adenocarcinoma cells correlates
RT with increased expression of mitochondrial RNA: effects of trehalose on
RT cell growth and maturation.";
RL Cancer Res. 52:3718-3725(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PRO-79.
RX PubMed=12022039; DOI=10.1086/341358;
RA Silva W.A. Jr., Bonatto S.L., Holanda A.J., Ribeiro-Dos-Santos A.K.,
RA Paixao B.M., Goldman G.H., Abe-Sandes K., Rodriguez-Delfin L., Barbosa M.,
RA Paco-Larson M.L., Petzl-Erler M.L., Valente V., Santos S.E., Zago M.A.;
RT "Mitochondrial genome diversity of native Americans supports a single early
RT entry of founder populations into America.";
RL Am. J. Hum. Genet. 71:187-192(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12949126; DOI=10.1093/molbev/msg230;
RA Moilanen J.S., Finnila S., Majamaa K.;
RT "Lineage-specific selection in human mtDNA: lack of polymorphisms in a
RT segment of MTND5 gene in haplogroup J.";
RL Mol. Biol. Evol. 20:2132-2142(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11130070; DOI=10.1038/35047064;
RA Ingman M., Kaessmann H., Paeaebo S., Gyllensten U.;
RT "Mitochondrial genome variation and the origin of modern humans.";
RL Nature 408:708-713(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12840039; DOI=10.1101/gr.686603;
RA Ingman M., Gyllensten U.;
RT "Mitochondrial genome variation and evolutionary history of Australian and
RT New Guinean aborigines.";
RL Genome Res. 13:1600-1606(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=14760490; DOI=10.1007/s00414-004-0427-6;
RA Coble M.D., Just R.S., O'Callaghan J.E., Letmanyi I.H., Peterson C.T.,
RA Irwin J.A., Parsons T.J.;
RT "Single nucleotide polymorphisms over the entire mtDNA genome that increase
RT the power of forensic testing in Caucasians.";
RL Int. J. Legal Med. 118:137-146(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 308-459.
RX PubMed=6284948; DOI=10.1007/bf01734101;
RA Brown W.M., Prager E.M., Wang A., Wilson A.C.;
RT "Mitochondrial DNA sequences of primates: tempo and mode of evolution.";
RL J. Mol. Evol. 18:225-239(1982).
RN [9]
RP IDENTIFICATION OF PROTEIN.
RX PubMed=3921850; DOI=10.1038/314592a0;
RA Chomyn A., Mariottini P., Cleeter M.W.J., Ragan C.I., Matsuno-Yagi A.,
RA Hatefi Y., Doolittle R.F., Attardi G.;
RT "Six unidentified reading frames of human mitochondrial DNA encode
RT components of the respiratory-chain NADH dehydrogenase.";
RL Nature 314:592-597(1985).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8344246; DOI=10.1002/j.1460-2075.1993.tb05973.x;
RA Hofhaus G., Attardi G.;
RT "Lack of assembly of mitochondrial DNA-encoded subunits of respiratory NADH
RT dehydrogenase and loss of enzyme activity in a human cell mutant lacking
RT the mitochondrial ND4 gene product.";
RL EMBO J. 12:3043-3048(1993).
RN [11]
RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12611891; DOI=10.1074/jbc.c300064200;
RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F.,
RA Ghosh S.S., Capaldi R.A.;
RT "The subunit composition of the human NADH dehydrogenase obtained by rapid
RT one-step immunopurification.";
RL J. Biol. Chem. 278:13619-13622(2003).
RN [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15250827; DOI=10.1042/bj20040256;
RA Bourges I., Ramus C., Mousson de Camaret B., Beugnot R., Remacle C.,
RA Cardol P., Hofhaus G., Issartel J.P.;
RT "Structural organization of mitochondrial human complex I: role of the ND4
RT and ND5 mitochondria-encoded subunits and interaction with prohibitin.";
RL Biochem. J. 383:491-499(2004).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP VARIANT LHON HIS-340.
RX PubMed=3201231; DOI=10.1126/science.3201231;
RA Wallace D.C., Singh G., Lott M.T., Hodge J.A., Schurr T.G., Lezza A.M.,
RA Elsas L.J. II, Nikoskelainen E.K.;
RT "Mitochondrial DNA mutation associated with Leber's hereditary optic
RT neuropathy.";
RL Science 242:1427-1430(1988).
RN [16]
RP CHARACTERIZATION OF VARIANT LHON HIS-340.
RX PubMed=1959619; DOI=10.1016/0014-5793(91)80886-8;
RA Majander A., Huoponen K., Savontaus M.-L., Nikoskelainen E., Wikstroem M.;
RT "Electron transfer properties of NADH:ubiquinone reductase in the ND1/3460
RT and the ND4/11778 mutations of the Leber hereditary optic neuroretinopathy
RT (LHON).";
RL FEBS Lett. 292:289-292(1991).
RN [17]
RP VARIANT LHON HIS-340.
RX PubMed=1959931; DOI=10.1007/bf00204937;
RA Kormann B.A., Schuster H., Berninger T.A., Leo-Kottler B.;
RT "Detection of the G to A mitochondrial DNA mutation at position 11778 in
RT German families with Leber's hereditary optic neuropathy.";
RL Hum. Genet. 88:98-100(1991).
RN [18]
RP VARIANTS PRO-79; PRO-109; THR-132 AND THR-294.
RX PubMed=1757091; DOI=10.1007/bf00206061;
RA Marzuki S., Noer A.S., Lertrit P., Thyagarajan D., Kapsa R.,
RA Utthanaphol P., Byrne E.;
RT "Normal variants of human mitochondrial DNA and translation products: the
RT building of a reference data base.";
RL Hum. Genet. 88:139-145(1991).
RN [19]
RP VARIANT MELAS ALA-109.
RX PubMed=1323207;
RA Lertrit P., Noer A.S., Jean-Francois M.J.B., Kapsa R., Dennett X.,
RA Thyagarajan D., Lethlean K., Byrne E., Marzuki S.;
RT "A new disease-related mutation for mitochondrial encephalopathy lactic
RT acidosis and strokelike episodes (MELAS) syndrome affects the ND4 subunit
RT of the respiratory complex I.";
RL Am. J. Hum. Genet. 51:457-468(1992).
RN [20]
RP VARIANT LDYT ILE-313, CHARACTERIZATION OF VARIANT LDYT ILE-313, FUNCTION,
RP AND CATALYTIC ACTIVITY.
RX PubMed=8644732;
RA de Vries D.D., Went L.N., Bruyn G.W., Scholte H.R., Hofstra R.M.W.,
RA Bolhuis P.A., van Oost B.A.;
RT "Genetic and biochemical impairment of mitochondrial complex I activity in
RT a family with Leber hereditary optic neuropathy and hereditary spastic
RT dystonia.";
RL Am. J. Hum. Genet. 58:703-711(1996).
RN [21]
RP VARIANT LHON HIS-340.
RX PubMed=9452107; DOI=10.1002/humu.1380110186;
RA Sudoyo H., Sitepu M., Malik S., Poesponegoro H.D., Marzuki S.;
RT "Leber's hereditary optic neuropathy in Indonesia: two families with the
RT mtDNA 11778G>A and 14484T>C mutations.";
RL Hum. Mutat. Suppl. 1:S271-S274(1998).
RN [22]
RP VARIANT ALA-420.
RX PubMed=20818383; DOI=10.1038/ng.659;
RA Calvo S.E., Tucker E.J., Compton A.G., Kirby D.M., Crawford G., Burtt N.P.,
RA Rivas M., Guiducci C., Bruno D.L., Goldberger O.A., Redman M.C.,
RA Wiltshire E., Wilson C.J., Altshuler D., Gabriel S.B., Daly M.J.,
RA Thorburn D.R., Mootha V.K.;
RT "High-throughput, pooled sequencing identifies mutations in NUBPL and
RT FOXRED1 in human complex I deficiency.";
RL Nat. Genet. 42:851-858(2010).
CC -!- FUNCTION: Core subunit of the mitochondrial membrane respiratory chain
CC NADH dehydrogenase (Complex I) which catalyzes electron transfer from
CC NADH through the respiratory chain, using ubiquinone as an electron
CC acceptor (PubMed:8644732, PubMed:8344246, PubMed:15250827). Essential
CC for the catalytic activity and assembly of complex I (PubMed:8644732,
CC PubMed:8344246, PubMed:15250827). {ECO:0000269|PubMed:15250827,
CC ECO:0000269|PubMed:8344246, ECO:0000269|PubMed:8644732}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ubiquinone + 5 H(+)(in) + NADH = a ubiquinol + 4 H(+)(out) +
CC NAD(+); Xref=Rhea:RHEA:29091, Rhea:RHEA-COMP:9565, Rhea:RHEA-
CC COMP:9566, ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=7.1.1.2;
CC Evidence={ECO:0000269|PubMed:15250827, ECO:0000269|PubMed:8344246,
CC ECO:0000269|PubMed:8644732};
CC -!- SUBUNIT: Core subunit of respiratory chain NADH dehydrogenase (Complex
CC I) which is composed of 45 different subunits.
CC {ECO:0000269|PubMed:12611891}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P03910}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DISEASE: Leber hereditary optic neuropathy (LHON) [MIM:535000]: A
CC maternally inherited form of Leber hereditary optic neuropathy, a
CC mitochondrial disease resulting in bilateral painless loss of central
CC vision due to selective degeneration of the retinal ganglion cells and
CC their axons. The disorder shows incomplete penetrance and male
CC predominance. Cardiac conduction defects and neurological defects have
CC also been described in some LHON patients. LHON results from primary
CC mitochondrial DNA mutations affecting the respiratory chain complexes.
CC {ECO:0000269|PubMed:1959619, ECO:0000269|PubMed:1959931,
CC ECO:0000269|PubMed:3201231, ECO:0000269|PubMed:9452107}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Leber hereditary optic neuropathy with dystonia (LDYT)
CC [MIM:500001]: A form of Leber hereditary optic neuropathy, a
CC mitochondrial disease resulting in bilateral painless loss of central
CC vision due to selective degeneration of the retinal ganglion cells and
CC their axons. The disorder shows incomplete penetrance and male
CC predominance. LDYT is characterized by the association of optic atrophy
CC and central vision loss with dystonia. {ECO:0000269|PubMed:8644732}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Mitochondrial encephalomyopathy with lactic acidosis and
CC stroke-like episodes syndrome (MELAS) [MIM:540000]: Genetically
CC heterogeneous disorder, characterized by episodic vomiting, seizures,
CC and recurrent cerebral insults resembling strokes and causing
CC hemiparesis, hemianopsia, or cortical blindness.
CC {ECO:0000269|PubMed:1323207}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the complex I subunit 4 family. {ECO:0000305}.
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DR EMBL; J01415; AAB58952.1; -; Genomic_DNA.
DR EMBL; V00662; CAA24035.1; -; Genomic_DNA.
DR EMBL; AY495090; AAR92505.1; -; Genomic_DNA.
DR EMBL; AY495091; AAR92518.1; -; Genomic_DNA.
DR EMBL; AY495092; AAR92531.1; -; Genomic_DNA.
DR EMBL; AY495093; AAR92544.1; -; Genomic_DNA.
DR EMBL; AY495094; AAR92557.1; -; Genomic_DNA.
DR EMBL; AY495095; AAR92570.1; -; Genomic_DNA.
DR EMBL; AY495096; AAR92583.1; -; Genomic_DNA.
DR EMBL; AY495097; AAR92596.1; -; Genomic_DNA.
DR EMBL; AY495098; AAR92609.1; -; Genomic_DNA.
DR EMBL; AY495099; AAR92622.1; -; Genomic_DNA.
DR EMBL; AY495100; AAR92635.1; -; Genomic_DNA.
DR EMBL; AY495101; AAR92648.1; -; Genomic_DNA.
DR EMBL; AY495102; AAR92661.1; -; Genomic_DNA.
DR EMBL; AY495103; AAR92674.1; -; Genomic_DNA.
DR EMBL; AY495104; AAR92687.1; -; Genomic_DNA.
DR EMBL; AY495106; AAR92713.1; -; Genomic_DNA.
DR EMBL; AY495107; AAR92726.1; -; Genomic_DNA.
DR EMBL; AY495108; AAR92739.1; -; Genomic_DNA.
DR EMBL; AY495109; AAR92752.1; -; Genomic_DNA.
DR EMBL; AY495110; AAR92765.1; -; Genomic_DNA.
DR EMBL; AY495111; AAR92778.1; -; Genomic_DNA.
DR EMBL; AY495112; AAR92791.1; -; Genomic_DNA.
DR EMBL; AY495113; AAR92804.1; -; Genomic_DNA.
DR EMBL; AY495114; AAR92817.1; -; Genomic_DNA.
DR EMBL; AY495115; AAR92830.1; -; Genomic_DNA.
DR EMBL; AY495116; AAR92843.1; -; Genomic_DNA.
DR EMBL; AY495117; AAR92856.1; -; Genomic_DNA.
DR EMBL; AY495118; AAR92869.1; -; Genomic_DNA.
DR EMBL; AY495119; AAR92882.1; -; Genomic_DNA.
DR EMBL; AY495120; AAR92895.1; -; Genomic_DNA.
DR EMBL; AY495121; AAR92908.1; -; Genomic_DNA.
DR EMBL; AY495122; AAR92921.1; -; Genomic_DNA.
DR EMBL; AY495123; AAR92934.1; -; Genomic_DNA.
DR EMBL; AY495124; AAR92947.1; -; Genomic_DNA.
DR EMBL; AY495125; AAR92960.1; -; Genomic_DNA.
DR EMBL; AY495126; AAR92973.1; -; Genomic_DNA.
DR EMBL; AY495127; AAR92986.1; -; Genomic_DNA.
DR EMBL; AY495128; AAR92999.1; -; Genomic_DNA.
DR EMBL; AY495129; AAR93012.1; -; Genomic_DNA.
DR EMBL; AY495130; AAR93025.1; -; Genomic_DNA.
DR EMBL; AY495131; AAR93038.1; -; Genomic_DNA.
DR EMBL; AY495132; AAR93051.1; -; Genomic_DNA.
DR EMBL; AY495133; AAR93064.1; -; Genomic_DNA.
DR EMBL; AY495134; AAR93077.1; -; Genomic_DNA.
DR EMBL; AY495135; AAR93090.1; -; Genomic_DNA.
DR EMBL; AY495136; AAR93103.1; -; Genomic_DNA.
DR EMBL; AY495137; AAR93116.1; -; Genomic_DNA.
DR EMBL; AY495138; AAR93129.1; -; Genomic_DNA.
DR EMBL; AY495139; AAR93142.1; -; Genomic_DNA.
DR EMBL; AY495140; AAR93155.1; -; Genomic_DNA.
DR EMBL; AY495141; AAR93168.1; -; Genomic_DNA.
DR EMBL; AY495142; AAR93181.1; -; Genomic_DNA.
DR EMBL; AY495143; AAR93194.1; -; Genomic_DNA.
DR EMBL; AY495144; AAR93207.1; -; Genomic_DNA.
DR EMBL; AY495145; AAR93220.1; -; Genomic_DNA.
DR EMBL; AY495146; AAR93233.1; -; Genomic_DNA.
DR EMBL; AY495147; AAR93246.1; -; Genomic_DNA.
DR EMBL; AY495148; AAR93259.1; -; Genomic_DNA.
DR EMBL; AY495149; AAR93272.1; -; Genomic_DNA.
DR EMBL; AY495150; AAR93285.1; -; Genomic_DNA.
DR EMBL; AY495151; AAR93298.1; -; Genomic_DNA.
DR EMBL; AY495152; AAR93311.1; -; Genomic_DNA.
DR EMBL; AY495153; AAR93324.1; -; Genomic_DNA.
DR EMBL; AY495154; AAR93337.1; -; Genomic_DNA.
DR EMBL; AY495155; AAR93350.1; -; Genomic_DNA.
DR EMBL; AY495156; AAR93363.1; -; Genomic_DNA.
DR EMBL; AY495157; AAR93376.1; -; Genomic_DNA.
DR EMBL; AY495158; AAR93389.1; -; Genomic_DNA.
DR EMBL; AY495159; AAR93402.1; -; Genomic_DNA.
DR EMBL; AY495160; AAR93415.1; -; Genomic_DNA.
DR EMBL; AY495161; AAR93428.1; -; Genomic_DNA.
DR EMBL; AY495162; AAR93441.1; -; Genomic_DNA.
DR EMBL; AY495163; AAR93454.1; -; Genomic_DNA.
DR EMBL; AY495164; AAR93467.1; -; Genomic_DNA.
DR EMBL; AY495165; AAR93480.1; -; Genomic_DNA.
DR EMBL; AY495167; AAR93506.1; -; Genomic_DNA.
DR EMBL; AY495168; AAR93519.1; -; Genomic_DNA.
DR EMBL; AY495169; AAR93532.1; -; Genomic_DNA.
DR EMBL; AY495171; AAR93558.1; -; Genomic_DNA.
DR EMBL; AY495172; AAR93571.1; -; Genomic_DNA.
DR EMBL; AY495173; AAR93584.1; -; Genomic_DNA.
DR EMBL; AY495174; AAR93597.1; -; Genomic_DNA.
DR EMBL; AY495175; AAR93610.1; -; Genomic_DNA.
DR EMBL; AY495176; AAR93623.1; -; Genomic_DNA.
DR EMBL; AY495177; AAR93636.1; -; Genomic_DNA.
DR EMBL; AY495178; AAR93649.1; -; Genomic_DNA.
DR EMBL; AY495179; AAR93662.1; -; Genomic_DNA.
DR EMBL; AY495180; AAR93675.1; -; Genomic_DNA.
DR EMBL; AY495181; AAR93688.1; -; Genomic_DNA.
DR EMBL; AY495182; AAR93701.1; -; Genomic_DNA.
DR EMBL; AY495183; AAR93714.1; -; Genomic_DNA.
DR EMBL; AY495184; AAR93727.1; -; Genomic_DNA.
DR EMBL; AY495185; AAR93740.1; -; Genomic_DNA.
DR EMBL; AY495186; AAR93753.1; -; Genomic_DNA.
DR EMBL; AY495187; AAR93766.1; -; Genomic_DNA.
DR EMBL; AY495188; AAR93779.1; -; Genomic_DNA.
DR EMBL; AY495189; AAR93792.1; -; Genomic_DNA.
DR EMBL; AY495190; AAR93805.1; -; Genomic_DNA.
DR EMBL; AY495191; AAR93818.1; -; Genomic_DNA.
DR EMBL; AY495192; AAR93831.1; -; Genomic_DNA.
DR EMBL; AY495193; AAR93844.1; -; Genomic_DNA.
DR EMBL; AY495194; AAR93857.1; -; Genomic_DNA.
DR EMBL; AY495239; AAR94442.1; -; Genomic_DNA.
DR EMBL; AY495240; AAR94455.1; -; Genomic_DNA.
DR EMBL; AY495241; AAR94468.1; -; Genomic_DNA.
DR EMBL; AY495242; AAR94481.1; -; Genomic_DNA.
DR EMBL; AY495244; AAR94507.1; -; Genomic_DNA.
DR EMBL; AY495246; AAR94533.1; -; Genomic_DNA.
DR EMBL; AY495247; AAR94546.1; -; Genomic_DNA.
DR EMBL; AY495248; AAR94559.1; -; Genomic_DNA.
DR EMBL; AY495249; AAR94572.1; -; Genomic_DNA.
DR EMBL; AY495252; AAR94611.1; -; Genomic_DNA.
DR EMBL; AY495267; AAR94806.1; -; Genomic_DNA.
DR EMBL; AY495268; AAR94819.1; -; Genomic_DNA.
DR EMBL; AY495269; AAR94832.1; -; Genomic_DNA.
DR EMBL; AY495270; AAR94845.1; -; Genomic_DNA.
DR EMBL; AY495271; AAR94858.1; -; Genomic_DNA.
DR EMBL; AY495272; AAR94871.1; -; Genomic_DNA.
DR EMBL; AY495273; AAR94884.1; -; Genomic_DNA.
DR EMBL; AY495274; AAR94897.1; -; Genomic_DNA.
DR EMBL; AY495275; AAR94910.1; -; Genomic_DNA.
DR EMBL; AY495276; AAR94923.1; -; Genomic_DNA.
DR EMBL; AY495277; AAR94936.1; -; Genomic_DNA.
DR EMBL; AY495278; AAR94949.1; -; Genomic_DNA.
DR EMBL; AY495279; AAR94962.1; -; Genomic_DNA.
DR EMBL; AY495280; AAR94975.1; -; Genomic_DNA.
DR EMBL; AY495281; AAR94988.1; -; Genomic_DNA.
DR EMBL; AY495282; AAR95001.1; -; Genomic_DNA.
DR EMBL; AY495283; AAR95014.1; -; Genomic_DNA.
DR EMBL; AY495284; AAR95027.1; -; Genomic_DNA.
DR EMBL; AY495285; AAR95040.1; -; Genomic_DNA.
DR EMBL; AY495286; AAR95053.1; -; Genomic_DNA.
DR EMBL; AY495287; AAR95066.1; -; Genomic_DNA.
DR EMBL; AY495288; AAR95079.1; -; Genomic_DNA.
DR EMBL; AY495289; AAR95092.1; -; Genomic_DNA.
DR EMBL; AY495290; AAR95105.1; -; Genomic_DNA.
DR EMBL; AY495291; AAR95118.1; -; Genomic_DNA.
DR EMBL; AY495292; AAR95131.1; -; Genomic_DNA.
DR EMBL; AY495293; AAR95144.1; -; Genomic_DNA.
DR EMBL; AY495294; AAR95157.1; -; Genomic_DNA.
DR EMBL; AY495295; AAR95170.1; -; Genomic_DNA.
DR EMBL; AY495297; AAR95196.1; -; Genomic_DNA.
DR EMBL; AY495298; AAR95209.1; -; Genomic_DNA.
DR EMBL; AY495299; AAR95222.1; -; Genomic_DNA.
DR EMBL; AY495300; AAR95235.1; -; Genomic_DNA.
DR EMBL; AY495301; AAR95248.1; -; Genomic_DNA.
DR EMBL; AY495302; AAR95261.1; -; Genomic_DNA.
DR EMBL; AY495303; AAR95274.1; -; Genomic_DNA.
DR EMBL; AY495304; AAR95287.1; -; Genomic_DNA.
DR EMBL; AY495305; AAR95300.1; -; Genomic_DNA.
DR EMBL; AY495306; AAR95313.1; -; Genomic_DNA.
DR EMBL; AY495307; AAR95326.1; -; Genomic_DNA.
DR EMBL; AY495308; AAR95339.1; -; Genomic_DNA.
DR EMBL; AY495309; AAR95352.1; -; Genomic_DNA.
DR EMBL; AY495310; AAR95365.1; -; Genomic_DNA.
DR EMBL; AY495311; AAR95378.1; -; Genomic_DNA.
DR EMBL; AY495312; AAR95391.1; -; Genomic_DNA.
DR EMBL; AY495313; AAR95404.1; -; Genomic_DNA.
DR EMBL; AY495314; AAR95417.1; -; Genomic_DNA.
DR EMBL; AY495315; AAR95430.1; -; Genomic_DNA.
DR EMBL; AY495316; AAR95443.1; -; Genomic_DNA.
DR EMBL; AY495317; AAR95456.1; -; Genomic_DNA.
DR EMBL; AY495318; AAR95469.1; -; Genomic_DNA.
DR EMBL; AY495319; AAR95482.1; -; Genomic_DNA.
DR EMBL; AY495320; AAR95495.1; -; Genomic_DNA.
DR EMBL; AY495321; AAR95508.1; -; Genomic_DNA.
DR EMBL; AY495322; AAR95521.1; -; Genomic_DNA.
DR EMBL; AY495323; AAR95534.1; -; Genomic_DNA.
DR EMBL; AY495324; AAR95547.1; -; Genomic_DNA.
DR EMBL; AY495325; AAR95560.1; -; Genomic_DNA.
DR EMBL; AY495326; AAR95573.1; -; Genomic_DNA.
DR EMBL; AY495327; AAR95586.1; -; Genomic_DNA.
DR EMBL; AY495328; AAR95599.1; -; Genomic_DNA.
DR EMBL; AY495329; AAR95612.1; -; Genomic_DNA.
DR EMBL; AY495330; AAR95625.1; -; Genomic_DNA.
DR EMBL; AF465942; AAN14556.1; -; Genomic_DNA.
DR EMBL; AF346963; AAK17216.1; -; Genomic_DNA.
DR EMBL; AF346964; AAK17229.2; -; Genomic_DNA.
DR EMBL; AF346966; AAK17255.1; -; Genomic_DNA.
DR EMBL; AF346967; AAK17268.2; -; Genomic_DNA.
DR EMBL; AF346968; AAK17281.2; -; Genomic_DNA.
DR EMBL; AF346969; AAK17294.2; -; Genomic_DNA.
DR EMBL; AF346971; AAK17320.2; -; Genomic_DNA.
DR EMBL; AF346974; AAK17359.2; -; Genomic_DNA.
DR EMBL; AF346975; AAK17372.2; -; Genomic_DNA.
DR EMBL; AF346977; AAK17398.1; -; Genomic_DNA.
DR EMBL; AF346978; AAK17411.1; -; Genomic_DNA.
DR EMBL; AF346980; AAK17437.2; -; Genomic_DNA.
DR EMBL; AF346981; AAK17450.2; -; Genomic_DNA.
DR EMBL; AF346982; AAK17463.1; -; Genomic_DNA.
DR EMBL; AF346985; AAK17502.2; -; Genomic_DNA.
DR EMBL; AF346986; AAK17515.2; -; Genomic_DNA.
DR EMBL; AF346987; AAK17528.2; -; Genomic_DNA.
DR EMBL; AF346989; AAK17554.2; -; Genomic_DNA.
DR EMBL; AF346990; AAK17567.1; -; Genomic_DNA.
DR EMBL; AF346993; AAK17606.2; -; Genomic_DNA.
DR EMBL; AF346994; AAK17619.2; -; Genomic_DNA.
DR EMBL; AF346996; AAK17645.2; -; Genomic_DNA.
DR EMBL; AF346997; AAK17658.2; -; Genomic_DNA.
DR EMBL; AF347000; AAK17697.1; -; Genomic_DNA.
DR EMBL; AF347002; AAK17723.2; -; Genomic_DNA.
DR EMBL; AF347003; AAK17736.2; -; Genomic_DNA.
DR EMBL; AF347004; AAK17749.2; -; Genomic_DNA.
DR EMBL; AF347005; AAK17762.2; -; Genomic_DNA.
DR EMBL; AF347006; AAK17775.2; -; Genomic_DNA.
DR EMBL; AF347007; AAK17788.2; -; Genomic_DNA.
DR EMBL; AF347010; AAK17827.2; -; Genomic_DNA.
DR EMBL; AF347011; AAK17840.2; -; Genomic_DNA.
DR EMBL; AF347012; AAK17853.2; -; Genomic_DNA.
DR EMBL; AF347013; AAK17866.2; -; Genomic_DNA.
DR EMBL; AF347014; AAK17879.2; -; Genomic_DNA.
DR EMBL; AF347015; AAK17892.2; -; Genomic_DNA.
DR EMBL; AY289051; AAP47889.1; -; Genomic_DNA.
DR EMBL; AY289052; AAP47902.1; -; Genomic_DNA.
DR EMBL; AY289055; AAP47941.1; -; Genomic_DNA.
DR EMBL; AY289056; AAP47954.1; -; Genomic_DNA.
DR EMBL; AY289058; AAP47980.1; -; Genomic_DNA.
DR EMBL; AY289059; AAP47993.1; -; Genomic_DNA.
DR EMBL; AY289060; AAP48006.1; -; Genomic_DNA.
DR EMBL; AY289061; AAP48019.1; -; Genomic_DNA.
DR EMBL; AY289062; AAP48032.1; -; Genomic_DNA.
DR EMBL; AY289063; AAP48045.1; -; Genomic_DNA.
DR EMBL; AY289065; AAP48071.1; -; Genomic_DNA.
DR EMBL; AY289068; AAP48110.1; -; Genomic_DNA.
DR EMBL; AY289069; AAP48123.1; -; Genomic_DNA.
DR EMBL; AY289070; AAP48136.1; -; Genomic_DNA.
DR EMBL; AY289071; AAP48149.1; -; Genomic_DNA.
DR EMBL; AY289073; AAP48175.1; -; Genomic_DNA.
DR EMBL; AY289074; AAP48188.1; -; Genomic_DNA.
DR EMBL; AY289075; AAP48201.1; -; Genomic_DNA.
DR EMBL; AY289076; AAP48214.1; -; Genomic_DNA.
DR EMBL; AY289077; AAP48227.1; -; Genomic_DNA.
DR EMBL; AY289079; AAP48253.1; -; Genomic_DNA.
DR EMBL; AY289080; AAP48266.1; -; Genomic_DNA.
DR EMBL; AY289081; AAP48279.1; -; Genomic_DNA.
DR EMBL; AY289082; AAP48292.1; -; Genomic_DNA.
DR EMBL; AY289083; AAP48305.1; -; Genomic_DNA.
DR EMBL; AY289084; AAP48318.1; -; Genomic_DNA.
DR EMBL; AY289085; AAP48331.1; -; Genomic_DNA.
DR EMBL; AY289087; AAP48357.1; -; Genomic_DNA.
DR EMBL; AY289088; AAP48370.1; -; Genomic_DNA.
DR EMBL; AY289090; AAP48396.1; -; Genomic_DNA.
DR EMBL; AY289091; AAP48409.1; -; Genomic_DNA.
DR EMBL; AY289092; AAP48422.1; -; Genomic_DNA.
DR EMBL; AY289093; AAP48434.1; -; Genomic_DNA.
DR EMBL; AY289094; AAP48447.1; -; Genomic_DNA.
DR EMBL; AY289095; AAP48460.1; -; Genomic_DNA.
DR EMBL; AY289096; AAP48473.1; -; Genomic_DNA.
DR EMBL; AY289097; AAP48486.1; -; Genomic_DNA.
DR EMBL; AY289098; AAP48499.1; -; Genomic_DNA.
DR EMBL; AY289099; AAP48512.1; -; Genomic_DNA.
DR EMBL; AY289100; AAP48525.1; -; Genomic_DNA.
DR EMBL; AY289101; AAP48538.1; -; Genomic_DNA.
DR EMBL; AY289102; AAP48551.1; -; Genomic_DNA.
DR PIR; A00434; DNHUN4.
DR RefSeq; YP_003024035.1; NC_012920.1.
DR PDB; 5XTC; EM; 3.70 A; r=1-459.
DR PDB; 5XTD; EM; 3.70 A; r=1-459.
DR PDB; 5XTH; EM; 3.90 A; r=1-459.
DR PDB; 5XTI; EM; 17.40 A; Br/r=1-459.
DR PDBsum; 5XTC; -.
DR PDBsum; 5XTD; -.
DR PDBsum; 5XTH; -.
DR PDBsum; 5XTI; -.
DR AlphaFoldDB; P03905; -.
DR SMR; P03905; -.
DR BioGRID; 110634; 76.
DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I.
DR CORUM; P03905; -.
DR IntAct; P03905; 38.
DR MINT; P03905; -.
DR STRING; 9606.ENSP00000354961; -.
DR BindingDB; P03905; -.
DR ChEMBL; CHEMBL4499; -.
DR DrugBank; DB00157; NADH.
DR DrugCentral; P03905; -.
DR GlyGen; P03905; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P03905; -.
DR PhosphoSitePlus; P03905; -.
DR BioMuta; MT-ND4; -.
DR DMDM; 128748; -.
DR EPD; P03905; -.
DR jPOST; P03905; -.
DR MassIVE; P03905; -.
DR PaxDb; P03905; -.
DR PeptideAtlas; P03905; -.
DR PRIDE; P03905; -.
DR ProteomicsDB; 51615; -.
DR Antibodypedia; 35362; 24 antibodies from 11 providers.
DR DNASU; 4538; -.
DR Ensembl; ENST00000361381.2; ENSP00000354961.2; ENSG00000198886.2.
DR GeneID; 4538; -.
DR KEGG; hsa:4538; -.
DR UCSC; uc064xpj.1; human.
DR CTD; 4538; -.
DR DisGeNET; 4538; -.
DR GeneCards; MT-ND4; -.
DR GeneReviews; MT-ND4; -.
DR HGNC; HGNC:7459; MT-ND4.
DR HPA; ENSG00000198886; Tissue enhanced (heart).
DR MalaCards; MT-ND4; -.
DR MIM; 500001; phenotype.
DR MIM; 516003; gene.
DR MIM; 535000; phenotype.
DR MIM; 540000; phenotype.
DR neXtProt; NX_P03905; -.
DR OpenTargets; ENSG00000198886; -.
DR Orphanet; 104; Leber hereditary optic neuropathy.
DR Orphanet; 99718; Leber plus disease.
DR Orphanet; 550; MELAS.
DR Orphanet; 255210; Mitochondrial DNA-associated Leigh syndrome.
DR Orphanet; 90641; Mitochondrial non-syndromic sensorineural deafness.
DR PharmGKB; PA31263; -.
DR VEuPathDB; HostDB:ENSG00000198886; -.
DR eggNOG; KOG4845; Eukaryota.
DR GeneTree; ENSGT00730000111316; -.
DR HOGENOM; CLU_007100_4_0_1; -.
DR InParanoid; P03905; -.
DR OMA; ITRWGNQ; -.
DR OrthoDB; 996580at2759; -.
DR PhylomeDB; P03905; -.
DR TreeFam; TF343520; -.
DR BioCyc; MetaCyc:HS00033-MON; -.
DR PathwayCommons; P03905; -.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR SignaLink; P03905; -.
DR SIGNOR; P03905; -.
DR BioGRID-ORCS; 4538; 0 hits in 2 CRISPR screens.
DR ChiTaRS; ND4; human.
DR GeneWiki; MT-ND4; -.
DR GenomeRNAi; 4538; -.
DR Pharos; P03905; Tclin.
DR PRO; PR:P03905; -.
DR Proteomes; UP000005640; Mitochondrion.
DR RNAct; P03905; protein.
DR Bgee; ENSG00000198886; Expressed in right uterine tube and 95 other tissues.
DR ExpressionAtlas; P03905; baseline and differential.
DR Genevisible; P03905; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal.
DR GO; GO:0005747; C:mitochondrial respiratory chain complex I; IDA:UniProtKB.
DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IMP:UniProtKB.
DR GO; GO:0048039; F:ubiquinone binding; IBA:GO_Central.
DR GO; GO:0009060; P:aerobic respiration; IBA:GO_Central.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
DR GO; GO:0015990; P:electron transport coupled proton transport; IBA:GO_Central.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IMP:UniProtKB.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB.
DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; IC:ComplexPortal.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR InterPro; IPR000260; NADH4_N.
DR InterPro; IPR010227; NADH_Q_OxRdtase_chainM/4.
DR InterPro; IPR003918; NADH_UbQ_OxRdtase.
DR InterPro; IPR001750; ND/Mrp_mem.
DR PANTHER; PTHR43507; PTHR43507; 1.
DR Pfam; PF01059; Oxidored_q5_N; 1.
DR Pfam; PF00361; Proton_antipo_M; 1.
DR PRINTS; PR01437; NUOXDRDTASE4.
DR TIGRFAMs; TIGR01972; NDH_I_M; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; Dystonia; Electron transport;
KW Leber hereditary optic neuropathy; MELAS syndrome; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; NAD; Primary mitochondrial disease;
KW Reference proteome; Respiratory chain; Translocase; Transmembrane;
KW Transmembrane helix; Transport; Ubiquinone.
FT CHAIN 1..459
FT /note="NADH-ubiquinone oxidoreductase chain 4"
FT /id="PRO_0000117942"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 145..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 196..216
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 224..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 257..277
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 284..303
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 308..330
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 351..371
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 391..411
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VARIANT 79
FT /note="A -> P"
FT /evidence="ECO:0000269|PubMed:12022039,
FT ECO:0000269|PubMed:1757091"
FT /id="VAR_008599"
FT VARIANT 109
FT /note="T -> A (in MELAS; dbSNP:rs199476113)"
FT /evidence="ECO:0000269|PubMed:1323207"
FT /id="VAR_004759"
FT VARIANT 109
FT /note="T -> P"
FT /evidence="ECO:0000269|PubMed:1757091"
FT /id="VAR_008600"
FT VARIANT 132
FT /note="I -> T (in dbSNP:rs1603223136)"
FT /evidence="ECO:0000269|PubMed:1757091"
FT /id="VAR_008601"
FT VARIANT 294
FT /note="M -> T"
FT /evidence="ECO:0000269|PubMed:1757091"
FT /id="VAR_008602"
FT VARIANT 313
FT /note="V -> I (in LDYT; possible rare primary mutation;
FT decrease in enzyme activity; dbSNP:rs200873900)"
FT /evidence="ECO:0000269|PubMed:8644732"
FT /id="VAR_008393"
FT VARIANT 340
FT /note="R -> H (in LHON; primary mutation; almost no vision
FT recovery; most frequent mutation; seems to have no effect
FT on electron transfer activity of the complex in inner
FT mitochondrial membrane preparations; dbSNP:rs199476112)"
FT /evidence="ECO:0000269|PubMed:1959619,
FT ECO:0000269|PubMed:1959931, ECO:0000269|PubMed:3201231,
FT ECO:0000269|PubMed:9452107"
FT /id="VAR_004760"
FT VARIANT 420
FT /note="T -> A (detected in a patient with mitochondrial
FT complex I deficiency; uncertain pathological significance;
FT dbSNP:rs879136236)"
FT /evidence="ECO:0000269|PubMed:20818383"
FT /id="VAR_064565"
FT CONFLICT 230
FT /note="V -> L (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 459 AA; 51581 MW; 2EEE581F3BD270AF CRC64;
MLKLIVPTIM LLPLTWLSKK HMIWINTTTH SLIISIIPLL FFNQINNNLF SCSPTFSSDP
LTTPLLMLTT WLLPLTIMAS QRHLSSEPLS RKKLYLSMLI SLQISLIMTF TATELIMFYI
FFETTLIPTL AIITRWGNQP ERLNAGTYFL FYTLVGSLPL LIALIYTHNT LGSLNILLLT
LTAQELSNSW ANNLMWLAYT MAFMVKMPLY GLHLWLPKAH VEAPIAGSMV LAAVLLKLGG
YGMMRLTLIL NPLTKHMAYP FLVLSLWGMI MTSSICLRQT DLKSLIAYSS ISHMALVVTA
ILIQTPWSFT GAVILMIAHG LTSSLLFCLA NSNYERTHSR IMILSQGLQT LLPLMAFWWL
LASLANLALP PTINLLGELS VLVTTFSWSN ITLLLTGLNM LVTALYSLYM FTTTQWGSLT
HHINNMKPSF TRENTLMFMH LSPILLLSLN PDIITGFSS
