NDUS3_HUMAN
ID NDUS3_HUMAN Reviewed; 264 AA.
AC O75489; B2R9J1; B4DFM8; Q9UNQ8;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial;
DE EC=7.1.1.2 {ECO:0000269|PubMed:14729820, ECO:0000269|PubMed:30140060};
DE AltName: Full=Complex I-30kD;
DE Short=CI-30kD;
DE AltName: Full=NADH-ubiquinone oxidoreductase 30 kDa subunit;
DE Flags: Precursor;
GN Name=NDUFS3;
OS Homo sapiens (Human).
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 [MRNA] (ISOFORM 1).
RX PubMed=9647766; DOI=10.1006/bbrc.1998.8882;
RA Loeffen J., van den Heuvel L., Smeets R., Triepels R., Sengers R.,
RA Trijbels F., Smeitink J.;
RT "cDNA sequence and chromosomal localization of the remaining three human
RT nuclear encoded iron sulphur protein (IP) subunits of complex I: the human
RT IP fraction is completed.";
RL Biochem. Biophys. Res. Commun. 247:751-758(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10967146; DOI=10.1007/s003350010160;
RA Procaccio V., Lescuyer P., Bourges I., Beugnot R., Duborjal H.,
RA Depetris D., Mousson B., Montfort M.F., Smeets H., De Coo R.,
RA Issartel J.P.;
RT "Human NDUFS3 gene coding for the 30-kDa subunit of mitochondrial Complex
RT I: genomic organization and expression.";
RL Mamm. Genome 11:808-810(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pituitary;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Amygdala, and Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 37-51.
RC TISSUE=Leukemic T-cell;
RX PubMed=19892738; DOI=10.1073/pnas.0908958106;
RA Xu G., Shin S.B., Jaffrey S.R.;
RT "Global profiling of protease cleavage sites by chemoselective labeling of
RT protein N-termini.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009).
RN [9]
RP PROTEIN SEQUENCE OF 126-136 AND 187-199, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [10]
RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
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 [11]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=17209039; DOI=10.1074/jbc.m609410200;
RA Vogel R.O., Dieteren C.E., van den Heuvel L.P., Willems P.H.,
RA Smeitink J.A., Koopman W.J., Nijtmans L.G.;
RT "Identification of mitochondrial complex I assembly intermediates by
RT tracing tagged NDUFS3 demonstrates the entry point of mitochondrial
RT subunits.";
RL J. Biol. Chem. 282:7582-7590(2007).
RN [12]
RP SUBUNIT, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=18826940; DOI=10.1074/jbc.m807323200;
RA Dieteren C.E., Willems P.H., Vogel R.O., Swarts H.G., Fransen J.,
RA Roepman R., Crienen G., Smeitink J.A., Nijtmans L.G., Koopman W.J.;
RT "Subunits of mitochondrial complex I exist as part of matrix- and membrane-
RT associated subcomplexes in living cells.";
RL J. Biol. Chem. 283:34753-34761(2008).
RN [13]
RP INTERACTION WITH NDUFAF3.
RX PubMed=19463981; DOI=10.1016/j.ajhg.2009.04.020;
RA Saada A., Vogel R.O., Hoefs S.J., van den Brand M.A., Wessels H.J.,
RA Willems P.H., Venselaar H., Shaag A., Barghuti F., Reish O., Shohat M.,
RA Huynen M.A., Smeitink J.A.M., van den Heuvel L.P., Nijtmans L.G.;
RT "Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting
RT complex I assembly protein, cause fatal neonatal mitochondrial disease.";
RL Am. J. Hum. Genet. 84:718-727(2009).
RN [14]
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 [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
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 [17]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH RAB5IF.
RX PubMed=31536960; DOI=10.1016/j.isci.2019.08.057;
RA Moutaoufik M.T., Malty R., Amin S., Zhang Q., Phanse S., Gagarinova A.,
RA Zilocchi M., Hoell L., Minic Z., Gagarinova M., Aoki H., Stockwell J.,
RA Jessulat M., Goebels F., Broderick K., Scott N.E., Vlasblom J., Musso G.,
RA Prasad B., Lamantea E., Garavaglia B., Rajput A., Murayama K., Okazaki Y.,
RA Foster L.J., Bader G.D., Cayabyab F.S., Babu M.;
RT "Rewiring of the Human Mitochondrial Interactome during Neuronal
RT Reprogramming Reveals Regulators of the Respirasome and Neurogenesis.";
RL IScience 19:1114-1132(2019).
RN [18]
RP INVOLVEMENT IN MC1DN8, VARIANTS MC1DN8 ILE-145 AND TRP-199,
RP CHARACTERIZATION OF VARIANTS MC1DN8 ILE-145 AND TRP-199, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=14729820; DOI=10.1136/jmg.2003.014316;
RA Benit P., Slama A., Cartault F., Giurgea I., Chretien D., Lebon S.,
RA Marsac C., Munnich A., Roetig A., Rustin P.;
RT "Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome.";
RL J. Med. Genet. 41:14-17(2004).
RN [19]
RP INVOLVEMENT IN MC1DN8, AND VARIANT MC1DN8 TRP-199.
RX PubMed=22499348; DOI=10.1136/jmedgenet-2012-100846;
RA Haack T.B., Haberberger B., Frisch E.M., Wieland T., Iuso A., Gorza M.,
RA Strecker V., Graf E., Mayr J.A., Herberg U., Hennermann J.B., Klopstock T.,
RA Kuhn K.A., Ahting U., Sperl W., Wilichowski E., Hoffmann G.F., Tesarova M.,
RA Hansikova H., Zeman J., Plecko B., Zeviani M., Wittig I., Strom T.M.,
RA Schuelke M., Freisinger P., Meitinger T., Prokisch H.;
RT "Molecular diagnosis in mitochondrial complex I deficiency using exome
RT sequencing.";
RL J. Med. Genet. 49:277-283(2012).
RN [20]
RP CHARACTERIZATION OF VARIANTS MC1DN8 ILE-145 AND TRP-199, AND FUNCTION.
RX PubMed=24028823; DOI=10.1016/j.biochi.2013.08.032;
RA Jaokar T.M., Patil D.P., Shouche Y.S., Gaikwad S.M., Suresh C.G.;
RT "Human mitochondrial NDUFS3 protein bearing Leigh syndrome mutation is more
RT prone to aggregation than its wild-type.";
RL Biochimie 95:2392-2403(2013).
RN [21]
RP VARIANTS MC1DN8 TRP-140 AND TRP-199, CHARACTERIZATION OF VARIANTS MC1DN8
RP TRP-140 AND TRP-199, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30140060; DOI=10.1038/s10038-018-0505-0;
RA Lou X., Shi H., Wen S., Li Y., Wei X., Xie J., Ma L., Yang Y., Fang H.,
RA Lyu J.;
RT "A Novel NDUFS3 mutation in a Chinese patient with severe Leigh syndrome.";
RL J. Hum. Genet. 63:1269-1272(2018).
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:14729820, PubMed:30140060). Essential for the
CC catalytic activity and assembly of complex I (PubMed:14729820,
CC PubMed:24028823, PubMed:30140060). {ECO:0000269|PubMed:14729820,
CC ECO:0000269|PubMed:24028823, ECO:0000269|PubMed:30140060}.
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:14729820, ECO:0000269|PubMed:30140060};
CC -!- SUBUNIT: Core subunit of respiratory chain NADH dehydrogenase (Complex
CC I) which is composed of 45 different subunits (PubMed:12611891).
CC Interacts with NDUFAF3 (PubMed:19463981). Interacts with RAB5IF
CC (PubMed:31536960). Found in subcomplexes containing subunits NDUFS2,
CC MT-ND1 and NDUFA13 (PubMed:17209039, PubMed:18826940).
CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:17209039,
CC ECO:0000269|PubMed:18826940, ECO:0000269|PubMed:19463981,
CC ECO:0000269|PubMed:31536960}.
CC -!- INTERACTION:
CC O75489; Q66PJ3-4: ARL6IP4; NbExp=3; IntAct=EBI-1224896, EBI-5280499;
CC O75489; Q5JUW0-3: KRBOX4; NbExp=3; IntAct=EBI-1224896, EBI-12893625;
CC O75489; Q9H8H3: METTL7A; NbExp=3; IntAct=EBI-1224896, EBI-1390168;
CC O75489; Q16718: NDUFA5; NbExp=12; IntAct=EBI-1224896, EBI-746417;
CC O75489; P51970: NDUFA8; NbExp=5; IntAct=EBI-1224896, EBI-1237250;
CC O75489; O75306: NDUFS2; NbExp=11; IntAct=EBI-1224896, EBI-1224806;
CC O75489; P17152: TMEM11; NbExp=3; IntAct=EBI-1224896, EBI-723946;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:18826940, ECO:0000305|PubMed:12611891,
CC ECO:0000305|PubMed:17209039}; Peripheral membrane protein
CC {ECO:0000305|PubMed:18826940}; Matrix side
CC {ECO:0000269|PubMed:18826940}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75489-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75489-2; Sequence=VSP_057065, VSP_057066;
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 8 (MC1DN8)
CC [MIM:618230]: A form of mitochondrial complex I deficiency, the most
CC common biochemical signature of mitochondrial disorders, a group of
CC highly heterogeneous conditions characterized by defective oxidative
CC phosphorylation, which collectively affects 1 in 5-10000 live births.
CC Clinical disorders have variable severity, ranging from lethal neonatal
CC disease to adult-onset neurodegenerative disorders. Phenotypes include
CC macrocephaly with progressive leukodystrophy, non-specific
CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh
CC syndrome, Leber hereditary optic neuropathy, and some forms of
CC Parkinson disease. MC1DN8 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:14729820,
CC ECO:0000269|PubMed:22499348, ECO:0000269|PubMed:24028823,
CC ECO:0000269|PubMed:30140060}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the complex I 30 kDa subunit family.
CC {ECO:0000305}.
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DR EMBL; AF067139; AAC27451.1; -; mRNA.
DR EMBL; AF200954; AAG17541.1; -; Genomic_DNA.
DR EMBL; AF100743; AAD40386.1; -; mRNA.
DR EMBL; AK294167; BAG57489.1; -; mRNA.
DR EMBL; AK313802; BAG36538.1; -; mRNA.
DR EMBL; AC090559; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104942; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW67895.1; -; Genomic_DNA.
DR EMBL; BC000617; AAH00617.1; -; mRNA.
DR CCDS; CCDS7941.1; -. [O75489-1]
DR PIR; JE0195; JE0195.
DR RefSeq; NP_004542.1; NM_004551.2. [O75489-1]
DR PDB; 5XTB; EM; 3.40 A; P=43-250.
DR PDB; 5XTD; EM; 3.70 A; P=43-250.
DR PDB; 5XTH; EM; 3.90 A; P=43-250.
DR PDB; 5XTI; EM; 17.40 A; BP/P=43-250.
DR PDBsum; 5XTB; -.
DR PDBsum; 5XTD; -.
DR PDBsum; 5XTH; -.
DR PDBsum; 5XTI; -.
DR AlphaFoldDB; O75489; -.
DR SMR; O75489; -.
DR BioGRID; 110801; 363.
DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I.
DR CORUM; O75489; -.
DR IntAct; O75489; 198.
DR MINT; O75489; -.
DR STRING; 9606.ENSP00000263774; -.
DR BindingDB; O75489; -.
DR ChEMBL; CHEMBL2363065; -.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB00157; NADH.
DR DrugCentral; O75489; -.
DR CarbonylDB; O75489; -.
DR GlyGen; O75489; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75489; -.
DR PhosphoSitePlus; O75489; -.
DR SwissPalm; O75489; -.
DR BioMuta; NDUFS3; -.
DR REPRODUCTION-2DPAGE; IPI00025796; -.
DR REPRODUCTION-2DPAGE; O75489; -.
DR CPTAC; CPTAC-100; -.
DR CPTAC; CPTAC-99; -.
DR EPD; O75489; -.
DR jPOST; O75489; -.
DR MassIVE; O75489; -.
DR MaxQB; O75489; -.
DR PaxDb; O75489; -.
DR PeptideAtlas; O75489; -.
DR PRIDE; O75489; -.
DR ProteomicsDB; 4061; -.
DR ProteomicsDB; 50046; -. [O75489-1]
DR TopDownProteomics; O75489-1; -. [O75489-1]
DR Antibodypedia; 1262; 305 antibodies from 35 providers.
DR DNASU; 4722; -.
DR Ensembl; ENST00000263774.9; ENSP00000263774.4; ENSG00000213619.11. [O75489-1]
DR Ensembl; ENST00000645714.2; ENSP00000496383.1; ENSG00000285387.2. [O75489-1]
DR Ensembl; ENST00000646736.1; ENSP00000494074.1; ENSG00000285387.2. [O75489-2]
DR GeneID; 4722; -.
DR KEGG; hsa:4722; -.
DR MANE-Select; ENST00000263774.9; ENSP00000263774.4; NM_004551.3; NP_004542.1.
DR UCSC; uc001nga.3; human. [O75489-1]
DR CTD; 4722; -.
DR DisGeNET; 4722; -.
DR GeneCards; NDUFS3; -.
DR GeneReviews; NDUFS3; -.
DR HGNC; HGNC:7710; NDUFS3.
DR HPA; ENSG00000213619; Tissue enhanced (skeletal).
DR MalaCards; NDUFS3; -.
DR MIM; 603846; gene.
DR MIM; 618230; phenotype.
DR neXtProt; NX_O75489; -.
DR NIAGADS; ENSG00000213619; -.
DR OpenTargets; ENSG00000213619; -.
DR Orphanet; 2609; Isolated complex I deficiency.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR PharmGKB; PA31520; -.
DR VEuPathDB; HostDB:ENSG00000213619; -.
DR eggNOG; KOG1713; Eukaryota.
DR GeneTree; ENSGT00390000017480; -.
DR HOGENOM; CLU_042628_0_1_1; -.
DR InParanoid; O75489; -.
DR OMA; PCRKNRF; -.
DR OrthoDB; 1276923at2759; -.
DR PhylomeDB; O75489; -.
DR TreeFam; TF314794; -.
DR BioCyc; MetaCyc:G66-32694-MON; -.
DR PathwayCommons; O75489; -.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR SignaLink; O75489; -.
DR SIGNOR; O75489; -.
DR BioGRID-ORCS; 4722; 205 hits in 1083 CRISPR screens.
DR ChiTaRS; NDUFS3; human.
DR GeneWiki; NDUFS3; -.
DR GenomeRNAi; 4722; -.
DR Pharos; O75489; Tclin.
DR PRO; PR:O75489; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O75489; protein.
DR Bgee; ENSG00000213619; Expressed in putamen and 98 other tissues.
DR ExpressionAtlas; O75489; baseline and differential.
DR Genevisible; O75489; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0005747; C:mitochondrial respiratory chain complex I; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0009055; F:electron transfer activity; NAS:UniProtKB.
DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IMP:UniProtKB.
DR GO; GO:0003954; F:NADH dehydrogenase activity; IMP:UniProtKB.
DR GO; GO:0009060; P:aerobic respiration; IC:ComplexPortal.
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:0030308; P:negative regulation of cell growth; IMP:UniProtKB.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; IC:ComplexPortal.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:UniProtKB.
DR GO; GO:0021762; P:substantia nigra development; HEP:UniProtKB.
DR Gene3D; 3.30.460.80; -; 1.
DR HAMAP; MF_01357; NDH1_NuoC; 1.
DR InterPro; IPR010218; NADH_DH_suC.
DR InterPro; IPR037232; NADH_quin_OxRdtase_su_C/D-like.
DR InterPro; IPR001268; NADH_UbQ_OxRdtase_30kDa_su.
DR InterPro; IPR020396; NADH_UbQ_OxRdtase_CS.
DR Pfam; PF00329; Complex1_30kDa; 1.
DR SUPFAM; SSF143243; SSF143243; 1.
DR TIGRFAMs; TIGR01961; NuoC_fam; 1.
DR PROSITE; PS00542; COMPLEX1_30K; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disease variant; Electron transport; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; NAD; Oxidoreductase;
KW Primary mitochondrial disease; Reference proteome; Respiratory chain;
KW Transit peptide; Translocase; Transport; Ubiquinone.
FT TRANSIT 1..36
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:19892738"
FT CHAIN 37..264
FT /note="NADH dehydrogenase [ubiquinone] iron-sulfur protein
FT 3, mitochondrial"
FT /id="PRO_0000019998"
FT VAR_SEQ 128..132
FT /note="IVYNL -> VSWEI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057065"
FT VAR_SEQ 133..264
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057066"
FT VARIANT 140
FT /note="R -> W (in MC1DN8; unknown pathological
FT significance; decrease in enzyme activity; impaired
FT assembly of complex I; dbSNP:rs142248674)"
FT /evidence="ECO:0000269|PubMed:30140060"
FT /id="VAR_081411"
FT VARIANT 145
FT /note="T -> I (in MC1DN8; decrease in enzyme activity;
FT increased protein instability and aggregation; compound
FT heterozygous with W-199; dbSNP:rs28939714)"
FT /evidence="ECO:0000269|PubMed:14729820,
FT ECO:0000269|PubMed:24028823"
FT /id="VAR_081412"
FT VARIANT 199
FT /note="R -> W (in MC1DN8; decrease in enzyme activity;
FT impaired assembly of complex I; increased protein
FT instability and aggregation; compound heterozygous with I-
FT 145; dbSNP:rs104894270)"
FT /evidence="ECO:0000269|PubMed:14729820,
FT ECO:0000269|PubMed:22499348, ECO:0000269|PubMed:24028823,
FT ECO:0000269|PubMed:30140060"
FT /id="VAR_081413"
FT VARIANT 249
FT /note="P -> Q (in dbSNP:rs9600)"
FT /id="VAR_012036"
FT CONFLICT 1..7
FT /note="MAAAAVA -> MAAGRY (in Ref. 3)"
FT /evidence="ECO:0000305"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 52..68
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 70..72
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 93..101
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 120..124
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 129..134
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 135..138
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 139..144
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 156..160
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 165..172
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 207..213
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 214..217
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 218..223
FT /evidence="ECO:0007829|PDB:5XTB"
SQ SEQUENCE 264 AA; 30242 MW; C058D62779BEF17B CRC64;
MAAAAVARLW WRGILGASAL TRGTGRPSVL LLPVRRESAG ADTRPTVRPR NDVAHKQLSA
FGEYVAEILP KYVQQVQVSC FNELEVCIHP DGVIPVLTFL RDHTNAQFKS LVDLTAVDVP
TRQNRFEIVY NLLSLRFNSR IRVKTYTDEL TPIESAVSVF KAANWYEREI WDMFGVFFAN
HPDLRRILTD YGFEGHPFRK DFPLSGYVEL RYDDEVKRVV AEPVELAQEF RKFDLNSPWE
AFPVYRQPPE SLKLEAGDKK PDAK
