NDUS2_HUMAN
ID NDUS2_HUMAN Reviewed; 463 AA.
AC O75306; D3DVG7; J3KPM7; Q5VTW0; Q969P3; Q9UEV3;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2002, sequence version 2.
DT 03-AUG-2022, entry version 213.
DE RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial;
DE EC=7.1.1.2 {ECO:0000269|PubMed:22036843, ECO:0000269|PubMed:30922174};
DE AltName: Full=Complex I-49kD;
DE Short=CI-49kD;
DE AltName: Full=NADH-ubiquinone oxidoreductase 49 kDa subunit;
DE Flags: Precursor;
GN Name=NDUFS2;
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].
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 [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=9585441; DOI=10.1007/s003359900803;
RA Procaccio V., de Sury R., Martinez P., Depetris D., Rabilloud T.,
RA Soularue P., Lunardi J., Issartel J.-P.;
RT "Mapping to 1q23 of the human gene (NDUFS2) encoding the 49-kDa subunit of
RT the mitochondrial respiratory complex I and immunodetection of the mature
RT protein in mitochondria.";
RL Mamm. Genome 9:482-484(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle, and Placenta;
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 [7]
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 [8]
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 [9]
RP INTERACTION WITH NDUFAF7.
RX PubMed=20406883; DOI=10.1242/jcs.066076;
RA Carilla-Latorre S., Gallardo M.E., Annesley S.J., Calvo-Garrido J.,
RA Grana O., Accari S.L., Smith P.K., Valencia A., Garesse R., Fisher P.R.,
RA Escalante R.;
RT "MidA is a putative methyltransferase that is required for mitochondrial
RT complex I function.";
RL J. Cell Sci. 123:1674-1683(2010).
RN [10]
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 [11]
RP METHYLATION AT ARG-118, AND INTERACTION WITH NDUFAF7.
RX PubMed=24089531; DOI=10.1074/jbc.m113.518803;
RA Rhein V.F., Carroll J., Ding S., Fearnley I.M., Walker J.E.;
RT "NDUFAF7 methylates arginine 85 in the NDUFS2 subunit of human complex I.";
RL J. Biol. Chem. 288:33016-33026(2013).
RN [12]
RP METHYLATION AT ARG-118.
RX PubMed=24838397; DOI=10.1093/hmg/ddu239;
RA Zurita Rendon O., Silva Neiva L., Sasarman F., Shoubridge E.A.;
RT "The arginine methyltransferase NDUFAF7 is essential for complex I assembly
RT and early vertebrate embryogenesis.";
RL Hum. Mol. Genet. 23:5159-5170(2014).
RN [13]
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 [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 FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30922174; DOI=10.1161/circresaha.118.314284;
RA Dunham-Snary K.J., Wu D., Potus F., Sykes E.A., Mewburn J.D., Charles R.L.,
RA Eaton P., Sultanian R.A., Archer S.L.;
RT "Ndufs2, a Core Subunit of Mitochondrial Complex I, Is Essential for Acute
RT Oxygen-Sensing and Hypoxic Pulmonary Vasoconstriction.";
RL Circ. Res. 124:1727-1746(2019).
RN [16]
RP INVOLVEMENT IN MC1DN6, AND VARIANTS MC1DN6 GLN-228; GLN-229 AND PRO-413.
RX PubMed=11220739;
RX DOI=10.1002/1531-8249(20010201)49:2<195::aid-ana39>3.0.co;2-m;
RA Loeffen J., Elpeleg O., Smeitink J., Smeets R., Stoeckler-Ipsiroglu S.,
RA Mandel H., Sengers R., Trijbels F., van den Heuvel L.;
RT "Mutations in the complex I NDUFS2 gene of patients with cardiomyopathy and
RT encephalomyopathy.";
RL Ann. Neurol. 49:195-201(2001).
RN [17]
RP VARIANT VAL-224.
RX PubMed=21057504; DOI=10.1038/ng.706;
RA Haack T.B., Danhauser K., Haberberger B., Hoser J., Strecker V., Boehm D.,
RA Uziel G., Lamantea E., Invernizzi F., Poulton J., Rolinski B., Iuso A.,
RA Biskup S., Schmidt T., Mewes H.W., Wittig I., Meitinger T., Zeviani M.,
RA Prokisch H.;
RT "Exome sequencing identifies ACAD9 mutations as a cause of complex I
RT deficiency.";
RL Nat. Genet. 42:1131-1134(2010).
RN [18]
RP VARIANT MC1DN6 ASN-446, CHARACTERIZATION OF VARIANT MC1DN6 ASN-446,
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22036843; DOI=10.1016/j.bbadis.2011.10.012;
RA Ngu L.H., Nijtmans L.G., Distelmaier F., Venselaar H.,
RA van Emst-de Vries S.E., van den Brand M.A., Stoltenborg B.J., Wintjes L.T.,
RA Willems P.H., van den Heuvel L.P., Smeitink J.A., Rodenburg R.J.;
RT "A catalytic defect in mitochondrial respiratory chain complex I due to a
RT mutation in NDUFS2 in a patient with Leigh syndrome.";
RL Biochim. Biophys. Acta 1822:168-175(2012).
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:30922174, PubMed:22036843). Essential for the
CC catalytic activity of complex I (PubMed:30922174, PubMed:22036843).
CC Essential for the assembly of complex I (By similarity). Redox-
CC sensitive, critical component of the oxygen-sensing pathway in the
CC pulmonary vasculature which plays a key role in acute pulmonary oxygen-
CC sensing and hypoxic pulmonary vasoconstriction (PubMed:30922174). Plays
CC an important role in carotid body sensing of hypoxia (By similarity).
CC Essential for glia-like neural stem and progenitor cell proliferation,
CC differentiation and subsequent oligodendrocyte or neuronal maturation
CC (By similarity). {ECO:0000250|UniProtKB:Q91WD5,
CC ECO:0000269|PubMed:22036843, ECO:0000269|PubMed:30922174}.
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:22036843, ECO:0000269|PubMed:30922174};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Note=Binds 1 [4Fe-4S] cluster.;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10.2 uM for decylubiquinone {ECO:0000269|PubMed:22036843};
CC KM=55 uM for ubiquinone-1 {ECO:0000269|PubMed:22036843};
CC -!- SUBUNIT: Core subunit of respiratory chain NADH dehydrogenase (Complex
CC I) which is composed of 45 different subunits. Component of the iron-
CC sulfur (IP) fragment of the enzyme (PubMed:12611891). Interacts with
CC NDUFAF3 (PubMed:19463981). Interacts with NDUFAF7 (PubMed:20406883,
CC PubMed:24089531). Interacts with CERS2 (By similarity).
CC {ECO:0000250|UniProtKB:Q91WD5, ECO:0000269|PubMed:12611891,
CC ECO:0000269|PubMed:19463981, ECO:0000269|PubMed:20406883,
CC ECO:0000269|PubMed:24089531}.
CC -!- INTERACTION:
CC O75306; O75489: NDUFS3; NbExp=11; IntAct=EBI-1224806, EBI-1224896;
CC O75306; Q99650: OSMR; NbExp=4; IntAct=EBI-1224806, EBI-2804080;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000305|PubMed:12611891, ECO:0000305|PubMed:9585441}; Peripheral
CC membrane protein {ECO:0000250|UniProtKB:Q641Y2}; Matrix side
CC {ECO:0000250|UniProtKB:Q641Y2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75306-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75306-2; Sequence=VSP_046466;
CC -!- PTM: Dimethylation at Arg-118 by NDUFAF7 takes place after NDUFS2
CC assembles into the complex I, leading to stabilize the early
CC intermediate complex (PubMed:24089531, PubMed:24838397).
CC {ECO:0000269|PubMed:24089531, ECO:0000269|PubMed:24838397}.
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 6 (MC1DN6)
CC [MIM:618228]: 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. MC1DN6 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:11220739,
CC ECO:0000269|PubMed:22036843}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the complex I 49 kDa subunit family.
CC {ECO:0000305}.
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DR EMBL; AF050640; AAC27453.1; -; mRNA.
DR EMBL; AF013160; AAC34362.1; -; mRNA.
DR EMBL; AK314807; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL590714; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW52625.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52626.1; -; Genomic_DNA.
DR EMBL; BC000170; AAH00170.1; -; mRNA.
DR EMBL; BC001456; AAH01456.1; -; mRNA.
DR EMBL; BC008868; AAH08868.1; -; mRNA.
DR CCDS; CCDS1224.1; -. [O75306-1]
DR CCDS; CCDS53404.1; -. [O75306-2]
DR PIR; JE0193; JE0193.
DR RefSeq; NP_001159631.1; NM_001166159.1. [O75306-2]
DR RefSeq; NP_004541.1; NM_004550.4. [O75306-1]
DR RefSeq; XP_005245265.1; XM_005245208.2.
DR RefSeq; XP_016856846.1; XM_017001357.1.
DR PDB; 5XTB; EM; 3.40 A; Q=79-463.
DR PDB; 5XTC; EM; 3.70 A; Q=34-79.
DR PDB; 5XTD; EM; 3.70 A; Q=34-463.
DR PDB; 5XTH; EM; 3.90 A; Q=34-463.
DR PDB; 5XTI; EM; 17.40 A; BQ/Q=34-463.
DR PDBsum; 5XTB; -.
DR PDBsum; 5XTC; -.
DR PDBsum; 5XTD; -.
DR PDBsum; 5XTH; -.
DR PDBsum; 5XTI; -.
DR AlphaFoldDB; O75306; -.
DR SMR; O75306; -.
DR BioGRID; 110800; 269.
DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I.
DR CORUM; O75306; -.
DR IntAct; O75306; 86.
DR MINT; O75306; -.
DR STRING; 9606.ENSP00000356972; -.
DR BindingDB; O75306; -.
DR ChEMBL; CHEMBL3039; -.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB00157; NADH.
DR DrugCentral; O75306; -.
DR iPTMnet; O75306; -.
DR PhosphoSitePlus; O75306; -.
DR SwissPalm; O75306; -.
DR BioMuta; NDUFS2; -.
DR EPD; O75306; -.
DR jPOST; O75306; -.
DR MassIVE; O75306; -.
DR MaxQB; O75306; -.
DR PaxDb; O75306; -.
DR PeptideAtlas; O75306; -.
DR PRIDE; O75306; -.
DR ProteomicsDB; 49883; -. [O75306-1]
DR TopDownProteomics; O75306-1; -. [O75306-1]
DR Antibodypedia; 34301; 310 antibodies from 33 providers.
DR DNASU; 4720; -.
DR Ensembl; ENST00000367993.7; ENSP00000356972.3; ENSG00000158864.13. [O75306-1]
DR Ensembl; ENST00000392179.5; ENSP00000376018.4; ENSG00000158864.13. [O75306-2]
DR Ensembl; ENST00000676600.1; ENSP00000503989.1; ENSG00000158864.13. [O75306-1]
DR Ensembl; ENST00000676972.1; ENSP00000503117.1; ENSG00000158864.13. [O75306-1]
DR Ensembl; ENST00000677457.1; ENSP00000503294.1; ENSG00000158864.13. [O75306-2]
DR Ensembl; ENST00000677550.1; ENSP00000503353.1; ENSG00000158864.13. [O75306-2]
DR Ensembl; ENST00000678507.1; ENSP00000504199.1; ENSG00000158864.13. [O75306-1]
DR Ensembl; ENST00000678511.1; ENSP00000504846.1; ENSG00000158864.13. [O75306-1]
DR Ensembl; ENST00000678605.1; ENSP00000503969.1; ENSG00000158864.13. [O75306-2]
DR Ensembl; ENST00000679176.1; ENSP00000504170.1; ENSG00000158864.13. [O75306-2]
DR GeneID; 4720; -.
DR KEGG; hsa:4720; -.
DR MANE-Select; ENST00000676972.1; ENSP00000503117.1; NM_001377299.1; NP_001364228.1.
DR UCSC; uc001fyv.4; human. [O75306-1]
DR CTD; 4720; -.
DR DisGeNET; 4720; -.
DR GeneCards; NDUFS2; -.
DR HGNC; HGNC:7708; NDUFS2.
DR HPA; ENSG00000158864; Tissue enhanced (skeletal muscle, tongue).
DR MalaCards; NDUFS2; -.
DR MIM; 602985; gene.
DR MIM; 618228; phenotype.
DR neXtProt; NX_O75306; -.
DR OpenTargets; ENSG00000158864; -.
DR Orphanet; 2609; Isolated complex I deficiency.
DR Orphanet; 104; Leber hereditary optic neuropathy.
DR Orphanet; 70474; Leigh syndrome with cardiomyopathy.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR PharmGKB; PA31519; -.
DR VEuPathDB; HostDB:ENSG00000158864; -.
DR eggNOG; KOG2870; Eukaryota.
DR GeneTree; ENSGT00390000009529; -.
DR HOGENOM; CLU_015134_1_1_1; -.
DR InParanoid; O75306; -.
DR OMA; IMGTSME; -.
DR OrthoDB; 444312at2759; -.
DR PhylomeDB; O75306; -.
DR TreeFam; TF300370; -.
DR BioCyc; MetaCyc:HS08339-MON; -.
DR PathwayCommons; O75306; -.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR SignaLink; O75306; -.
DR SIGNOR; O75306; -.
DR BioGRID-ORCS; 4720; 331 hits in 1087 CRISPR screens.
DR ChiTaRS; NDUFS2; human.
DR GeneWiki; NDUFS2; -.
DR GenomeRNAi; 4720; -.
DR Pharos; O75306; Tclin.
DR PRO; PR:O75306; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O75306; protein.
DR Bgee; ENSG00000158864; Expressed in apex of heart and 202 other tissues.
DR Genevisible; O75306; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005747; C:mitochondrial respiratory chain complex I; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0009055; F:electron transfer activity; NAS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; NAS:UniProtKB.
DR GO; GO:0019826; F:oxygen sensor activity; IMP:UniProtKB.
DR GO; GO:0048038; F:quinone binding; IEA:InterPro.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0009060; P:aerobic respiration; IC:ComplexPortal.
DR GO; GO:0071453; P:cellular response to oxygen levels; IMP:UniProtKB.
DR GO; GO:0042063; P:gliogenesis; ISS:UniProtKB.
DR GO; GO:0042775; P:mitochondrial ATP synthesis coupled electron transport; IMP:CAFA.
DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IMP:UniProtKB.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; ISS:UniProtKB.
DR GO; GO:0061351; P:neural precursor cell proliferation; ISS:UniProtKB.
DR GO; GO:0022008; P:neurogenesis; ISS:UniProtKB.
DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; IC:ComplexPortal.
DR GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB.
DR Gene3D; 1.10.645.10; -; 1.
DR HAMAP; MF_01358; NDH1_NuoD; 1.
DR InterPro; IPR001135; NADH_Q_OxRdtase_suD.
DR InterPro; IPR014029; NADH_UbQ_OxRdtase_49kDa_CS.
DR InterPro; IPR022885; NDH1_su_D/H.
DR InterPro; IPR029014; NiFe-Hase_large.
DR PANTHER; PTHR11993; PTHR11993; 1.
DR Pfam; PF00346; Complex1_49kDa; 1.
DR SUPFAM; SSF56762; SSF56762; 1.
DR TIGRFAMs; TIGR01962; NuoD; 1.
DR PROSITE; PS00535; COMPLEX1_49K; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Acetylation; Alternative splicing; Disease variant;
KW Electron transport; Iron; Iron-sulfur; Membrane; Metal-binding;
KW Methylation; Mitochondrion; Mitochondrion inner membrane; NAD;
KW Oxidoreductase; Primary mitochondrial disease; Reference proteome;
KW Respiratory chain; Transit peptide; Translocase; Transport; Ubiquinone.
FT TRANSIT 1..33
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P17694"
FT CHAIN 34..463
FT /note="NADH dehydrogenase [ubiquinone] iron-sulfur protein
FT 2, mitochondrial"
FT /id="PRO_0000019981"
FT BINDING 326
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255"
FT BINDING 332
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255"
FT BINDING 347
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255"
FT MOD_RES 62
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91WD5"
FT MOD_RES 118
FT /note="Symmetric dimethylarginine"
FT /evidence="ECO:0000269|PubMed:24089531,
FT ECO:0000269|PubMed:24838397"
FT VAR_SEQ 454..463
FT /note="QDIVFGEVDR -> RPIV (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_046466"
FT VARIANT 20
FT /note="P -> T (in dbSNP:rs11538340)"
FT /id="VAR_034150"
FT VARIANT 224
FT /note="A -> V"
FT /evidence="ECO:0000269|PubMed:21057504"
FT /id="VAR_071891"
FT VARIANT 228
FT /note="R -> Q (in MC1DN6; dbSNP:rs121434427)"
FT /evidence="ECO:0000269|PubMed:11220739"
FT /id="VAR_019535"
FT VARIANT 229
FT /note="P -> A (in dbSNP:rs16827493)"
FT /id="VAR_034151"
FT VARIANT 229
FT /note="P -> Q (in MC1DN6; dbSNP:rs121434428)"
FT /evidence="ECO:0000269|PubMed:11220739"
FT /id="VAR_019536"
FT VARIANT 352
FT /note="P -> A (in dbSNP:rs11576415)"
FT /id="VAR_034152"
FT VARIANT 413
FT /note="S -> P (in MC1DN6; dbSNP:rs121434429)"
FT /evidence="ECO:0000269|PubMed:11220739"
FT /id="VAR_019537"
FT VARIANT 446
FT /note="D -> N (in MC1DN6; loss of catalytic activity; no
FT change in Km value for ubiquinone-1)"
FT /evidence="ECO:0000269|PubMed:22036843"
FT /id="VAR_084193"
FT CONFLICT 24
FT /note="V -> G (in Ref. 2; AAC34362)"
FT /evidence="ECO:0000305"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 89..94
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 96..105
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 120..125
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 129..132
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 134..137
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 145..158
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 165..193
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 198..218
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 219..223
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 231..234
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 240..249
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 251..259
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 260..264
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 266..272
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 280..286
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 291..294
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 295..297
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 310..312
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 326..349
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 361..363
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 368..371
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 375..384
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 385..387
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 393..402
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 405..413
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 415..423
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 427..439
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 444..453
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 458..461
FT /evidence="ECO:0007829|PDB:5XTB"
SQ SEQUENCE 463 AA; 52546 MW; A2BF56F008B6312C CRC64;
MAALRALCGF RGVAAQVLRP GAGVRLPIQP SRGVRQWQPD VEWAQQFGGA VMYPSKETAH
WKPPPWNDVD PPKDTIVKNI TLNFGPQHPA AHGVLRLVME LSGEMVRKCD PHIGLLHRGT
EKLIEYKTYL QALPYFDRLD YVSMMCNEQA YSLAVEKLLN IRPPPRAQWI RVLFGEITRL
LNHIMAVTTH ALDLGAMTPF FWLFEEREKM FEFYERVSGA RMHAAYIRPG GVHQDLPLGL
MDDIYQFSKN FSLRLDELEE LLTNNRIWRN RTIDIGVVTA EEALNYGFSG VMLRGSGIQW
DLRKTQPYDV YDQVEFDVPV GSRGDCYDRY LCRVEEMRQS LRIIAQCLNK MPPGEIKVDD
AKVSPPKRAE MKTSMESLIH HFKLYTEGYQ VPPGATYTAI EAPKGEFGVY LVSDGSSRPY
RCKIKAPGFA HLAGLDKMSK GHMLADVVAI IGTQDIVFGE VDR
