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 27-MAR-2024, entry version 222. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 285. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O75306; -. DR IntAct; O75306; 88. 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 GlyGen; O75306; 1 site, 1 O-linked glycan (1 site). 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; 9606-ENSP00000356972; -. DR PeptideAtlas; O75306; -. DR ProteomicsDB; 49883; -. [O75306-1] DR Pumba; O75306; -. DR TopDownProteomics; O75306-1; -. [O75306-1] DR Antibodypedia; 34301; 345 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 AGR; HGNC:7708; -. 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 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; 191at2759; -. DR PhylomeDB; O75306; -. DR TreeFam; TF300370; -. DR BioCyc; MetaCyc:HS08339-MONOMER; -. 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; 352 hits in 1168 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 204 other cell types or tissues. 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:HPA. 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; NAS: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; NAS:ComplexPortal. DR GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB. DR Gene3D; 1.10.645.10; Cytochrome-c3 Hydrogenase, chain B; 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 NCBIfam; TIGR01962; NuoD; 1. DR PANTHER; PTHR11993:SF10; NADH DEHYDROGENASE [UBIQUINONE] IRON-SULFUR PROTEIN 2, MITOCHONDRIAL; 1. DR PANTHER; PTHR11993; NADH-UBIQUINONE OXIDOREDUCTASE 49 KDA SUBUNIT; 1. DR Pfam; PF00346; Complex1_49kDa; 1. DR SUPFAM; SSF56762; HydB/Nqo4-like; 1. DR PROSITE; PS00535; COMPLEX1_49K; 1. DR Genevisible; O75306; HS. 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 //