NDUS1_HUMAN
ID NDUS1_HUMAN Reviewed; 727 AA.
AC P28331; B4DIN9; B4DJA0; B4DPG1; B4DUC1; E7ENF3; Q53TR8; Q8N1C4; Q8TCC9;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 3.
DT 03-AUG-2022, entry version 227.
DE RecName: Full=NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial;
DE EC=7.1.1.2 {ECO:0000269|PubMed:30879903, ECO:0000269|PubMed:31557978};
DE AltName: Full=Complex I-75kD;
DE Short=CI-75kD;
DE Flags: Precursor;
GN Name=NDUFS1;
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), AND VARIANT PHE-649.
RX PubMed=1935949; DOI=10.1111/j.1432-1033.1991.tb16313.x;
RA Chow W., Ragan I., Robinson B.H.;
RT "Determination of the cDNA sequence for the human mitochondrial 75-kDa Fe-S
RT protein of NADH-coenzyme Q reductase.";
RL Eur. J. Biochem. 201:547-550(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3; 4 AND 5).
RC TISSUE=Hippocampus, Kidney, and Substantia nigra;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLN-241.
RC TISSUE=Brain, and Liver;
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 [6]
RP PROTEIN SEQUENCE OF 185-200; 247-266; 277-289; 312-325; 361-382; 451-467;
RP 471-499; 519-538; 544-557 AND 625-655, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
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 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 [9]
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 [10]
RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER THR-23, AND
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 [11]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH MDM2.
RX PubMed=30879903; DOI=10.1016/j.molcel.2019.02.012;
RA Elkholi R., Abraham-Enachescu I., Trotta A.P., Rubio-Patino C.,
RA Mohammed J.N., Luna-Vargas M.P.A., Gelles J.D., Kaminetsky J.R.,
RA Serasinghe M.N., Zou C., Ali S., McStay G.P., Pfleger C.M., Chipuk J.E.;
RT "MDM2 Integrates Cellular Respiration and Apoptotic Signaling through
RT NDUFS1 and the Mitochondrial Network.";
RL Mol. Cell 74:452-465(2019).
RN [12]
RP INVOLVEMENT IN MC1DN5, AND VARIANTS MC1DN5 TRP-241 AND GLY-252.
RX PubMed=11349233; DOI=10.1086/320603;
RA Benit P., Chretien D., Kadhom N., de Lonlay-Debeney P., Cormier-Daire V.,
RA Cabral A., Peudenier S., Rustin P., Munnich A., Roetig A.;
RT "Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1
RT genes in mitochondrial complex I deficiency.";
RL Am. J. Hum. Genet. 68:1344-1352(2001).
RN [13]
RP VARIANT GLY-253.
RX PubMed=22499341; DOI=10.1136/jmedgenet-2012-100836;
RA Shamseldin H.E., Alshammari M., Al-Sheddi T., Salih M.A., Alkhalidi H.,
RA Kentab A., Repetto G.M., Hashem M., Alkuraya F.S.;
RT "Genomic analysis of mitochondrial diseases in a consanguineous population
RT reveals novel candidate disease genes.";
RL J. Med. Genet. 49:234-241(2012).
RN [14]
RP VARIANTS MC1DN5 ALA-228 AND GLY-252, CHARACTERIZATION OF VARIANTS MC1DN5
RP ALA-228 AND GLY-252, FUNCTION, SUBUNIT, AND CATALYTIC ACTIVITY.
RX PubMed=31557978; DOI=10.3390/cells8101149;
RA Ni Y., Hagras M.A., Konstantopoulou V., Mayr J.A., Stuchebrukhov A.A.,
RA Meierhofer D.;
RT "Mutations in NDUFS1 Cause Metabolic Reprogramming and Disruption of the
RT Electron Transfer.";
RL Cells 8:0-0(2019).
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:30879903, PubMed:31557978). Essential for catalysing
CC the entry and efficient transfer of electrons within complex I
CC (PubMed:31557978). Plays a key role in the assembly and stability of
CC complex I and participates in the association of complex I with
CC ubiquinol-cytochrome reductase complex (Complex III) to form
CC supercomplexes (PubMed:30879903, PubMed:31557978).
CC {ECO:0000269|PubMed:30879903, ECO:0000269|PubMed:31557978}.
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:30879903, ECO:0000269|PubMed:31557978};
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000250|UniProtKB:Q56223};
CC Note=Binds 1 [2Fe-2S] cluster per subunit.
CC {ECO:0000250|UniProtKB:Q56223};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:Q56223};
CC Note=Binds 2 [4Fe-4S] clusters per subunit.
CC {ECO:0000250|UniProtKB:Q56223};
CC -!- SUBUNIT: Core subunit of respiratory chain NADH dehydrogenase (Complex
CC I) which is composed of 45 different subunits (PubMed:12611891). This
CC is the largest subunit of complex I and it is a component of the iron-
CC sulfur (IP) fragment of the enzyme (By similarity). Complex I
CC associates with ubiquinol-cytochrome reductase complex (Complex III) to
CC form supercomplexes (PubMed:30879903, PubMed:31557978). Interacts with
CC MDM2 (PubMed:30879903). Interacts with AKAP1 (By similarity).
CC {ECO:0000250|UniProtKB:P15690, ECO:0000250|UniProtKB:Q91VD9,
CC ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:30879903,
CC ECO:0000269|PubMed:31557978}.
CC -!- INTERACTION:
CC P28331; Q99650: OSMR; NbExp=4; IntAct=EBI-1043922, EBI-2804080;
CC P28331-2; Q0VDD7: BRME1; NbExp=3; IntAct=EBI-6190702, EBI-741210;
CC P28331-2; Q96MW5: COG8; NbExp=3; IntAct=EBI-6190702, EBI-720875;
CC P28331-2; P24310: COX7A1; NbExp=3; IntAct=EBI-6190702, EBI-25876196;
CC P28331-2; Q14154: DELE1; NbExp=3; IntAct=EBI-6190702, EBI-2805660;
CC P28331-2; Q9BPU6: DPYSL5; NbExp=3; IntAct=EBI-6190702, EBI-724653;
CC P28331-2; Q49AJ0-4: FAM135B; NbExp=3; IntAct=EBI-6190702, EBI-25835236;
CC P28331-2; Q99871: HAUS7; NbExp=3; IntAct=EBI-6190702, EBI-395719;
CC P28331-2; Q6ZU52: KIAA0408; NbExp=3; IntAct=EBI-6190702, EBI-739493;
CC P28331-2; Q13887: KLF5; NbExp=3; IntAct=EBI-6190702, EBI-2696013;
CC P28331-2; Q92615: LARP4B; NbExp=3; IntAct=EBI-6190702, EBI-1052558;
CC P28331-2; Q9BV99: LRRC61; NbExp=3; IntAct=EBI-6190702, EBI-2350424;
CC P28331-2; Q8N6F8: METTL27; NbExp=3; IntAct=EBI-6190702, EBI-8487781;
CC P28331-2; Q13562: NEUROD1; NbExp=3; IntAct=EBI-6190702, EBI-3908303;
CC P28331-2; P22061-2: PCMT1; NbExp=3; IntAct=EBI-6190702, EBI-12386584;
CC P28331-2; Q8WTV1: THAP3; NbExp=3; IntAct=EBI-6190702, EBI-17438286;
CC P28331-5; Q96IK1-2: BOD1; NbExp=3; IntAct=EBI-25876328, EBI-18924329;
CC P28331-5; P42858: HTT; NbExp=6; IntAct=EBI-25876328, EBI-466029;
CC P28331-5; O60333-2: KIF1B; NbExp=3; IntAct=EBI-25876328, EBI-10975473;
CC P28331-5; O76024: WFS1; NbExp=3; IntAct=EBI-25876328, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000305|PubMed:12611891, ECO:0000305|PubMed:30879903}; Peripheral
CC membrane protein {ECO:0000250|UniProtKB:P15690}; Matrix side
CC {ECO:0000250|UniProtKB:P15690}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=P28331-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P28331-2; Sequence=VSP_042682;
CC Name=3;
CC IsoId=P28331-3; Sequence=VSP_043728, VSP_043729;
CC Name=4;
CC IsoId=P28331-4; Sequence=VSP_043727;
CC Name=5;
CC IsoId=P28331-5; Sequence=VSP_045864;
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 5 (MC1DN5)
CC [MIM:618226]: 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. MC1DN5 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:11349233,
CC ECO:0000269|PubMed:31557978}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the complex I 75 kDa subunit family.
CC {ECO:0000305}.
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DR EMBL; X61100; CAA43412.1; -; mRNA.
DR EMBL; AK295705; BAG58551.1; -; mRNA.
DR EMBL; AK295987; BAG58762.1; -; mRNA.
DR EMBL; AK298320; BAG60573.1; -; mRNA.
DR EMBL; AK300585; BAG62283.1; -; mRNA.
DR EMBL; AC007383; AAY15061.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70379.1; -; Genomic_DNA.
DR EMBL; BC022368; AAH22368.1; -; mRNA.
DR EMBL; BC030833; AAH30833.1; -; mRNA.
DR CCDS; CCDS2366.1; -. [P28331-1]
DR CCDS; CCDS56162.1; -. [P28331-4]
DR CCDS; CCDS56163.1; -. [P28331-3]
DR CCDS; CCDS56164.1; -. [P28331-5]
DR CCDS; CCDS56165.1; -. [P28331-2]
DR PIR; S17854; S17854.
DR RefSeq; NP_001186910.1; NM_001199981.1. [P28331-5]
DR RefSeq; NP_001186911.1; NM_001199982.1. [P28331-3]
DR RefSeq; NP_001186912.1; NM_001199983.1. [P28331-4]
DR RefSeq; NP_001186913.1; NM_001199984.1. [P28331-2]
DR RefSeq; NP_004997.4; NM_005006.6. [P28331-1]
DR PDB; 5XTB; EM; 3.40 A; M=30-716.
DR PDB; 5XTD; EM; 3.70 A; M=30-716.
DR PDB; 5XTH; EM; 3.90 A; M=30-716.
DR PDB; 5XTI; EM; 17.40 A; BM/M=30-716.
DR PDBsum; 5XTB; -.
DR PDBsum; 5XTD; -.
DR PDBsum; 5XTH; -.
DR PDBsum; 5XTI; -.
DR AlphaFoldDB; P28331; -.
DR SMR; P28331; -.
DR BioGRID; 110799; 344.
DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I.
DR CORUM; P28331; -.
DR IntAct; P28331; 108.
DR MINT; P28331; -.
DR STRING; 9606.ENSP00000392709; -.
DR BindingDB; P28331; -.
DR ChEMBL; CHEMBL2363065; -.
DR DrugBank; DB00157; NADH.
DR DrugCentral; P28331; -.
DR CarbonylDB; P28331; -.
DR GlyGen; P28331; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P28331; -.
DR MetOSite; P28331; -.
DR PhosphoSitePlus; P28331; -.
DR SwissPalm; P28331; -.
DR BioMuta; NDUFS1; -.
DR DMDM; 92090799; -.
DR REPRODUCTION-2DPAGE; IPI00604664; -.
DR REPRODUCTION-2DPAGE; P28331; -.
DR UCD-2DPAGE; P28331; -.
DR CPTAC; CPTAC-413; -.
DR CPTAC; CPTAC-414; -.
DR EPD; P28331; -.
DR jPOST; P28331; -.
DR MassIVE; P28331; -.
DR MaxQB; P28331; -.
DR PaxDb; P28331; -.
DR PeptideAtlas; P28331; -.
DR PRIDE; P28331; -.
DR ProteomicsDB; 17145; -.
DR ProteomicsDB; 54470; -. [P28331-1]
DR ProteomicsDB; 54471; -. [P28331-2]
DR ProteomicsDB; 54472; -. [P28331-3]
DR ProteomicsDB; 54473; -. [P28331-4]
DR Antibodypedia; 34175; 317 antibodies from 37 providers.
DR DNASU; 4719; -.
DR Ensembl; ENST00000233190.11; ENSP00000233190.5; ENSG00000023228.14. [P28331-1]
DR Ensembl; ENST00000423725.5; ENSP00000397760.1; ENSG00000023228.14. [P28331-4]
DR Ensembl; ENST00000432169.5; ENSP00000409689.1; ENSG00000023228.14. [P28331-3]
DR Ensembl; ENST00000440274.5; ENSP00000409766.1; ENSG00000023228.14. [P28331-5]
DR Ensembl; ENST00000449699.5; ENSP00000399912.1; ENSG00000023228.14. [P28331-1]
DR Ensembl; ENST00000455934.6; ENSP00000392709.2; ENSG00000023228.14. [P28331-2]
DR Ensembl; ENST00000635748.2; ENSP00000489640.1; ENSG00000283447.2. [P28331-1]
DR Ensembl; ENST00000636505.1; ENSP00000490898.1; ENSG00000283447.2. [P28331-1]
DR Ensembl; ENST00000637298.1; ENSP00000490583.1; ENSG00000283447.2. [P28331-4]
DR Ensembl; ENST00000637631.1; ENSP00000489705.1; ENSG00000283447.2. [P28331-3]
DR Ensembl; ENST00000637733.1; ENSP00000490092.1; ENSG00000283447.2. [P28331-2]
DR Ensembl; ENST00000637990.1; ENSP00000490766.1; ENSG00000283447.2. [P28331-5]
DR GeneID; 4719; -.
DR KEGG; hsa:4719; -.
DR MANE-Select; ENST00000233190.11; ENSP00000233190.5; NM_005006.7; NP_004997.4.
DR UCSC; uc002vbe.4; human. [P28331-1]
DR CTD; 4719; -.
DR DisGeNET; 4719; -.
DR GeneCards; NDUFS1; -.
DR GeneReviews; NDUFS1; -.
DR HGNC; HGNC:7707; NDUFS1.
DR HPA; ENSG00000023228; Tissue enhanced (skeletal muscle, tongue).
DR MalaCards; NDUFS1; -.
DR MIM; 157655; gene.
DR MIM; 618226; phenotype.
DR neXtProt; NX_P28331; -.
DR OpenTargets; ENSG00000023228; -.
DR Orphanet; 2609; Isolated complex I deficiency.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR PharmGKB; PA31518; -.
DR VEuPathDB; HostDB:ENSG00000023228; -.
DR eggNOG; KOG2282; Eukaryota.
DR GeneTree; ENSGT00940000153514; -.
DR HOGENOM; CLU_000422_11_2_1; -.
DR InParanoid; P28331; -.
DR OMA; HKNVGPL; -.
DR OrthoDB; 1095510at2759; -.
DR PhylomeDB; P28331; -.
DR TreeFam; TF105756; -.
DR BioCyc; MetaCyc:HS00422-MON; -.
DR PathwayCommons; P28331; -.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR SignaLink; P28331; -.
DR SIGNOR; P28331; -.
DR BioGRID-ORCS; 4719; 274 hits in 1090 CRISPR screens.
DR ChiTaRS; NDUFS1; human.
DR GeneWiki; NDUFS1; -.
DR GenomeRNAi; 4719; -.
DR Pharos; P28331; Tclin.
DR PRO; PR:P28331; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P28331; protein.
DR Bgee; ENSG00000023228; Expressed in corpus callosum and 107 other tissues.
DR ExpressionAtlas; P28331; baseline and differential.
DR Genevisible; P28331; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB.
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:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IBA:GO_Central.
DR GO; GO:0009055; F:electron transfer activity; NAS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IMP:UniProtKB.
DR GO; GO:0009060; P:aerobic respiration; IC:ComplexPortal.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IDA:UniProtKB.
DR GO; GO:0046034; P:ATP metabolic process; IMP:UniProtKB.
DR GO; GO:0045333; P:cellular respiration; IMP:UniProtKB.
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:0072593; P:reactive oxygen species metabolic process; IMP:UniProtKB.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IMP:UniProtKB.
DR CDD; cd00207; fer2; 1.
DR InterPro; IPR036010; 2Fe-2S_ferredoxin-like_sf.
DR InterPro; IPR001041; 2Fe-2S_ferredoxin-type.
DR InterPro; IPR006656; Mopterin_OxRdtase.
DR InterPro; IPR006963; Mopterin_OxRdtase_4Fe-4S_dom.
DR InterPro; IPR000283; NADH_UbQ_OxRdtase_75kDa_su_CS.
DR InterPro; IPR010228; NADH_UbQ_OxRdtase_Gsu.
DR InterPro; IPR019574; NADH_UbQ_OxRdtase_Gsu_4Fe4S-bd.
DR InterPro; IPR015405; NuoG_C.
DR Pfam; PF00384; Molybdopterin; 1.
DR Pfam; PF10588; NADH-G_4Fe-4S_3; 1.
DR Pfam; PF09326; NADH_dhqG_C; 1.
DR SMART; SM00929; NADH-G_4Fe-4S_3; 1.
DR SUPFAM; SSF54292; SSF54292; 1.
DR TIGRFAMs; TIGR01973; NuoG; 1.
DR PROSITE; PS51085; 2FE2S_FER_2; 1.
DR PROSITE; PS51839; 4FE4S_HC3; 1.
DR PROSITE; PS51669; 4FE4S_MOW_BIS_MGD; 1.
DR PROSITE; PS00641; COMPLEX1_75K_1; 1.
DR PROSITE; PS00642; COMPLEX1_75K_2; 1.
DR PROSITE; PS00643; COMPLEX1_75K_3; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; 3D-structure; 4Fe-4S; Acetylation; Alternative splicing;
KW Direct protein sequencing; Disease variant; Electron transport; Iron;
KW Iron-sulfur; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; NAD; Oxidoreductase;
KW Primary mitochondrial disease; Reference proteome; Respiratory chain;
KW Transit peptide; Translocase; Transport; Ubiquinone.
FT TRANSIT 1..23
FT /note="Mitochondrion"
FT /evidence="ECO:0007744|PubMed:25944712"
FT CHAIN 24..727
FT /note="NADH-ubiquinone oxidoreductase 75 kDa subunit,
FT mitochondrial"
FT /id="PRO_0000019968"
FT DOMAIN 30..108
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT DOMAIN 108..147
FT /note="4Fe-4S His(Cys)3-ligated-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184"
FT DOMAIN 245..301
FT /note="4Fe-4S Mo/W bis-MGD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01004"
FT BINDING 64
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT BINDING 75
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT BINDING 78
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT BINDING 92
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT BINDING 124
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184"
FT BINDING 128
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184"
FT BINDING 131
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184"
FT BINDING 137
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184"
FT BINDING 176
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 179
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 182
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 226
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 84
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91VD9"
FT MOD_RES 467
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91VD9"
FT MOD_RES 499
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91VD9"
FT MOD_RES 709
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91VD9"
FT VAR_SEQ 1..57
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043727"
FT VAR_SEQ 1..2
FT /note="ML -> MW (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043728"
FT VAR_SEQ 1
FT /note="M -> MRIRGSSGTLSRINM (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_042682"
FT VAR_SEQ 3..113
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043729"
FT VAR_SEQ 52..87
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045864"
FT VARIANT 228
FT /note="V -> A (in MC1DN5; loss of catalytic activity)"
FT /evidence="ECO:0000269|PubMed:31557978"
FT /id="VAR_084177"
FT VARIANT 241
FT /note="R -> Q (in dbSNP:rs17856901)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_025511"
FT VARIANT 241
FT /note="R -> W (in MC1DN5; unknown pathological
FT significance; dbSNP:rs199422225)"
FT /evidence="ECO:0000269|PubMed:11349233"
FT /id="VAR_019532"
FT VARIANT 252
FT /note="D -> G (in MC1DN5; also found in a patient with
FT muscular hypotonia; loss of catalytic activity;
FT dbSNP:rs199422224)"
FT /evidence="ECO:0000269|PubMed:11349233,
FT ECO:0000269|PubMed:31557978"
FT /id="VAR_019533"
FT VARIANT 253
FT /note="V -> G (in dbSNP:rs786205666)"
FT /evidence="ECO:0000269|PubMed:22499341"
FT /id="VAR_069506"
FT VARIANT 649
FT /note="V -> F (in dbSNP:rs1044049)"
FT /evidence="ECO:0000269|PubMed:1935949"
FT /id="VAR_018463"
FT CONFLICT 8
FT /note="K -> R (in Ref. 1; CAA43412)"
FT /evidence="ECO:0000305"
FT CONFLICT 417
FT /note="R -> W (in Ref. 1; CAA43412)"
FT /evidence="ECO:0000305"
FT CONFLICT 572
FT /note="H -> L (in Ref. 2; BAG58551)"
FT /evidence="ECO:0000305"
FT CONFLICT 691
FT /note="I -> L (in Ref. 1; CAA43412)"
FT /evidence="ECO:0000305"
FT STRAND 32..43
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 49..56
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 107..120
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 138..145
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 181..186
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 187..190
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 221..225
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 235..238
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 246..251
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 269..275
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 279..282
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 288..291
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 293..298
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 319..330
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 335..337
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 340..342
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 348..360
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 368..370
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 380..382
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 383..385
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 391..393
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 394..396
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 407..409
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 412..423
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 448..457
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 461..468
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 469..471
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 478..481
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 482..485
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 486..503
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 522..527
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 535..537
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 545..548
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 552..554
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 576..579
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 581..583
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 589..591
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 595..597
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 603..605
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 613..615
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 619..629
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 639..647
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 652..654
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 666..673
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 674..676
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 691..695
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 699..703
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 705..715
FT /evidence="ECO:0007829|PDB:5XTB"
SQ SEQUENCE 727 AA; 79468 MW; 9C35F4B8294771FB CRC64;
MLRIPVRKAL VGLSKSPKGC VRTTATAASN LIEVFVDGQS VMVEPGTTVL QACEKVGMQI
PRFCYHERLS VAGNCRMCLV EIEKAPKVVA ACAMPVMKGW NILTNSEKSK KAREGVMEFL
LANHPLDCPI CDQGGECDLQ DQSMMFGNDR SRFLEGKRAV EDKNIGPLVK TIMTRCIQCT
RCIRFASEIA GVDDLGTTGR GNDMQVGTYI EKMFMSELSG NIIDICPVGA LTSKPYAFTA
RPWETRKTES IDVMDAVGSN IVVSTRTGEV MRILPRMHED INEEWISDKT RFAYDGLKRQ
RLTEPMVRNE KGLLTYTSWE DALSRVAGML QSFQGKDVAA IAGGLVDAEA LVALKDLLNR
VDSDTLCTEE VFPTAGAGTD LRSNYLLNTT IAGVEEADVV LLVGTNPRFE APLFNARIRK
SWLHNDLKVA LIGSPVDLTY TYDHLGDSPK ILQDIASGSH PFSQVLKEAK KPMVVLGSSA
LQRNDGAAIL AAVSSIAQKI RMTSGVTGDW KVMNILHRIA SQVAALDLGY KPGVEAIRKN
PPKVLFLLGA DGGCITRQDL PKDCFIIYQG HHGDVGAPIA DVILPGAAYT EKSATYVNTE
GRAQQTKVAV TPPGLAREDW KIIRALSEIA GMTLPYDTLD QVRNRLEEVS PNLVRYDDIE
GANYFQQANE LSKLVNQQLL ADPLVPPQLT IKDFYMTDSI SRASQTMAKC VKAVTEGAQA
VEEPSIC
