NDUS3_MOUSE
ID NDUS3_MOUSE Reviewed; 263 AA.
AC Q9DCT2; Q8BTZ3; Q8R073;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial;
DE EC=7.1.1.2 {ECO:0000269|PubMed:31916679, ECO:0000269|PubMed:33148885};
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Kidney, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP PROTEIN SEQUENCE OF 109-121; 125-135; 186-198; 200-210 AND 218-245, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain, and Hippocampus;
RA Lubec G., Klug S., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP 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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=31916679; DOI=10.15252/emmm.201910674;
RA Pereira C.V., Peralta S., Arguello T., Bacman S.R., Diaz F., Moraes C.T.;
RT "Myopathy reversion in mice after restauration of mitochondrial complex
RT I.";
RL EMBO Mol. Med. 12:e10674-e10674(2020).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=33148885; DOI=10.1172/jci.insight.141183;
RA Peralta S., Pinto M., Arguello T., Garcia S., Diaz F., Moraes C.T.;
RT "Metformin delays neurological symptom onset in a mouse model of neuronal
RT complex I deficiency.";
RL JCI Insight 5:0-0(2020).
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:31916679, PubMed:33148885). Essential for the
CC catalytic activity and assembly of complex I (PubMed:31916679,
CC PubMed:33148885). {ECO:0000269|PubMed:31916679,
CC ECO:0000269|PubMed:33148885}.
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:31916679, ECO:0000269|PubMed:33148885};
CC -!- SUBUNIT: Core subunit of respiratory chain NADH dehydrogenase (Complex
CC I) which is composed of 45 different subunits (By similarity).
CC Interacts with NDUFAF3 (By similarity). Interacts with RAB5IF
CC (PubMed:31536960). Found in subcomplexes containing subunits NDUFS2,
CC MT-ND1 and NDUFA13 (By similarity). {ECO:0000250|UniProtKB:O75489,
CC ECO:0000269|PubMed:31536960}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:O75489}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O75489}; Matrix side
CC {ECO:0000250|UniProtKB:O75489}.
CC -!- DISRUPTION PHENOTYPE: Conditional knockout (KO) in the forebrain
CC neurons results in reduced complex I activity, altered brain energy
CC metabolism, increased locomotor activity with impaired motor
CC coordination, balance and stereotyped behavior, neuroinflammation in
CC cortex and hippocampus, and neuronal death in hippocampus
CC (PubMed:33148885). Conditional KO in skeletal muscle results in
CC development of a progressive myopathy resulting in premature death,
CC muscle degeneration accompanied by increased mitochondrial
CC proliferation and serum lactic acidosis and a decrease in complex I
CC activity, assembly and expression in muscle (PubMed:31916679).
CC {ECO:0000269|PubMed:31916679, ECO:0000269|PubMed:33148885}.
CC -!- SIMILARITY: Belongs to the complex I 30 kDa subunit family.
CC {ECO:0000305}.
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DR EMBL; AK002501; BAB22149.1; -; mRNA.
DR EMBL; AK088337; BAC40291.1; -; mRNA.
DR EMBL; AL672241; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027270; AAH27270.1; -; mRNA.
DR EMBL; BC119267; AAI19268.1; -; mRNA.
DR EMBL; BC119269; AAI19270.1; -; mRNA.
DR CCDS; CCDS16418.1; -.
DR RefSeq; NP_080964.1; NM_026688.2.
DR PDB; 6G2J; EM; 3.30 A; C=1-263.
DR PDB; 6G72; EM; 3.90 A; C=1-263.
DR PDB; 6ZR2; EM; 3.10 A; C=1-263.
DR PDB; 6ZTQ; EM; 3.00 A; C=1-263.
DR PDB; 7AK5; EM; 3.17 A; C=1-263.
DR PDB; 7AK6; EM; 3.82 A; C=1-263.
DR PDB; 7B93; EM; 3.04 A; C=1-263.
DR PDB; 7PSA; EM; 3.40 A; C=1-263.
DR PDBsum; 6G2J; -.
DR PDBsum; 6G72; -.
DR PDBsum; 6ZR2; -.
DR PDBsum; 6ZTQ; -.
DR PDBsum; 7AK5; -.
DR PDBsum; 7AK6; -.
DR PDBsum; 7B93; -.
DR PDBsum; 7PSA; -.
DR AlphaFoldDB; Q9DCT2; -.
DR SMR; Q9DCT2; -.
DR BioGRID; 212816; 83.
DR ComplexPortal; CPX-266; Mitochondrial respiratory chain complex I.
DR CORUM; Q9DCT2; -.
DR DIP; DIP-32378N; -.
DR IntAct; Q9DCT2; 10.
DR MINT; Q9DCT2; -.
DR STRING; 10090.ENSMUSP00000005647; -.
DR iPTMnet; Q9DCT2; -.
DR PhosphoSitePlus; Q9DCT2; -.
DR SwissPalm; Q9DCT2; -.
DR World-2DPAGE; 0004:Q9DCT2; -.
DR EPD; Q9DCT2; -.
DR jPOST; Q9DCT2; -.
DR MaxQB; Q9DCT2; -.
DR PaxDb; Q9DCT2; -.
DR PeptideAtlas; Q9DCT2; -.
DR PRIDE; Q9DCT2; -.
DR ProteomicsDB; 253047; -.
DR TopDownProteomics; Q9DCT2; -.
DR Antibodypedia; 1262; 305 antibodies from 35 providers.
DR Ensembl; ENSMUST00000005647; ENSMUSP00000005647; ENSMUSG00000005510.
DR GeneID; 68349; -.
DR KEGG; mmu:68349; -.
DR UCSC; uc008ktr.1; mouse.
DR CTD; 4722; -.
DR MGI; MGI:1915599; Ndufs3.
DR VEuPathDB; HostDB:ENSMUSG00000005510; -.
DR eggNOG; KOG1713; Eukaryota.
DR GeneTree; ENSGT00390000017480; -.
DR HOGENOM; CLU_042628_0_1_1; -.
DR InParanoid; Q9DCT2; -.
DR OMA; PCRKNRF; -.
DR OrthoDB; 1276923at2759; -.
DR PhylomeDB; Q9DCT2; -.
DR TreeFam; TF314794; -.
DR Reactome; R-MMU-611105; Respiratory electron transport.
DR Reactome; R-MMU-6799198; Complex I biogenesis.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR BioGRID-ORCS; 68349; 15 hits in 72 CRISPR screens.
DR ChiTaRS; Ndufs3; mouse.
DR PRO; PR:Q9DCT2; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9DCT2; protein.
DR Bgee; ENSMUSG00000005510; Expressed in quadriceps femoris and 87 other tissues.
DR Genevisible; Q9DCT2; MM.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0005747; C:mitochondrial respiratory chain complex I; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IMP:UniProtKB.
DR GO; GO:0003954; F:NADH dehydrogenase activity; ISS: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; ISS:UniProtKB.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; ISS: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; ISS: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; Direct protein sequencing; Electron transport; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; NAD; Oxidoreductase;
KW Reference proteome; Respiratory chain; Transit peptide; Translocase;
KW Transport; Ubiquinone.
FT TRANSIT 1..35
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 36..263
FT /note="NADH dehydrogenase [ubiquinone] iron-sulfur protein
FT 3, mitochondrial"
FT /id="PRO_0000019999"
FT CONFLICT 20
FT /note="G -> D (in Ref. 1; BAB22149)"
FT /evidence="ECO:0000305"
FT CONFLICT 23
FT /note="A -> P (in Ref. 3; AAH27270)"
FT /evidence="ECO:0000305"
FT CONFLICT 49
FT /note="R -> W (in Ref. 3; AAH27270)"
FT /evidence="ECO:0000305"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT HELIX 52..67
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 79..81
FT /evidence="ECO:0007829|PDB:7B93"
FT STRAND 83..87
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT HELIX 92..101
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:7B93"
FT STRAND 109..116
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 119..123
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 126..132
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 134..137
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 139..145
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT TURN 156..158
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT HELIX 162..173
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:7B93"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 198..201
FT /evidence="ECO:0007829|PDB:7AK5"
FT STRAND 206..212
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT TURN 213..216
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 217..222
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:6ZTQ"
SQ SEQUENCE 263 AA; 30149 MW; 482F6C4D5E991B7F CRC64;
MAAAAARVWC RGLLGAASVG RGAGRPSVLW QHVRRESAAA DKRPTVRPRS DVTHKQLSAF
GEYVAEILPK YVQQVQVSCL DELEICIHPD GVIPTLTFLR DHTNAQFKSL ADLTAVDVPT
RQNRFEIVYN LLSLRFNSRI RVKTYADELT PIDSIVSVHI AANWYEREVW DMFGVFFFNH
PDLRRILTDY GFEGHPFRKD FPLTGYVELR YDDEVKRVVA EPVELAQEFR KFDLNSPWEA
FPAYRQPPES LKLEAGDKKP ETK
