NDUS8_DROME
ID NDUS8_DROME Reviewed; 217 AA.
AC Q9VF27; Q8SZF2;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=NADH dehydrogenase (ubiquinone) 23 kDa subunit {ECO:0000303|PubMed:29496745, ECO:0000312|EMBL:AAF55234.1};
DE EC=7.1.1.2 {ECO:0000250|UniProtKB:Q56224};
DE Flags: Precursor;
GN Name=ND-23 {ECO:0000303|PubMed:29496745, ECO:0000312|FlyBase:FBgn0017567};
GN Synonyms=dNDUFS8 {ECO:0000303|PubMed:28683319},
GN NUIM {ECO:0000312|FlyBase:FBgn0017567};
GN ORFNames=CG3944 {ECO:0000312|FlyBase:FBgn0017567};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAL48541.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL48541.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAL48541.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000305}
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, IDENTIFICATION IN THE
RP NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=28683319; DOI=10.1016/j.celrep.2017.06.015;
RA Garcia C.J., Khajeh J., Coulanges E., Chen E.I., Owusu-Ansah E.;
RT "Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight
RT Muscles.";
RL Cell Rep. 20:264-278(2017).
RN [5] {ECO:0000305}
RP MUTAGENESIS OF GLY-199.
RX PubMed=29496745; DOI=10.1534/genetics.118.300818;
RA Loewen C.A., Ganetzky B.;
RT "Mito-Nuclear Interactions Affecting Lifespan and Neurodegeneration in a
RT Drosophila Model of Leigh Syndrome.";
RL Genetics 208:1535-1552(2018).
RN [6] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=29285794; DOI=10.1002/glia.23290;
RA Cabirol-Pol M.J., Khalil B., Rival T., Faivre-Sarrailh C., Besson M.T.;
RT "Glial lipid droplets and neurodegeneration in a Drosophila model of
RT complex I deficiency.";
RL Glia 66:874-888(2018).
CC -!- FUNCTION: Core subunit of the mitochondrial membrane respiratory chain
CC NADH dehydrogenase (Complex I) that is believed to belong to the
CC minimal assembly required for catalysis. Complex I functions in the
CC transfer of electrons from NADH to the respiratory chain. The immediate
CC electron acceptor for the enzyme is believed to be ubiquinone.
CC {ECO:0000305|PubMed:28683319}.
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:0000250|UniProtKB:Q56224};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:Q56224};
CC Note=Binds 2 [4Fe-4S] cluster. {ECO:0000250|UniProtKB:Q56224};
CC -!- SUBUNIT: Part of the mitochondrial membrane respiratory chain NADH
CC dehydrogenase (Complex I) (PubMed:28683319). This is a component of the
CC iron-sulfur (IP) fragment of the enzyme (PubMed:28683319).
CC {ECO:0000269|PubMed:28683319}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:28683319}.
CC -!- TISSUE SPECIFICITY: Expressed in muscles (at protein level).
CC {ECO:0000269|PubMed:28683319}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown is lethal
CC (PubMed:29285794). RNAi-mediated knockdown in the muscles impairs
CC biogenesis of the mitochondrial membrane respiratory chain NADH
CC dehydrogenase (Complex I) (PubMed:28683319). RNAi-mediated knockdown in
CC neurons impairs neuronal ATP production, reduces locomotor activity and
CC shortens lifespan (PubMed:29285794). In addition, results in large
CC vacuoles in the retina, ommatidia disorganization and selective axonal
CC alterations in mushroom bodies (PubMed:29285794). RNAi-mediated
CC knockdown in glia results in large vacuoles and lipid droplets in both
CC cortical region of the brain and optic lobes suggesting altered lipid
CC metabolism; does not alter lifespan or behavior (PubMed:29285794).
CC {ECO:0000269|PubMed:28683319, ECO:0000269|PubMed:29285794}.
CC -!- SIMILARITY: Belongs to the complex I 23 kDa subunit family.
CC {ECO:0000305}.
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DR EMBL; AE014297; AAF55234.1; -; Genomic_DNA.
DR EMBL; AY060840; AAL28388.1; -; mRNA.
DR EMBL; AY070919; AAL48541.1; -; mRNA.
DR RefSeq; NP_524719.1; NM_079980.4.
DR AlphaFoldDB; Q9VF27; -.
DR SMR; Q9VF27; -.
DR IntAct; Q9VF27; 1.
DR STRING; 7227.FBpp0082645; -.
DR PaxDb; Q9VF27; -.
DR PRIDE; Q9VF27; -.
DR DNASU; 44207; -.
DR EnsemblMetazoa; FBtr0083191; FBpp0082645; FBgn0017567.
DR GeneID; 44207; -.
DR KEGG; dme:Dmel_CG3944; -.
DR UCSC; CG3944-RA; d. melanogaster.
DR CTD; 44207; -.
DR FlyBase; FBgn0017567; ND-23.
DR VEuPathDB; VectorBase:FBgn0017567; -.
DR eggNOG; KOG3256; Eukaryota.
DR GeneTree; ENSGT00390000003049; -.
DR HOGENOM; CLU_067218_5_1_1; -.
DR InParanoid; Q9VF27; -.
DR OMA; RGDLYYT; -.
DR OrthoDB; 1283957at2759; -.
DR PhylomeDB; Q9VF27; -.
DR Reactome; R-DME-611105; Respiratory electron transport.
DR Reactome; R-DME-6799198; Complex I biogenesis.
DR SignaLink; Q9VF27; -.
DR BioGRID-ORCS; 44207; 0 hits in 1 CRISPR screen.
DR ChiTaRS; N; fly.
DR GenomeRNAi; 44207; -.
DR PRO; PR:Q9VF27; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0017567; Expressed in insect adult head and 28 other tissues.
DR GO; GO:0005747; C:mitochondrial respiratory chain complex I; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; HDA:FlyBase.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IEA:UniProtKB-EC.
DR GO; GO:0009060; P:aerobic respiration; IBA:GO_Central.
DR GO; GO:0042775; P:mitochondrial ATP synthesis coupled electron transport; IMP:UniProtKB.
DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IBA:GO_Central.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IBA:GO_Central.
DR HAMAP; MF_01351; NDH1_NuoI; 1.
DR InterPro; IPR017896; 4Fe4S_Fe-S-bd.
DR InterPro; IPR017900; 4Fe4S_Fe_S_CS.
DR InterPro; IPR010226; NADH_quinone_OxRdtase_chainI.
DR PANTHER; PTHR10849; PTHR10849; 1.
DR Pfam; PF12838; Fer4_7; 1.
DR TIGRFAMs; TIGR01971; NuoI; 1.
DR PROSITE; PS00198; 4FE4S_FER_1; 2.
DR PROSITE; PS51379; 4FE4S_FER_2; 2.
PE 1: Evidence at protein level;
KW 4Fe-4S; Electron transport; Iron; Iron-sulfur; Metal-binding;
KW Mitochondrion; Oxidoreductase; Reference proteome; Transit peptide;
KW Translocase; Transport; Ubiquinone.
FT TRANSIT 1..26
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 27..217
FT /note="NADH dehydrogenase (ubiquinone) 23 kDa subunit"
FT /evidence="ECO:0000255"
FT /id="PRO_0000450675"
FT DOMAIN 109..138
FT /note="4Fe-4S ferredoxin-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT DOMAIN 148..177
FT /note="4Fe-4S ferredoxin-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT BINDING 118
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT BINDING 121
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT BINDING 124
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT BINDING 128
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT BINDING 157
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT BINDING 160
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT BINDING 163
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT BINDING 167
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT MUTAGEN 199
FT /note="G->D: Disrupts mitochondrial function and results in
FT enlarged mitochondria. Neurons present vacuolar lesions
FT leading to neurodegeneration in the central brain. Results
FT in behavioral defects and shorten lifespan."
FT /evidence="ECO:0000269|PubMed:29496745"
FT CONFLICT 170
FT /note="D -> G (in Ref. 3; AAL48541)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 217 AA; 24578 MW; D4ED522CA1BC6BA2 CRC64;
MSLTMRIFTA SRNGQRLFGS HGARLLAAQR AEPKDIVEVP KGYVYVNNKE LSMEFADITD
RAASTMFFGE LLRGFAVTLA HIFKEPATIN YPFEKGPLSP RFRGEHALRR YPSGEERCIA
CKLCEAICPA QAITIEAEER ADGSRRTTRY DIDMTKCIYC GFCQEACPVD AIVEGPNFEF
STETHEELLY NKEKLLCNGD KWESEIASNL QADHLYR
