NDUS4_DROME
ID NDUS4_DROME Reviewed; 183 AA.
AC Q9VWI0; Q1EC13; Q8SZL0;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial {ECO:0000255|RuleBase:RU367010, ECO:0000303|PubMed:25594180};
DE Flags: Precursor;
GN Name=ND-18 {ECO:0000303|PubMed:29590638, ECO:0000312|FlyBase:FBgn0031021};
GN Synonyms=dNDUFS4 {ECO:0000303|PubMed:25594180},
GN NUYM {ECO:0000312|EMBL:AAN09490.1};
GN ORFNames=CG12203 {ECO:0000312|FlyBase:FBgn0031021};
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:AAL48151.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL48151.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAL48151.1};
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:0000312|EMBL:ABG02165.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 26-183.
RA Stapleton M., Carlson J., Chavez C., Frise E., George R., Pacleb J.,
RA Park S., Wan K., Yu C., Celniker S.;
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP PHOSPHORYLATION AT SER-181.
RX PubMed=20433953; DOI=10.1016/j.mito.2010.04.005;
RA De Rasmo D., Palmisano G., Scacco S., Technikova-Dobrova Z., Panelli D.,
RA Cocco T., Sardanelli A.M., Gnoni A., Micelli L., Trani A., Di Luccia A.,
RA Papa S.;
RT "Phosphorylation pattern of the NDUFS4 subunit of complex I of the
RT mammalian respiratory chain.";
RL Mitochondrion 10:464-471(2010).
RN [6] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=25594180; DOI=10.1016/j.cell.2014.12.019;
RA Liu L., Zhang K., Sandoval H., Yamamoto S., Jaiswal M., Sanz E., Li Z.,
RA Hui J., Graham B.H., Quintana A., Bellen H.J.;
RT "Glial lipid droplets and ROS induced by mitochondrial defects promote
RT neurodegeneration.";
RL Cell 160:177-190(2015).
RN [7] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=29590638; DOI=10.1242/dmm.032482;
RA Foriel S., Beyrath J., Eidhof I., Rodenburg R.J., Schenck A.,
RA Smeitink J.A.M.;
RT "Feeding difficulties, a key feature of the Drosophila NDUFS4 mitochondrial
RT disease model.";
RL Dis. Model. Mech. 11:0-0(2018).
CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory
CC chain NADH dehydrogenase (Complex I), that is believed not to be
CC involved in catalysis. Complex I functions in the transfer of electrons
CC from NADH to the respiratory chain. The immediate electron acceptor for
CC the enzyme is believed to be ubiquinone.
CC {ECO:0000255|RuleBase:RU367010}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000255|RuleBase:RU367010}; Peripheral membrane protein
CC {ECO:0000255|RuleBase:RU367010}; Matrix side
CC {ECO:0000255|RuleBase:RU367010}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in mitochondrial
CC membrane respiratory chain NADH dehydrogenase (Complex I) deficiency
CC (PubMed:29590638). Mitochondria in the flight muscle shows a wide range
CC of structural abnormalities including dispersed cristae, onion-like
CC swirling membranes, swollen mitochondria, sparse matrix and irregular
CC cristae densities (PubMed:29590638). Eclosion rate is reduced,
CC locomotion and feeding are severely impaired and lifespan shortened
CC (PubMed:29590638). In the brain, there is a pericerebral fat body
CC deficit (PubMed:29590638). RNAi-mediated knockdown in neurons shortens
CC lifespan and results in mild defects in feeding behavior and geotaxis
CC response (PubMed:29590638). Results in lipid droplet accumulation in
CC the glia (PubMed:25594180). RNAi-mediated knockdown in the glia results
CC in no lipid droplet accumulation (PubMed:25594180). RNAi-mediated
CC knockdown in differentiated muscle impairs feeding and locomotion, and
CC shortens lifespan (PubMed:29590638). {ECO:0000269|PubMed:25594180,
CC ECO:0000269|PubMed:29590638}.
CC -!- SIMILARITY: Belongs to the complex I NDUFS4 subunit family.
CC {ECO:0000255|RuleBase:RU367010}.
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DR EMBL; AY070680; AAL48151.1; -; mRNA.
DR EMBL; BT025921; ABG02165.1; -; mRNA.
DR EMBL; AE014298; AAN09490.1; -; Genomic_DNA.
DR RefSeq; NP_573385.1; NM_133157.4.
DR AlphaFoldDB; Q9VWI0; -.
DR SMR; Q9VWI0; -.
DR IntAct; Q9VWI0; 1.
DR STRING; 7227.FBpp0074481; -.
DR PaxDb; Q9VWI0; -.
DR PRIDE; Q9VWI0; -.
DR DNASU; 32936; -.
DR EnsemblMetazoa; FBtr0074712; FBpp0074481; FBgn0031021.
DR GeneID; 32936; -.
DR KEGG; dme:Dmel_CG12203; -.
DR UCSC; CG12203-RA; d. melanogaster.
DR CTD; 32936; -.
DR FlyBase; FBgn0031021; ND-18.
DR VEuPathDB; VectorBase:FBgn0031021; -.
DR eggNOG; KOG3389; Eukaryota.
DR GeneTree; ENSGT00390000013835; -.
DR HOGENOM; CLU_077196_3_1_1; -.
DR InParanoid; Q9VWI0; -.
DR OMA; WRWYVDG; -.
DR OrthoDB; 1507807at2759; -.
DR PhylomeDB; Q9VWI0; -.
DR Reactome; R-DME-611105; Respiratory electron transport.
DR Reactome; R-DME-6799198; Complex I biogenesis.
DR BioGRID-ORCS; 32936; 0 hits in 1 CRISPR screen.
DR ChiTaRS; ND-18; fly.
DR GenomeRNAi; 32936; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0031021; Expressed in adult hindgut (Drosophila) and 36 other tissues.
DR ExpressionAtlas; Q9VWI0; baseline and differential.
DR GO; GO:0005747; C:mitochondrial respiratory chain complex I; ISS:FlyBase.
DR GO; GO:0022900; P:electron transport chain; IEA:InterPro.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; ISS:FlyBase.
DR Gene3D; 3.30.160.190; -; 1.
DR InterPro; IPR006885; NADH_UbQ_FeS_4_mit.
DR InterPro; IPR038532; NDUFS4-like_sf.
DR PANTHER; PTHR12219; PTHR12219; 1.
DR Pfam; PF04800; ETC_C1_NDUFA4; 1.
PE 1: Evidence at protein level;
KW Electron transport; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Phosphoprotein; Reference proteome; Respiratory chain; Transit peptide;
KW Transport; Ubiquinone.
FT TRANSIT 1..28
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 29..183
FT /note="NADH dehydrogenase [ubiquinone] iron-sulfur protein
FT 4, mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000451402"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20433953"
SQ SEQUENCE 183 AA; 20681 MW; 87C85CA6852A209C CRC64;
MSALRQVMCR STASLQLYQA NRAAAARWAS TATDGGPLDP KTALARPEEL EQRNKLSGKI
TVPTAVNLSP ISGVPEEHIR ERRVRIHIPP KNAMQSGTDN VNTWQIEFDN RERWENPLMG
WASSGDPLSN MNVQFGSPEE AITFCERNGW RWYVDGAAKP KKERVKNYGI NFAWNKRTRV
STK
