NDUS4_MOUSE
ID NDUS4_MOUSE Reviewed; 175 AA.
AC Q9CXZ1; Q9WUB1;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 3.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial;
DE AltName: Full=Complex I-18 kDa;
DE Short=CI-18 kDa;
DE AltName: Full=Complex I-AQDQ;
DE Short=CI-AQDQ;
DE AltName: Full=NADH-ubiquinone oxidoreductase 18 kDa subunit;
DE Flags: Precursor;
GN Name=Ndufs4;
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; TISSUE=Liver;
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 [MRNA] OF 7-175.
RC STRAIN=BALB/cJ; TISSUE=Skeletal muscle;
RX PubMed=10318868; DOI=10.1074/jbc.274.20.14429;
RA Murdock D.G., Boone B.E., Esposito L.A., Wallace D.C.;
RT "Up-regulation of nuclear and mitochondrial genes in the skeletal muscle of
RT mice lacking the heart/muscle isoform of the adenine nucleotide
RT translocator.";
RL J. Biol. Chem. 274:14429-14433(1999).
RN [3]
RP PROTEIN SEQUENCE OF 49-73; 132-150 AND 159-168, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=18396137; DOI=10.1016/j.cmet.2008.02.004;
RA Kruse S.E., Watt W.C., Marcinek D.J., Kapur R.P., Schenkman K.A.,
RA Palmiter R.D.;
RT "Mice with mitochondrial complex I deficiency develop a fatal
RT encephalomyopathy.";
RL Cell Metab. 7:312-320(2008).
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 PHOSPHORYLATION AT SER-173.
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 [7]
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 [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=31403401; DOI=10.7554/elife.47163;
RA Bolea I., Gella A., Sanz E., Prada-Dacasa P., Menardy F., Bard A.M.,
RA Machuca-Marquez P., Eraso-Pichot A., Modol-Caballero G., Navarro X.,
RA Kalume F., Quintana A.;
RT "Defined neuronal populations drive fatal phenotype in a mouse model of
RT Leigh syndrome.";
RL Elife 8:0-0(2019).
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:0000250|UniProtKB:O43181}.
CC -!- SUBUNIT: Mammalian complex I is composed of 45 different subunits. This
CC is a component of the iron-sulfur (IP) fragment of the enzyme.
CC Interacts with BCAP31 and TOMM40; the interaction mediates its
CC translocation to the mitochondria; the interaction with BCAP31 is
CC direct. {ECO:0000250|UniProtKB:O43181}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:O43181}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O43181}; Matrix side
CC {ECO:0000250|UniProtKB:O43181}. Note=The interaction with BCAP31
CC mediates mitochondria localization. {ECO:0000250|UniProtKB:O43181}.
CC -!- DISRUPTION PHENOTYPE: Reduces the levels of assembled mitochondrial
CC membrane respiratory chain NADH dehydrogenase (Complex I) and the rate
CC of Complex I-driven oxygen consumption (PubMed:18396137,
CC PubMed:25594180). Growth is retarded although activity and behavior are
CC not affected during the first 4 weeks (PubMed:18396137). With aging,
CC results in increasing lethargy, rapid deterioration of motor ability,
CC weight loss followed by death (PubMed:18396137). Mitochondrial
CC ultrastructure is normal, although large subsarcolemmal clusters of
CC mitochondria are present in the soleus (PubMed:25594180). Exhibits
CC glial lipid droplets accumulation in the olfactory bulb and vestibular
CC nucleus prior to the onset of the physical signs of neurodegeneration
CC (PubMed:25594180). Treatment with anti-oxidant treatment ameliorates
CC the phenotype (PubMed:25594180). Conditional knockout in Vglut2-
CC expressing glutamatergic neurons leads to decreased neuronal firing,
CC brainstem inflammation, motor and respiratory deficits, and early death
CC (PubMed:31403401). Conditional knockout in GABAergic neurons causes
CC basal ganglia inflammation without motor or respiratory involvement,
CC but accompanied by hypothermia and severe epileptic seizures preceding
CC death (PubMed:31403401). Conditional knockout in cholinergic neurons
CC has no effect on survival, body weight, or motor function
CC (PubMed:31403401). {ECO:0000269|PubMed:18396137,
CC ECO:0000269|PubMed:25594180, ECO:0000269|PubMed:31403401}.
CC -!- SIMILARITY: Belongs to the complex I NDUFS4 subunit family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD30474.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK011124; BAB27417.2; -; mRNA.
DR EMBL; AF124785; AAD30474.1; ALT_INIT; mRNA.
DR CCDS; CCDS49368.1; -.
DR RefSeq; NP_035017.2; NM_010887.2.
DR PDB; 6G2J; EM; 3.30 A; Q=1-175.
DR PDB; 6G72; EM; 3.90 A; Q=1-175.
DR PDB; 6ZR2; EM; 3.10 A; Q=1-175.
DR PDB; 6ZTQ; EM; 3.00 A; Q=1-175.
DR PDB; 7AK5; EM; 3.17 A; Q=1-175.
DR PDB; 7AK6; EM; 3.82 A; Q=1-175.
DR PDB; 7B93; EM; 3.04 A; Q=1-175.
DR PDB; 7PSA; EM; 3.40 A; Q=1-175.
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; Q9CXZ1; -.
DR SMR; Q9CXZ1; -.
DR BioGRID; 201718; 49.
DR ComplexPortal; CPX-266; Mitochondrial respiratory chain complex I.
DR CORUM; Q9CXZ1; -.
DR IntAct; Q9CXZ1; 6.
DR MINT; Q9CXZ1; -.
DR STRING; 10090.ENSMUSP00000022286; -.
DR iPTMnet; Q9CXZ1; -.
DR PhosphoSitePlus; Q9CXZ1; -.
DR EPD; Q9CXZ1; -.
DR jPOST; Q9CXZ1; -.
DR MaxQB; Q9CXZ1; -.
DR PaxDb; Q9CXZ1; -.
DR PeptideAtlas; Q9CXZ1; -.
DR PRIDE; Q9CXZ1; -.
DR ProteomicsDB; 253048; -.
DR DNASU; 17993; -.
DR GeneID; 17993; -.
DR KEGG; mmu:17993; -.
DR CTD; 4724; -.
DR MGI; MGI:1343135; Ndufs4.
DR eggNOG; KOG3389; Eukaryota.
DR InParanoid; Q9CXZ1; -.
DR OrthoDB; 1507807at2759; -.
DR PhylomeDB; Q9CXZ1; -.
DR Reactome; R-MMU-611105; Respiratory electron transport.
DR Reactome; R-MMU-6799198; Complex I biogenesis.
DR BioGRID-ORCS; 17993; 6 hits in 74 CRISPR screens.
DR ChiTaRS; Ndufs4; mouse.
DR PRO; PR:Q9CXZ1; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9CXZ1; protein.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI.
DR GO; GO:0005747; C:mitochondrial respiratory chain complex I; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IDA:MGI.
DR GO; GO:0030534; P:adult behavior; IMP:MGI.
DR GO; GO:0007628; P:adult walking behavior; IMP:MGI.
DR GO; GO:0009060; P:aerobic respiration; IC:ComplexPortal.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0045333; P:cellular respiration; ISO:MGI.
DR GO; GO:0071453; P:cellular response to oxygen levels; IMP:MGI.
DR GO; GO:0050890; P:cognition; IMP:MGI.
DR GO; GO:0042417; P:dopamine metabolic process; IMP:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; IMP:MGI.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:MGI.
DR GO; GO:0070997; P:neuron death; IMP:MGI.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:MGI.
DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; IC:ComplexPortal.
DR GO; GO:0036343; P:psychomotor behavior; IMP:MGI.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:MGI.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IMP:MGI.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0022904; P:respiratory electron transport chain; IMP:MGI.
DR GO; GO:0003016; P:respiratory system process; IMP:MGI.
DR GO; GO:0051591; P:response to cAMP; ISO:MGI.
DR GO; GO:0014876; P:response to injury involved in regulation of muscle adaptation; IMP:MGI.
DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
DR GO; GO:0006099; P:tricarboxylic acid cycle; TAS:MGI.
DR GO; GO:0007601; P:visual perception; IMP:MGI.
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 3D-structure; Direct protein sequencing; Electron transport; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Phosphoprotein;
KW Reference proteome; Respiratory chain; Transit peptide; Transport.
FT TRANSIT 1..42
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 43..175
FT /note="NADH dehydrogenase [ubiquinone] iron-sulfur protein
FT 4, mitochondrial"
FT /id="PRO_0000020039"
FT MOD_RES 173
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20433953"
FT CONFLICT 68
FT /note="P -> Q (in Ref. 1; BAB27417)"
FT /evidence="ECO:0000305"
FT HELIX 62..65
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT HELIX 70..73
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 95..101
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:7B93"
FT STRAND 126..131
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT HELIX 132..141
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:6ZTQ"
SQ SEQUENCE 175 AA; 19785 MW; 33D565B204D1C7A2 CRC64;
MAAVSISVSL RQAMLGRRAM ATAAVSVCRV PSRLLSTSTW KLADNQTRDT QLITVDEKLD
ITTLTGVPEE HIKTRKVRIF VPARNNMQSG VNNTKKWKME FDTRERWENP LMGWASTADP
LSNMVLTFSA KEDAIAFAEK NGWSYDVEEK KVPKPKSKSY GANFSWNKRT RVSTK
