ETFD_HUMAN
ID ETFD_HUMAN Reviewed; 617 AA.
AC Q16134; B4E3R9; J3KND9; Q7Z347;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 2.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial {ECO:0000305};
DE Short=ETF-QO;
DE Short=ETF-ubiquinone oxidoreductase;
DE EC=1.5.5.1 {ECO:0000269|PubMed:12049629};
DE AltName: Full=Electron-transferring-flavoprotein dehydrogenase;
DE Short=ETF dehydrogenase;
DE Flags: Precursor;
GN Name=ETFDH {ECO:0000312|HGNC:HGNC:3483};
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), FUNCTION, CATALYTIC ACTIVITY, AND
RP VARIANT ILE-31.
RC TISSUE=Fetal liver;
RX PubMed=8306995; DOI=10.1111/j.1432-1033.1994.tb19939.x;
RA Goodman S.I., Axtell K.M., Bindoff L.A., Beard S.E., Gill R.E.,
RA Frerman F.E.;
RT "Molecular cloning and expression of a cDNA encoding human electron
RT transfer flavoprotein-ubiquinone oxidoreductase.";
RL Eur. J. Biochem. 219:277-286(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
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 MRNA] (ISOFORM 1), AND VARIANT ILE-31.
RC TISSUE=Small intestine;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-31.
RC TISSUE=Lung;
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 FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=12049629; DOI=10.1042/bj20020042;
RA Simkovic M., Degala G.D., Eaton S.S., Frerman F.E.;
RT "Expression of human electron transfer flavoprotein-ubiquinone
RT oxidoreductase from a baculovirus vector: kinetic and spectral
RT characterization of the human protein.";
RL Biochem. J. 364:659-667(2002).
RN [7]
RP INVOLVEMENT IN GA2C.
RX PubMed=12815589; DOI=10.1002/humu.10226;
RA Olsen R.K.J., Andresen B.S., Christensen E., Bross P., Skovby F.,
RA Gregersen N.;
RT "Clear relationship between ETF/ETFDH genotype and phenotype in patients
RT with multiple acyl-CoA dehydrogenation deficiency.";
RL Hum. Mutat. 22:12-23(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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-551, AND IDENTIFICATION BY
RP 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 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 VARIANTS GA2C CYS-49; PHE-82; PRO-82; ARG-138; ASN-218; PRO-222; PHE-262;
RP PRO-334; ARG-346; LYS-452; LEU-456; LEU-562 AND GLU-611, AND VARIANTS
RP CYS-16 AND ILE-31.
RX PubMed=12359134; DOI=10.1016/s1096-7192(02)00138-5;
RA Goodman S.I., Binard R.J., Woontner M.R., Frerman F.E.;
RT "Glutaric acidemia type II: gene structure and mutations of the electron
RT transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) gene.";
RL Mol. Genet. Metab. 77:86-90(2002).
RN [12]
RP VARIANTS GA2C TYR-112 AND THR-456.
RX PubMed=16527485; DOI=10.1016/j.nmd.2006.01.001;
RA Beresford M.W., Pourfarzam M., Turnbull D.M., Davidson J.E.;
RT "So doctor, what exactly is wrong with my muscles? Glutaric aciduria type
RT II presenting in a teenager.";
RL Neuromuscul. Disord. 16:269-273(2006).
RN [13]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-565.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [14]
RP VARIANTS GA2C PRO-377; LEU-456; LEU-483 AND GLU-590.
RX PubMed=17412732; DOI=10.1093/brain/awm054;
RA Gempel K., Topaloglu H., Talim B., Schneiderat P., Schoser B.G., Hans V.H.,
RA Palmafy B., Kale G., Tokatli A., Quinzii C., Hirano M., Naini A.,
RA DiMauro S., Prokisch H., Lochmueller H., Horvath R.;
RT "The myopathic form of coenzyme Q10 deficiency is caused by mutations in
RT the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene.";
RL Brain 130:2037-2044(2007).
RN [15]
RP VARIANTS GA2C THR-84; HIS-127 AND LEU-175.
RX PubMed=19249206; DOI=10.1016/j.nmd.2009.01.008;
RA Liang W.C., Ohkuma A., Hayashi Y.K., Lopez L.C., Hirano M., Nonaka I.,
RA Noguchi S., Chen L.H., Jong Y.J., Nishino I.;
RT "ETFDH mutations, CoQ10 levels, and respiratory chain activities in
RT patients with riboflavin-responsive multiple acyl-CoA dehydrogenase
RT deficiency.";
RL Neuromuscul. Disord. 19:212-216(2009).
RN [16]
RP VARIANTS GA2C THR-84 AND HIS-175.
RX PubMed=20370797; DOI=10.1111/j.1399-0004.2010.01421.x;
RA Lan M.Y., Fu M.H., Liu Y.F., Huang C.C., Chang Y.Y., Liu J.S., Peng C.H.,
RA Chen S.S.;
RT "High frequency of ETFDH c.250G>A mutation in Taiwanese patients with late-
RT onset lipid storage myopathy.";
RL Clin. Genet. 78:565-569(2010).
CC -!- FUNCTION: Accepts electrons from ETF and reduces ubiquinone.
CC {ECO:0000269|PubMed:12049629}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ubiquinone + reduced [electron-transfer flavoprotein] = a
CC ubiquinol + H(+) + oxidized [electron-transfer flavoprotein];
CC Xref=Rhea:RHEA:24052, Rhea:RHEA-COMP:9565, Rhea:RHEA-COMP:9566,
CC Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16389, ChEBI:CHEBI:17976, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307; EC=1.5.5.1;
CC Evidence={ECO:0000269|PubMed:12049629};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24053;
CC Evidence={ECO:0000305|PubMed:12049629};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Note=Binds 1 [4Fe-4S] cluster.;
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.1 uM for ubiquinone-1 (in the presence of 6 mM CHAPS)
CC {ECO:0000269|PubMed:12049629};
CC KM=4.9 uM for ubiquinone-2 (in the presence of 6 mM CHAPS)
CC {ECO:0000269|PubMed:12049629};
CC KM=14.8 uM for ubiquinone-4 (in the presence of 11 mM CHAPS)
CC {ECO:0000269|PubMed:12049629};
CC KM=8.4 uM for 6-decylubiquinone {ECO:0000269|PubMed:12049629};
CC KM=0.13 uM for oxidized [electron-transfer flavoprotein]
CC {ECO:0000269|PubMed:12049629};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:12049629}.
CC -!- INTERACTION:
CC Q16134; O15499: GSC2; NbExp=3; IntAct=EBI-2870454, EBI-19954058;
CC Q16134; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-2870454, EBI-1052037;
CC Q16134; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-2870454, EBI-11953846;
CC Q16134; A7E2Y1-2: MYH7B; NbExp=3; IntAct=EBI-2870454, EBI-12813813;
CC Q16134; P32242: OTX1; NbExp=3; IntAct=EBI-2870454, EBI-740446;
CC Q16134; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-2870454, EBI-11525489;
CC Q16134; Q9P0T4: ZNF581; NbExp=3; IntAct=EBI-2870454, EBI-745520;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q16134-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16134-3; Sequence=VSP_055158;
CC -!- DISEASE: Glutaric aciduria 2C (GA2C) [MIM:231680]: An autosomal
CC recessively inherited disorder of fatty acid, amino acid, and choline
CC metabolism. It is characterized by multiple acyl-CoA dehydrogenase
CC deficiencies resulting in large excretion not only of glutaric acid,
CC but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-
CC butyric, and isovaleric acids. {ECO:0000269|PubMed:12359134,
CC ECO:0000269|PubMed:12815589, ECO:0000269|PubMed:16527485,
CC ECO:0000269|PubMed:17412732, ECO:0000269|PubMed:19249206,
CC ECO:0000269|PubMed:20370797}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ETF-QO/FixC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD98030.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; S69232; AAC60628.1; -; mRNA.
DR EMBL; AK304838; BAG65581.1; -; mRNA.
DR EMBL; BX538129; CAD98030.1; ALT_SEQ; mRNA.
DR EMBL; AC107219; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC011890; AAH11890.1; -; mRNA.
DR CCDS; CCDS3800.1; -. [Q16134-1]
DR CCDS; CCDS64090.1; -. [Q16134-3]
DR PIR; S41115; S41115.
DR RefSeq; NP_001268666.1; NM_001281737.1. [Q16134-3]
DR RefSeq; NP_004444.2; NM_004453.3. [Q16134-1]
DR AlphaFoldDB; Q16134; -.
DR SMR; Q16134; -.
DR BioGRID; 108411; 26.
DR IntAct; Q16134; 10.
DR STRING; 9606.ENSP00000426638; -.
DR DrugBank; DB04141; 2-Hexyloxy-6-Hydroxymethyl-Tetrahydro-Pyran-3,4,5-Triol.
DR DrugBank; DB00331; Metformin.
DR iPTMnet; Q16134; -.
DR PhosphoSitePlus; Q16134; -.
DR SwissPalm; Q16134; -.
DR BioMuta; ETFDH; -.
DR DMDM; 292495008; -.
DR EPD; Q16134; -.
DR jPOST; Q16134; -.
DR MassIVE; Q16134; -.
DR MaxQB; Q16134; -.
DR PaxDb; Q16134; -.
DR PeptideAtlas; Q16134; -.
DR PRIDE; Q16134; -.
DR ProteomicsDB; 60832; -. [Q16134-1]
DR Antibodypedia; 45630; 289 antibodies from 32 providers.
DR DNASU; 2110; -.
DR Ensembl; ENST00000307738.5; ENSP00000303552.5; ENSG00000171503.13. [Q16134-3]
DR Ensembl; ENST00000511912.6; ENSP00000426638.1; ENSG00000171503.13. [Q16134-1]
DR GeneID; 2110; -.
DR KEGG; hsa:2110; -.
DR MANE-Select; ENST00000511912.6; ENSP00000426638.1; NM_004453.4; NP_004444.2.
DR UCSC; uc003iqb.5; human. [Q16134-1]
DR CTD; 2110; -.
DR DisGeNET; 2110; -.
DR GeneCards; ETFDH; -.
DR GeneReviews; ETFDH; -.
DR HGNC; HGNC:3483; ETFDH.
DR HPA; ENSG00000171503; Tissue enhanced (liver, tongue).
DR MalaCards; ETFDH; -.
DR MIM; 231675; gene.
DR MIM; 231680; phenotype.
DR neXtProt; NX_Q16134; -.
DR OpenTargets; ENSG00000171503; -.
DR Orphanet; 394532; Multiple acyl-CoA dehydrogenase deficiency, mild type.
DR Orphanet; 394529; Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type.
DR PharmGKB; PA27899; -.
DR VEuPathDB; HostDB:ENSG00000171503; -.
DR eggNOG; KOG2415; Eukaryota.
DR GeneTree; ENSGT00390000010773; -.
DR HOGENOM; CLU_009667_4_0_1; -.
DR InParanoid; Q16134; -.
DR OMA; GGGWMYH; -.
DR PhylomeDB; Q16134; -.
DR TreeFam; TF105687; -.
DR BioCyc; MetaCyc:HS10326-MON; -.
DR BRENDA; 1.5.5.1; 2681.
DR PathwayCommons; Q16134; -.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR SignaLink; Q16134; -.
DR BioGRID-ORCS; 2110; 8 hits in 1081 CRISPR screens.
DR ChiTaRS; ETFDH; human.
DR GeneWiki; ETFDH; -.
DR GenomeRNAi; 2110; -.
DR Pharos; Q16134; Tbio.
DR PRO; PR:Q16134; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q16134; protein.
DR Bgee; ENSG00000171503; Expressed in apex of heart and 194 other tissues.
DR ExpressionAtlas; Q16134; baseline and differential.
DR Genevisible; Q16134; HS.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0009055; F:electron transfer activity; IDA:UniProtKB.
DR GO; GO:0004174; F:electron-transferring-flavoprotein dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:UniProtKB.
DR GO; GO:0048038; F:quinone binding; IDA:UniProtKB.
DR GO; GO:0048039; F:ubiquinone binding; IDA:UniProtKB.
DR GO; GO:0022900; P:electron transport chain; IDA:UniProtKB.
DR GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; IMP:BHF-UCL.
DR GO; GO:0022904; P:respiratory electron transport chain; TAS:Reactome.
DR GO; GO:0006979; P:response to oxidative stress; ISS:UniProtKB.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR017896; 4Fe4S_Fe-S-bd.
DR InterPro; IPR040156; ETF-QO.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR PANTHER; PTHR10617; PTHR10617; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR PROSITE; PS51379; 4FE4S_FER_2; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Acetylation; Alternative splicing; Disease variant;
KW Electron transport; FAD; Flavoprotein; Glutaricaciduria; Iron; Iron-sulfur;
KW Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Transit peptide;
KW Transport; Ubiquinone.
FT TRANSIT 1..33
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 34..617
FT /note="Electron transfer flavoprotein-ubiquinone
FT oxidoreductase, mitochondrial"
FT /id="PRO_0000008661"
FT INTRAMEM 109..130
FT /evidence="ECO:0000250"
FT INTRAMEM 428..447
FT /evidence="ECO:0000250"
FT DOMAIN 577..606
FT /note="4Fe-4S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT BINDING 71..85
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT BINDING 305
FT /ligand="a ubiquinone"
FT /ligand_id="ChEBI:CHEBI:16389"
FT /evidence="ECO:0000250"
FT BINDING 306
FT /ligand="a ubiquinone"
FT /ligand_id="ChEBI:CHEBI:16389"
FT /evidence="ECO:0000250"
FT BINDING 561
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255"
FT BINDING 586
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255"
FT BINDING 589
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255"
FT BINDING 592
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255"
FT MOD_RES 96
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q921G7"
FT MOD_RES 132
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q921G7"
FT MOD_RES 223
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q921G7"
FT MOD_RES 357
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q921G7"
FT MOD_RES 551
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 12..58
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055158"
FT VARIANT 16
FT /note="F -> C"
FT /evidence="ECO:0000269|PubMed:12359134"
FT /id="VAR_075438"
FT VARIANT 31
FT /note="T -> I (in dbSNP:rs11559290)"
FT /evidence="ECO:0000269|PubMed:12359134,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005,
FT ECO:0000269|PubMed:8306995"
FT /id="VAR_062966"
FT VARIANT 49
FT /note="Y -> C (in GA2C; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:12359134"
FT /id="VAR_075439"
FT VARIANT 82
FT /note="S -> F (in GA2C; dbSNP:rs887871605)"
FT /evidence="ECO:0000269|PubMed:12359134"
FT /id="VAR_075440"
FT VARIANT 82
FT /note="S -> P (in GA2C)"
FT /evidence="ECO:0000269|PubMed:12359134"
FT /id="VAR_075441"
FT VARIANT 84
FT /note="A -> T (in GA2C; dbSNP:rs121964954)"
FT /evidence="ECO:0000269|PubMed:19249206,
FT ECO:0000269|PubMed:20370797"
FT /id="VAR_075442"
FT VARIANT 94
FT /note="H -> R (in dbSNP:rs1140065)"
FT /id="VAR_055711"
FT VARIANT 112
FT /note="H -> Y (in GA2C)"
FT /evidence="ECO:0000269|PubMed:16527485"
FT /id="VAR_075443"
FT VARIANT 127
FT /note="L -> H (in GA2C; dbSNP:rs121964956)"
FT /evidence="ECO:0000269|PubMed:19249206"
FT /id="VAR_075444"
FT VARIANT 138
FT /note="L -> R (in GA2C; unknown pathological significance;
FT dbSNP:rs779896449)"
FT /evidence="ECO:0000269|PubMed:12359134"
FT /id="VAR_075445"
FT VARIANT 175
FT /note="R -> H (in GA2C; dbSNP:rs121964955)"
FT /evidence="ECO:0000269|PubMed:20370797"
FT /id="VAR_075446"
FT VARIANT 175
FT /note="R -> L (in GA2C; dbSNP:rs121964955)"
FT /evidence="ECO:0000269|PubMed:19249206"
FT /id="VAR_075447"
FT VARIANT 218
FT /note="D -> N (in GA2C; unknown pathological significance;
FT dbSNP:rs748289922)"
FT /evidence="ECO:0000269|PubMed:12359134"
FT /id="VAR_075448"
FT VARIANT 222
FT /note="Q -> P (in GA2C; unknown pathological significance;
FT dbSNP:rs1482632936)"
FT /evidence="ECO:0000269|PubMed:12359134"
FT /id="VAR_075449"
FT VARIANT 262
FT /note="L -> F (in GA2C; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:12359134"
FT /id="VAR_075450"
FT VARIANT 334
FT /note="L -> P (in GA2C; unknown pathological significance;
FT dbSNP:rs377686388)"
FT /evidence="ECO:0000269|PubMed:12359134"
FT /id="VAR_075451"
FT VARIANT 346
FT /note="H -> R (in GA2C; unknown pathological significance;
FT dbSNP:rs1358691961)"
FT /evidence="ECO:0000269|PubMed:12359134"
FT /id="VAR_075452"
FT VARIANT 377
FT /note="L -> P (in GA2C; unknown pathological significance;
FT dbSNP:rs387907170)"
FT /evidence="ECO:0000269|PubMed:17412732"
FT /id="VAR_075453"
FT VARIANT 452
FT /note="R -> K (in GA2C; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:12359134"
FT /id="VAR_075454"
FT VARIANT 456
FT /note="P -> L (in GA2C; dbSNP:rs398124152)"
FT /evidence="ECO:0000269|PubMed:12359134,
FT ECO:0000269|PubMed:17412732"
FT /id="VAR_075455"
FT VARIANT 456
FT /note="P -> T (in GA2C)"
FT /evidence="ECO:0000269|PubMed:16527485"
FT /id="VAR_075456"
FT VARIANT 483
FT /note="P -> L (in GA2C; unknown pathological significance;
FT dbSNP:rs377656387)"
FT /evidence="ECO:0000269|PubMed:17412732"
FT /id="VAR_075457"
FT VARIANT 562
FT /note="P -> L (in GA2C; dbSNP:rs993314323)"
FT /evidence="ECO:0000269|PubMed:12359134"
FT /id="VAR_075458"
FT VARIANT 565
FT /note="V -> L (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs769893690)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036134"
FT VARIANT 590
FT /note="K -> E (in GA2C)"
FT /evidence="ECO:0000269|PubMed:17412732"
FT /id="VAR_075459"
FT VARIANT 611
FT /note="G -> E (in GA2C; dbSNP:rs761669036)"
FT /evidence="ECO:0000269|PubMed:12359134"
FT /id="VAR_075460"
FT CONFLICT 109
FT /note="I -> V (in Ref. 3; CAD98030)"
FT /evidence="ECO:0000305"
FT CONFLICT 456
FT /note="P -> S (in Ref. 2; BAG65581)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 617 AA; 68495 MW; 099EBA36C59AF3D6 CRC64;
MLVPLAKLSC LAYQCFHALK IKKNYLPLCA TRWSSTSTVP RITTHYTIYP RDKDKRWEGV
NMERFAEEAD VVIVGAGPAG LSAAVRLKQL AVAHEKDIRV CLVEKAAQIG AHTLSGACLD
PGAFKELFPD WKEKGAPLNT PVTEDRFGIL TEKYRIPVPI LPGLPMNNHG NYIVRLGHLV
SWMGEQAEAL GVEVYPGYAA AEVLFHDDGS VKGIATNDVG IQKDGAPKAT FERGLELHAK
VTIFAEGCHG HLAKQLYKKF DLRANCEPQT YGIGLKELWV IDEKNWKPGR VDHTVGWPLD
RHTYGGSFLY HLNEGEPLVA LGLVVGLDYQ NPYLSPFREF QRWKHHPSIR PTLEGGKRIA
YGARALNEGG FQSIPKLTFP GGLLIGCSPG FMNVPKIKGT HTAMKSGILA AESIFNQLTS
ENLQSKTIGL HVTEYEDNLK NSWVWKELYS VRNIRPSCHG VLGVYGGMIY TGIFYWILRG
MEPWTLKHKG SDFERLKPAK DCTPIEYPKP DGQISFDLLS SVALSGTNHE HDQPAHLTLR
DDSIPVNRNL SIYDGPEQRF CPAGVYEFVP VEQGDGFRLQ INAQNCVHCK TCDIKDPSQN
INWVVPEGGG GPAYNGM
