ETFA_HUMAN
ID ETFA_HUMAN Reviewed; 333 AA.
AC P13804; B4DT43; Q53XN3;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 225.
DE RecName: Full=Electron transfer flavoprotein subunit alpha, mitochondrial;
DE Short=Alpha-ETF;
DE Flags: Precursor;
GN Name=ETFA;
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).
RX PubMed=3170610; DOI=10.1016/s0021-9258(19)37655-0;
RA Finocchiaro G., Ito M., Ikeda Y., Tanaka K.;
RT "Molecular cloning and nucleotide sequence of cDNAs encoding the alpha-
RT subunit of human electron transfer flavoprotein.";
RL J. Biol. Chem. 263:15773-15780(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, FUNCTION, AND
RP VARIANT GA2A MET-266.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Trachea;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Chondrosarcoma, and Colon;
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 [8]
RP PROTEIN SEQUENCE OF 86-101 AND 170-203, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [9]
RP REVIEW.
RX PubMed=17941859; DOI=10.1111/j.1742-4658.2007.06107.x;
RA Toogood H.S., Leys D., Scrutton N.S.;
RT "Dynamics driving function: new insights from electron transferring
RT flavoproteins and partner complexes.";
RL FEBS J. 274:5481-5504(2007).
RN [10]
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 [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140, 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 [13]
RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER PHE-19, AND
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 [14]
RP FUNCTION, INTERACTION WITH ETFRF1, AND IDENTIFICATION IN A COMPLEX WITH
RP ETFB AND ETFRF1.
RX PubMed=27499296; DOI=10.1016/j.molcel.2016.06.033;
RA Floyd B.J., Wilkerson E.M., Veling M.T., Minogue C.E., Xia C., Beebe E.T.,
RA Wrobel R.L., Cho H., Kremer L.S., Alston C.L., Gromek K.A., Dolan B.K.,
RA Ulbrich A., Stefely J.A., Bohl S.L., Werner K.M., Jochem A.,
RA Westphall M.S., Rensvold J.W., Taylor R.W., Prokisch H., Kim J.J.,
RA Coon J.J., Pagliarini D.J.;
RT "Mitochondrial protein interaction mapping identifies regulators of
RT respiratory chain function.";
RL Mol. Cell 63:621-632(2016).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 20-333 IN COMPLEX WITH FAD AND
RP ETFB, SUBUNIT, COFACTOR, AND DOMAIN.
RX PubMed=8962055; DOI=10.1073/pnas.93.25.14355;
RA Roberts D.L., Frerman F.E., Kim J.-J.P.;
RT "Three-dimensional structure of human electron transfer flavoprotein to
RT 2.1-A resolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:14355-14360(1996).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH ETFB AND ACADM,
RP FUNCTION, AND SUBUNIT.
RX PubMed=15159392; DOI=10.1074/jbc.m404884200;
RA Toogood H.S., van Thiel A., Basran J., Sutcliffe M.J., Scrutton N.S.,
RA Leys D.;
RT "Extensive domain motion and electron transfer in the human electron
RT transferring flavoprotein.medium chain acyl-CoA dehydrogenase complex.";
RL J. Biol. Chem. 279:32904-32912(2004).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) IN COMPLEX WITH FAD; ETFB AND ACADM,
RP FUNCTION, COFACTOR, AND MUTAGENESIS OF ARG-249.
RX PubMed=15975918; DOI=10.1074/jbc.m505562200;
RA Toogood H.S., van Thiel A., Scrutton N.S., Leys D.;
RT "Stabilization of non-productive conformations underpins rapid electron
RT transfer to electron-transferring flavoprotein.";
RL J. Biol. Chem. 280:30361-30366(2005).
RN [18]
RP VARIANT GA2A GLY-157, AND FUNCTION.
RX PubMed=1882842;
RA Indo Y., Glassberg R., Yokota I., Tanaka K.;
RT "Molecular characterization of variant alpha-subunit of electron transfer
RT flavoprotein in three patients with glutaric acidemia type II -- and
RT identification of glycine substitution for valine-157 in the sequence of
RT the precursor, producing an unstable mature protein in a patient.";
RL Am. J. Hum. Genet. 49:575-580(1991).
RN [19]
RP VARIANTS GA2A ARG-116 AND MET-266, FUNCTION, AND CHARACTERIZATION OF
RP VARIANT GA2A MET-266.
RX PubMed=1430199; DOI=10.1172/jci116040;
RA Freneaux E., Sheffield V.C., Molin L., Shires A., Rhead W.;
RT "Glutaric acidemia type II. Heterogeneity in beta-oxidation flux,
RT polypeptide synthesis, and complementary DNA mutations in the alpha subunit
RT of electron transfer flavoprotein in eight patients.";
RL J. Clin. Invest. 90:1679-1686(1992).
RN [20]
RP CHARACTERIZATION OF VARIANTS GA2A ARG-116 AND MET-266, FUNCTION, COFACTOR,
RP AND SUBUNIT.
RX PubMed=9334218; DOI=10.1074/jbc.272.42.26425;
RA Salazar D., Zhang L., deGala G.D., Frerman F.E.;
RT "Expression and characterization of two pathogenic mutations in human
RT electron transfer flavoprotein.";
RL J. Biol. Chem. 272:26425-26433(1997).
RN [21]
RP VARIANT ILE-171, CHARACTERIZATION OF VARIANT ILE-171, AND FUNCTION.
RX PubMed=10356313; DOI=10.1006/mgme.1999.2856;
RA Bross P., Pedersen P., Winter V., Nyholm M., Johansen B.N., Olsen R.K.,
RA Corydon M.J., Andresen B.S., Eiberg H., Kolvraa S., Gregersen N.;
RT "A polymorphic variant in the human electron transfer flavoprotein alpha-
RT chain (alpha-T171) displays decreased thermal stability and is
RT overrepresented in very-long-chain acyl-CoA dehydrogenase-deficient
RT patients with mild childhood presentation.";
RL Mol. Genet. Metab. 67:138-147(1999).
CC -!- FUNCTION: Heterodimeric electron transfer flavoprotein that accepts
CC electrons from several mitochondrial dehydrogenases, including acyl-CoA
CC dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase
CC (PubMed:27499296, PubMed:15159392, PubMed:15975918, PubMed:9334218,
CC PubMed:10356313). It transfers the electrons to the main mitochondrial
CC respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase)
CC (PubMed:9334218). Required for normal mitochondrial fatty acid
CC oxidation and normal amino acid metabolism (PubMed:12815589,
CC PubMed:1882842, PubMed:1430199). {ECO:0000269|PubMed:10356313,
CC ECO:0000269|PubMed:12815589, ECO:0000269|PubMed:1430199,
CC ECO:0000269|PubMed:15159392, ECO:0000269|PubMed:15975918,
CC ECO:0000269|PubMed:27499296, ECO:0000269|PubMed:9334218,
CC ECO:0000303|PubMed:17941859, ECO:0000305|PubMed:1882842}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:15975918, ECO:0000269|PubMed:8962055,
CC ECO:0000269|PubMed:9334218};
CC Note=Binds 1 FAD per dimer. {ECO:0000269|PubMed:15975918,
CC ECO:0000269|PubMed:8962055};
CC -!- SUBUNIT: Heterodimer composed of ETFA and ETFB (PubMed:8962055,
CC PubMed:15159392, PubMed:15975918, PubMed:9334218). Identified in a
CC complex that contains ETFA, ETFB and ETFRF1 (PubMed:27499296).
CC Interaction with ETFRF1 promotes dissociation of the bound FAD and loss
CC of electron transfer activity (PubMed:27499296). Interacts with TASOR
CC (By similarity). {ECO:0000250|UniProtKB:Q99LC5,
CC ECO:0000269|PubMed:15159392, ECO:0000269|PubMed:15975918,
CC ECO:0000269|PubMed:27499296, ECO:0000269|PubMed:8962055}.
CC -!- INTERACTION:
CC P13804; P38117: ETFB; NbExp=2; IntAct=EBI-1052886, EBI-1056543;
CC P13804; Q8IWL3: HSCB; NbExp=3; IntAct=EBI-1052886, EBI-1805738;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P13804-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P13804-2; Sequence=VSP_043246;
CC -!- DOMAIN: Domain I shares an identical polypeptide fold with the beta
CC subunit ETFB though there is no sequence similarity.
CC {ECO:0000269|PubMed:8962055}.
CC -!- PTM: The N-terminus is blocked.
CC -!- DISEASE: Glutaric aciduria 2A (GA2A) [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:12815589,
CC ECO:0000269|PubMed:1430199, ECO:0000269|PubMed:1882842,
CC ECO:0000269|PubMed:9334218}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ETF alpha-subunit/FixB family.
CC {ECO:0000305}.
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DR EMBL; J04058; AAA52406.1; -; mRNA.
DR EMBL; S55815; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; S55816; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AJ224002; CAA11802.1; -; Genomic_DNA.
DR EMBL; AF436657; AAN03712.1; -; Genomic_DNA.
DR EMBL; AF436646; AAN03712.1; JOINED; Genomic_DNA.
DR EMBL; AF436647; AAN03712.1; JOINED; Genomic_DNA.
DR EMBL; AF436648; AAN03712.1; JOINED; Genomic_DNA.
DR EMBL; AF436649; AAN03712.1; JOINED; Genomic_DNA.
DR EMBL; AF436650; AAN03712.1; JOINED; Genomic_DNA.
DR EMBL; AF436651; AAN03712.1; JOINED; Genomic_DNA.
DR EMBL; AF436652; AAN03712.1; JOINED; Genomic_DNA.
DR EMBL; AF436653; AAN03712.1; JOINED; Genomic_DNA.
DR EMBL; AF436654; AAN03712.1; JOINED; Genomic_DNA.
DR EMBL; AF436655; AAN03712.1; JOINED; Genomic_DNA.
DR EMBL; AF436656; AAN03712.1; JOINED; Genomic_DNA.
DR EMBL; BT009796; AAP88798.1; -; mRNA.
DR EMBL; AK292979; BAF85668.1; -; mRNA.
DR EMBL; AK300044; BAG61855.1; -; mRNA.
DR EMBL; AC027243; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091100; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471136; EAW99221.1; -; Genomic_DNA.
DR EMBL; BC015526; AAH15526.1; -; mRNA.
DR EMBL; BC095457; AAH95457.1; -; mRNA.
DR CCDS; CCDS32299.1; -. [P13804-1]
DR CCDS; CCDS45311.1; -. [P13804-2]
DR PIR; A31998; A31998.
DR RefSeq; NP_000117.1; NM_000126.3. [P13804-1]
DR RefSeq; NP_001121188.1; NM_001127716.1. [P13804-2]
DR PDB; 1EFV; X-ray; 2.10 A; A=20-333.
DR PDB; 1T9G; X-ray; 2.90 A; R=1-333.
DR PDB; 2A1T; X-ray; 2.80 A; R=1-333.
DR PDB; 2A1U; X-ray; 2.11 A; A=1-333.
DR PDBsum; 1EFV; -.
DR PDBsum; 1T9G; -.
DR PDBsum; 2A1T; -.
DR PDBsum; 2A1U; -.
DR AlphaFoldDB; P13804; -.
DR SMR; P13804; -.
DR BioGRID; 108409; 248.
DR ComplexPortal; CPX-2731; Mitochondrial electron transfer flavoprotein complex.
DR DIP; DIP-6161N; -.
DR IntAct; P13804; 73.
DR MINT; P13804; -.
DR STRING; 9606.ENSP00000452762; -.
DR CarbonylDB; P13804; -.
DR GlyGen; P13804; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P13804; -.
DR MetOSite; P13804; -.
DR PhosphoSitePlus; P13804; -.
DR SwissPalm; P13804; -.
DR BioMuta; ETFA; -.
DR DMDM; 119636; -.
DR UCD-2DPAGE; P13804; -.
DR CPTAC; CPTAC-365; -.
DR CPTAC; CPTAC-366; -.
DR EPD; P13804; -.
DR jPOST; P13804; -.
DR MassIVE; P13804; -.
DR MaxQB; P13804; -.
DR PaxDb; P13804; -.
DR PeptideAtlas; P13804; -.
DR PRIDE; P13804; -.
DR ProteomicsDB; 52989; -. [P13804-1]
DR ProteomicsDB; 52990; -. [P13804-2]
DR TopDownProteomics; P13804-1; -. [P13804-1]
DR TopDownProteomics; P13804-2; -. [P13804-2]
DR Antibodypedia; 14895; 375 antibodies from 33 providers.
DR DNASU; 2108; -.
DR Ensembl; ENST00000433983.6; ENSP00000399273.2; ENSG00000140374.17. [P13804-2]
DR Ensembl; ENST00000557943.6; ENSP00000452762.1; ENSG00000140374.17. [P13804-1]
DR Ensembl; ENST00000690610.1; ENSP00000510473.1; ENSG00000140374.17. [P13804-1]
DR GeneID; 2108; -.
DR KEGG; hsa:2108; -.
DR MANE-Select; ENST00000557943.6; ENSP00000452762.1; NM_000126.4; NP_000117.1.
DR UCSC; uc002bbt.3; human. [P13804-1]
DR CTD; 2108; -.
DR DisGeNET; 2108; -.
DR GeneCards; ETFA; -.
DR GeneReviews; ETFA; -.
DR HGNC; HGNC:3481; ETFA.
DR HPA; ENSG00000140374; Tissue enhanced (liver, tongue).
DR MalaCards; ETFA; -.
DR MIM; 231680; phenotype.
DR MIM; 608053; gene.
DR neXtProt; NX_P13804; -.
DR OpenTargets; ENSG00000140374; -.
DR Orphanet; 394532; Multiple acyl-CoA dehydrogenase deficiency, mild type.
DR Orphanet; 394529; Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type.
DR PharmGKB; PA27897; -.
DR VEuPathDB; HostDB:ENSG00000140374; -.
DR eggNOG; KOG3954; Eukaryota.
DR GeneTree; ENSGT00390000013422; -.
DR HOGENOM; CLU_034178_0_0_1; -.
DR InParanoid; P13804; -.
DR OMA; WRPYAEQ; -.
DR PhylomeDB; P13804; -.
DR TreeFam; TF105763; -.
DR PathwayCommons; P13804; -.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR SignaLink; P13804; -.
DR BioGRID-ORCS; 2108; 10 hits in 1085 CRISPR screens.
DR ChiTaRS; ETFA; human.
DR EvolutionaryTrace; P13804; -.
DR GeneWiki; ETFA; -.
DR GenomeRNAi; 2108; -.
DR Pharos; P13804; Tbio.
DR PRO; PR:P13804; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P13804; protein.
DR Bgee; ENSG00000140374; Expressed in oocyte and 205 other tissues.
DR ExpressionAtlas; P13804; baseline and differential.
DR Genevisible; P13804; HS.
DR GO; GO:0045251; C:electron transfer flavoprotein complex; IPI:ComplexPortal.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0009055; F:electron transfer activity; IDA:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:UniProtKB.
DR GO; GO:0009063; P:cellular amino acid catabolic process; IDA:ComplexPortal.
DR GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; IDA:UniProtKB.
DR GO; GO:0022904; P:respiratory electron transport chain; IDA:ComplexPortal.
DR CDD; cd01715; ETF_alpha; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR014730; ETF_a/b_N.
DR InterPro; IPR001308; ETF_a/FixB.
DR InterPro; IPR033947; ETF_alpha_N.
DR InterPro; IPR014731; ETF_asu_C.
DR InterPro; IPR018206; ETF_asu_C_CS.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR PANTHER; PTHR43153; PTHR43153; 1.
DR Pfam; PF01012; ETF; 1.
DR Pfam; PF00766; ETF_alpha; 1.
DR PIRSF; PIRSF000089; Electra_flavoP_a; 1.
DR SMART; SM00893; ETF; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS00696; ETF_ALPHA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing;
KW Disease variant; Electron transport; FAD; Flavoprotein; Glutaricaciduria;
KW Mitochondrion; Phosphoprotein; Reference proteome; Transit peptide;
KW Transport.
FT TRANSIT 1..19
FT /note="Mitochondrion"
FT /evidence="ECO:0000255, ECO:0007744|PubMed:25944712"
FT CHAIN 20..333
FT /note="Electron transfer flavoprotein subunit alpha,
FT mitochondrial"
FT /id="PRO_0000008650"
FT REGION 20..204
FT /note="Domain I"
FT /evidence="ECO:0000269|PubMed:8962055"
FT REGION 205..333
FT /note="Domain II"
FT /evidence="ECO:0000269|PubMed:8962055"
FT BINDING 223
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:15975918,
FT ECO:0000269|PubMed:8962055, ECO:0007744|PDB:1EFV,
FT ECO:0007744|PDB:2A1T"
FT BINDING 248
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:15975918,
FT ECO:0000269|PubMed:8962055, ECO:0007744|PDB:1EFV,
FT ECO:0007744|PDB:2A1T"
FT BINDING 263..266
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:15975918,
FT ECO:0000269|PubMed:8962055, ECO:0007744|PDB:1EFV,
FT ECO:0007744|PDB:2A1T"
FT BINDING 281..286
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:15975918,
FT ECO:0000269|PubMed:8962055, ECO:0007744|PDB:1EFV,
FT ECO:0007744|PDB:2A1T"
FT BINDING 300
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:15975918,
FT ECO:0000269|PubMed:8962055, ECO:0007744|PDB:1EFV,
FT ECO:0007744|PDB:2A1T"
FT BINDING 318..319
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:15975918,
FT ECO:0000269|PubMed:8962055, ECO:0007744|PDB:1EFV,
FT ECO:0007744|PDB:2A1T"
FT MOD_RES 59
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 59
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 62
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 69
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 69
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 75
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 85
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 85
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 93
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 101
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 139
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 158
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 158
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 164
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 187
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 203
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 203
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 216
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 226
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 226
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 232
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 232
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT MOD_RES 301
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LC5"
FT VAR_SEQ 14..62
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043246"
FT VARIANT 116
FT /note="G -> R (in GA2A; impaired protein stability and loss
FT of electron transfer activity; dbSNP:rs119458971)"
FT /evidence="ECO:0000269|PubMed:1430199,
FT ECO:0000269|PubMed:9334218"
FT /id="VAR_002366"
FT VARIANT 157
FT /note="V -> G (in GA2A; dbSNP:rs119458969)"
FT /evidence="ECO:0000269|PubMed:1882842"
FT /id="VAR_002367"
FT VARIANT 171
FT /note="T -> I (decreased protein stability;
FT dbSNP:rs1801591)"
FT /evidence="ECO:0000269|PubMed:10356313"
FT /id="VAR_008547"
FT VARIANT 266
FT /note="T -> M (in GA2A; decreased electron transfer
FT activity; dbSNP:rs119458970)"
FT /evidence="ECO:0000269|PubMed:12815589,
FT ECO:0000269|PubMed:1430199"
FT /id="VAR_002368"
FT MUTAGEN 249
FT /note="R->A: Loss of electron transfer activity."
FT /evidence="ECO:0000269|PubMed:15975918"
FT STRAND 21..25
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:2A1U"
FT HELIX 36..45
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 49..58
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 61..69
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 89..103
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 106..113
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 114..127
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 132..135
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 137..140
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:1EFV"
FT TURN 149..152
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 162..168
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 196..204
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 216..221
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 223..225
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 229..231
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 232..241
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 249..253
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 273..279
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 284..287
FT /evidence="ECO:0007829|PDB:1EFV"
FT TURN 288..292
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 294..301
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 306..309
FT /evidence="ECO:0007829|PDB:1EFV"
FT STRAND 312..317
FT /evidence="ECO:0007829|PDB:1EFV"
FT HELIX 319..329
FT /evidence="ECO:0007829|PDB:1EFV"
SQ SEQUENCE 333 AA; 35080 MW; 2EC6D1ADE68CBDB5 CRC64;
MFRAAAPGQL RRAASLLRFQ STLVIAEHAN DSLAPITLNT ITAATRLGGE VSCLVAGTKC
DKVAQDLCKV AGIAKVLVAQ HDVYKGLLPE ELTPLILATQ KQFNYTHICA GASAFGKNLL
PRVAAKLEVA PISDIIAIKS PDTFVRTIYA GNALCTVKCD EKVKVFSVRG TSFDAAATSG
GSASSEKASS TSPVEISEWL DQKLTKSDRP ELTGAKVVVS GGRGLKSGEN FKLLYDLADQ
LHAAVGASRA AVDAGFVPND MQVGQTGKIV APELYIAVGI SGAIQHLAGM KDSKTIVAIN
KDPEAPIFQV ADYGIVADLF KVVPEMTEIL KKK
