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 27-MAR-2024, entry version 234. 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; P13569: CFTR; NbExp=7; IntAct=EBI-1052886, EBI-349854; 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}. 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; 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; 286. DR ComplexPortal; CPX-2731; Mitochondrial electron transfer flavoprotein complex. DR DIP; DIP-6161N; -. DR IntAct; P13804; 76. 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 CPTAC; CPTAC-365; -. DR CPTAC; CPTAC-366; -. DR EPD; P13804; -. DR jPOST; P13804; -. DR MassIVE; P13804; -. DR MaxQB; P13804; -. DR PaxDb; 9606-ENSP00000452762; -. DR PeptideAtlas; P13804; -. DR ProteomicsDB; 52989; -. [P13804-1] DR ProteomicsDB; 52990; -. [P13804-2] DR Pumba; P13804; -. DR TopDownProteomics; P13804-1; -. [P13804-1] DR TopDownProteomics; P13804-2; -. [P13804-2] DR Antibodypedia; 14895; 408 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 AGR; HGNC:3481; -. DR CTD; 2108; -. DR DisGeNET; 2108; -. DR GeneCards; ETFA; -. DR GeneReviews; ETFA; -. DR HGNC; HGNC:3481; ETFA. DR HPA; ENSG00000140374; Tissue enhanced (liver, skeletal muscle, 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 OrthoDB; 5481222at2759; -. DR PhylomeDB; P13804; -. DR TreeFam; TF105763; -. DR PathwayCommons; P13804; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR SignaLink; P13804; -. DR SIGNOR; P13804; -. DR BioGRID-ORCS; 2108; 11 hits in 1169 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 207 other cell types or tissues. DR ExpressionAtlas; P13804; baseline and differential. 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: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; HUPs; 1. DR Gene3D; 3.40.50.1220; TPP-binding domain; 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; ELECTRON TRANSFER FLAVOPROTEIN ALPHA; 1. DR PANTHER; PTHR43153:SF1; ELECTRON TRANSFER FLAVOPROTEIN SUBUNIT ALPHA, MITOCHONDRIAL; 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; SSF52402; Adenine nucleotide alpha hydrolases-like; 1. DR SUPFAM; SSF52467; DHS-like NAD/FAD-binding domain; 1. DR PROSITE; PS00696; ETF_ALPHA; 1. DR UCD-2DPAGE; P13804; -. DR Genevisible; P13804; HS. 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 //