ACADV_HUMAN
ID ACADV_HUMAN Reviewed; 655 AA.
AC P49748; B4DEB6; F5H2A9; O76056; Q8WUL0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Very long-chain specific acyl-CoA dehydrogenase, mitochondrial {ECO:0000305|PubMed:7668252};
DE Short=VLCAD {ECO:0000303|PubMed:7668252};
DE EC=1.3.8.9 {ECO:0000269|PubMed:17374501, ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:7668252, ECO:0000269|PubMed:9461620, ECO:0000269|PubMed:9599005, ECO:0000269|PubMed:9839948};
DE Flags: Precursor;
GN Name=ACADVL {ECO:0000312|HGNC:HGNC:92};
GN Synonyms=VLCAD {ECO:0000303|PubMed:7668252};
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), PARTIAL PROTEIN SEQUENCE, FUNCTION,
RP CATALYTIC ACTIVITY, PATHWAY, INVOLVEMENT IN ACADVLD, AND TRANSIT PEPTIDE.
RX PubMed=7668252;
RA Aoyama T., Souri M., Ueno I., Kamijo T., Yamaguchi S., Rhead W.J.,
RA Tanaka K., Hashimoto T.;
RT "Cloning of human very-long-chain acyl-coenzyme A dehydrogenase and
RT molecular characterization of its deficiency in two patients.";
RL Am. J. Hum. Genet. 57:273-283(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANTS
RP ACADVLD MET-260; ASP-281; ALA-283; ALA-317; CYS-366; GLU-381 DEL; ASP-441
RP AND ILE-602.
RC TISSUE=Placenta;
RX PubMed=8845838; DOI=10.1093/hmg/5.4.461;
RA Andresen B.S., Bross P., Vianey-Saban C., Divry P., Zabot M.-T., Roe C.R.,
RA Nada M.A., Byskov A., Kruse T.A., Neve S., Kristiansen K., Knudsen I.,
RA Corydon M.J., Gregersen N.;
RT "Cloning and characterization of human very-long-chain acyl-CoA
RT dehydrogenase cDNA, chromosomal assignment of the gene and identification
RT in four patients of nine different mutations within the VLCAD gene.";
RL Hum. Mol. Genet. 5:461-472(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC TISSUE=Peripheral blood;
RX PubMed=8554625; DOI=10.1006/bbrc.1995.2867;
RA Orii K.O., Aoyama T., Souri M., Orii K.E., Kondo N., Orii T., Hashimoto T.;
RT "Genomic DNA organization of human mitochondrial very-long-chain acyl-CoA
RT dehydrogenase and mutation analysis.";
RL Biochem. Biophys. Res. Commun. 217:987-992(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Cerebellum;
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=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Liver, Lung, and Pancreas;
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 [7]
RP CHARACTERIZATION.
RX PubMed=7769092; DOI=10.1172/jci117947;
RA Aoyama T., Souri M., Ushikubo S., Kamijo T., Yamaguchi S., Kelley R.I.,
RA Rhead W.J., Uetake K., Tanaka K., Hashimoto T.;
RT "Purification of human very-long-chain acyl-coenzyme A dehydrogenase and
RT characterization of its deficiency in seven patients.";
RL J. Clin. Invest. 95:2465-2473(1995).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF PHE-458 AND GLU-462, ACTIVE
RP SITE, AND CHARACTERIZATION OF VARIANT ACADVLD LEU-458.
RX PubMed=9461620; DOI=10.1074/jbc.273.7.4227;
RA Souri M., Aoyama T., Cox G.F., Hashimoto T.;
RT "Catalytic and FAD-binding residues of mitochondrial very long chain acyl-
RT coenzyme A dehydrogenase.";
RL J. Biol. Chem. 273:4227-4231(1998).
RN [9]
RP VARIANTS ACADVLD MET-260; ALA-283; TRP-469; PRO-502 AND TRP-613.
RX PubMed=9973285; DOI=10.1086/302261;
RA Andresen B.S., Olpin S., Poorthuis B.J.H.M., Scholte H.R., Vianey-Saban C.,
RA Wanders R., Ijlst L., Morris A., Pourfarzam M., Bartlett K.,
RA Baumgartner E.R., de Klerk J.B.C., Schroeder L.D., Corydon T.J., Lund H.,
RA Winter V., Bross P., Bolund L., Gregersen N.;
RT "Clear correlation of genotype with disease phenotype in very-long-chain
RT acyl-CoA dehydrogenase deficiency.";
RL Am. J. Hum. Genet. 64:479-494(1999).
RN [10]
RP CATALYTIC ACTIVITY (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), TOPOLOGY
RP (ISOFORM 2), AND CHARACTERIZATION OF VARIANT ACADVLD MET-260; ALA-283;
RP TRP-469; PRO-490; PRO-502 AND TRP-613.
RX PubMed=17374501; DOI=10.1016/j.ymgme.2007.01.013;
RA Goetzman E.S., Wang Y., He M., Mohsen A.W., Ninness B.K., Vockley J.;
RT "Expression and characterization of mutations in human very long-chain
RT acyl-CoA dehydrogenase using a prokaryotic system.";
RL Mol. Genet. Metab. 91:138-147(2007).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-239 AND LYS-331, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
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 [13]
RP CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=21237683; DOI=10.1016/j.ymgme.2010.12.005;
RA He M., Pei Z., Mohsen A.W., Watkins P., Murdoch G., Van Veldhoven P.P.,
RA Ensenauer R., Vockley J.;
RT "Identification and characterization of new long chain acyl-CoA
RT dehydrogenases.";
RL Mol. Genet. Metab. 102:418-429(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-517 AND SER-522, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [15]
RP IDENTIFICATION BY 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 [16]
RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER TYR-40, 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 [17] {ECO:0007744|PDB:2UXW}
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 69-655 IN COMPLEX WITH FAD AND
RP SUBSTRATE ANALOG.
RA Pike A.C.W., Hozjan V., Smee C., Berridge G., Burgess N., Salah E.,
RA Bunkoczi G., Uppenberg J., Ugochukwu E., von Delft F., Arrowsmith C.H.,
RA Edwards A., Weigelt J., Sundstrom M., Oppermann U.;
RT "Crystal Structure of Human Very Long Chain Acyl- Coa Dehydrogenase
RT (Acadvl).";
RL Submitted (MAR-2007) to the PDB data bank.
RN [18] {ECO:0007744|PDB:3B96}
RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 69-655 IN COMPLEX WITH
RP TETRADECANOYL-COA AND FAD, FUNCTION, SUBUNIT, COFACTOR, AND ACTIVE SITE.
RX PubMed=18227065; DOI=10.1074/jbc.m709135200;
RA McAndrew R.P., Wang Y., Mohsen A.W., He M., Vockley J., Kim J.J.;
RT "Structural basis for substrate fatty acyl chain specificity: crystal
RT structure of human very-long-chain acyl-CoA dehydrogenase.";
RL J. Biol. Chem. 283:9435-9443(2008).
RN [19]
RP VARIANTS ACADVLD GLU-130 DEL; LYS-299 DEL; GLN-382 AND TRP-613.
RX PubMed=8554073;
RA Souri M., Aoyama T., Orii K., Yamaguchi S., Hashimoto T.;
RT "Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD)
RT deficiency: identification and characterization of mutant VLCAD cDNAs from
RT four patients.";
RL Am. J. Hum. Genet. 58:97-106(1996).
RN [20]
RP VARIANT ACADVLD HIS-450.
RX PubMed=9546340; DOI=10.1002/ana.410430422;
RA Smelt A.H., Poorthuis B.J.H.M., Onkenhout W., Scholte H.R., Andresen B.S.,
RA van Duinen S.G., Gregersen N., Wintzen A.R.;
RT "Very long chain acyl-coenzyme A dehydrogenase deficiency with adult
RT onset.";
RL Ann. Neurol. 43:540-544(1998).
RN [21]
RP VARIANT ACADVLD PRO-490, CHARACTERIZATION OF VARIANT ACADVLD PRO-490,
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBSTRATE SPECIFICITY, AND
RP MUTAGENESIS OF ALA-490.
RX PubMed=9839948; DOI=10.1046/j.1432-1327.1998.2570592.x;
RA Souri M., Aoyama T., Yamaguchi S., Hashimoto T.;
RT "Relationship between structure and substrate-chain-length specificity of
RT mitochondrial very-long-chain acyl-coenzyme A dehydrogenase.";
RL Eur. J. Biochem. 257:592-598(1998).
RN [22]
RP VARIANT ACADVLD TRP-583, CHARACTERIZATION OF VARIANT ACADVLD TRP-583,
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBUNIT, SUBCELLULAR LOCATION, AND
RP TOPOLOGY.
RX PubMed=9599005; DOI=10.1016/s0014-5793(98)00343-3;
RA Souri M., Aoyama T., Hoganson G., Hashimoto T.;
RT "Very-long-chain acyl-CoA dehydrogenase subunit assembles to the dimer form
RT on mitochondrial inner membrane.";
RL FEBS Lett. 426:187-190(1998).
RN [23]
RP VARIANTS ACADVLD GLU-130 DEL; PRO-213; GLU-247; MET-260; LYS-278 DEL;
RP ALA-283; ASP-441; LEU-458; PRO-490; LYS-534; TRP-613 AND GLN-615.
RX PubMed=10077518; DOI=10.1161/01.cir.99.10.1337;
RA Mathur A., Sims H.F., Gopalakrishnan D., Gibson B., Rinaldo P., Vockley J.,
RA Hug G., Strauss A.W.;
RT "Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase
RT deficiency causing pediatric cardiomyopathy and sudden death.";
RL Circulation 99:1337-1343(1999).
CC -!- FUNCTION: Very long-chain specific acyl-CoA dehydrogenase is one of the
CC acyl-CoA dehydrogenases that catalyze the first step of mitochondrial
CC fatty acid beta-oxidation, an aerobic process breaking down fatty acids
CC into acetyl-CoA and allowing the production of energy from fats
CC (PubMed:7668252, PubMed:9461620, PubMed:18227065, PubMed:9839948,
CC PubMed:9599005). The first step of fatty acid beta-oxidation consists
CC in the removal of one hydrogen from C-2 and C-3 of the straight-chain
CC fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-
CC CoA (PubMed:7668252, PubMed:9461620, PubMed:18227065, PubMed:9839948).
CC Among the different mitochondrial acyl-CoA dehydrogenases, very long-
CC chain specific acyl-CoA dehydrogenase acts specifically on acyl-CoAs
CC with saturated 12 to 24 carbons long primary chains (PubMed:21237683,
CC PubMed:9839948). {ECO:0000269|PubMed:18227065,
CC ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:7668252,
CC ECO:0000269|PubMed:9461620, ECO:0000269|PubMed:9599005,
CC ECO:0000269|PubMed:9839948}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a very-long-chain 2,3-saturated fatty acyl-CoA + H(+) +
CC oxidized [electron-transfer flavoprotein] = a very-long-chain (2E)-
CC enoyl-CoA + reduced [electron-transfer flavoprotein];
CC Xref=Rhea:RHEA:19181, Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:83724, ChEBI:CHEBI:83728; EC=1.3.8.9;
CC Evidence={ECO:0000269|PubMed:17374501, ECO:0000269|PubMed:21237683,
CC ECO:0000269|PubMed:7668252, ECO:0000269|PubMed:9461620,
CC ECO:0000269|PubMed:9599005, ECO:0000269|PubMed:9839948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19182;
CC Evidence={ECO:0000269|PubMed:7668252};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=decanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-decenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:48176, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:61406, ChEBI:CHEBI:61430;
CC Evidence={ECO:0000269|PubMed:21237683};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48177;
CC Evidence={ECO:0000305|PubMed:21237683};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-dodecenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:47296, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57330, ChEBI:CHEBI:57375,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307;
CC Evidence={ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:9839948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47297;
CC Evidence={ECO:0000269|PubMed:9839948};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxidized [electron-transfer flavoprotein] +
CC tetradecanoyl-CoA = (2E)-tetradecenoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:47316, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57385,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:61405;
CC Evidence={ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:9839948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47317;
CC Evidence={ECO:0000269|PubMed:9839948};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexadecanoyl-CoA + oxidized [electron-transfer
CC flavoprotein] = (2E)-hexadecenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:43448, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57379, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:61526;
CC Evidence={ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:7668252,
CC ECO:0000269|PubMed:9461620, ECO:0000269|PubMed:9599005,
CC ECO:0000269|PubMed:9839948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43449;
CC Evidence={ECO:0000269|PubMed:7668252};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + octadecanoyl-CoA + oxidized [electron-transfer
CC flavoprotein] = (2E)-octadecenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:47240, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57394, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:71412;
CC Evidence={ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:9839948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47241;
CC Evidence={ECO:0000269|PubMed:9839948};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eicosanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-eicosenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:47236, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57380, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:74691;
CC Evidence={ECO:0000269|PubMed:21237683};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47237;
CC Evidence={ECO:0000305|PubMed:21237683};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=docosanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-docosenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:47228, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:65059, ChEBI:CHEBI:74692;
CC Evidence={ECO:0000269|PubMed:21237683};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47229;
CC Evidence={ECO:0000305|PubMed:21237683};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxidized [electron-transfer flavoprotein] +
CC tetracosanoyl-CoA = (2E)-tetracosenoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:47232, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:65052, ChEBI:CHEBI:74693;
CC Evidence={ECO:0000269|PubMed:21237683};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47233;
CC Evidence={ECO:0000305|PubMed:21237683};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=a very-long-chain 2,3-saturated fatty acyl-CoA + H(+) +
CC oxidized [electron-transfer flavoprotein] = a very-long-chain (2E)-
CC enoyl-CoA + reduced [electron-transfer flavoprotein];
CC Xref=Rhea:RHEA:19181, Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:83724, ChEBI:CHEBI:83728; EC=1.3.8.9;
CC Evidence={ECO:0000269|PubMed:17374501};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19182;
CC Evidence={ECO:0000305|PubMed:17374501};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=H(+) + oxidized [electron-transfer flavoprotein] +
CC tetradecanoyl-CoA = (2E)-tetradecenoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:47316, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57385,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:61405;
CC Evidence={ECO:0000269|PubMed:17374501};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47317;
CC Evidence={ECO:0000305|PubMed:17374501};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=H(+) + hexadecanoyl-CoA + oxidized [electron-transfer
CC flavoprotein] = (2E)-hexadecenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:43448, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57379, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:61526;
CC Evidence={ECO:0000269|PubMed:17374501};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43449;
CC Evidence={ECO:0000305|PubMed:17374501};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=(9Z)-hexadecenoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E,9Z)-hexadecadienoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:47304, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:61540, ChEBI:CHEBI:77549;
CC Evidence={ECO:0000269|PubMed:17374501};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47305;
CC Evidence={ECO:0000305|PubMed:17374501};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=H(+) + octadecanoyl-CoA + oxidized [electron-transfer
CC flavoprotein] = (2E)-octadecenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:47240, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57394, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:71412;
CC Evidence={ECO:0000269|PubMed:17374501};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47241;
CC Evidence={ECO:0000305|PubMed:17374501};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=(9Z)-octadecenoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E,9Z)-octadecadienoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:47300, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57387,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:77553;
CC Evidence={ECO:0000269|PubMed:17374501};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47301;
CC Evidence={ECO:0000305|PubMed:17374501};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=eicosanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-eicosenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:47236, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57380, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:74691;
CC Evidence={ECO:0000269|PubMed:17374501};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47237;
CC Evidence={ECO:0000305|PubMed:17374501};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:18227065, ECO:0000269|PubMed:9461620};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.4 uM for hexadecanoyl-CoA {ECO:0000269|PubMed:9461620};
CC -!- PATHWAY: Lipid metabolism; mitochondrial fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:7668252, ECO:0000269|PubMed:9599005,
CC ECO:0000269|PubMed:9839948}.
CC -!- SUBUNIT: Homodimer (PubMed:9461620, PubMed:18227065, PubMed:9599005).
CC Homodimerizes after import into the mitochondrion (PubMed:9599005).
CC {ECO:0000269|PubMed:18227065, ECO:0000269|PubMed:9461620,
CC ECO:0000269|PubMed:9599005}.
CC -!- INTERACTION:
CC P49748; Q53T94: TAF1B; NbExp=3; IntAct=EBI-727618, EBI-1560239;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:9461620, ECO:0000269|PubMed:9599005}; Peripheral
CC membrane protein {ECO:0000269|PubMed:9599005}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:17374501}; Peripheral membrane protein
CC {ECO:0000269|PubMed:17374501}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P49748-1; Sequence=Displayed;
CC Name=2; Synonyms=DeltaEx3 VLCAD {ECO:0000303|PubMed:17374501};
CC IsoId=P49748-2; Sequence=VSP_007734;
CC Name=3;
CC IsoId=P49748-3; Sequence=VSP_046031;
CC -!- PTM: S-nitrosylation at Cys-237 in liver improves catalytic efficiency.
CC {ECO:0000250|UniProtKB:P50544}.
CC -!- DISEASE: Acyl-CoA dehydrogenase very long-chain deficiency (ACADVLD)
CC [MIM:201475]: An inborn error of mitochondrial fatty acid beta-
CC oxidation which leads to impaired long-chain fatty acid beta-oxidation.
CC It is clinically heterogeneous, with three major phenotypes: a severe
CC childhood form characterized by early onset, high mortality and high
CC incidence of cardiomyopathy; a milder childhood form with later onset,
CC characterized by hypoketotic hypoglycemia, low mortality and rare
CC cardiomyopathy; an adult form, with isolated skeletal muscle
CC involvement, rhabdomyolysis and myoglobinuria, usually triggered by
CC exercise or fasting. {ECO:0000269|PubMed:10077518,
CC ECO:0000269|PubMed:17374501, ECO:0000269|PubMed:7668252,
CC ECO:0000269|PubMed:8554073, ECO:0000269|PubMed:8845838,
CC ECO:0000269|PubMed:9461620, ECO:0000269|PubMed:9546340,
CC ECO:0000269|PubMed:9599005, ECO:0000269|PubMed:9839948,
CC ECO:0000269|PubMed:9973285}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; D43682; BAA07781.1; -; mRNA.
DR EMBL; L46590; AAA79002.1; -; Genomic_DNA.
DR EMBL; X86556; CAA60253.1; -; mRNA.
DR EMBL; D78298; BAA29057.1; -; Genomic_DNA.
DR EMBL; AK293549; BAG57027.1; -; mRNA.
DR EMBL; AC120057; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000399; AAH00399.1; -; mRNA.
DR EMBL; BC012912; AAH12912.1; -; mRNA.
DR EMBL; BC020218; AAH20218.1; -; mRNA.
DR CCDS; CCDS11090.1; -. [P49748-1]
DR CCDS; CCDS42249.1; -. [P49748-2]
DR CCDS; CCDS58509.1; -. [P49748-3]
DR PIR; S54183; S54183.
DR RefSeq; NP_000009.1; NM_000018.3. [P49748-1]
DR RefSeq; NP_001029031.1; NM_001033859.2. [P49748-2]
DR RefSeq; NP_001257376.1; NM_001270447.1. [P49748-3]
DR PDB; 2UXW; X-ray; 1.45 A; A=72-655.
DR PDB; 3B96; X-ray; 1.91 A; A=69-655.
DR PDBsum; 2UXW; -.
DR PDBsum; 3B96; -.
DR AlphaFoldDB; P49748; -.
DR SASBDB; P49748; -.
DR SMR; P49748; -.
DR BioGRID; 106555; 115.
DR IntAct; P49748; 41.
DR MINT; P49748; -.
DR STRING; 9606.ENSP00000438689; -.
DR ChEMBL; CHEMBL4105892; -.
DR SwissLipids; SLP:000001330; -. [P49748-2]
DR SwissLipids; SLP:000001332; -.
DR CarbonylDB; P49748; -.
DR GlyGen; P49748; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P49748; -.
DR PhosphoSitePlus; P49748; -.
DR SwissPalm; P49748; -.
DR BioMuta; ACADVL; -.
DR DMDM; 1703068; -.
DR CPTAC; CPTAC-454; -.
DR CPTAC; CPTAC-455; -.
DR EPD; P49748; -.
DR jPOST; P49748; -.
DR MassIVE; P49748; -.
DR MaxQB; P49748; -.
DR PaxDb; P49748; -.
DR PeptideAtlas; P49748; -.
DR PRIDE; P49748; -.
DR ProteomicsDB; 25916; -.
DR ProteomicsDB; 56061; -. [P49748-1]
DR ProteomicsDB; 56062; -. [P49748-2]
DR Antibodypedia; 11798; 304 antibodies from 34 providers.
DR DNASU; 37; -.
DR Ensembl; ENST00000350303.9; ENSP00000344152.5; ENSG00000072778.20. [P49748-2]
DR Ensembl; ENST00000356839.10; ENSP00000349297.5; ENSG00000072778.20. [P49748-1]
DR Ensembl; ENST00000543245.6; ENSP00000438689.2; ENSG00000072778.20. [P49748-3]
DR GeneID; 37; -.
DR KEGG; hsa:37; -.
DR MANE-Select; ENST00000356839.10; ENSP00000349297.5; NM_000018.4; NP_000009.1.
DR UCSC; uc002gev.5; human. [P49748-1]
DR CTD; 37; -.
DR DisGeNET; 37; -.
DR GeneCards; ACADVL; -.
DR GeneReviews; ACADVL; -.
DR HGNC; HGNC:92; ACADVL.
DR HPA; ENSG00000072778; Tissue enhanced (skeletal muscle, tongue).
DR MalaCards; ACADVL; -.
DR MIM; 201475; phenotype.
DR MIM; 609575; gene.
DR neXtProt; NX_P49748; -.
DR OpenTargets; ENSG00000072778; -.
DR Orphanet; 26793; Very long chain acyl-CoA dehydrogenase deficiency.
DR PharmGKB; PA24428; -.
DR VEuPathDB; HostDB:ENSG00000072778; -.
DR eggNOG; KOG0137; Eukaryota.
DR GeneTree; ENSGT00940000158535; -.
DR HOGENOM; CLU_018204_11_2_1; -.
DR InParanoid; P49748; -.
DR OMA; NAFMGLR; -.
DR OrthoDB; 819314at2759; -.
DR PhylomeDB; P49748; -.
DR TreeFam; TF105053; -.
DR BioCyc; MetaCyc:ENSG00000072778-MON; -.
DR BRENDA; 1.3.8.8; 2681.
DR BRENDA; 1.3.8.9; 2681.
DR PathwayCommons; P49748; -.
DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes.
DR Reactome; R-HSA-77305; Beta oxidation of palmitoyl-CoA to myristoyl-CoA.
DR SignaLink; P49748; -.
DR SIGNOR; P49748; -.
DR UniPathway; UPA00660; -.
DR BioGRID-ORCS; 37; 9 hits in 1078 CRISPR screens.
DR ChiTaRS; ACADVL; human.
DR EvolutionaryTrace; P49748; -.
DR GenomeRNAi; 37; -.
DR Pharos; P49748; Tbio.
DR PRO; PR:P49748; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P49748; protein.
DR Bgee; ENSG00000072778; Expressed in right adrenal gland cortex and 201 other tissues.
DR ExpressionAtlas; P49748; baseline and differential.
DR Genevisible; P49748; HS.
DR GO; GO:0031314; C:extrinsic component of mitochondrial inner membrane; IMP:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:BHF-UCL.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0003995; F:acyl-CoA dehydrogenase activity; IMP:UniProtKB.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; IBA:GO_Central.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0004466; F:long-chain-acyl-CoA dehydrogenase activity; IDA:BHF-UCL.
DR GO; GO:0017099; F:very-long-chain-acyl-CoA dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0015980; P:energy derivation by oxidation of organic compounds; TAS:ProtInc.
DR GO; GO:0030855; P:epithelial cell differentiation; IEP:UniProtKB.
DR GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; IDA:BHF-UCL.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0046322; P:negative regulation of fatty acid oxidation; ISS:BHF-UCL.
DR GO; GO:0090181; P:regulation of cholesterol metabolic process; ISS:BHF-UCL.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR GO; GO:0001659; P:temperature homeostasis; ISS:BHF-UCL.
DR Gene3D; 1.10.540.10; -; 1.
DR Gene3D; 2.40.110.10; -; 1.
DR InterPro; IPR006089; Acyl-CoA_DH_CS.
DR InterPro; IPR006091; Acyl-CoA_Oxase/DH_mid-dom.
DR InterPro; IPR046373; Acyl-CoA_Oxase/DH_mid-dom_sf.
DR InterPro; IPR036250; AcylCo_DH-like_C.
DR InterPro; IPR009075; AcylCo_DH/oxidase_C.
DR InterPro; IPR013786; AcylCoA_DH/ox_N.
DR InterPro; IPR037069; AcylCoA_DH/ox_N_sf.
DR InterPro; IPR009100; AcylCoA_DH/oxidase_NM_dom.
DR Pfam; PF00441; Acyl-CoA_dh_1; 1.
DR Pfam; PF02770; Acyl-CoA_dh_M; 1.
DR Pfam; PF02771; Acyl-CoA_dh_N; 1.
DR SUPFAM; SSF47203; SSF47203; 1.
DR SUPFAM; SSF56645; SSF56645; 1.
DR PROSITE; PS00072; ACYL_COA_DH_1; 1.
DR PROSITE; PS00073; ACYL_COA_DH_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cardiomyopathy;
KW Direct protein sequencing; Disease variant; FAD; Fatty acid metabolism;
KW Flavoprotein; Lipid metabolism; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Oxidoreductase; Phosphoprotein;
KW Reference proteome; S-nitrosylation; Transit peptide.
FT TRANSIT 1..40
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:7668252,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 41..655
FT /note="Very long-chain specific acyl-CoA dehydrogenase,
FT mitochondrial"
FT /id="PRO_0000000515"
FT REGION 23..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 41..482
FT /note="Catalytic"
FT /evidence="ECO:0000305|PubMed:18227065"
FT REGION 483..516
FT /note="Membrane-anchoring"
FT /evidence="ECO:0000305|PubMed:18227065"
FT ACT_SITE 462
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:18227065,
FT ECO:0000269|PubMed:9461620, ECO:0007744|PDB:2UXW,
FT ECO:0007744|PDB:3B96"
FT BINDING 214..223
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:18227065,
FT ECO:0007744|PDB:2UXW, ECO:0007744|PDB:3B96"
FT BINDING 249..251
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:18227065,
FT ECO:0007744|PDB:2UXW, ECO:0007744|PDB:3B96"
FT BINDING 461..463
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18227065,
FT ECO:0007744|PDB:2UXW, ECO:0007744|PDB:3B96"
FT BINDING 464..466
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:18227065,
FT ECO:0007744|PDB:2UXW, ECO:0007744|PDB:3B96"
FT BINDING 562
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:18227065,
FT ECO:0007744|PDB:2UXW, ECO:0007744|PDB:3B96"
FT MOD_RES 51
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 71
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 71
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 195
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 237
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 239
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 239
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 276
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 276
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 278
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 278
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 298
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 331
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 331
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 372
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 482
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 482
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 517
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 522
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 550
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 556
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 556
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 639
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT VAR_SEQ 1..20
FT /note="MQAARMAASLGRQLLRLGGG -> MLGGLAAAAGTRIMGKEIEAEAQRPLRQ
FT TWRPGQPPAMTAKTM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046031"
FT VAR_SEQ 47..68
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007734"
FT VARIANT 17
FT /note="L -> F (in dbSNP:rs2230179)"
FT /id="VAR_029286"
FT VARIANT 43
FT /note="G -> D (in dbSNP:rs2230178)"
FT /id="VAR_000330"
FT VARIANT 65
FT /note="P -> L (in dbSNP:rs28934585)"
FT /id="VAR_048176"
FT VARIANT 130
FT /note="Missing (in ACADVLD; dbSNP:rs387906251)"
FT /evidence="ECO:0000269|PubMed:10077518,
FT ECO:0000269|PubMed:8554073"
FT /id="VAR_000331"
FT VARIANT 158
FT /note="T -> N (in ACADVLD)"
FT /id="VAR_000332"
FT VARIANT 159
FT /note="Q -> R (in ACADVLD; dbSNP:rs746688190)"
FT /id="VAR_000333"
FT VARIANT 174
FT /note="V -> M (in ACADVLD; dbSNP:rs369560930)"
FT /id="VAR_000334"
FT VARIANT 185
FT /note="G -> S (in ACADVLD; dbSNP:rs545215807)"
FT /id="VAR_000335"
FT VARIANT 213
FT /note="A -> P (in ACADVLD; dbSNP:rs140629318)"
FT /evidence="ECO:0000269|PubMed:10077518"
FT /id="VAR_010101"
FT VARIANT 218
FT /note="E -> K (in ACADVLD; dbSNP:rs1432183079)"
FT /id="VAR_000336"
FT VARIANT 243
FT /note="L -> R (in ACADVLD)"
FT /id="VAR_000337"
FT VARIANT 247
FT /note="K -> E (in ACADVLD; dbSNP:rs387906253)"
FT /evidence="ECO:0000269|PubMed:10077518"
FT /id="VAR_010102"
FT VARIANT 247
FT /note="K -> T (in ACADVLD)"
FT /id="VAR_000338"
FT VARIANT 260
FT /note="T -> M (in ACADVLD; decreased protein abundance;
FT loss of fatty acid beta-oxidation; dbSNP:rs113994168)"
FT /evidence="ECO:0000269|PubMed:10077518,
FT ECO:0000269|PubMed:17374501, ECO:0000269|PubMed:8845838,
FT ECO:0000269|PubMed:9973285"
FT /id="VAR_000339"
FT VARIANT 278
FT /note="Missing (in ACADVLD)"
FT /evidence="ECO:0000269|PubMed:10077518"
FT /id="VAR_000340"
FT VARIANT 281
FT /note="A -> D (in ACADVLD)"
FT /evidence="ECO:0000269|PubMed:8845838"
FT /id="VAR_000341"
FT VARIANT 283
FT /note="V -> A (in ACADVLD; decreased protein abundance;
FT decreased fatty acid beta-oxidation; dbSNP:rs113994167)"
FT /evidence="ECO:0000269|PubMed:10077518,
FT ECO:0000269|PubMed:17374501, ECO:0000269|PubMed:8845838,
FT ECO:0000269|PubMed:9973285"
FT /id="VAR_000342"
FT VARIANT 290
FT /note="G -> D (in ACADVLD; dbSNP:rs866464446)"
FT /id="VAR_000343"
FT VARIANT 294
FT /note="G -> E (in ACADVLD; dbSNP:rs200573371)"
FT /id="VAR_000344"
FT VARIANT 299
FT /note="K -> N (in ACADVLD; dbSNP:rs774716484)"
FT /id="VAR_000345"
FT VARIANT 299
FT /note="Missing (in ACADVLD)"
FT /evidence="ECO:0000269|PubMed:8554073"
FT /id="VAR_000346"
FT VARIANT 317
FT /note="V -> A (in ACADVLD; dbSNP:rs398123095)"
FT /evidence="ECO:0000269|PubMed:8845838"
FT /id="VAR_000347"
FT VARIANT 352
FT /note="M -> V (in ACADVLD)"
FT /id="VAR_000348"
FT VARIANT 359
FT /note="A -> S (in dbSNP:rs1051701)"
FT /id="VAR_011990"
FT VARIANT 366
FT /note="R -> C (in ACADVLD; dbSNP:rs771874163)"
FT /evidence="ECO:0000269|PubMed:8845838"
FT /id="VAR_000349"
FT VARIANT 366
FT /note="R -> H (in ACADVLD; dbSNP:rs112406105)"
FT /id="VAR_000350"
FT VARIANT 381
FT /note="Missing (in ACADVLD; dbSNP:rs1057517281)"
FT /evidence="ECO:0000269|PubMed:8845838"
FT /id="VAR_000351"
FT VARIANT 382
FT /note="K -> Q (in ACADVLD; dbSNP:rs118204015)"
FT /evidence="ECO:0000269|PubMed:8554073"
FT /id="VAR_000352"
FT VARIANT 405
FT /note="D -> H (in ACADVLD)"
FT /id="VAR_000353"
FT VARIANT 441
FT /note="G -> D (in ACADVLD; dbSNP:rs2309689)"
FT /evidence="ECO:0000269|PubMed:10077518,
FT ECO:0000269|PubMed:8845838"
FT /id="VAR_000354"
FT VARIANT 450
FT /note="R -> H (in ACADVLD; dbSNP:rs118204016)"
FT /evidence="ECO:0000269|PubMed:9546340"
FT /id="VAR_000355"
FT VARIANT 453
FT /note="R -> Q (in ACADVLD; dbSNP:rs138058572)"
FT /id="VAR_000356"
FT VARIANT 454
FT /note="D -> N (in ACADVLD; dbSNP:rs1419606204)"
FT /id="VAR_000357"
FT VARIANT 456
FT /note="R -> H (in ACADVLD; dbSNP:rs794727112)"
FT /id="VAR_000358"
FT VARIANT 458
FT /note="F -> L (in ACADVLD; loss of acyl-CoA dehydrogenase
FT activity; Loss of FAD cofactor-binding; dbSNP:rs118204017)"
FT /evidence="ECO:0000269|PubMed:10077518,
FT ECO:0000269|PubMed:9461620"
FT /id="VAR_010103"
FT VARIANT 459
FT /note="R -> W (in ACADVLD; dbSNP:rs766742117)"
FT /id="VAR_000359"
FT VARIANT 463
FT /note="G -> E (in ACADVLD; dbSNP:rs200366828)"
FT /id="VAR_000360"
FT VARIANT 469
FT /note="R -> Q (in ACADVLD; dbSNP:rs398123083)"
FT /id="VAR_000361"
FT VARIANT 469
FT /note="R -> W (in ACADVLD; decreased protein abundance;
FT loss of fatty acid beta-oxidation; dbSNP:rs113994170)"
FT /evidence="ECO:0000269|PubMed:17374501,
FT ECO:0000269|PubMed:9973285"
FT /id="VAR_000362"
FT VARIANT 490
FT /note="A -> P (in ACADVLD; decreased association with
FT mitochondrial inner membrane; could change substrate
FT specificity with decreased affinity for tetradecanoyl-CoA
FT and hexadecanoyl-CoA; dbSNP:rs759775666)"
FT /evidence="ECO:0000269|PubMed:10077518,
FT ECO:0000269|PubMed:17374501, ECO:0000269|PubMed:9839948"
FT /id="VAR_010104"
FT VARIANT 502
FT /note="L -> P (in ACADVLD; decreased association with
FT mitochondrial inner membrane; no effect on acyl-CoA
FT dehydrogenase activity)"
FT /evidence="ECO:0000269|PubMed:17374501,
FT ECO:0000269|PubMed:9973285"
FT /id="VAR_000363"
FT VARIANT 534
FT /note="E -> K (in ACADVLD; unknown pathological
FT significance; dbSNP:rs2230180)"
FT /evidence="ECO:0000269|PubMed:10077518"
FT /id="VAR_010105"
FT VARIANT 583
FT /note="S -> W (in ACADVLD; Loss of homodimerization; loss
FT of localization to mitochondrial inner membrane;
FT dbSNP:rs1085307648)"
FT /evidence="ECO:0000269|PubMed:9599005"
FT /id="VAR_083892"
FT VARIANT 602
FT /note="L -> I (in ACADVLD)"
FT /evidence="ECO:0000269|PubMed:8845838"
FT /id="VAR_000364"
FT VARIANT 613
FT /note="R -> W (in ACADVLD; loss of protein expression;
FT dbSNP:rs118204014)"
FT /evidence="ECO:0000269|PubMed:10077518,
FT ECO:0000269|PubMed:8554073, ECO:0000269|PubMed:9973285"
FT /id="VAR_000365"
FT VARIANT 615
FT /note="R -> Q (in ACADVLD; dbSNP:rs148584617)"
FT /evidence="ECO:0000269|PubMed:10077518"
FT /id="VAR_010106"
FT VARIANT 623
FT /note="S -> F (in dbSNP:rs13383)"
FT /id="VAR_011991"
FT MUTAGEN 458
FT /note="F->T: Decreased acyl-CoA dehydrogenase activity.
FT Decreased affinity for acyl-CoA. No effect on FAD cofactor-
FT binding."
FT /evidence="ECO:0000269|PubMed:9461620"
FT MUTAGEN 458
FT /note="F->V: Loss of acyl-CoA dehydrogenase activity. Loss
FT of FAD cofactor-binding."
FT /evidence="ECO:0000269|PubMed:9461620"
FT MUTAGEN 458
FT /note="F->Y: Decreased acyl-CoA dehydrogenase activity. No
FT effect on affinity for acyl-CoA. Decreased FAD cofactor-
FT binding."
FT /evidence="ECO:0000269|PubMed:9461620"
FT MUTAGEN 462
FT /note="E->D: Decreased acyl-CoA dehydrogenase activity. No
FT effect on affinity for acyl-CoA. No effect on FAD cofactor-
FT binding."
FT /evidence="ECO:0000269|PubMed:9461620"
FT MUTAGEN 462
FT /note="E->Q: Loss of acyl-CoA dehydrogenase activity. No
FT effect on FAD cofactor-binding."
FT /evidence="ECO:0000269|PubMed:9461620"
FT MUTAGEN 490
FT /note="A->G,V,S,D,H: Changed substrate specificity with
FT decreased affinity for tetradecanoyl-CoA and hexadecanoyl-
FT CoA."
FT /evidence="ECO:0000269|PubMed:9839948"
FT CONFLICT 193
FT /note="G -> C (in Ref. 3; BAA29057)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="K -> E (in Ref. 4; BAG57027)"
FT /evidence="ECO:0000305"
FT CONFLICT 541
FT /note="E -> K (in Ref. 4; BAG57027)"
FT /evidence="ECO:0000305"
FT HELIX 73..77
FT /evidence="ECO:0007829|PDB:2UXW"
FT TURN 78..80
FT /evidence="ECO:0007829|PDB:2UXW"
FT TURN 85..87
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 96..115
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 119..125
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 130..138
FT /evidence="ECO:0007829|PDB:2UXW"
FT TURN 139..142
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 157..170
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 172..182
FT /evidence="ECO:0007829|PDB:2UXW"
FT TURN 183..186
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 187..192
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 195..206
FT /evidence="ECO:0007829|PDB:2UXW"
FT STRAND 212..215
FT /evidence="ECO:0007829|PDB:2UXW"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:2UXW"
FT STRAND 231..234
FT /evidence="ECO:0007829|PDB:2UXW"
FT STRAND 238..251
FT /evidence="ECO:0007829|PDB:2UXW"
FT TURN 252..255
FT /evidence="ECO:0007829|PDB:2UXW"
FT STRAND 257..268
FT /evidence="ECO:0007829|PDB:2UXW"
FT TURN 270..272
FT /evidence="ECO:0007829|PDB:2UXW"
FT STRAND 275..285
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 286..288
FT /evidence="ECO:0007829|PDB:2UXW"
FT STRAND 289..293
FT /evidence="ECO:0007829|PDB:2UXW"
FT STRAND 307..318
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:2UXW"
FT STRAND 322..325
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 329..365
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 373..375
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 377..405
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 412..437
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 439..442
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 448..455
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 456..459
FT /evidence="ECO:0007829|PDB:2UXW"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 465..485
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 486..488
FT /evidence="ECO:0007829|PDB:2UXW"
FT TURN 522..524
FT /evidence="ECO:0007829|PDB:3B96"
FT HELIX 527..529
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 530..554
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 555..560
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 562..591
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 596..622
FT /evidence="ECO:0007829|PDB:2UXW"
FT HELIX 627..644
FT /evidence="ECO:0007829|PDB:2UXW"
SQ SEQUENCE 655 AA; 70390 MW; A5594D1EA7911D19 CRC64;
MQAARMAASL GRQLLRLGGG SSRLTALLGQ PRPGPARRPY AGGAAQLALD KSDSHPSDAL
TRKKPAKAES KSFAVGMFKG QLTTDQVFPY PSVLNEEQTQ FLKELVEPVS RFFEEVNDPA
KNDALEMVEE TTWQGLKELG AFGLQVPSEL GGVGLCNTQY ARLVEIVGMH DLGVGITLGA
HQSIGFKGIL LFGTKAQKEK YLPKLASGET VAAFCLTEPS SGSDAASIRT SAVPSPCGKY
YTLNGSKLWI SNGGLADIFT VFAKTPVTDP ATGAVKEKIT AFVVERGFGG ITHGPPEKKM
GIKASNTAEV FFDGVRVPSE NVLGEVGSGF KVAMHILNNG RFGMAAALAG TMRGIIAKAV
DHATNRTQFG EKIHNFGLIQ EKLARMVMLQ YVTESMAYMV SANMDQGATD FQIEAAISKI
FGSEAAWKVT DECIQIMGGM GFMKEPGVER VLRDLRIFRI FEGTNDILRL FVALQGCMDK
GKELSGLGSA LKNPFGNAGL LLGEAGKQLR RRAGLGSGLS LSGLVHPELS RSGELAVRAL
EQFATVVEAK LIKHKKGIVN EQFLLQRLAD GAIDLYAMVV VLSRASRSLS EGHPTAQHEK
MLCDTWCIEA AARIREGMAA LQSDPWQQEL YRNFKSISKA LVERGGVVTS NPLGF
