ACAD8_HUMAN
ID ACAD8_HUMAN Reviewed; 415 AA.
AC Q9UKU7; B7Z5W4; Q6ZWP6; Q9BUS8;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Isobutyryl-CoA dehydrogenase, mitochondrial;
DE Short=IBDH {ECO:0000303|PubMed:12359132};
DE EC=1.3.8.- {ECO:0000269|PubMed:11013134, ECO:0000269|PubMed:12359132, ECO:0000269|PubMed:16857760};
DE AltName: Full=Activator-recruited cofactor 42 kDa component;
DE Short=ARC42;
DE AltName: Full=Acyl-CoA dehydrogenase family member 8;
DE Short=ACAD-8;
DE Flags: Precursor;
GN Name=ACAD8; Synonyms=ARC42, IBD;
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).
RC TISSUE=Brain, and Skin fibroblast;
RX PubMed=10524212; DOI=10.1016/s0167-4781(99)00102-5;
RA Telford E.A.R., Moynihan L.M., Markham A.F., Lench N.J.;
RT "Isolation and characterisation of a cDNA encoding the precursor for a
RT novel member of the acyl-CoA dehydrogenase gene family.";
RL Biochim. Biophys. Acta 1446:371-376(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=11013134; DOI=10.1086/303105;
RA Andresen B.S., Christensen E., Corydon T.J., Bross P., Pilgaard B.,
RA Wanders R.J.A., Ruiter J.P.N., Simonsen H., Winter V., Knudsen I.,
RA Schroeder L.D., Gregersen N., Skovby F.;
RT "Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA
RT dehydrogenase deficiency: identification of a new enzyme defect, resolution
RT of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases
RT in isoleucine and valine metabolism.";
RL Am. J. Hum. Genet. 67:1095-1103(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain, and Embryo;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix;
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 IDENTIFICATION IN ARC COMPLEX, AND PROTEIN SEQUENCE OF 50-61; 70-80 AND
RP 345-355.
RX PubMed=10235267; DOI=10.1038/19789;
RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.;
RT "Composite co-activator ARC mediates chromatin-directed transcriptional
RT activation.";
RL Nature 398:828-832(1999).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 24-415 IN COMPLEX WITH FAD AND
RP SUBSTRATE ANALOG, COFACTOR, SUBUNIT, ACTIVE SITE, AND REGION.
RX PubMed=14752098; DOI=10.1074/jbc.m400034200;
RA Battaile K.P., Nguyen T.V., Vockley J., Kim J.-J.P.;
RT "Structures of isobutyryl-CoA dehydrogenase and enzyme-product complex:
RT comparison with isovaleryl- and short-chain acyl-CoA dehydrogenases.";
RL J. Biol. Chem. 279:16526-16534(2004).
RN [10]
RP VARIANT IBDD GLN-302, CHARACTERIZATION OF VARIANT IBDD GLN-302, INVOLVEMENT
RP IN IBDD, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBSTRATE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=12359132; DOI=10.1016/s1096-7192(02)00152-x;
RA Nguyen T.V., Andresen B.S., Corydon T.J., Ghisla S., Abd El-Razik N.,
RA Mohsen A.W., Cederbaum S.D., Roe D.S., Roe C.R., Lench N.J., Vockley J.;
RT "Identification of isobutyryl-CoA dehydrogenase and its deficiency in
RT humans.";
RL Mol. Genet. Metab. 77:68-79(2002).
RN [11]
RP VARIANTS IBDD ILE-128 AND ILE-203.
RX PubMed=15505379; DOI=10.1023/b:boli.0000045798.12425.1b;
RA Sass J.O., Sander S., Zschocke J.;
RT "Isobutyryl-CoA dehydrogenase deficiency: isobutyrylglycinuria and ACAD8
RT gene mutations in two infants.";
RL J. Inherit. Metab. Dis. 27:741-745(2004).
RN [12]
RP VARIANTS IBDD TYR-134; ARG-137; THR-152; GLN-302; THR-320; CYS-334 AND
RP ARG-385, CHARACTERIZATION OF VARIANTS IBDD ARG-137; GLN-302 AND THR-320,
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=16857760; DOI=10.1203/01.pdr.0000233085.72522.04;
RA Pedersen C.B., Bischoff C., Christensen E., Simonsen H., Lund A.M.,
RA Young S.P., Koeberl D.D., Millington D.S., Roe C.R., Roe D.S.,
RA Wanders R.J.A., Ruiter J.P.N., Keppen L.D., Stein Q., Knudsen I.,
RA Gregersen N., Andresen B.S.;
RT "Variations in IBD (ACAD8) in children with elevated C4-carnitine detected
RT by tandem mass spectrometry newborn screening.";
RL Pediatr. Res. 60:315-320(2006).
CC -!- FUNCTION: Isobutyryl-CoA dehydrogenase which catalyzes one of the steps
CC of the valine catabolic pathway (PubMed:11013134, PubMed:12359132,
CC PubMed:16857760). To a lesser extent, is also able to catalyze the
CC oxidation of (2S)-2-methylbutanoyl-CoA (PubMed:11013134,
CC PubMed:12359132). {ECO:0000269|PubMed:11013134,
CC ECO:0000269|PubMed:12359132, ECO:0000269|PubMed:16857760}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylpropanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-2-methylpropenoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:44180, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57338,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:62500;
CC Evidence={ECO:0000269|PubMed:11013134, ECO:0000269|PubMed:12359132,
CC ECO:0000269|PubMed:16857760};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44181;
CC Evidence={ECO:0000269|PubMed:12359132, ECO:0000269|PubMed:16857760};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S)-2-methylbutanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-2-methylbut-2-enoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:48256, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57337,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:88166;
CC Evidence={ECO:0000269|PubMed:11013134, ECO:0000269|PubMed:12359132};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48257;
CC Evidence={ECO:0000305|PubMed:12359132};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxidized [electron-transfer flavoprotein] + propanoyl-
CC CoA = acryloyl-CoA + reduced [electron-transfer flavoprotein];
CC Xref=Rhea:RHEA:31287, Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57367, ChEBI:CHEBI:57392,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307;
CC Evidence={ECO:0000269|PubMed:12359132};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31288;
CC Evidence={ECO:0000305|PubMed:12359132};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:14752098};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.6 uM for 2-methylpropanoyl-CoA {ECO:0000269|PubMed:12359132};
CC KM=18 uM for (2S)-2-methylbutanoyl-CoA {ECO:0000269|PubMed:12359132};
CC KM=24 uM for n-propionyl-CoA {ECO:0000269|PubMed:12359132};
CC Note=kcat is 2.0 sec(-1) for the oxidation of 2-methylpropanoyl-CoA
CC (PubMed:12359132). kcat is 4.1 sec(-1) for the oxidation of (2S)-
CC methylbutanoyl-CoA (PubMed:12359132). kcat is 0.83 sec(-1) for the
CC oxidation of n-propionyl-CoA (PubMed:12359132).
CC {ECO:0000269|PubMed:12359132};
CC -!- PATHWAY: Amino-acid degradation; L-valine degradation.
CC {ECO:0000269|PubMed:12359132, ECO:0000269|PubMed:16857760}.
CC -!- SUBUNIT: Homotetramer, formed by a dimer of dimers (PubMed:11013134,
CC PubMed:14752098). May be part of the large multiprotein complex
CC ARC/DRIP (PubMed:10235267). {ECO:0000269|PubMed:10235267,
CC ECO:0000269|PubMed:11013134, ECO:0000269|PubMed:14752098}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:11013134,
CC ECO:0000269|PubMed:12359132}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UKU7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UKU7-2; Sequence=VSP_055780, VSP_055781;
CC Name=3;
CC IsoId=Q9UKU7-3; Sequence=VSP_055779, VSP_055782;
CC -!- TISSUE SPECIFICITY: Detected at comparable levels in all tissues
CC examined (heart, lung, brain, skeletal muscle, pancreas and placenta).
CC Weakly expressed in liver and kidney.
CC -!- DISEASE: Isobutyryl-CoA dehydrogenase deficiency (IBDD) [MIM:611283]:
CC An autosomal recessive metabolic disorder characterized by plasma
CC carnitine deficiency and elevated C4-acylcarnitine. Patients manifest
CC variable clinical features including failure to thrive, seizures,
CC anemia, muscular hypotonia and developmental delay. Some patients may
CC be asymptomatic. {ECO:0000269|PubMed:12359132,
CC ECO:0000269|PubMed:15505379, ECO:0000269|PubMed:16857760}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AF126245; AAF12736.1; -; mRNA.
DR EMBL; AF260689; AAF97922.1; -; Genomic_DNA.
DR EMBL; AF260679; AAF97922.1; JOINED; Genomic_DNA.
DR EMBL; AF260680; AAF97922.1; JOINED; Genomic_DNA.
DR EMBL; AF260681; AAF97922.1; JOINED; Genomic_DNA.
DR EMBL; AF260682; AAF97922.1; JOINED; Genomic_DNA.
DR EMBL; AF260683; AAF97922.1; JOINED; Genomic_DNA.
DR EMBL; AF260684; AAF97922.1; JOINED; Genomic_DNA.
DR EMBL; AF260685; AAF97922.1; JOINED; Genomic_DNA.
DR EMBL; AF260686; AAF97922.1; JOINED; Genomic_DNA.
DR EMBL; AF260687; AAF97922.1; JOINED; Genomic_DNA.
DR EMBL; AF260688; AAF97922.1; JOINED; Genomic_DNA.
DR EMBL; AK000359; BAA91109.1; -; mRNA.
DR EMBL; AK074640; BAC11107.1; -; mRNA.
DR EMBL; AK299492; BAH13050.1; -; mRNA.
DR EMBL; AP000859; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471065; EAW67833.1; -; Genomic_DNA.
DR EMBL; BC001964; AAH01964.1; -; mRNA.
DR CCDS; CCDS8498.1; -. [Q9UKU7-1]
DR RefSeq; NP_055199.1; NM_014384.2. [Q9UKU7-1]
DR PDB; 1RX0; X-ray; 1.77 A; A/B/C/D=24-415.
DR PDBsum; 1RX0; -.
DR AlphaFoldDB; Q9UKU7; -.
DR SMR; Q9UKU7; -.
DR BioGRID; 117965; 31.
DR CORUM; Q9UKU7; -.
DR IntAct; Q9UKU7; 16.
DR STRING; 9606.ENSP00000281182; -.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR DrugBank; DB01675; Methacrylyl-Coenzyme A.
DR SwissLipids; SLP:000001420; -.
DR iPTMnet; Q9UKU7; -.
DR PhosphoSitePlus; Q9UKU7; -.
DR BioMuta; ACAD8; -.
DR DMDM; 26006699; -.
DR UCD-2DPAGE; Q9UKU7; -.
DR EPD; Q9UKU7; -.
DR jPOST; Q9UKU7; -.
DR MassIVE; Q9UKU7; -.
DR MaxQB; Q9UKU7; -.
DR PaxDb; Q9UKU7; -.
DR PeptideAtlas; Q9UKU7; -.
DR PRIDE; Q9UKU7; -.
DR ProteomicsDB; 6725; -.
DR ProteomicsDB; 68496; -.
DR ProteomicsDB; 84879; -. [Q9UKU7-1]
DR Antibodypedia; 33180; 191 antibodies from 22 providers.
DR DNASU; 27034; -.
DR Ensembl; ENST00000281182.9; ENSP00000281182.5; ENSG00000151498.12. [Q9UKU7-1]
DR Ensembl; ENST00000374752.6; ENSP00000363884.4; ENSG00000151498.12. [Q9UKU7-2]
DR GeneID; 27034; -.
DR KEGG; hsa:27034; -.
DR MANE-Select; ENST00000281182.9; ENSP00000281182.5; NM_014384.3; NP_055199.1.
DR UCSC; uc001qhk.4; human. [Q9UKU7-1]
DR CTD; 27034; -.
DR DisGeNET; 27034; -.
DR GeneCards; ACAD8; -.
DR HGNC; HGNC:87; ACAD8.
DR HPA; ENSG00000151498; Low tissue specificity.
DR MalaCards; ACAD8; -.
DR MIM; 604773; gene.
DR MIM; 611283; phenotype.
DR neXtProt; NX_Q9UKU7; -.
DR OpenTargets; ENSG00000151498; -.
DR Orphanet; 79159; Isobutyryl-CoA dehydrogenase deficiency.
DR PharmGKB; PA24423; -.
DR VEuPathDB; HostDB:ENSG00000151498; -.
DR eggNOG; KOG0140; Eukaryota.
DR GeneTree; ENSGT00940000157590; -.
DR HOGENOM; CLU_018204_0_2_1; -.
DR InParanoid; Q9UKU7; -.
DR OMA; NMATWML; -.
DR OrthoDB; 819314at2759; -.
DR PhylomeDB; Q9UKU7; -.
DR TreeFam; TF105052; -.
DR PathwayCommons; Q9UKU7; -.
DR Reactome; R-HSA-70895; Branched-chain amino acid catabolism.
DR SignaLink; Q9UKU7; -.
DR UniPathway; UPA00362; -.
DR BioGRID-ORCS; 27034; 19 hits in 1070 CRISPR screens.
DR ChiTaRS; ACAD8; human.
DR EvolutionaryTrace; Q9UKU7; -.
DR GeneWiki; ACAD8; -.
DR GenomeRNAi; 27034; -.
DR Pharos; Q9UKU7; Tbio.
DR PRO; PR:Q9UKU7; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9UKU7; protein.
DR Bgee; ENSG00000151498; Expressed in right lobe of thyroid gland and 187 other tissues.
DR ExpressionAtlas; Q9UKU7; baseline and differential.
DR Genevisible; Q9UKU7; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0003995; F:acyl-CoA dehydrogenase activity; TAS:ProtInc.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR GO; GO:0006574; P:valine catabolic process; IEA:UniProtKB-UniPathway.
DR CDD; cd01162; IBD; 1.
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 InterPro; IPR034178; IBD.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing;
KW Branched-chain amino acid catabolism; Direct protein sequencing;
KW Disease variant; FAD; Flavoprotein; Mitochondrion; Oxidoreductase;
KW Reference proteome; Transcription; Transcription regulation;
KW Transit peptide.
FT TRANSIT 1..22
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 23..415
FT /note="Isobutyryl-CoA dehydrogenase, mitochondrial"
FT /id="PRO_0000000522"
FT ACT_SITE 398
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:14752098"
FT BINDING 158..167
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:14752098"
FT BINDING 167
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:14752098"
FT BINDING 191..193
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:14752098"
FT BINDING 274..277
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:14752098"
FT BINDING 302
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:14752098"
FT BINDING 312..313
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:14752098"
FT BINDING 371..375
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:14752098"
FT BINDING 400..402
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:14752098"
FT BINDING 410
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:14752098"
FT MOD_RES 50
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9D7B6"
FT MOD_RES 50
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9D7B6"
FT MOD_RES 213
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D7B6"
FT MOD_RES 231
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D7B6"
FT VAR_SEQ 1..77
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055779"
FT VAR_SEQ 37
FT /note="P -> R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055780"
FT VAR_SEQ 38..164
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055781"
FT VAR_SEQ 399..415
FT /note="GSNEVMRILISRSLLQE -> ELFWQGPGVQSRSFVPFGGPQIALLLPFSSG
FT DLREG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055782"
FT VARIANT 128
FT /note="M -> I (in IBDD; dbSNP:rs374317179)"
FT /evidence="ECO:0000269|PubMed:15505379"
FT /id="VAR_035071"
FT VARIANT 134
FT /note="D -> Y (in IBDD; dbSNP:rs367857040)"
FT /evidence="ECO:0000269|PubMed:16857760"
FT /id="VAR_035072"
FT VARIANT 137
FT /note="G -> R (in IBDD; loss of protein solubility;
FT complete loss of isobutyryl-CoA dehydrogenase activity;
FT dbSNP:rs371449613)"
FT /evidence="ECO:0000269|PubMed:16857760"
FT /id="VAR_035073"
FT VARIANT 152
FT /note="M -> T (in IBDD; dbSNP:rs121908418)"
FT /evidence="ECO:0000269|PubMed:16857760"
FT /id="VAR_035074"
FT VARIANT 203
FT /note="V -> I (in IBDD; dbSNP:rs759877257)"
FT /evidence="ECO:0000269|PubMed:15505379"
FT /id="VAR_035075"
FT VARIANT 302
FT /note="R -> Q (in IBDD; no effect on localization to the
FT mitochondrion; complete loss of isobutyryl-CoA
FT dehydrogenase activity; loss of protein expression in
FT patient cells; dbSNP:rs121908422)"
FT /evidence="ECO:0000269|PubMed:12359132,
FT ECO:0000269|PubMed:16857760"
FT /id="VAR_035076"
FT VARIANT 320
FT /note="A -> T (in IBDD; decreased isobutyryl-CoA
FT dehydrogenase activity; less than 20% of wild-type;
FT dbSNP:rs200620279)"
FT /evidence="ECO:0000269|PubMed:16857760"
FT /id="VAR_035077"
FT VARIANT 334
FT /note="R -> C (in IBDD; dbSNP:rs778823613)"
FT /evidence="ECO:0000269|PubMed:16857760"
FT /id="VAR_035078"
FT VARIANT 385
FT /note="Q -> R (in IBDD; dbSNP:rs367996531)"
FT /evidence="ECO:0000269|PubMed:16857760"
FT /id="VAR_035079"
FT CONFLICT 210
FT /note="P -> L (in Ref. 6; AAH01964)"
FT /evidence="ECO:0000305"
FT TURN 37..40
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 43..59
FT /evidence="ECO:0007829|PDB:1RX0"
FT TURN 60..63
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 64..70
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 75..83
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 102..113
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 117..136
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 139..150
FT /evidence="ECO:0007829|PDB:1RX0"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:1RX0"
FT STRAND 165..168
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:1RX0"
FT STRAND 175..179
FT /evidence="ECO:0007829|PDB:1RX0"
FT STRAND 182..193
FT /evidence="ECO:0007829|PDB:1RX0"
FT TURN 194..197
FT /evidence="ECO:0007829|PDB:1RX0"
FT STRAND 199..211
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:1RX0"
FT STRAND 215..221
FT /evidence="ECO:0007829|PDB:1RX0"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:1RX0"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:1RX0"
FT STRAND 243..254
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:1RX0"
FT STRAND 258..261
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 265..301
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 309..311
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 313..341
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 347..372
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 373..378
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 384..393
FT /evidence="ECO:0007829|PDB:1RX0"
FT TURN 394..396
FT /evidence="ECO:0007829|PDB:1RX0"
FT STRAND 397..399
FT /evidence="ECO:0007829|PDB:1RX0"
FT HELIX 401..414
FT /evidence="ECO:0007829|PDB:1RX0"
SQ SEQUENCE 415 AA; 45070 MW; CAFFE91B74E2362D CRC64;
MLWSGCRRFG ARLGCLPGGL RVLVQTGHRS LTSCIDPSMG LNEEQKEFQK VAFDFAAREM
APNMAEWDQK ELFPVDVMRK AAQLGFGGVY IQTDVGGSGL SRLDTSVIFE ALATGCTSTT
AYISIHNMCA WMIDSFGNEE QRHKFCPPLC TMEKFASYCL TEPGSGSDAA SLLTSAKKQG
DHYILNGSKA FISGAGESDI YVVMCRTGGP GPKGISCIVV EKGTPGLSFG KKEKKVGWNS
QPTRAVIFED CAVPVANRIG SEGQGFLIAV RGLNGGRINI ASCSLGAAHA SVILTRDHLN
VRKQFGEPLA SNQYLQFTLA DMATRLVAAR LMVRNAAVAL QEERKDAVAL CSMAKLFATD
ECFAICNQAL QMHGGYGYLK DYAVQQYVRD SRVHQILEGS NEVMRILISR SLLQE
