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 27-MAR-2024, entry version 197. DE RecName: Full=Isobutyryl-CoA dehydrogenase, mitochondrial; DE Short=IBDH {ECO:0000303|PubMed:12359132}; DE EC=1.3.8.5 {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 {ECO:0000303|PubMed:10524212}; DE Short=ACAD-8 {ECO:0000303|PubMed:10524212}; DE Flags: Precursor; GN Name=ACAD8 {ECO:0000312|HGNC:HGNC:87}; 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), AND TISSUE SPECIFICITY. 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 the conversion CC of 2-methylpropanoyl-CoA to (2E)-2-methylpropenoyl-CoA in the valine CC catabolic pathway (PubMed:11013134, PubMed:12359132, PubMed:16857760). CC To a lesser extent, also able to catalyze the oxidation of (2S)-2- CC methylbutanoyl-CoA (PubMed:11013134, PubMed:12359132). CC {ECO:0000269|PubMed:11013134, ECO:0000269|PubMed:12359132, CC 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; EC=1.3.8.5; 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 CC (2S)-methylbutanoyl-CoA (PubMed:12359132). kcat is 0.83 sec(-1) for CC the 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 heart, lung, CC brain, skeletal muscle, pancreas and placenta. Weakly expressed in CC liver and kidney. {ECO:0000269|PubMed:10524212}. 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}. 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; 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; 35. DR CORUM; Q9UKU7; -. DR IntAct; Q9UKU7; 17. 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 SwissPalm; Q9UKU7; -. DR BioMuta; ACAD8; -. DR DMDM; 26006699; -. DR EPD; Q9UKU7; -. DR jPOST; Q9UKU7; -. DR MassIVE; Q9UKU7; -. DR MaxQB; Q9UKU7; -. DR PaxDb; 9606-ENSP00000281182; -. DR PeptideAtlas; Q9UKU7; -. DR ProteomicsDB; 6725; -. DR ProteomicsDB; 68496; -. DR ProteomicsDB; 84879; -. [Q9UKU7-1] DR Pumba; Q9UKU7; -. DR Antibodypedia; 33180; 203 antibodies from 23 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 AGR; HGNC:87; -. 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; 275353at2759; -. 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; 21 hits in 1151 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 189 other cell types or tissues. DR ExpressionAtlas; Q9UKU7; baseline and differential. 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; Acyl-CoA dehydrogenase/oxidase, N-terminal domain; 1. DR Gene3D; 2.40.110.10; Butyryl-CoA Dehydrogenase, subunit A, domain 2; 1. DR Gene3D; 1.20.140.10; Butyryl-CoA Dehydrogenase, subunit A, domain 3; 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_sf. DR InterPro; IPR034178; IBD. DR PANTHER; PTHR43831; ISOBUTYRYL-COA DEHYDROGENASE; 1. DR PANTHER; PTHR43831:SF1; ISOBUTYRYL-COA DEHYDROGENASE, MITOCHONDRIAL; 1. 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 PIRSF; PIRSF016578; HsaA; 1. DR SUPFAM; SSF47203; Acyl-CoA dehydrogenase C-terminal domain-like; 1. DR SUPFAM; SSF56645; Acyl-CoA dehydrogenase NM domain-like; 1. DR PROSITE; PS00072; ACYL_COA_DH_1; 1. DR UCD-2DPAGE; Q9UKU7; -. DR Genevisible; Q9UKU7; HS. 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 //