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Identification
HMDB Protein ID HMDBP05273
Secondary Accession Numbers
  • 10872
Name Isobutyryl-CoA dehydrogenase, mitochondrial
Synonyms
  1. ACAD-8
  2. ARC42
  3. Activator-recruited cofactor 42 kDa component
  4. Acyl-CoA dehydrogenase family member 8
Gene Name ACAD8
Protein Type Unknown
Biological Properties
General Function Involved in acyl-CoA dehydrogenase activity
Specific Function Has very high activity toward isobutyryl-CoA. Is an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Plays a role in transcriptional coactivation within the ARC complex.
Pathways
  • 2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency
  • 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency
  • 3-hydroxyisobutyric acid dehydrogenase deficiency
  • 3-hydroxyisobutyric aciduria
  • 3-Methylcrotonyl Coa Carboxylase Deficiency Type I
  • 3-Methylglutaconic Aciduria Type I
  • 3-Methylglutaconic Aciduria Type III
  • 3-Methylglutaconic Aciduria Type IV
  • Beta-Ketothiolase Deficiency
  • Isobutyryl-coa dehydrogenase deficiency
  • Isovaleric acidemia
  • Isovaleric Aciduria
  • L-valine degradation
  • Maple Syrup Urine Disease
  • Methylmalonate Semialdehyde Dehydrogenase Deficiency
  • Methylmalonic Aciduria
  • Propionic Acidemia
  • Valine, Leucine and Isoleucine Degradation
  • Valine, leucine and isoleucine degradation
Reactions
Isobutyryl-CoA + ETF → methylacrylyl-CoA + reduced ETF details
Isobutyryl-CoA + Acceptor → Methacrylyl-CoA + Reduced acceptor details
GO Classification
Biological Process
branched-chain amino acid catabolic process
cellular nitrogen compound metabolic process
lipid metabolic process
regulation of transcription, DNA-dependent
transcription, DNA-dependent
valine catabolic process
Cellular Component
mitochondrial matrix
Function
oxidoreductase activity, acting on the ch-ch group of donors
acyl-coa dehydrogenase activity
binding
catalytic activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
oxidoreductase activity
fad or fadh2 binding
Molecular Function
acyl-CoA dehydrogenase activity
flavin adenine dinucleotide binding
Process
metabolic process
oxidation reduction
Cellular Location
  1. Mitochondrion
Gene Properties
Chromosome Location 11
Locus 11q25
SNPs ACAD8
Gene Sequence
>1248 bp
ATGCTGTGGAGCGGCTGCCGGCGTTTCGGGGCGCGCCTCGGCTGCCTGCCCGGCGGTCTC
CGGGTCCTCGTCCAGACCGGCCACCGGAGCTTGACCTCCTGCATCGACCCTTCCATGGGA
CTTAATGAAGAGCAGAAAGAATTTCAAAAAGTGGCCTTTGACTTTGCTGCCCGAGAGATG
GCTCCAAATATGGCAGAGTGGGACCAGAAGGAGCTGTTCCCAGTGGATGTGATGCGGAAG
GCAGCCCAGCTAGGCTTCGGAGGGGTCTACATACAAACAGATGTGGGCGGGTCTGGGCTG
TCACGTCTTGATACCTCTGTCATTTTTGAAGCCTTGGCTACAGGCTGCACCAGCACCACA
GCCTATATAAGCATCCACAACATGTGTGCCTGGATGATTGATAGCTTCGGAAATGAGGAA
CAGAGGCACAAATTTTGCCCACCGCTCTGTACCATGGAGAAGTTTGCTTCCTACTGCCTC
ACTGAACCAGGAAGTGGGAGTGATGCTGCCTCTCTTCTGACCTCCGCTAAGAAACAGGGA
GATCATTACATCCTCAATGGCTCCAAGGCCTTCATCAGTGGTGCTGGTGAGTCAGACATC
TATGTGGTCATGTGCCGAACAGGAGGACCAGGCCCCAAGGGCATCTCATGCATAGTTGTT
GAGAAGGGGACCCCTGGCCTCAGCTTTGGCAAGAAGGAGAAAAAGGTGGGGTGGAACTCC
CAGCCAACACGAGCTGTGATCTTCGAAGACTGTGCTGTCCCTGTGGCCAACAGAATTGGG
AGCGAGGGGCAGGGCTTCCTCATTGCCGTGAGAGGACTGAACGGAGGGAGGATCAATATT
GCTTCCTGCTCCCTGGGGGCTGCCCACGCCTCTGTCATCCTCACCCGAGACCACCTCAAT
GTCCGGAAGCAGTTTGGAGAGCCTCTGGCCAGTAACCAGTACTTGCAATTCACACTGGCT
GATATGGCAACAAGGCTGGTGGCCGCGCGGCTGATGGTCCGCAATGCAGCAGTGGCTCTG
CAGGAGGAGAGGAAGGATGCAGTGGCCTTGTGCTCCATGGCCAAGCTCTTTGCTACAGAT
GAATGCTTTGCCATCTGCAACCAGGCCTTGCAGATGCACGGGGGCTACGGCTACCTGAAG
GATTACGCTGTTCAGCAGTACGTGCGGGACTCCAGGGTCCACCAGATTCTAGAAGGTAGC
AATGAAGTGATGAGGATACTGATCTCTAGAAGCCTGCTTCAGGAGTAG
Protein Properties
Number of Residues 415
Molecular Weight 45069.39
Theoretical pI 7.849
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Isobutyryl-CoA dehydrogenase, mitochondrial
MLWSGCRRFGARLGCLPGGLRVLVQTGHRSLTSCIDPSMGLNEEQKEFQKVAFDFAAREM
APNMAEWDQKELFPVDVMRKAAQLGFGGVYIQTDVGGSGLSRLDTSVIFEALATGCTSTT
AYISIHNMCAWMIDSFGNEEQRHKFCPPLCTMEKFASYCLTEPGSGSDAASLLTSAKKQG
DHYILNGSKAFISGAGESDIYVVMCRTGGPGPKGISCIVVEKGTPGLSFGKKEKKVGWNS
QPTRAVIFEDCAVPVANRIGSEGQGFLIAVRGLNGGRINIASCSLGAAHASVILTRDHLN
VRKQFGEPLASNQYLQFTLADMATRLVAARLMVRNAAVALQEERKDAVALCSMAKLFATD
ECFAICNQALQMHGGYGYLKDYAVQQYVRDSRVHQILEGSNEVMRILISRSLLQE
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q9UKU7
UniProtKB/Swiss-Prot Entry Name ACAD8_HUMAN
PDB IDs
GenBank Gene ID AF126245
GeneCard ID ACAD8
GenAtlas ID ACAD8
HGNC ID HGNC:87
References
General References
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  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Andresen BS, Christensen E, Corydon TJ, Bross P, Pilgaard B, Wanders RJ, Ruiter JP, Simonsen H, Winter V, Knudsen I, Schroeder LD, Gregersen N, Skovby F: Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase deficiency: identification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in isoleucine and valine metabolism. Am J Hum Genet. 2000 Nov;67(5):1095-103. Epub 2000 Sep 29. [PubMed:11013134 ]
  4. Naar AM, Beaurang PA, Zhou S, Abraham S, Solomon W, Tjian R: Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature. 1999 Apr 29;398(6730):828-32. [PubMed:10235267 ]
  5. Telford EA, Moynihan LM, Markham AF, Lench NJ: Isolation and characterisation of a cDNA encoding the precursor for a novel member of the acyl-CoA dehydrogenase gene family. Biochim Biophys Acta. 1999 Sep 3;1446(3):371-6. [PubMed:10524212 ]
  6. Battaile KP, Nguyen TV, Vockley J, Kim JJ: Structures of isobutyryl-CoA dehydrogenase and enzyme-product complex: comparison with isovaleryl- and short-chain acyl-CoA dehydrogenases. J Biol Chem. 2004 Apr 16;279(16):16526-34. Epub 2004 Jan 28. [PubMed:14752098 ]
  7. Nguyen TV, Andresen BS, Corydon TJ, Ghisla S, Abd-El Razik N, Mohsen AW, Cederbaum SD, Roe DS, Roe CR, Lench NJ, Vockley J: Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans. Mol Genet Metab. 2002 Sep-Oct;77(1-2):68-79. [PubMed:12359132 ]
  8. Sass JO, Sander S, Zschocke J: Isobutyryl-CoA dehydrogenase deficiency: isobutyrylglycinuria and ACAD8 gene mutations in two infants. J Inherit Metab Dis. 2004;27(6):741-5. [PubMed:15505379 ]
  9. Pedersen CB, Bischoff C, Christensen E, Simonsen H, Lund AM, Young SP, Koeberl DD, Millington DS, Roe CR, Roe DS, Wanders RJ, Ruiter JP, Keppen LD, Stein Q, Knudsen I, Gregersen N, Andresen BS: Variations in IBD (ACAD8) in children with elevated C4-carnitine detected by tandem mass spectrometry newborn screening. Pediatr Res. 2006 Sep;60(3):315-20. Epub 2006 Jul 20. [PubMed:16857760 ]