ACAD8

Protein identityUniProt · HPA

UniProt accession

Q9UKU7

Gene

ACAD8

Ensembl

ENSG00000151498

Chromosome

11

Canonical length

415 aa

Protein class

Disease related genes, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene encodes a member of the acyl-CoA dehydrogenase family of enzymes that catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids. The encoded protein is a mitochondrial enzyme that functions in catabolism of the branched-chain amino acid valine. Defects in this gene are the cause of isobutyryl-CoA dehydrogenase deficiency.[provided by RefSeq, Nov 2009]

Canonical amino-acid sequenceUniProt

415 residues, UniProt reviewed canonical sequence.

>Q9UKU7|ACAD8
     1  MLWSGCRRFG ARLGCLPGGL RVLVQTGHRS LTSCIDPSMG LNEEQKEFQK VAFDFAAREM
    61  APNMAEWDQK ELFPVDVMRK AAQLGFGGVY IQTDVGGSGL SRLDTSVIFE ALATGCTSTT
   121  AYISIHNMCA WMIDSFGNEE QRHKFCPPLC TMEKFASYCL TEPGSGSDAA SLLTSAKKQG
   181  DHYILNGSKA FISGAGESDI YVVMCRTGGP GPKGISCIVV EKGTPGLSFG KKEKKVGWNS
   241  QPTRAVIFED CAVPVANRIG SEGQGFLIAV RGLNGGRINI ASCSLGAAHA SVILTRDHLN
   301  VRKQFGEPLA SNQYLQFTLA DMATRLVAAR LMVRNAAVAL QEERKDAVAL CSMAKLFATD
   361  ECFAICNQAL QMHGGYGYLK DYAVQQYVRD SRVHQILEGS NEVMRILISR SLLQE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ACAD8 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

37 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ACAD8.

Disease | AllUniProt

Conditions ACAD8 is implicated in, by any mechanism.

• Isobutyryl-CoA dehydrogenase deficiency (IBDD) MIM:611283

Disease | GeneticClinVar

37 pathogenic / likely-pathogenic of 316 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Deficiency of isobutyryl-CoA dehydrogenase
• ACAD8-related disorder
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.27

gnomAD pLI

0

gnomAD missense Z

0.22

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• L-valine catabolic process
• lipid metabolic process

Molecular functions

• acyl-CoA dehydrogenase activity
• flavin adenine dinucleotide binding
• short-chain 2-methyl fatty acyl-CoA dehydrogenase activity

Cellular components

• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Acyl-CoA dehydrogenase, conserved site
• Acyl-CoA dehydrogenase/oxidase, middle domain
• Acyl-CoA dehydrogenase/oxidase, C-terminal
• Acyl-CoA dehydrogenase/oxidase, N-terminal and middle domain superfamily
• Acyl-CoA dehydrogenase/oxidase, N-terminal
• Acyl-CoA dehydrogenase-like, C-terminal
• Acyl-CoA dehydrogenase/oxidase, N-terminal domain superfamily
• Acyl-CoA oxidase/dehydrogenase, middle domain superfamily
• Acyl-CoA dehydrogenase, C-terminal domain
• Acyl-CoA dehydrogenase, middle domain
• Acyl-CoA dehydrogenase, N-terminal domain
• Isobutyryl-CoA dehydrogenase
• Mitochondrial Isobutyryl-CoA Dehydrogenase

KeywordsUniProt

• Acetylation
• Activator
• Branched-chain amino acid catabolism
• FAD
• Flavoprotein
• Mitochondrion
• Oxidoreductase
• Transcription
• Transcription regulation
• Transit peptide