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Q9UKU7 (ACAD8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Isobutyryl-CoA dehydrogenase, mitochondrial

EC=1.3.99.-
Alternative name(s):
Activator-recruited cofactor 42 kDa component
Short name=ARC42
Acyl-CoA dehydrogenase family member 8
Short name=ACAD-8
Gene names
Name:ACAD8
Synonyms:ARC42, IBD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length415 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.2 Ref.8

Catalytic activity

Isobutyryl-CoA + ETF = methylacrylyl-CoA + reduced ETF.

Cofactor

FAD.

Pathway

Amino-acid degradation; L-valine degradation.

Subunit structure

Homotetramer, formed by a dimer of dimers. Subunit of the large multiprotein complex ARC/DRIP. Ref.2 Ref.5 Ref.7

Subcellular location

Mitochondrion Ref.2.

Tissue specificity

Detected at comparable levels in all tissues examined (heart, lung, brain, skeletal muscle, pancreas and placenta). Weakly expressed in liver and kidney.

Involvement in disease

Isobutyryl-CoA dehydrogenase deficiency (IBDD) [MIM:611283]: The symptoms of IBDD generally appear until late in infancy or in childhood and can include poor feeding and growth (failure to thrive), a weakened and enlarged heart (dilated cardiomyopathy), seizures, and low numbers of red blood cells (anemia).
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.10

Sequence similarities

Belongs to the acyl-CoA dehydrogenase family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2222Mitochondrion Potential
Chain23 – 415393Isobutyryl-CoA dehydrogenase, mitochondrial
PRO_0000000522

Regions

Nucleotide binding158 – 16710FAD
Nucleotide binding191 – 1933FAD
Nucleotide binding312 – 3132FAD; shared with dimeric partner
Nucleotide binding371 – 3755FAD; shared with dimeric partner
Nucleotide binding400 – 4023FAD
Region274 – 2774Substrate binding

Sites

Active site3981Proton acceptor
Binding site1671Substrate; via carbonyl oxygen
Binding site3021FAD; shared with dimeric partner
Binding site3991Substrate; via amide nitrogen
Binding site4101Substrate

Amino acid modifications

Modified residue501N6-acetyllysine; alternate By similarity
Modified residue501N6-succinyllysine; alternate By similarity
Modified residue2131N6-succinyllysine By similarity
Modified residue2311N6-acetyllysine By similarity

Natural variations

Natural variant1281M → I in IBDD. Ref.9
VAR_035071
Natural variant1341D → Y in IBDD. Ref.10
VAR_035072
Natural variant1371G → R in IBDD; complete loss of activity. Ref.10
VAR_035073
Natural variant1521M → T in IBDD. Ref.10
VAR_035074
Natural variant2031V → I in IBDD. Ref.9
VAR_035075
Natural variant3021R → Q in IBDD; complete loss of activity. Ref.8 Ref.10
VAR_035076
Natural variant3201A → T in IBDD; <20% of wild-type activity. Ref.10
VAR_035077
Natural variant3341R → C in IBDD. Ref.10
VAR_035078
Natural variant3851Q → R in IBDD. Ref.10
VAR_035079

Experimental info

Sequence conflict2101P → L in AAH01964. Ref.4

Secondary structure

...................................................... 415
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UKU7 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: CAFFE91B74E2362D

FASTA41545,070
        10         20         30         40         50         60 
MLWSGCRRFG ARLGCLPGGL RVLVQTGHRS LTSCIDPSMG LNEEQKEFQK VAFDFAAREM 

        70         80         90        100        110        120 
APNMAEWDQK ELFPVDVMRK AAQLGFGGVY IQTDVGGSGL SRLDTSVIFE ALATGCTSTT 

       130        140        150        160        170        180 
AYISIHNMCA WMIDSFGNEE QRHKFCPPLC TMEKFASYCL TEPGSGSDAA SLLTSAKKQG 

       190        200        210        220        230        240 
DHYILNGSKA FISGAGESDI YVVMCRTGGP GPKGISCIVV EKGTPGLSFG KKEKKVGWNS 

       250        260        270        280        290        300 
QPTRAVIFED CAVPVANRIG SEGQGFLIAV RGLNGGRINI ASCSLGAAHA SVILTRDHLN 

       310        320        330        340        350        360 
VRKQFGEPLA SNQYLQFTLA DMATRLVAAR LMVRNAAVAL QEERKDAVAL CSMAKLFATD 

       370        380        390        400        410 
ECFAICNQAL QMHGGYGYLK DYAVQQYVRD SRVHQILEGS NEVMRILISR SLLQE 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and characterisation of a cDNA encoding the precursor for a novel member of the acyl-CoA dehydrogenase gene family."
Telford E.A.R., Moynihan L.M., Markham A.F., Lench N.J.
Biochim. Biophys. Acta 1446:371-376(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain and Skin fibroblast.
[2]"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."
Andresen B.S., Christensen E., Corydon T.J., Bross P., Pilgaard B., Wanders R.J.A., Ruiter J.P.N., Simonsen H., Winter V., Knudsen I., Schroeder L.D., Gregersen N., Skovby F.
Am. J. Hum. Genet. 67:1095-1103(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROBABLE FUNCTION, SUBCELLULAR LOCATION, SUBUNIT.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Cervix.
[5]"Composite co-activator ARC mediates chromatin-directed transcriptional activation."
Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.
Nature 398:828-832(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN ARC COMPLEX, PROTEIN SEQUENCE OF 50-61; 70-80 AND 345-355.
[6]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Structures of isobutyryl-CoA dehydrogenase and enzyme-product complex: comparison with isovaleryl- and short-chain acyl-CoA dehydrogenases."
Battaile K.P., Nguyen T.V., Vockley J., Kim J.-J.P.
J. Biol. Chem. 279:16526-16534(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 24-415 IN COMPLEX WITH FAD AND PRODUCT, SUBUNIT.
[8]"Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans."
Nguyen T.V., Andresen B.S., Corydon T.J., Ghisla S., Abd El-Razik N., Mohsen A.W., Cederbaum S.D., Roe D.S., Roe C.R., Lench N.J., Vockley J.
Mol. Genet. Metab. 77:68-79(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IBDD GLN-302, FUNCTION.
[9]"Isobutyryl-CoA dehydrogenase deficiency: isobutyrylglycinuria and ACAD8 gene mutations in two infants."
Sass J.O., Sander S., Zschocke J.
J. Inherit. Metab. Dis. 27:741-745(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IBDD ILE-128 AND ILE-203.
[10]"Variations in IBD (ACAD8) in children with elevated C4-carnitine detected by tandem mass spectrometry newborn screening."
Pedersen C.B., Bischoff C., Christensen E., Simonsen H., Lund A.M., Young S.P., Koeberl D.D., Millington D.S., Roe C.R., Roe D.S., Wanders R.J.A., Ruiter J.P.N., Keppen L.D., Stein Q., Knudsen I., Gregersen N., Andresen B.S.
Pediatr. Res. 60:315-320(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IBDD TYR-134; ARG-137; THR-152; GLN-302; THR-320; CYS-334 AND ARG-385, CHARACTERIZATION OF VARIANTS IBDD ARG-137; GLN-302 AND THR-320.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF126245 mRNA. Translation: AAF12736.1.
AF260689 expand/collapse EMBL AC list , AF260679, AF260680, AF260681, AF260682, AF260683, AF260684, AF260685, AF260686, AF260687, AF260688 Genomic DNA. Translation: AAF97922.1.
AK000359 mRNA. Translation: BAA91109.1.
BC001964 mRNA. Translation: AAH01964.1.
RefSeqNP_055199.1. NM_014384.2.
UniGeneHs.14791.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1RX0X-ray1.77A/B/C/D24-415[»]
ProteinModelPortalQ9UKU7.
SMRQ9UKU7. Positions 32-415.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117965. 2 interactions.
IntActQ9UKU7. 3 interactions.
STRING9606.ENSP00000281182.

PTM databases

PhosphoSiteQ9UKU7.

Polymorphism databases

DMDM26006699.

2D gel databases

UCD-2DPAGEQ9UKU7.

Proteomic databases

PaxDbQ9UKU7.
PRIDEQ9UKU7.

Protocols and materials databases

DNASU27034.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000281182; ENSP00000281182; ENSG00000151498.
GeneID27034.
KEGGhsa:27034.
UCSCuc001qhk.3. human.

Organism-specific databases

CTD27034.
GeneCardsGC11P134123.
HGNCHGNC:87. ACAD8.
HPAHPA040689.
HPA043903.
MIM604773. gene.
611283. phenotype.
neXtProtNX_Q9UKU7.
Orphanet79159. Isobutyryl-CoA dehydrogenase deficiency.
PharmGKBPA24423.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1960.
HOGENOMHOG000131659.
HOVERGENHBG000224.
InParanoidQ9UKU7.
KOK11538.
OMAMRMIISR.
OrthoDBEOG74FF0S.
PhylomeDBQ9UKU7.
TreeFamTF105052.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
UniPathwayUPA00362.

Gene expression databases

ArrayExpressQ9UKU7.
BgeeQ9UKU7.
CleanExHS_ACAD8.
GenevestigatorQ9UKU7.

Family and domain databases

Gene3D1.10.540.10. 1 hit.
2.40.110.10. 1 hit.
InterProIPR006089. Acyl-CoA_DH_CS.
IPR006091. Acyl-CoA_Oxase/DH_cen-dom.
IPR009075. AcylCo_DH/oxidase_C.
IPR013786. AcylCoA_DH/ox_N.
IPR009100. AcylCoA_DH/oxidase_NM_dom.
[Graphical view]
PfamPF00441. Acyl-CoA_dh_1. 1 hit.
PF02770. Acyl-CoA_dh_M. 1 hit.
PF02771. Acyl-CoA_dh_N. 1 hit.
[Graphical view]
SUPFAMSSF47203. SSF47203. 1 hit.
SSF56645. SSF56645. 1 hit.
PROSITEPS00072. ACYL_COA_DH_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9UKU7.
GeneWikiACAD8.
GenomeRNAi27034.
NextBio49582.
PROQ9UKU7.
SOURCESearch...

Entry information

Entry nameACAD8_HUMAN
AccessionPrimary (citable) accession number: Q9UKU7
Secondary accession number(s): Q9BUS8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM