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Protein

Isobutyryl-CoA dehydrogenase, mitochondrial

Gene

ACAD8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

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

Cofactori

FAD1 Publication

Pathwayi: L-valine degradation

This protein is involved in the pathway L-valine degradation, which is part of Amino-acid degradation.
View all proteins of this organism that are known to be involved in the pathway L-valine degradation and in Amino-acid degradation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei167Substrate; via carbonyl oxygen1
Binding sitei302FAD; shared with dimeric partner1 Publication1
Active sitei398Proton acceptor1
Binding sitei399Substrate; via amide nitrogen1
Binding sitei410Substrate1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi158 – 167FAD1 Publication10
Nucleotide bindingi191 – 193FAD1 Publication3
Nucleotide bindingi312 – 313FAD; shared with dimeric partner1 Publication2
Nucleotide bindingi371 – 375FAD; shared with dimeric partner1 Publication5
Nucleotide bindingi400 – 402FAD1 Publication3

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Oxidoreductase

Keywords - Biological processi

Branched-chain amino acid catabolism, Transcription, Transcription regulation

Keywords - Ligandi

FAD, Flavoprotein

Enzyme and pathway databases

BioCyciZFISH:HS07742-MONOMER.
ReactomeiR-HSA-70895. Branched-chain amino acid catabolism.
UniPathwayiUPA00362.

Chemistry databases

SwissLipidsiSLP:000001420.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:ACAD8
Synonyms:ARC42, IBD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:87. ACAD8.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Isobutyryl-CoA dehydrogenase deficiency (IBDD)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionThe 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).
See also OMIM:611283
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035071128M → I in IBDD. 1 PublicationCorresponds to variant rs374317179dbSNPEnsembl.1
Natural variantiVAR_035072134D → Y in IBDD. 1 PublicationCorresponds to variant rs367857040dbSNPEnsembl.1
Natural variantiVAR_035073137G → R in IBDD; complete loss of activity. 1 PublicationCorresponds to variant rs371449613dbSNPEnsembl.1
Natural variantiVAR_035074152M → T in IBDD. 1 PublicationCorresponds to variant rs121908418dbSNPEnsembl.1
Natural variantiVAR_035075203V → I in IBDD. 1 PublicationCorresponds to variant rs759877257dbSNPEnsembl.1
Natural variantiVAR_035076302R → Q in IBDD; complete loss of activity. 2 PublicationsCorresponds to variant rs121908422dbSNPEnsembl.1
Natural variantiVAR_035077320A → T in IBDD; <20% of wild-type activity. 1 PublicationCorresponds to variant rs200620279dbSNPEnsembl.1
Natural variantiVAR_035078334R → C in IBDD. 1 PublicationCorresponds to variant rs778823613dbSNPEnsembl.1
Natural variantiVAR_035079385Q → R in IBDD. 1 PublicationCorresponds to variant rs367996531dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi27034.
MalaCardsiACAD8.
MIMi611283. phenotype.
OpenTargetsiENSG00000151498.
Orphaneti79159. Isobutyryl-CoA dehydrogenase deficiency.
PharmGKBiPA24423.

Chemistry databases

DrugBankiDB03147. Flavin adenine dinucleotide.

Polymorphism and mutation databases

BioMutaiACAD8.
DMDMi26006699.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 22MitochondrionSequence analysisAdd BLAST22
ChainiPRO_000000052223 – 415Isobutyryl-CoA dehydrogenase, mitochondrialAdd BLAST393

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei50N6-acetyllysine; alternateBy similarity1
Modified residuei50N6-succinyllysine; alternateBy similarity1
Modified residuei213N6-succinyllysineBy similarity1
Modified residuei231N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9UKU7.
PaxDbiQ9UKU7.
PeptideAtlasiQ9UKU7.
PRIDEiQ9UKU7.

2D gel databases

UCD-2DPAGEQ9UKU7.

PTM databases

iPTMnetiQ9UKU7.
PhosphoSitePlusiQ9UKU7.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000151498.
CleanExiHS_ACAD8.
ExpressionAtlasiQ9UKU7. baseline and differential.
GenevisibleiQ9UKU7. HS.

Organism-specific databases

HPAiHPA040689.
HPA043903.

Interactioni

Subunit structurei

Homotetramer, formed by a dimer of dimers. Subunit of the large multiprotein complex ARC/DRIP.3 Publications

Protein-protein interaction databases

BioGridi117965. 19 interactors.
IntActiQ9UKU7. 8 interactors.
STRINGi9606.ENSP00000281182.

Structurei

Secondary structure

1415
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni37 – 40Combined sources4
Helixi43 – 59Combined sources17
Turni60 – 63Combined sources4
Helixi64 – 70Combined sources7
Helixi75 – 83Combined sources9
Helixi93 – 95Combined sources3
Helixi102 – 113Combined sources12
Helixi117 – 136Combined sources20
Helixi139 – 150Combined sources12
Beta strandi156 – 159Combined sources4
Beta strandi165 – 168Combined sources4
Helixi169 – 171Combined sources3
Beta strandi175 – 179Combined sources5
Beta strandi182 – 193Combined sources12
Turni194 – 197Combined sources4
Beta strandi199 – 211Combined sources13
Helixi212 – 214Combined sources3
Beta strandi215 – 221Combined sources7
Beta strandi227 – 229Combined sources3
Beta strandi235 – 237Combined sources3
Beta strandi243 – 254Combined sources12
Helixi255 – 257Combined sources3
Beta strandi258 – 261Combined sources4
Helixi265 – 301Combined sources37
Helixi309 – 311Combined sources3
Helixi313 – 341Combined sources29
Helixi347 – 372Combined sources26
Helixi373 – 378Combined sources6
Helixi384 – 393Combined sources10
Turni394 – 396Combined sources3
Beta strandi397 – 399Combined sources3
Helixi401 – 414Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1RX0X-ray1.77A/B/C/D24-415[»]
ProteinModelPortaliQ9UKU7.
SMRiQ9UKU7.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UKU7.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni274 – 277Substrate binding4

Sequence similaritiesi

Belongs to the acyl-CoA dehydrogenase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0140. Eukaryota.
COG1960. LUCA.
GeneTreeiENSGT00760000119007.
HOGENOMiHOG000131659.
HOVERGENiHBG000224.
InParanoidiQ9UKU7.
KOiK11538.
OMAiLVQTGHR.
OrthoDBiEOG091G04BS.
PhylomeDBiQ9UKU7.
TreeFamiTF105052.

Family and domain databases

Gene3Di1.10.540.10. 1 hit.
InterProiIPR006089. 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]
PfamiPF00441. Acyl-CoA_dh_1. 1 hit.
PF02770. Acyl-CoA_dh_M. 1 hit.
PF02771. Acyl-CoA_dh_N. 1 hit.
[Graphical view]
SUPFAMiSSF47203. SSF47203. 1 hit.
SSF56645. SSF56645. 1 hit.
PROSITEiPS00072. ACYL_COA_DH_1. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UKU7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLWSGCRRFG ARLGCLPGGL RVLVQTGHRS LTSCIDPSMG LNEEQKEFQK
60 70 80 90 100
VAFDFAAREM APNMAEWDQK ELFPVDVMRK AAQLGFGGVY IQTDVGGSGL
110 120 130 140 150
SRLDTSVIFE ALATGCTSTT AYISIHNMCA WMIDSFGNEE QRHKFCPPLC
160 170 180 190 200
TMEKFASYCL TEPGSGSDAA SLLTSAKKQG DHYILNGSKA FISGAGESDI
210 220 230 240 250
YVVMCRTGGP GPKGISCIVV EKGTPGLSFG KKEKKVGWNS QPTRAVIFED
260 270 280 290 300
CAVPVANRIG SEGQGFLIAV RGLNGGRINI ASCSLGAAHA SVILTRDHLN
310 320 330 340 350
VRKQFGEPLA SNQYLQFTLA DMATRLVAAR LMVRNAAVAL QEERKDAVAL
360 370 380 390 400
CSMAKLFATD ECFAICNQAL QMHGGYGYLK DYAVQQYVRD SRVHQILEGS
410
NEVMRILISR SLLQE
Length:415
Mass (Da):45,070
Last modified:May 1, 2000 - v1
Checksum:iCAFFE91B74E2362D
GO
Isoform 2 (identifier: Q9UKU7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     37-37: P → R
     38-164: Missing.

Note: No experimental confirmation available.
Show »
Length:288
Mass (Da):31,024
Checksum:i731C090A54E4BCAB
GO
Isoform 3 (identifier: Q9UKU7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-77: Missing.
     399-415: GSNEVMRILISRSLLQE → ELFWQGPGVQSRSFVPFGGPQIALLLPFSSGDLREG

Note: No experimental confirmation available.
Show »
Length:357
Mass (Da):38,359
Checksum:iFFFBC112FA06E2FB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti210P → L in AAH01964 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035071128M → I in IBDD. 1 PublicationCorresponds to variant rs374317179dbSNPEnsembl.1
Natural variantiVAR_035072134D → Y in IBDD. 1 PublicationCorresponds to variant rs367857040dbSNPEnsembl.1
Natural variantiVAR_035073137G → R in IBDD; complete loss of activity. 1 PublicationCorresponds to variant rs371449613dbSNPEnsembl.1
Natural variantiVAR_035074152M → T in IBDD. 1 PublicationCorresponds to variant rs121908418dbSNPEnsembl.1
Natural variantiVAR_035075203V → I in IBDD. 1 PublicationCorresponds to variant rs759877257dbSNPEnsembl.1
Natural variantiVAR_035076302R → Q in IBDD; complete loss of activity. 2 PublicationsCorresponds to variant rs121908422dbSNPEnsembl.1
Natural variantiVAR_035077320A → T in IBDD; <20% of wild-type activity. 1 PublicationCorresponds to variant rs200620279dbSNPEnsembl.1
Natural variantiVAR_035078334R → C in IBDD. 1 PublicationCorresponds to variant rs778823613dbSNPEnsembl.1
Natural variantiVAR_035079385Q → R in IBDD. 1 PublicationCorresponds to variant rs367996531dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0557791 – 77Missing in isoform 3. 1 PublicationAdd BLAST77
Alternative sequenceiVSP_05578037P → R in isoform 2. 1 Publication1
Alternative sequenceiVSP_05578138 – 164Missing in isoform 2. 1 PublicationAdd BLAST127
Alternative sequenceiVSP_055782399 – 415GSNEV…SLLQE → ELFWQGPGVQSRSFVPFGGP QIALLLPFSSGDLREG in isoform 3. 1 PublicationAdd BLAST17

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF126245 mRNA. Translation: AAF12736.1.
AF260689
, AF260679, AF260680, AF260681, AF260682, AF260683, AF260684, AF260685, AF260686, AF260687, AF260688 Genomic DNA. Translation: AAF97922.1.
AK000359 mRNA. Translation: BAA91109.1.
AK074640 mRNA. Translation: BAC11107.1.
AK299492 mRNA. Translation: BAH13050.1.
AP000859 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67833.1.
BC001964 mRNA. Translation: AAH01964.1.
CCDSiCCDS8498.1. [Q9UKU7-1]
RefSeqiNP_055199.1. NM_014384.2. [Q9UKU7-1]
UniGeneiHs.14791.

Genome annotation databases

EnsembliENST00000281182; ENSP00000281182; ENSG00000151498. [Q9UKU7-1]
ENST00000374752; ENSP00000363884; ENSG00000151498. [Q9UKU7-2]
GeneIDi27034.
KEGGihsa:27034.
UCSCiuc001qhk.4. human. [Q9UKU7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF126245 mRNA. Translation: AAF12736.1.
AF260689
, AF260679, AF260680, AF260681, AF260682, AF260683, AF260684, AF260685, AF260686, AF260687, AF260688 Genomic DNA. Translation: AAF97922.1.
AK000359 mRNA. Translation: BAA91109.1.
AK074640 mRNA. Translation: BAC11107.1.
AK299492 mRNA. Translation: BAH13050.1.
AP000859 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67833.1.
BC001964 mRNA. Translation: AAH01964.1.
CCDSiCCDS8498.1. [Q9UKU7-1]
RefSeqiNP_055199.1. NM_014384.2. [Q9UKU7-1]
UniGeneiHs.14791.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1RX0X-ray1.77A/B/C/D24-415[»]
ProteinModelPortaliQ9UKU7.
SMRiQ9UKU7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117965. 19 interactors.
IntActiQ9UKU7. 8 interactors.
STRINGi9606.ENSP00000281182.

Chemistry databases

DrugBankiDB03147. Flavin adenine dinucleotide.
SwissLipidsiSLP:000001420.

PTM databases

iPTMnetiQ9UKU7.
PhosphoSitePlusiQ9UKU7.

Polymorphism and mutation databases

BioMutaiACAD8.
DMDMi26006699.

2D gel databases

UCD-2DPAGEQ9UKU7.

Proteomic databases

EPDiQ9UKU7.
PaxDbiQ9UKU7.
PeptideAtlasiQ9UKU7.
PRIDEiQ9UKU7.

Protocols and materials databases

DNASUi27034.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000281182; ENSP00000281182; ENSG00000151498. [Q9UKU7-1]
ENST00000374752; ENSP00000363884; ENSG00000151498. [Q9UKU7-2]
GeneIDi27034.
KEGGihsa:27034.
UCSCiuc001qhk.4. human. [Q9UKU7-1]

Organism-specific databases

CTDi27034.
DisGeNETi27034.
GeneCardsiACAD8.
HGNCiHGNC:87. ACAD8.
HPAiHPA040689.
HPA043903.
MalaCardsiACAD8.
MIMi604773. gene.
611283. phenotype.
neXtProtiNX_Q9UKU7.
OpenTargetsiENSG00000151498.
Orphaneti79159. Isobutyryl-CoA dehydrogenase deficiency.
PharmGKBiPA24423.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0140. Eukaryota.
COG1960. LUCA.
GeneTreeiENSGT00760000119007.
HOGENOMiHOG000131659.
HOVERGENiHBG000224.
InParanoidiQ9UKU7.
KOiK11538.
OMAiLVQTGHR.
OrthoDBiEOG091G04BS.
PhylomeDBiQ9UKU7.
TreeFamiTF105052.

Enzyme and pathway databases

UniPathwayiUPA00362.
BioCyciZFISH:HS07742-MONOMER.
ReactomeiR-HSA-70895. Branched-chain amino acid catabolism.

Miscellaneous databases

EvolutionaryTraceiQ9UKU7.
GeneWikiiACAD8.
GenomeRNAii27034.
PROiQ9UKU7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000151498.
CleanExiHS_ACAD8.
ExpressionAtlasiQ9UKU7. baseline and differential.
GenevisibleiQ9UKU7. HS.

Family and domain databases

Gene3Di1.10.540.10. 1 hit.
InterProiIPR006089. 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]
PfamiPF00441. Acyl-CoA_dh_1. 1 hit.
PF02770. Acyl-CoA_dh_M. 1 hit.
PF02771. Acyl-CoA_dh_N. 1 hit.
[Graphical view]
SUPFAMiSSF47203. SSF47203. 1 hit.
SSF56645. SSF56645. 1 hit.
PROSITEiPS00072. ACYL_COA_DH_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiACAD8_HUMAN
AccessioniPrimary (citable) accession number: Q9UKU7
Secondary accession number(s): B7Z5W4, Q6ZWP6, Q9BUS8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: May 1, 2000
Last modified: November 2, 2016
This is version 157 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.