Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Isobutyryl-CoA dehydrogenase, mitochondrial

Gene

ACAD8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionActivator, Oxidoreductase
Biological processBranched-chain amino acid catabolism, Transcription, Transcription regulation
LigandFAD, Flavoprotein

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000151498.11
HGNCiHGNC:87 ACAD8
MIMi604773 gene
neXtProtiNX_Q9UKU7

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs374317179EnsemblClinVar.1
Natural variantiVAR_035072134D → Y in IBDD. 1 PublicationCorresponds to variant dbSNP:rs367857040EnsemblClinVar.1
Natural variantiVAR_035073137G → R in IBDD; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs371449613EnsemblClinVar.1
Natural variantiVAR_035074152M → T in IBDD. 1 PublicationCorresponds to variant dbSNP:rs121908418EnsemblClinVar.1
Natural variantiVAR_035075203V → I in IBDD. 1 PublicationCorresponds to variant dbSNP:rs759877257Ensembl.1
Natural variantiVAR_035076302R → Q in IBDD; complete loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs121908422EnsemblClinVar.1
Natural variantiVAR_035077320A → T in IBDD; <20% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs200620279EnsemblClinVar.1
Natural variantiVAR_035078334R → C in IBDD. 1 PublicationCorresponds to variant dbSNP:rs778823613Ensembl.1
Natural variantiVAR_035079385Q → R in IBDD. 1 PublicationCorresponds to variant dbSNP:rs367996531Ensembl.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
DB01675 Methacrylyl-Coenzyme A

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
ProteomicsDBi84879

2D gel databases

UCD-2DPAGEiQ9UKU7

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, 27 interactors
CORUMiQ9UKU7
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

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
OMAiVYVVMCR
OrthoDBiEOG091G04BS
PhylomeDBiQ9UKU7
TreeFamiTF105052

Family and domain databases

CDDicd01162 IBD, 1 hit
Gene3Di1.10.540.10, 1 hit
InterProiView protein in InterPro
IPR006089 Acyl-CoA_DH_CS
IPR006091 Acyl-CoA_Oxase/DH_cen-dom
IPR036250 AcylCo_DH-like_C
IPR009075 AcylCo_DH/oxidase_C
IPR013786 AcylCoA_DH/ox_N
IPR037069 AcylCoA_DH/ox_N_sf
IPR009100 AcylCoA_DH/oxidase_NM_dom
IPR034178 IBD
PfamiView protein in Pfam
PF00441 Acyl-CoA_dh_1, 1 hit
PF02770 Acyl-CoA_dh_M, 1 hit
PF02771 Acyl-CoA_dh_N, 1 hit
SUPFAMiSSF47203 SSF47203, 1 hit
SSF56645 SSF56645, 1 hit
PROSITEiView protein in PROSITE
PS00072 ACYL_COA_DH_1, 1 hit

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 dbSNP:rs374317179EnsemblClinVar.1
Natural variantiVAR_035072134D → Y in IBDD. 1 PublicationCorresponds to variant dbSNP:rs367857040EnsemblClinVar.1
Natural variantiVAR_035073137G → R in IBDD; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs371449613EnsemblClinVar.1
Natural variantiVAR_035074152M → T in IBDD. 1 PublicationCorresponds to variant dbSNP:rs121908418EnsemblClinVar.1
Natural variantiVAR_035075203V → I in IBDD. 1 PublicationCorresponds to variant dbSNP:rs759877257Ensembl.1
Natural variantiVAR_035076302R → Q in IBDD; complete loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs121908422EnsemblClinVar.1
Natural variantiVAR_035077320A → T in IBDD; <20% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs200620279EnsemblClinVar.1
Natural variantiVAR_035078334R → C in IBDD. 1 PublicationCorresponds to variant dbSNP:rs778823613Ensembl.1
Natural variantiVAR_035079385Q → R in IBDD. 1 PublicationCorresponds to variant dbSNP:rs367996531Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiACAD8_HUMAN
AccessioniPrimary (citable) accession number: Q9UKU7
Secondary accession number(s): B7Z5W4, Q6ZWP6, Q9BUS8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: May 1, 2000
Last modified: June 20, 2018
This is version 165 of the entry and version 1 of the sequence. See 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

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health