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Reviewed, UniProtKB/Swiss-Prot P45954 (ACDSB_HUMAN)

Last modified July 7, 2009. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial
      Short name=SBCAD
    EC=1.3.99.-
Alternative name(s):
    2-methyl branched chain acyl-CoA dehydrogenase
      Short name=2-MEBCAD
    2-methylbutyryl-coenzyme A dehydrogenase
      Short name=2-methylbutyryl-CoA dehydrogenase
Gene names
Name: ACADSB
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length432 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Has greatest activity toward short branched chain acyl-CoA derivative such as (s)-2-methylbutyryl-CoA, isobutyryl-CoA, and 2-methylhexanoyl-CoA as well as toward short straight chain acyl-CoAs such as butyryl-CoA and hexanoyl-CoA. Can use valproyl-CoA as substrate and may play a role in controlling the metabolic flux of valproic acid in the development of toxicity of this agent.

Catalytic activity

Acyl-CoA + ETF = 2,3-dehydroacyl-CoA + reduced ETF.

Cofactor

FAD.

Pathway

Lipid metabolism; mitochondrial fatty acid beta-oxidation.

Subunit structure

Homotetramer.

Subcellular location

Mitochondrion matrix.

Tissue specificity

Ubiquitous.

Involvement in disease

Defects in ACADSB are the cause of short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) [MIM:610006]; also called 2-methylbutyryl-CoA dehydrogenase deficiency or 2-methylbutyryl glycinuria. SBCADD is an autosomal recessive disorder and consists of a defect in catabolism of L-isoleucine which is characterized by an increase of 2-methylbutyrylglycine and 2-methylbutyrylcarnitine in blood and urine. Affected individuals have seizures and psychomotor delay as the main clinical features. Ref.6 Ref.7

Sequence similarities

Belongs to the acyl-CoA dehydrogenase family.

Ontologies

Keywords
   Biological processFatty acid metabolism
Lipid metabolism
   Cellular componentMitochondrion
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainTransit peptide
   LigandFAD
Flavoprotein
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processfatty acid metabolic process Ref.1

Traceable author statement. Source: ProtInc

oxidation reduction

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentmitochondrial matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionFAD binding

Inferred from electronic annotation. Source: InterPro

acyl-CoA dehydrogenase activity Ref.1

Traceable author statement. Source: ProtInc

electron carrier activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3333Mitochondrion
Chain34 – 432399Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial
PRO_0000000519

Sites

Active site4141Proton acceptor By similarity

Amino acid modifications

Modified residue2841N6-acetyllysine By similarity

Natural variations

Natural variant131R → K: dbSNP rs12263012. Ref.3 Ref.4
VAR_048177
Natural variant2091S → G: dbSNP rs1799823.
VAR_014749
Natural variant2551L → F in SBCADD. Ref.6 Ref.7
VAR_013010
Natural variant3161I → V: dbSNP rs1131430. Ref.4
VAR_048178
Natural variant3761E → G: dbSNP rs12357783.
VAR_048179

Secondary structure

.......................................................... 432
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P45954-1 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 1EB5F894B1944E99

FASTA43247,485
        10         20         30         40         50         60 
MEGLAVRLLR GSRLLRRNFL TCLSSWKIPP HVSKSSQSEA LLNITNNGIH FAPLQTFTDE 

        70         80         90        100        110        120 
EMMIKSSVKK FAQEQIAPLV STMDENSKME KSVIQGLFQQ GLMGIEVDPE YGGTGASFLS 

       130        140        150        160        170        180 
TVLVIEELAK VDASVAVFCE IQNTLINTLI RKHGTEEQKA TYLPQLTTEK VGSFCLSEAG 

       190        200        210        220        230        240 
AGSDSFALKT RADKEGDYYV LNGSKMWISS AEHAGLFLVM ANVDPTIGYK GITSFLVDRD 

       250        260        270        280        290        300 
TPGLHIGKPE NKLGLRASST CPLTFENVKV PEANILGQIG HGYKYAIGSL NEGRIGIAAQ 

       310        320        330        340        350        360 
MLGLAQGCFD YTIPYIKERI QFGKRLFDFQ GLQHQVAHVA TQLEAARLLT YNAARLLEAG 

       370        380        390        400        410        420 
KPFIKEASMA KYYASEIAGQ TTSKCIEWMG GVGYTKDYPV EKYFRDAKIG TIYEGASNIQ 

       430 
LNTIAKHIDA EY 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and expression of a cDNA encoding the precursor for a novel member (ACADSB) of the acyl-CoA dehydrogenase gene family."
Rozen R., Vockley J., Zhou L., Milos R., Willard J., Fu K., Vicanek C., Low-Nang L., Torban E., Fournier B.
Genomics 24:280-287(1994) [PubMed: 7698750] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[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: 11013134] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LYS-13.
Tissue: Mammary gland.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-432, VARIANTS LYS-13 AND VAL-316.
Tissue: Skeletal muscle.
[5]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[6]"2-methylbutyryl-coenzyme A dehydrogenase deficiency: a new inborn error of L-isoleucine metabolism."
Gibson K.M., Burlingame T.G., Hogema B., Jakobs C., Schutgens R.B.H., Millington D., Roe C.R., Roe D.S., Sweetman L., Steiner R.D., Linck L., Pohowalla P., Sacks M., Kiss D., Rinaldo P., Vockley J.
Pediatr. Res. 47:830-833(2000) [PubMed: 10832746] [Abstract]
Cited for: VARIANT SBCADD PHE-255.
[7]"Short/branched-chain acyl-CoA dehydrogenase deficiency due to an IVS3+3A>G mutation that causes exon skipping."
Madsen P.P., Kibaek M., Roca X., Sachidanandam R., Krainer A.R., Christensen E., Steiner R.D., Gibson K.M., Corydon T.J., Knudsen I., Wanders R.J., Ruiter J.P.N., Gregersen N., Andresen B.S.
Hum. Genet. 118:680-690(2006) [PubMed: 16317551] [Abstract]
Cited for: VARIANT SBCADD PHE-255.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

U12778 mRNA. Translation: AAA74424.1.
AF260678 expand/collapse EMBL AC list , AF260668, AF260669, AF260670, AF260671, AF260672, AF260673, AF260674, AF260675, AF260676, AF260677 Genomic DNA. Translation: AAF97921.1.
BC013756 mRNA. Translation: AAH13756.1.
AL831821 mRNA. Translation: CAD38535.2.
IPIIPI00024623.
PIRA55680.
RefSeqNP_001600.1.
UniGeneHs.81934

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
2JIFX-ray2.00A/B/C/D52-432[»]
ModBaseSearch...

PTM databases

PhosphoSiteP45954.

Proteomic databases

PeptideAtlasP45954.
PRIDEP45954.

Genome annotation databases

EnsemblENSG00000196177. Homo sapiens. [Contig view]
GeneID36.
KEGGhsa:36.
UCSCuc001lhb.1. human.

Organism-specific databases

GeneCardsGC10P124758.
H-InvDBHIX0009278.
HGNCHGNC:91. ACADSB.
MIM600301. gene.
610006. phenotype.
Orphanet79157. Developmental delay due to 2-methylbutyryl-CoA dehydrogenase deficiency.
PharmGKBPA24427.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP45954.
HOVERGENP45954.
OMAP45954. IEWMGGV.

Enzyme and pathway databases

ReactomeREACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpressP45954.
BgeeP45954.
CleanExHS_ACADSB.
GermOnlineENSG00000196177. Homo sapiens.

Family and domain databases

InterProIPR006089. Acyl-CoA_DH_CS.
IPR006092. Acyl-CoA_DH_N.
IPR006090. Acyl-CoA_Oxase/DH_1.
IPR006091. Acyl-CoA_Oxase/DH_M.
IPR013786. AcylCoA_DH/ox_N.
IPR013764. AcylCoA_oxidase/DH_1/2_C.
[Graphical view]
Gene3DG3DSA:2.40.110.10. Acyl_CoA_DH/ox_M. 1 hit.
G3DSA:1.10.540.10. AcylCoA_DH/ox_N. 1 hit.
G3DSA:1.20.140.10. AcylCoA_DH_1/2_C. 1 hit.
PfamPF00441. Acyl-CoA_dh_1. 1 hit.
PF02770. Acyl-CoA_dh_M. 1 hit.
PF02771. Acyl-CoA_dh_N. 1 hit.
[Graphical view]
PROSITEPS00072. ACYL_COA_DH_1. 1 hit.
PS00073. ACYL_COA_DH_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00167. L-Isoleucine.
NextBio139.
SOURCESearch...

Entry information

Entry nameACDSB_HUMAN
AccessionPrimary (citable) accession number: P45954
Secondary accession number(s): Q96CX7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 7, 2009
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents