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P16219 (ACADS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 169. 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:
Short-chain specific acyl-CoA dehydrogenase, mitochondrial

Short name=SCAD
EC=1.3.8.1
Alternative name(s):
Butyryl-CoA dehydrogenase
Gene names
Name:ACADS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length412 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

Butanoyl-CoA + electron-transfer flavoprotein = 2-butenoyl-CoA + reduced electron-transfer flavoprotein.

Cofactor

FAD.

Pathway

Lipid metabolism; mitochondrial fatty acid beta-oxidation.

Subunit structure

Homotetramer.

Subcellular location

Mitochondrion matrix.

Involvement in disease

Acyl-CoA dehydrogenase short-chain deficiency (ACADSD) [MIM:201470]: An inborn error of mitochondrial fatty acid beta-oxidation resulting in acute acidosis and muscle weakness in infants, and a form of lipid-storage myopathy in adults.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.10

Miscellaneous

A number of straight-chain acyl-CoA dehydrogenases of different substrate specificities are present in mammalian tissues.

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
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbutyrate catabolic process

Inferred from electronic annotation. Source: Ensembl

cellular lipid metabolic process

Traceable author statement. Source: Reactome

fatty acid beta-oxidation

Traceable author statement. Source: Reactome

fatty acid beta-oxidation using acyl-CoA dehydrogenase

Inferred from electronic annotation. Source: Ensembl

protein homotetramerization

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to starvation

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentmitochondrial matrix

Traceable author statement. Source: Reactome

mitochondrial membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from direct assay PubMed 16729965. Source: MGI

nucleus

Inferred from direct assay PubMed 21630459. Source: UniProt

   Molecular_functionacyl-CoA dehydrogenase activity

Traceable author statement. Source: Reactome

butyryl-CoA dehydrogenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

fatty-acyl-CoA binding

Inferred from electronic annotation. Source: Ensembl

flavin adenine dinucleotide binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2424Mitochondrion Ref.5
Chain25 – 412388Short-chain specific acyl-CoA dehydrogenase, mitochondrial
PRO_0000000498

Regions

Nucleotide binding152 – 16110FAD
Nucleotide binding185 – 1873FAD
Nucleotide binding365 – 3695FAD; shared with dimeric partner
Nucleotide binding394 – 3963FAD
Region269 – 2724Substrate binding

Sites

Active site3921Proton acceptor By similarity
Binding site1611Substrate; via carbonyl oxygen
Binding site2971FAD; shared with dimeric partner
Binding site3081FAD
Binding site3931Substrate; via amide nitrogen

Amino acid modifications

Modified residue511N6-acetyllysine; alternate By similarity
Modified residue511N6-succinyllysine; alternate By similarity
Modified residue721N6-acetyllysine By similarity
Modified residue1291N6-acetyllysine; alternate By similarity
Modified residue1291N6-succinyllysine; alternate By similarity
Modified residue2081N6-acetyllysine By similarity
Modified residue2621N6-acetyllysine; alternate By similarity
Modified residue2621N6-succinyllysine; alternate By similarity
Modified residue3061N6-acetyllysine; alternate By similarity
Modified residue3061N6-succinyllysine; alternate By similarity

Natural variations

Natural variant461R → W in ACADSD.
VAR_000310
Natural variant901G → S in ACADSD; no detectable activity. Ref.10
VAR_013565
Natural variant921G → C in ACADSD. Ref.9
VAR_000311
Natural variant1041Missing in ACADSD; no detectable activity. Ref.10
VAR_013566
Natural variant1071R → C in ACADSD.
VAR_000312
Natural variant1711R → W 69% of wild-type activity; confers susceptibility to ethylmalonicaciduria. Ref.9 Ref.10
Corresponds to variant rs1800556 [ dbSNP | Ensembl ].
VAR_013567
Natural variant1771W → R in ACADSD. Ref.9
Corresponds to variant rs57443665 [ dbSNP | Ensembl ].
VAR_000314
Natural variant1921A → V in ACADSD; no detectable activity. Ref.10
Corresponds to variant rs28940874 [ dbSNP | Ensembl ].
VAR_013568
Natural variant2091G → S 86% of wild-type activity; confers susceptibility to ethylmalonicaciduria. Ref.9 Ref.10
Corresponds to variant rs1799958 [ dbSNP | Ensembl ].
VAR_000315
Natural variant3251R → W in ACADSD; no detectable activity. Ref.10
VAR_013569
Natural variant3531S → L in ACADSD; no detectable activity. Ref.10
Corresponds to variant rs28941773 [ dbSNP | Ensembl ].
VAR_013570
Natural variant3801R → W in ACADSD; no detectable activity. Ref.10
Corresponds to variant rs28940875 [ dbSNP | Ensembl ].
VAR_013571
Natural variant3831R → C in ACADSD. Ref.9
Corresponds to variant rs28940872 [ dbSNP | Ensembl ].
VAR_000316
Natural variant3831R → H.
Corresponds to variant rs35233375 [ dbSNP | Ensembl ].
VAR_033458

Secondary structure

........................................................... 412
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P16219 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: 3E946ADFC3DA3C0E

FASTA41244,297
        10         20         30         40         50         60 
MAAALLARAS GPARRALCPR AWRQLHTIYQ SVELPETHQM LLQTCRDFAE KELFPIAAQV 

        70         80         90        100        110        120 
DKEHLFPAAQ VKKMGGLGLL AMDVPEELGG AGLDYLAYAI AMEEISRGCA STGVIMSVNN 

       130        140        150        160        170        180 
SLYLGPILKF GSKEQKQAWV TPFTSGDKIG CFALSEPGNG SDAGAASTTA RAEGDSWVLN 

       190        200        210        220        230        240 
GTKAWITNAW EASAAVVFAS TDRALQNKGI SAFLVPMPTP GLTLGKKEDK LGIRGSSTAN 

       250        260        270        280        290        300 
LIFEDCRIPK DSILGEPGMG FKIAMQTLDM GRIGIASQAL GIAQTALDCA VNYAENRMAF 

       310        320        330        340        350        360 
GAPLTKLQVI QFKLADMALA LESARLLTWR AAMLKDNKKP FIKEAAMAKL AASEAATAIS 

       370        380        390        400        410 
HQAIQILGGM GYVTEMPAER HYRDARITEI YEGTSEIQRL VIAGHLLRSY RS 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and nucleotide sequence of complementary DNAs encoding human short chain acyl-coenzyme A dehydrogenase and the study of the molecular basis of human short chain acyl-coenzyme A dehydrogenase deficiency."
Naito E., Ozasa H., Ikeda Y., Tanaka K.
J. Clin. Invest. 83:1605-1613(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Structural organization of the human short-chain acyl-CoA dehydrogenase gene."
Corydon M.J., Andresen B.S., Bross P., Kjeldsen M., Andreasen P.H., Eiberg H., Koelvraa S., Gregersen N.
Mamm. Genome 8:922-926(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Transcription map of the 5cM region surrounding the hepatocyte nuclear factor-1a/MODY3 gene on chromosome 12."
Yamagata K., Oda N., Furuta H., Vaxillaire M., Southam L., Boriraj V., Chen X., Oda Y., Takeda J., Yamada S., Nishigori H., Lebeau M.M., Lathrop M., Cox R.D., Bell G.I.
Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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: Retinal pigment epithelium.
[5]"Human liver protein map: a reference database established by microsequencing and gel comparison."
Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F., Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R., Appel R.D., Hughes G.J.
Electrophoresis 13:992-1001(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 25-34.
Tissue: Liver.
[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]"Crystal structure of human RAB14."
Structural genomics consortium (SGC)
Submitted (FEB-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 30-412 IN COMPLEX WITH FAD AND SUBSTRATE ANALOG.
[8]"Identification of two variant short chain acyl-coenzyme A dehydrogenase alleles, each containing a different point mutation in a patient with short chain acyl-coenzyme A dehydrogenase deficiency."
Naito E., Indo Y., Tanaka K.
J. Clin. Invest. 85:1575-1582(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ACADSD.
[9]"Identification of four new mutations in the short-chain acyl-CoA dehydrogenase (SCAD) gene in two patients: one of the variant alleles, 511C-->T, is present at an unexpectedly high frequency in the general population, as was the case for 625G-->A, together conferring susceptibility to ethylmalonic aciduria."
Gregersen N., Winter V.S., Corydon M.J., Corydon T.J., Rinaldo P., Ribes A., Martinez G., Bennett M.J., Vianey-Saban C., Bhala A., Hale D.E., Lehnert W., Kmoch S., Roig M., Riudor E., Eiberg H., Andresen B.S., Bross P., Bolund L.A., Koelvraa S.
Hum. Mol. Genet. 7:619-627(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ACADSD CYS-92; ARG-177 AND CYS-383, VARIANTS TRP-171 AND SER-209.
[10]"Role of common gene variations in the molecular pathogenesis of short-chain acyl-CoA dehydrogenase deficiency."
Corydon M.J., Vockley J., Rinaldo P., Rhead W.J., Kjeldsen M., Winter V.S., Riggs C., Babovic-Vuksanovic D., Smeitink J., De Jong J., Levy H., Sewell A.C., Roe C., Matern D., Dasouki M., Gregersen N.
Pediatr. Res. 49:18-23(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ACADSD SER-90; GLU-104 DEL; VAL-192; TRP-325; LEU-353 AND TRP-380, VARIANTS TRP-171 AND SER-209.
+Additional computationally mapped references.

Web resources

Wikipedia

Butyryl-CoA dehydrogenase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M26393 mRNA. Translation: AAA60307.1.
Z80345, Z80347 Genomic DNA. Translation: CAB02492.1.
U83992, U83991 Genomic DNA. Translation: AAD00552.1.
BC025963 mRNA. Translation: AAH25963.1.
CCDSCCDS9207.1.
PIRA30605.
RefSeqNP_000008.1. NM_000017.2.
UniGeneHs.507076.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2VIGX-ray1.90A/B/C/D/E/F/G/H30-412[»]
ProteinModelPortalP16219.
SMRP16219. Positions 34-412.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106553. 1 interaction.
IntActP16219. 2 interactions.
STRING9606.ENSP00000242592.

Chemistry

DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP16219.

Polymorphism databases

DMDM113019.

2D gel databases

DOSAC-COBS-2DPAGEP16219.
SWISS-2DPAGEP16219.
UCD-2DPAGEP16219.

Proteomic databases

MaxQBP16219.
PaxDbP16219.
PeptideAtlasP16219.
PRIDEP16219.

Protocols and materials databases

DNASU35.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000242592; ENSP00000242592; ENSG00000122971.
GeneID35.
KEGGhsa:35.
UCSCuc001tza.4. human.

Organism-specific databases

CTD35.
GeneCardsGC12P121163.
GeneReviewsACADS.
HGNCHGNC:90. ACADS.
HPACAB019284.
HPA004799.
HPA022271.
MIM201470. phenotype.
606885. gene.
neXtProtNX_P16219.
Orphanet26792. Short chain acyl-CoA dehydrogenase deficiency.
PharmGKBPA24426.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1960.
HOGENOMHOG000131659.
HOVERGENHBG000224.
InParanoidP16219.
KOK00248.
OMAAVTLNNC.
OrthoDBEOG74FF0S.
PhylomeDBP16219.
TreeFamTF105019.

Enzyme and pathway databases

BioCycMetaCyc:HS04619-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP16219.
UniPathwayUPA00660.

Gene expression databases

ArrayExpressP16219.
BgeeP16219.
CleanExHS_ACADS.
GenevestigatorP16219.

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.
PS00073. ACYL_COA_DH_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP16219.
GenomeRNAi35.
NextBio135.
PROP16219.
SOURCESearch...

Entry information

Entry nameACADS_HUMAN
AccessionPrimary (citable) accession number: P16219
Secondary accession number(s): P78331
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: July 9, 2014
This is version 169 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 12

Human chromosome 12: entries, gene names and cross-references to MIM