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P45954 (ACDSB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 153. 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·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial

Short name=SBCAD
EC=1.3.8.5
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) [Reference 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 + acceptor = 2,3-dehydroacyl-CoA + reduced acceptor.

2-methylbutanoyl-CoA + electron-transfer flavoprotein = (E)-2-methylbut-2-enoyl-CoA + reduced electron-transfer flavoprotein + H+.

Cofactor

FAD.

Pathway

Lipid metabolism; mitochondrial fatty acid beta-oxidation.

Subunit structure

Homotetramer. Ref.10

Subcellular location

Mitochondrion matrix.

Tissue specificity

Ubiquitous.

Involvement in disease

Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) [MIM:610006]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12

Sequence similarities

Belongs to the acyl-CoA dehydrogenase family.

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

Regions

Nucleotide binding174 – 18310FAD
Nucleotide binding207 – 2093FAD
Nucleotide binding387 – 3915FAD; shared with dimeric partner
Nucleotide binding416 – 4183FAD
Region229 – 2302Substrate binding
Region291 – 2944Substrate binding

Sites

Active site4141Proton acceptor By similarity
Binding site1831Substrate; via carbonyl oxygen
Binding site2831Substrate
Binding site3191FAD; shared with dimeric partner
Binding site3301FAD; shared with dimeric partner
Binding site4151Substrate; via amide nitrogen

Amino acid modifications

Modified residue701N6-acetyllysine; alternate By similarity
Modified residue701N6-succinyllysine; alternate By similarity
Modified residue2841N6-acetyllysine; alternate Ref.8
Modified residue2841N6-succinyllysine; alternate By similarity
Modified residue4261N6-acetyllysine By similarity

Natural variations

Natural variant131R → K. Ref.6 Ref.7
Corresponds to variant rs12263012 [ dbSNP | Ensembl ].
VAR_048177
Natural variant2091S → G.
Corresponds to variant rs1799823 [ dbSNP | Ensembl ].
VAR_014749
Natural variant2551L → F in SBCADD. Ref.11 Ref.12
VAR_013010
Natural variant3161I → V. Ref.7
Corresponds to variant rs1131430 [ dbSNP | Ensembl ].
VAR_048178
Natural variant3761E → G.
Corresponds to variant rs12357783 [ dbSNP | Ensembl ].
VAR_048179

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
P45954 [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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].
Tissue: Mammary gland.
[4]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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], VARIANT LYS-13.
Tissue: Mammary gland.
[7]"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., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-432, VARIANTS LYS-13 AND VAL-316.
Tissue: Skeletal muscle.
[8]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-284, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"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].
[10]"Crystal structure of human short-branched chain acyl-CoA dehydrogenase."
Structural genomics consortium (SGC)
Submitted (FEB-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 52-432 IN COMPLEX WITH FAD AND SUBSTRATE ANALOG, SUBUNIT.
[11]"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] [Europe PMC] [Abstract]
Cited for: VARIANT SBCADD PHE-255.
[12]"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] [Europe PMC] [Abstract]
Cited for: VARIANT SBCADD PHE-255.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
AK314241 mRNA. Translation: BAG36909.1.
AL731666, AC012391, AC073585 Genomic DNA. Translation: CAI10847.1.
CH471066 Genomic DNA. Translation: EAW49291.1.
BC013756 mRNA. Translation: AAH13756.1.
AL831821 mRNA. Translation: CAD38535.2.
CCDSCCDS7634.1.
PIRA55680.
RefSeqNP_001600.1. NM_001609.3.
UniGeneHs.81934.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JIFX-ray2.00A/B/C/D52-432[»]
ProteinModelPortalP45954.
SMRP45954. Positions 52-432.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106554. 3 interactions.
IntActP45954. 1 interaction.
STRING9606.ENSP00000357873.

Chemistry

DrugBankDB00167. L-Isoleucine.

PTM databases

PhosphoSiteP45954.

Polymorphism databases

DMDM1168283.

Proteomic databases

MaxQBP45954.
PaxDbP45954.
PeptideAtlasP45954.
PRIDEP45954.

Protocols and materials databases

DNASU36.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000358776; ENSP00000357873; ENSG00000196177.
GeneID36.
KEGGhsa:36.
UCSCuc001lhb.3. human.

Organism-specific databases

CTD36.
GeneCardsGC10P124758.
HGNCHGNC:91. ACADSB.
HPAHPA041458.
MIM600301. gene.
610006. phenotype.
neXtProtNX_P45954.
Orphanet79157. 2-methylbutyryl-CoA dehydrogenase deficiency.
PharmGKBPA24427.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1960.
HOGENOMHOG000131659.
HOVERGENHBG000224.
InParanoidP45954.
KOK09478.
OMAFLIFANV.
PhylomeDBP45954.
TreeFamTF105055.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
UniPathwayUPA00660.

Gene expression databases

ArrayExpressP45954.
BgeeP45954.
CleanExHS_ACADSB.
GenevestigatorP45954.

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

ChiTaRSACADSB. human.
EvolutionaryTraceP45954.
GenomeRNAi36.
NextBio139.
PROP45954.
SOURCESearch...

Entry information

Entry nameACDSB_HUMAN
AccessionPrimary (citable) accession number: P45954
Secondary accession number(s): Q5SQN6, Q96CX7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 153 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 10

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