P45954 (ACDSB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	432 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
Cofactor	FAD.
Pathway	Lipid metabolism; mitochondrial fatty acid beta-oxidation.
Subunit structure	Homotetramer. Ref.7
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 known as 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.8 Ref.9
Sequence similarities	Belongs to the acyl-CoA dehydrogenase family.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	branched chain family amino acid catabolic process Traceable author statement. Source: Reactome fatty acid metabolic process Traceable author statement. Source: ProtInc
Cellular component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular function	flavin adenine dinucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 33

33

Mitochondrion

Chain

34 – 432

399

Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial

PRO_0000000519

Regions

Nucleotide binding

174 – 183

10

FAD

Nucleotide binding

207 – 209

3

FAD

Nucleotide binding

387 – 391

5

FAD; shared with dimeric partner

Nucleotide binding

416 – 418

3

FAD

Region

229 – 230

2

Substrate binding

Region

291 – 294

4

Substrate binding

Sites

Active site

414

1

Proton acceptor By similarity

Binding site

183

1

Substrate; via carbonyl oxygen

Binding site

283

1

Substrate

Binding site

319

1

FAD; shared with dimeric partner

Binding site

330

1

FAD; shared with dimeric partner

Binding site

415

1

Substrate; via amide nitrogen

Amino acid modifications

Modified residue

284

1

N6-acetyllysine Ref.5

Natural variations

Natural variant

13

1

R → K. Ref.3 Ref.4
Corresponds to variant rs12263012 [ dbSNP | Ensembl ].

VAR_048177

Natural variant

209

1

S → G.
Corresponds to variant rs1799823 [ dbSNP | Ensembl ].

VAR_014749

Natural variant

255

1

L → F in SBCADD. Ref.8 Ref.9

VAR_013010

Natural variant

316

1

I → V. Ref.4
Corresponds to variant rs1131430 [ dbSNP | Ensembl ].

VAR_048178

Natural variant

376

1

E → G.
Corresponds to variant rs12357783 [ dbSNP | Ensembl ].

VAR_048179

Secondary structure

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432

Helix Strand Turn

Details...

Helix

59 – 75

17

Helix

77 – 79

3

Helix

80 – 86

7

Helix

91 – 99

9

Turn

100 – 103

4

Beta strand

104 – 107

4

Helix

109 – 111

3

Helix

118 – 129

12

Helix

133 – 144

12

Helix

146 – 153

8

Helix

156 – 168

13

Beta strand

172 – 175

4

Beta strand

181 – 184

4

Helix

185 – 187

3

Beta strand

191 – 195

5

Beta strand

198 – 209

12

Turn

210 – 213

4

Beta strand

215 – 223

9

Helix

225 – 231

7

Beta strand

232 – 238

7

Beta strand

244 – 246

3

Beta strand

252 – 254

3

Beta strand

260 – 271

12

Helix

272 – 274

3

Beta strand

275 – 278

4

Helix

282 – 318

37

Helix

326 – 328

3

Helix

330 – 358

29

Helix

364 – 389

26

Helix

390 – 394

5

Helix

400 – 407

8

Helix

408 – 411

4

Turn

412 – 414

3

Helix

417 – 431

15

Sequences

	Sequence		Length	Mass (Da)
	P45954 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 1EB5F894B1944E99	FASTA	432	47,485
	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

References

	« Hide 'large scale' referencesShow '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., 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: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-432, VARIANTS LYS-13 AND VAL-316. Tissue: Skeletal muscle.
[5]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-284, MASS SPECTROMETRY.
[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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"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.
[8]	"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.
[9]	"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

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U12778 mRNA. Translation: AAA74424.1.
AF260678 , 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.

IPI

IPI00024623.

PIR

A55680.

RefSeq

NP_001600.1. NM_001609.3.

UniGene

Hs.81934.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JIF	X-ray	2.00	A/B/C/D	52-432	[»]

ProteinModelPortal

P45954.

SMR

P45954. Positions 52-432.

ModBase

Search...

Protein-protein interaction databases

IntAct

P45954. 1 interaction.

STRING

P45954.

PTM databases

PhosphoSite

P45954.

Polymorphism databases

DMDM

1168283.

Proteomic databases

PeptideAtlas

P45954.

PRIDE

P45954.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000358776; ENSP00000357873; ENSG00000196177.

GeneID

36.

KEGG

hsa:36.

UCSC

uc001lhb.1. human.

Organism-specific databases

CTD

36.

GeneCards

GC10P124758.

H-InvDB

HIX0009278.

HGNC

HGNC:91. ACADSB.

MIM

600301. gene.
610006. phenotype.

neXtProt

NX_P45954.

Orphanet

79157. Developmental delay due to 2-methylbutyryl-CoA dehydrogenase deficiency.

PharmGKB

PA24427.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17028.

HOGENOM

HBG699365.

HOVERGEN

HBG000224.

InParanoid

P45954.

OMA

DIHNTLV.

OrthoDB

EOG4RNB8F.

PhylomeDB

P45954.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P45954.

Bgee

P45954.

CleanEx

HS_ACADSB.

Genevestigator

P45954.

GermOnline

ENSG00000196177. Homo sapiens.

Family and domain databases

InterPro

IPR006089. Acyl-CoA_DH_CS.
IPR006092. Acyl-CoA_DH_N.
IPR006090. Acyl-CoA_Oxase/DH_1.
IPR006091. Acyl-CoA_Oxase/DH_cen-dom.
IPR009075. AcylCo_DH/oxidase_C.
IPR013786. AcylCoA_DH/ox_N.
IPR009100. AcylCoA_DH/oxidase.
[Graphical view]

Gene3D

G3DSA: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.

KO

K09478.

Pfam

PF00441. Acyl-CoA_dh_1. 1 hit.
PF02770. Acyl-CoA_dh_M. 1 hit.
PF02771. Acyl-CoA_dh_N. 1 hit.
[Graphical view]

SUPFAM

SSF56645. AcylCoA_dehyd_NM. 1 hit.
SSF47203. AcylCoADH_C_like. 1 hit.

PROSITE

PS00072. ACYL_COA_DH_1. 1 hit.
PS00073. ACYL_COA_DH_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00167. L-Isoleucine.

NextBio

139.

SOURCE

Search...

Entry information

Entry name

ACDSB_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 126 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.