Reviewed, UniProtKB/Swiss-Prot P16219 (ACADS_HUMAN)

Names and origin

Protein names

Recommended name:
    Short-chain specific acyl-CoA dehydrogenase, mitochondrial
      Short name=SCAD
    EC=1.3.99.2
Alternative name(s):
    Butyryl-CoA dehydrogenase

Gene names

Name:

ACADS

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	412 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)

Catalytic activity	Butanoyl-CoA + acceptor = 2-butenoyl-CoA + reduced acceptor.
Cofactor	FAD.
Pathway	Lipid metabolism; mitochondrial fatty acid beta-oxidation.
Subunit structure	Homotetramer.
Subcellular location	Mitochondrion matrix.
Involvement in disease	Defects in ACADS are the cause of short-chain acyl-CoA dehydrogenase deficiency (SCAD deficiency) [MIM:201470]. It is an autosomal recessive disorder resulting in acute acidosis and muscle weakness in infants, and a form of lipid-storage myopathy in adults.
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 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
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	fatty acid beta-oxidation Traceable author statement. Source: ProtInc
Molecular function	acyl-CoA dehydrogenase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Transit peptide	1 – 24	24	Mitochondrion
	Chain	25 – 412	388	Short-chain specific acyl-CoA dehydrogenase, mitochondrial
Regions
	Nucleotide binding	152 – 161	10	FAD By similarity
	Nucleotide binding	185 – 187	3	FAD By similarity
	Nucleotide binding	365 – 369	5	FAD By similarity
	Nucleotide binding	394 – 396	3	FAD By similarity
Sites
	Active site	392	1	Proton acceptor By similarity
	Binding site	297	1	FAD By similarity
Natural variations
	Natural variant	46	1	R → W in SCAD deficiency.
	Natural variant	90	1	G → S in SCAD deficiency; no detectable activity.
	Natural variant	92	1	G → C in SCAD deficiency.
	Natural variant	104	1	Missing in SCAD deficiency; no detectable activity.
	Natural variant	107	1	R → C in SCAD deficiency.
	Natural variant	171	1	R → W 69% of wild-type activity; confers susceptibility to ethylmalonicaciduria. dbSNP rs1800556.
	Natural variant	177	1	W → R in SCAD deficiency.
	Natural variant	192	1	A → V in SCAD deficiency; no detectable activity.
	Natural variant	209	1	G → S 86% of wild-type activity; confers susceptibility to ethylmalonicaciduria. dbSNP rs1799958.
	Natural variant	325	1	R → W in SCAD deficiency; no detectable activity.
	Natural variant	353	1	S → L in SCAD deficiency; no detectable activity.
	Natural variant	380	1	R → W in SCAD deficiency; no detectable activity.
	Natural variant	383	1	R → C in SCAD deficiency.
	Natural variant	383	1	R → H: dbSNP rs35233375.

Sequences

	Sequence		Length	Mass (Da)
	P16219-1 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 3E946ADFC3DA3C0E	FASTA	412	44,297
	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

References

	« Hide 'large scale' referencesShow '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: 2565344] [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: 9383286] [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: 15489334] [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: 1286669] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-34. Tissue: Liver.
[6]	"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: 1692038] [Abstract] Cited for: VARIANTS SCAD DEFICIENCY.
[7]	"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: 9499414] [Abstract] Cited for: VARIANTS SCAD DEFICIENCY CYS-92; ARG-177 AND CYS-383, VARIANTS TRP-171 AND SER-209.
[8]	"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: 11134486] [Abstract] Cited for: VARIANTS SCAD DEFICIENCY 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

GeneReviews

Wikipedia

Butyryl-CoA dehydrogenase entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

M26393 mRNA. Translation: AAA60307.1.
Z80345, Z80347 Genomic DNA. Translation: CAB02492.1.
U83992, U83991 Genomic DNA. Translation: AAD00552.1.
BC025963 mRNA. Translation: AAH25963.1.

PIR

A30605.

RefSeq

NP_000008.1.

UniGene

Hs.507076

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VIG	X-ray	1.90	A/B/C/D/E/F/G/H	30-412	[»]

SMR

P16219. Positions 28-411.

ModBase

Search...

2-D gel databases

SWISS-2DPAGE

P16219.

DOSAC-COBS-2DPAGE

P16219.

Proteomic databases

PeptideAtlas

P16219.

Genome annotation databases

Ensembl

ENSG00000122971. Homo sapiens. [Contig view]

GeneID

35.

KEGG

hsa:35.

NMPDR

fig|9606.3.peg.8377.

Organism-specific databases

H-InvDB

HIX0011071.

HGNC

HGNC:90. ACADS.

HPA

HPA004799.

MIM

201470. phenotype.
606885. gene.

Orphanet

26792. SCAD deficiency.

PharmGKB

PA24426.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P16219.

HOVERGEN

P16219.

Enzyme and pathway databases

Reactome

REACT_602. Lipid and lipoprotein metabolism.

Gene expression databases

ArrayExpress

P16219.

CleanEx

HS_ACADS.

GermOnline

ENSG00000122971. Homo sapiens.

Family and domain databases

InterPro

IPR006091. Acyl-CoA_DHase/Oxase_M.
IPR006089. Acyl-CoA_DHase_CS.
IPR006092. Acyl-CoA_DHase_N.
IPR006090. Acyl-CoA_Oxase/DHase_1.
IPR013786. AcylCoA_DH/ox_N.
IPR013764. AcylCoA_oxidase/DH_1/2_C.
[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.

Pfam

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

PROSITE

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

ProDom

P16219.
[Graphical view] [Entries sharing at least one domain]

BLOCKS

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Other Resources

DrugBank

DB00157. NADH.

SOURCE

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ProtoNet

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Entry information

Entry name

ACADS_HUMAN

Accession

Primary (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:	September 2, 2008
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)