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) [Complete proteome]

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 Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	fatty acid beta-oxidation Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	FAD binding Inferred from electronic annotation. Source: InterPro butyryl-CoA dehydrogenase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 24

24

Mitochondrion Ref.5

Chain

25 – 412

388

Short-chain specific acyl-CoA dehydrogenase, mitochondrial

PRO_0000000498

Regions

Nucleotide binding

152 – 161

10

FAD

Nucleotide binding

185 – 187

3

FAD

Nucleotide binding

365 – 369

5

FAD; shared with dimeric partner

Nucleotide binding

394 – 396

3

FAD

Region

269 – 272

4

Substrate binding

Sites

Active site

392

1

Proton acceptor By similarity

Binding site

161

1

Substrate; via carbonyl oxygen

Binding site

297

1

FAD By similarity

Binding site

297

1

FAD; shared with dimeric partner

Binding site

308

1

FAD

Binding site

393

1

Substrate; via amide nitrogen

Natural variations

Natural variant

46

1

R → W in SCAD deficiency.

VAR_000310

Natural variant

90

1

G → S in SCAD deficiency; no detectable activity. Ref.10

VAR_013565

Natural variant

92

1

G → C in SCAD deficiency. Ref.9

VAR_000311

Natural variant

104

1

Missing in SCAD deficiency; no detectable activity.

VAR_013566

Natural variant

107

1

R → C in SCAD deficiency.

VAR_000312

Natural variant

171

1

R → W 69% of wild-type activity; confers susceptibility to ethylmalonicaciduria. dbSNP rs1800556. Ref.10 Ref.9

VAR_013567

Natural variant

177

1

W → R in SCAD deficiency. dbSNP rs57443665. Ref.9

VAR_000314

Natural variant

192

1

A → V in SCAD deficiency; no detectable activity. dbSNP rs28940874. Ref.10

VAR_013568

Natural variant

209

1

G → S 86% of wild-type activity; confers susceptibility to ethylmalonicaciduria. dbSNP rs1799958. Ref.10 Ref.9

VAR_000315

Natural variant

325

1

R → W in SCAD deficiency; no detectable activity. Ref.10

VAR_013569

Natural variant

353

1

S → L in SCAD deficiency; no detectable activity. dbSNP rs28941773. Ref.10

VAR_013570

Natural variant

380

1

R → W in SCAD deficiency; no detectable activity. dbSNP rs28940875. Ref.10

VAR_013571

Natural variant

383

1

R → C in SCAD deficiency. dbSNP rs28940872. Ref.9

VAR_000316

Natural variant

383

1

R → H: dbSNP rs35233375.

VAR_033458

Secondary structure

1

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412

Helix Strand Turn

Details...

Helix

36 – 52

17

Turn

53 – 56

4

Helix

57 – 63

7

Helix

68 – 73

6

Helix

95 – 106

12

Helix

115 – 121

7

Turn

127 – 129

3

Helix

133 – 139

7

Helix

141 – 143

3

Beta strand

169 – 172

4

Beta strand

176 – 180

5

Beta strand

183 – 187

5

Turn

188 – 191

4

Beta strand

193 – 200

8

Beta strand

203 – 205

3

Beta strand

210 – 218

9

Beta strand

238 – 242

5

Beta strand

244 – 249

6

Helix

250 – 252

3

Helix

262 – 269

8

Helix

276 – 279

4

Helix

283 – 296

14

Helix

304 – 306

3

Helix

308 – 336

29

Helix

342 – 366

25

Helix

378 – 388

11

Helix

395 – 402

8

Helix

406 – 411

6

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]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[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: 1692038] [Abstract] Cited for: VARIANTS SCAD DEFICIENCY.
[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: 9499414] [Abstract] Cited for: VARIANTS SCAD DEFICIENCY 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: 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

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.

IPI

IPI00027701.

PIR

A30605.

RefSeq

NP_000008.1.

UniGene

Hs.507076

3D structure databases

PDBe
RCSB PDB
PDBj

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

ModBase

Search...

Protein-protein interaction databases

STRING

P16219.

2-D gel databases

SWISS-2DPAGE

P16219.

DOSAC-COBS-2DPAGE

P16219.

Proteomic databases

PeptideAtlas

P16219.

PRIDE

P16219.

Genome annotation databases

Ensembl

ENST00000242592; ENSP00000242592; ENSG00000122971; Homo sapiens. [Genome view]

GeneID

35.

KEGG

hsa:35.

NMPDR

fig|9606.3.peg.8377.

UCSC

uc001tza.2. human.

Organism-specific databases

CTD

35.

GeneCards

GC12P119648.

H-InvDB

HIX0011071.

HGNC

HGNC:90. ACADS.

HPA

CAB019284.
HPA004799.
HPA022271.

MIM

201470. phenotype.
606885. gene.

Orphanet

26792. Deficiency of short chain Acyl-CoA dehydrogenase.

PharmGKB

PA24426.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG10082.

HOGENOM

HBG699365.

HOVERGEN

P16219.

InParanoid

P16219.

OMA

DYLAYSI.

OrthoDB

EOG9FFGM4.

PhylomeDB

P16219.

Enzyme and pathway databases

BRENDA

1.3.99.2. 247.

Reactome

REACT_602. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

P16219.

Bgee

P16219.

CleanEx

HS_ACADS.

Genevestigator

P16219.

GermOnline

ENSG00000122971. 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.
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]

ProtoNet

Search...

Other Resources

DrugBank

DB00157. NADH.

NextBio

135.

SOURCE

Search...

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:	February 9, 2010
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.