P16219 (ACADS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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 + 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 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 Reference proteome
Gene Ontology (GO)
Biological_process	butyrate catabolic process Inferred from electronic annotation. Source: Compara fatty acid beta-oxidation Traceable author statement. Source: Reactome fatty acid beta-oxidation using acyl-CoA dehydrogenase Inferred from electronic annotation. Source: Compara protein homotetramerization Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to starvation Inferred from electronic annotation. Source: Compara
Cellular_component	mitochondrial matrix Traceable author statement. Source: Reactome mitochondrial membrane Inferred from electronic annotation. Source: Compara
Molecular_function	acyl-CoA dehydrogenase activity Traceable author statement. Source: Reactome butyryl-CoA dehydrogenase activity Inferred from electronic annotation. Source: EC fatty-acyl-CoA binding Inferred from electronic annotation. Source: Compara 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 – 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; 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 ACADSD.

VAR_000310

Natural variant

90

1

G → S in ACADSD; no detectable activity. Ref.10

VAR_013565

Natural variant

92

1

G → C in ACADSD. Ref.9

VAR_000311

Natural variant

104

1

Missing in ACADSD; no detectable activity. Ref.10

VAR_013566

Natural variant

107

1

R → C in ACADSD.

VAR_000312

Natural variant

171

1

R → W 69% of wild-type activity; confers susceptibility to ethylmalonicaciduria. Ref.9 Ref.10
Corresponds to variant rs1800556 [ dbSNP | Ensembl ].

VAR_013567

Natural variant

177

1

W → R in ACADSD. Ref.9
Corresponds to variant rs57443665 [ dbSNP | Ensembl ].

VAR_000314

Natural variant

192

1

A → V in ACADSD; no detectable activity. Ref.10
Corresponds to variant rs28940874 [ dbSNP | Ensembl ].

VAR_013568

Natural variant

209

1

G → S 86% of wild-type activity; confers susceptibility to ethylmalonicaciduria. Ref.9 Ref.10
Corresponds to variant rs1799958 [ dbSNP | Ensembl ].

VAR_000315

Natural variant

325

1

R → W in ACADSD; no detectable activity. Ref.10

VAR_013569

Natural variant

353

1

S → L in ACADSD; no detectable activity. Ref.10
Corresponds to variant rs28941773 [ dbSNP | Ensembl ].

VAR_013570

Natural variant

380

1

R → W in ACADSD; no detectable activity. Ref.10
Corresponds to variant rs28940875 [ dbSNP | Ensembl ].

VAR_013571

Natural variant

383

1

R → C in ACADSD. Ref.9
Corresponds to variant rs28940872 [ dbSNP | Ensembl ].

VAR_000316

Natural variant

383

1

R → H.
Corresponds to variant rs35233375 [ dbSNP | Ensembl ].

VAR_033458

Secondary structure

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412

Helix Strand Turn

Details...

Helix

36 – 52

17

Turn

53 – 56

4

Helix

57 – 63

7

Helix

68 – 77

10

Turn

78 – 80

3

Helix

86 – 88

3

Helix

95 – 108

14

Helix

110 – 121

12

Helix

124 – 130

7

Helix

133 – 139

7

Helix

141 – 143

3

Beta strand

144 – 147

4

Beta strand

150 – 153

4

Beta strand

159 – 162

4

Helix

163 – 165

3

Beta strand

169 – 173

5

Beta strand

176 – 187

12

Turn

188 – 191

4

Beta strand

193 – 200

8

Beta strand

203 – 205

3

Beta strand

210 – 218

9

Beta strand

222 – 224

3

Beta strand

230 – 232

3

Beta strand

238 – 249

12

Helix

250 – 252

3

Beta strand

253 – 256

4

Helix

260 – 296

37

Helix

304 – 306

3

Helix

308 – 336

29

Helix

342 – 367

26

Helix

368 – 372

5

Helix

378 – 388

11

Turn

389 – 392

4

Helix

395 – 411

17

Sequences

	Sequence		Length	Mass (Da)
	P16219 [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] [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

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. NM_000017.2.

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	[»]

ProteinModelPortal

P16219.

ModBase

Search...

Protein-protein interaction databases

IntAct

P16219. 1 interaction.

STRING

9606.ENSP00000242592.

PTM databases

PhosphoSite

P16219.

Polymorphism databases

DMDM

113019.

2D gel databases

DOSAC-COBS-2DPAGE

P16219.

SWISS-2DPAGE

P16219.

UCD-2DPAGE

P16219.

Proteomic databases

PaxDb

P16219.

PeptideAtlas

P16219.

PRIDE

P16219.

Protocols and materials databases

DNASU

35.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000242592; ENSP00000242592; ENSG00000122971.

GeneID

35.

KEGG

hsa:35.

UCSC

uc001tza.4. human.

Organism-specific databases

CTD

35.

GeneCards

GC12P121163.

HGNC

HGNC:90. ACADS.

HPA

CAB019284.
HPA004799.
HPA022271.

MIM

201470. phenotype.
606885. gene.

neXtProt

NX_P16219.

Orphanet

26792. Deficiency of short chain acyl-CoA dehydrogenase.

PharmGKB

PA24426.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1960.

HOGENOM

HOG000131659.

HOVERGEN

HBG000224.

InParanoid

P16219.

KO

K00248.

OMA

YRDAKLN.

OrthoDB

EOG4ZPDVH.

PhylomeDB

P16219.

Enzyme and pathway databases

BioCyc

MetaCyc:HS04619-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P16219.

UniPathway

UPA00660.

Gene expression databases

ArrayExpress

P16219.

Bgee

P16219.

CleanEx

HS_ACADS.

Genevestigator

P16219.

GermOnline

ENSG00000122971. Homo sapiens.

Family and domain databases

Gene3D

1.10.540.10. 1 hit.
2.40.110.10. 1 hit.

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]

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

DB00157. NADH.

EvolutionaryTrace

P16219.

GenomeRNAi

35.

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:	May 1, 2013
This is version 156 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.