P55809 (SCOT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial
EC=2.8.3.5

Alternative name(s):
3-oxoacid CoA-transferase 1
Somatic-type succinyl-CoA:3-oxoacid CoA-transferase
Short name=SCOT-s

Gene names

Name:	OXCT1
Synonyms:	OXCT, SCOT

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	520 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	Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate.
Catalytic activity	Succinyl-CoA + a 3-oxo acid = succinate + a 3-oxoacyl-CoA.
Pathway	Ketone metabolism; succinyl-CoA degradation; acetoacetyl-CoA from succinyl-CoA: step 1/1.
Subunit structure	Homodimer.
Subcellular location	Mitochondrion matrix.
Tissue specificity	Abundant in heart, followed in order by kidney, brain, and muscle, whereas in liver it is undetectable; also detectable in leukocytes and fibroblasts.
Involvement in disease	Succinyl-CoA-3-ketoacid-CoA transferase deficiency (SCOTD) [MIM:245050]: A disorder of ketone body metabolism, characterized by episodic ketoacidosis. Patients are usually asymptomatic between episodes. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.10 Ref.11
Sequence similarities	Belongs to the 3-oxoacid CoA-transferase family.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Molecular function	Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	adipose tissue development Inferred from electronic annotation. Source: Compara brain development Inferred from electronic annotation. Source: Compara cellular lipid metabolic process Traceable author statement. Source: Reactome cellular response to acid Inferred from electronic annotation. Source: Compara cellular response to glucose stimulus Inferred from electronic annotation. Source: Compara heart development Inferred from electronic annotation. Source: Compara ketone body catabolic process Traceable author statement. Source: Reactome ketone catabolic process Inferred from electronic annotation. Source: Compara positive regulation of insulin secretion Inferred from electronic annotation. Source: Compara response to activity Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to hormone stimulus Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara response to starvation Inferred from electronic annotation. Source: Compara
Cellular_component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	3-oxoacid CoA-transferase activity Inferred from mutant phenotype Ref.2Ref.1. Source: UniProtKB protein homodimerization activity Non-traceable author statement Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 39

39

Mitochondrion Ref.4

Chain

40 – 520

481

Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial

PRO_0000002413

Sites

Active site

344

1

Acyl-thioester intermediate By similarity

Amino acid modifications

Modified residue

170

1

Phosphoserine Ref.7

Natural variations

Natural variant

58

1

T → M. Ref.10 Ref.11

VAR_000695

Natural variant

133

1

V → E in SCOTD. Ref.10

VAR_000696

Natural variant

215

1

A → V in SCOTD; partial loss of activity. Ref.11

VAR_065564

Natural variant

219

1

G → E in SCOTD. Ref.2

VAR_010337

Natural variant

221

1

V → M in SCOTD. Ref.2

VAR_010338

Natural variant

226

1

S → N in SCOTD; loss of activity. Ref.11

VAR_065565

Natural variant

324

1

G → E in SCOTD. Ref.2

VAR_010339

Natural variant

327

1

L → P in SCOTD; partial loss of activity. Ref.11

VAR_065566

Natural variant

404

1

V → F in SCOTD; loss of activity. Ref.11

VAR_065567

Natural variant

405

1

S → P in SCOTD; loss of activity. Ref.11

VAR_065568

Natural variant

456

1

C → F in SCOTD. Ref.10

VAR_000697

Natural variant

468

1

R → C in SCOTD; partial loss of activity; the mutant retains half of the activity of the wild-type at 30 degrees. Ref.11

VAR_065569

Secondary structure

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520

Helix Strand Turn

Details...

Beta strand

41 – 44

4

Helix

46 – 50

5

Beta strand

58 – 61

4

Helix

71 – 80

10

Beta strand

84 – 88

5

Helix

100 – 104

5

Beta strand

108 – 114

7

Helix

120 – 127

8

Beta strand

130 – 135

6

Helix

138 – 150

13

Beta strand

154 – 158

5

Turn

159 – 162

4

Helix

164 – 167

4

Beta strand

171 – 174

4

Beta strand

178 – 183

6

Beta strand

189 – 192

4

Beta strand

195 – 201

7

Beta strand

205 – 211

7

Beta strand

213 – 216

4

Helix

225 – 227

3

Helix

231 – 234

4

Beta strand

237 – 249

13

Helix

256 – 258

3

Helix

263 – 265

3

Beta strand

268 – 271

4

Helix

300 – 309

10

Helix

310 – 312

3

Beta strand

318 – 321

4

Helix

325 – 329

5

Helix

330 – 332

3

Beta strand

340 – 343

4

Turn

344 – 346

3

Beta strand

347 – 350

4

Helix

356 – 358

3

Beta strand

368 – 370

3

Beta strand

373 – 379

7

Helix

382 – 390

9

Beta strand

395 – 399

5

Beta strand

402 – 405

4

Beta strand

413 – 415

3

Turn

416 – 418

3

Helix

426 – 429

4

Beta strand

435 – 440

6

Helix

446 – 448

3

Beta strand

450 – 455

6

Beta strand

461 – 464

4

Beta strand

468 – 470

3

Beta strand

472 – 479

8

Turn

480 – 482

3

Beta strand

483 – 489

7

Helix

495 – 499

5

Beta strand

502 – 504

3

Beta strand

507 – 514

8

Sequences

	Sequence		Length	Mass (Da)
	P55809 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 54DA790FB8EDA546	FASTA	520	56,158
	10 20 30 40 50 60 MAALKLLSSG LRLCASARGS GATWYKGCVC SFSTSAHRHT KFYTDPVEAV KDIPDGATVL 70 80 90 100 110 120 VGGFGLCGIP ENLIDALLKT GVKGLTAVSN NAGVDNFGLG LLLRSKQIKR MVSSYVGENA 130 140 150 160 170 180 EFERQYLSGE LEVELTPQGT LAERIRAGGA GVPAFYTPTG YGTLVQEGGS PIKYNKDGSV 190 200 210 220 230 240 AIASKPREVR EFNGQHFILE EAITGDFALV KAWKADRAGN VIFRKSARNF NLPMCKAAET 250 260 270 280 290 300 TVVEVEEIVD IGAFAPEDIH IPQIYVHRLI KGEKYEKRIE RLSIRKEGDG EAKSAKPGDD 310 320 330 340 350 360 VRERIIKRAA LEFEDGMYAN LGIGIPLLAS NFISPNITVH LQSENGVLGL GPYPRQHEAD 370 380 390 400 410 420 ADLINAGKET VTILPGASFF SSDESFAMIR GGHVDLTMLG AMQVSKYGDL ANWMIPGKMV 430 440 450 460 470 480 KGMGGAMDLV SSAKTKVVVT MEHSAKGNAH KIMEKCTLPL TGKQCVNRII TEKAVFDVDK 490 500 510 520 KKGLTLIELW EGLTVDDVQK STGCDFAVSP KLMPMQQIAN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Succinyl CoA:3-oxoacid CoA transferase (SCOT): human cDNA cloning, human chromosomal mapping to 5p13, and mutation detection in a SCOT-deficient patient." Kassovska-Bratinova S., Fukao T., Song X.-Q., Duncan A.M.V., Chen H.S., Robert M.-F., Perez-Cerda C., Ugarte M., Chartrand C., Vobecky S., Kondo N., Mitchell G.A. Am. J. Hum. Genet. 59:519-528(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Heart.
[2]	"Succinyl-CoA:3-ketoacid CoA transferase (SCOT): cloning of the human SCOT gene, tertiary structural modeling of the human SCOT monomer, and characterization of three pathogenic mutations." Fukao T., Mitchell G.A., Song X.-Q., Nakamura H., Kassovska-Bratinova S., Orii K.E., Wraith J.E., Besley G., Wanders R.J.A., Niezen-Koning K.E., Berry G.T., Palmieri M., Kondo N. Genomics 68:144-151(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SCOTD GLU-219; MET-221 AND GLU-324.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	Reymond M.A., Sanchez J.-C., Hughes G.J., Riese J., Tortola S., Peinado M.A., Kirchner T., Hohenberger W., Hochstrasser D.F., Kockerling F. Submitted (FEB-1997) to UniProtKB Cited for: PROTEIN SEQUENCE OF 40-50. Tissue: Colon.
[5]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 84-104; 111-124; 147-173; 191-211; 391-418; 422-434 AND 501-511, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[6]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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].
[9]	"Crystal structure of human 3-oxoacid CoA transferase 1." Structural genomics consortium (SGC) Submitted (AUG-2008) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 40-520.
[10]	"Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency: two pathogenic mutations, V133E and C456F, in Japanese siblings." Song X.-Q., Fukao T., Watanabe H., Shintaku H., Hirayama K., Kassovska-Bratinova S., Kondo N., Mitchell G.A. Hum. Mutat. 12:83-88(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SCOTD GLU-133 AND PHE-456, VARIANT MET-58.
[11]	"Clinical and molecular characterization of five patients with succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency." Fukao T., Sass J.O., Kursula P., Thimm E., Wendel U., Ficicioglu C., Monastiri K., Guffon N., Baric I., Zabot M.T., Kondo N. Biochim. Biophys. Acta 1812:619-624(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SCOTD VAL-215; ASN-226; PRO-327; PHE-404; PRO-405 AND CYS-468, VARIANT MET-58, CHARACTERIZATION OF VARIANTS SCOTD VAL-215; ASN-226; PRO-327; PHE-404; PRO-405 AND CYS-468.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U62961 mRNA. Translation: AAB07366.1.
AB029576 Genomic DNA. Translation: BAB13733.1.
BC009001 mRNA. Translation: AAH09001.1.

IPI

IPI00026516.

RefSeq

NP_000427.1. NM_000436.3.

UniGene

Hs.278277.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3DLX	X-ray	2.20	A/B/C/D	40-520	[»]

ProteinModelPortal

P55809.

ModBase

Search...

Protein-protein interaction databases

IntAct

P55809. 3 interactions.

STRING

9606.ENSP00000196371.

PTM databases

PhosphoSite

P55809.

Polymorphism databases

DMDM

2492998.

2D gel databases

UCD-2DPAGE

P55809.

Proteomic databases

PaxDb

P55809.

PeptideAtlas

P55809.

PRIDE

P55809.

Protocols and materials databases

DNASU

5019.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000196371; ENSP00000196371; ENSG00000083720.

GeneID

5019.

KEGG

hsa:5019.

UCSC

uc003jmn.3. human.

Organism-specific databases

CTD

5019.

GeneCards

GC05M041765.

HGNC

HGNC:8527. OXCT1.

HPA

HPA012047.

MIM

245050. phenotype.
601424. gene.

neXtProt

NX_P55809.

Orphanet

832. Succinyl-CoA acetoacetate transferase deficiency.

PharmGKB

PA32855.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1788.

HOGENOM

HOG000221244.

HOVERGEN

HBG002310.

InParanoid

P55809.

KO

K01027.

OMA

KGTEDAD.

OrthoDB

EOG4GMTWV.

PhylomeDB

P55809.

Enzyme and pathway databases

BioCyc

MetaCyc:HS01447-MONOMER.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00929; UER00894.

Gene expression databases

ArrayExpress

P55809.

Bgee

P55809.

CleanEx

HS_OXCT1.

Genevestigator

P55809.

GermOnline

ENSG00000083720. Homo sapiens.

Family and domain databases

InterPro

IPR012792. 3-oxoacid_CoA-transf_A.
IPR012791. 3-oxoacid_CoA-transf_B.
IPR014388. 3-oxoacid_CoA-transferase.
IPR004165. CoA_trans_fam_I.
IPR004164. CoA_transf_AS.
IPR004163. CoA_transf_BS.
[Graphical view]

PANTHER

PTHR13707. PTHR13707. 1 hit.

Pfam

PF01144. CoA_trans. 2 hits.
[Graphical view]

PIRSF

PIRSF000858. SCOT-t. 1 hit.

SMART

SM00882. CoA_trans. 2 hits.
[Graphical view]

TIGRFAMs

TIGR02429. pcaI_scoA_fam. 1 hit.
TIGR02428. pcaJ_scoB_fam. 1 hit.

PROSITE

PS01273. COA_TRANSF_1. 1 hit.
PS01274. COA_TRANSF_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00139. Succinic acid.

EvolutionaryTrace

P55809.

GenomeRNAi

5019.

NextBio

19324.

SOURCE

Search...

Entry information

Entry name

SCOT1_HUMAN

Accession

Primary (citable) accession number: P55809

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 131 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.