Acetyl-CoA acetyltransferase, mitochondrial precursor

Names and origin

Protein names

Recommended name:
    Acetyl-CoA acetyltransferase, mitochondrial
    EC=2.3.1.9
Alternative name(s):
    Acetoacetyl-CoA thiolase
    T2

Gene names

Name:	ACAT1
Synonyms:	ACAT, MAT

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	427 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Plays a major role in ketone body metabolism.
Catalytic activity	2 acetyl-CoA = CoA + acetoacetyl-CoA.
Subunit structure	Homotetramer.
Subcellular location	Mitochondrion.
Involvement in disease	Defects in ACAT1 are a cause of 3-ketothiolase deficiency (3KTD) [MIM:203750]; also known as alpha-methylacetoaceticaciduria. 3KTD is an inborn error of isoleucine catabolism characterized by intermittent ketoacidotic attacks associated with unconsciousness. Some patients die during an attack or are mentally retarded. Urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, triglylglycine, butanone is increased. It seems likely that the severity of this disease correlates better with the environmental or acquired factors than with the ACAT1 genotype.
Sequence similarities	Belongs to the thiolase family.

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Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Molecular function	Acyltransferase Transferase
PTM	Acetylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Cellular component	mitochondrial matrix Inferred from Experiment. Source: Reactome
Molecular function	acetyl-CoA C-acetyltransferase activity Ref.1 Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF1B	O60739	1	EBI-1051459,EBI-1043343

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Transit peptide

1 – 33

33

Mitochondrion By similarity

Chain

34 – 427

394

Acetyl-CoA acetyltransferase, mitochondrial

Sites

Active site

126

1

Acyl-thioester intermediate By similarity

Active site

385

1

Proton acceptor By similarity

Active site

413

1

Proton acceptor By similarity

Amino acid modifications

Modified residue

174

1

N6-acetyllysine By similarity

Modified residue

190

1

N6-acetyllysine By similarity

Modified residue

230

1

N6-acetyllysine By similarity

Modified residue

338

1

N6-acetyllysine By similarity

Natural variations

Natural variant

5

1

A → P: dbSNP rs3741056.

Natural variant

85

1

Missing in 3KTD.

Natural variant

93

1

N → S in 3KTD; 10% activity.

Natural variant

152

1

G → A in 3KTD.

Natural variant

158

1

N → D in 3KTD; no activity.

Natural variant

183

1

G → R in 3KTD; no activity.

Natural variant

297

1

T → M in 3KTD; 10% normal activity.

Natural variant

301

1

A → P in 3KTD; 5% normal activity.

Natural variant

312

1

I → T in 3KTD; 10% activity.

Natural variant

333

1

A → P in 3KTD; no activity.

Natural variant

379

1

G → V in 3KTD.

Natural variant

380

1

A → T in 3KTD; 7% normal activity.

Experimental info

Sequence conflict

340

1

V → M in BAA01387. Ref.2

Sequence conflict

346

1

D → N in BAA01387. Ref.2

Sequence conflict

380

1

A → S in BAA01387. Ref.2

Sequence conflict

412

1

I → F in BAA01387. Ref.2

Secondary structure

1

.

427

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P24752-1 [UniParc].

Last modified March 1, 1992. Version 1.
Checksum: 2E81168EB39D0142
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FASTA

427

45,200

        10         20         30         40         50         60 
MAVLAALLRS GARSRSPLLR RLVQEIRYVE RSYVSKPTLK EVVIVSATRT PIGSFLGSLS 

        70         80         90        100        110        120 
LLPATKLGSI AIQGAIEKAG IPKEEVKEAY MGNVLQGGEG QAPTRQAVLG AGLPISTPCT 

       130        140        150        160        170        180 
TINKVCASGM KAIMMASQSL MCGHQDVMVA GGMESMSNVP YVMNRGSTPY GGVKLEDLIV 

       190        200        210        220        230        240 
KDGLTDVYNK IHMGSCAENT AKKLNIARNE QDAYAINSYT RSKAAWEAGK FGNEVIPVTV 

       250        260        270        280        290        300 
TVKGQPDVVV KEDEEYKRVD FSKVPKLKTV FQKENGTVTA ANASTLNDGA AALVLMTADA 

       310        320        330        340        350        360 
AKRLNVTPLA RIVAFADAAV EPIDFPIAPV YAASMVLKDV GLKKEDIAMW EVNEAFSLVV 

       370        380        390        400        410        420 
LANIKMLEID PQKVNINGGA VSLGHPIGMS GARIVGHLTH ALKQGEYGLA SICNGGGGAS 


AMLIQKL

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References

[1]	"Molecular cloning and sequence of the complementary DNA encoding human mitochondrial acetoacetyl-coenzyme A thiolase and study of the variant enzymes in cultured fibroblasts from patients with 3-ketothiolase deficiency." Fukao T., Yamaguchi S., Kano M., Orii T., Fujiki Y., Osumi T., Hashimoto T. J. Clin. Invest. 86:2086-2092(1990) [PubMed: 1979337] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure and expression of the human mitochondrial acetoacetyl-CoA thiolase-encoding gene." Kano M., Fukao T., Yamaguchi S., Orii T., Osumi T., Hashimoto T. Gene 109:285-290(1991) [PubMed: 1684944] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.
[3]	"Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes." Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V. Biochem. J. 383:237-248(2004) [PubMed: 15242332] [Abstract] Cited for: PROTEIN SEQUENCE OF 50-78 AND 312-338. Tissue: Adipocyte.
[4]	"Molecular basis of beta-ketothiolase deficiency: mutations and polymorphisms in the human mitochondrial acetoacetyl-coenzyme A thiolase gene." Fukao T., Yamaguchi S., Orii T., Hashimoto T. Hum. Mutat. 5:113-120(1995) [PubMed: 7749408] [Abstract] Cited for: REVIEW ON 3KTD VARIANTS.
[5]	"Identification of three mutant alleles of the gene for mitochondrial acetoacetyl-coenzyme A thiolase. A complete analysis of two generations of a family with 3-ketothiolase deficiency." Fukao T., Yamaguchi S., Orii T., Schutgens R.B.H., Osumi T., Hashimoto T. J. Clin. Invest. 89:474-479(1992) [PubMed: 1346617] [Abstract] Cited for: VARIANT 3KTD ARG-183.
[6]	"Evidence for a structural mutation (347Ala to Thr) in a German family with 3-ketothiolase deficiency." Fukao T., Yamaguchi S., Tomatsu S., Orii T., Frauendienst-Egger G., Schrod L., Osumi T., Hashimoto T. Biochem. Biophys. Res. Commun. 179:124-129(1991) [PubMed: 1715688] [Abstract] Cited for: VARIANT 3KTD THR-380.
[7]	"Molecular, biochemical, and clinical characterization of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in two further patients." Wakazono A., Fukao T., Yamaguchi S., Hori T., Orii T., Lambert M., Mitchell G.A., Lee G.W., Hashimoto T. Hum. Mutat. 5:34-42(1995) [PubMed: 7728148] [Abstract] Cited for: VARIANTS 3KTD ASP-158; MET-297 AND PRO-301.
[8]	"Characterization of N93S, I312T, and A333P missense mutations in two Japanese families with mitochondrial acetoacetyl-CoA thiolase deficiency." Fukao T., Nakamura H., Song X.-Q., Nakamura K., Orii K.E., Kohno Y., Kano M., Yamaguchi S., Hashimoto T., Orii T., Kondo N. Hum. Mutat. 12:245-254(1998) [PubMed: 9744475] [Abstract] Cited for: VARIANTS 3KTD SER-93; THR-312 AND PRO-333.
+	Additional computationally mapped references.

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Web resources

GeneReviews

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Cross-references

Sequence databases

D90228 mRNA. Translation: BAA14278.1.
D10511 Genomic DNA. Translation: BAA01387.1.

PIR

JH0255.

RefSeq

NP_000010.1.

UniGene

Hs.232375

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2F2S	X-ray	2.00	A/B/C/D	41-427	[»]
2IB7	X-ray	2.05	A/B/C/D	35-427	[»]
2IB8	X-ray	1.85	A/B/C/D	35-427	[»]
2IB9	X-ray	2.05	A/B/C/D	35-427	[»]
2IBU	X-ray	1.90	A/B/C/D	35-427	[»]
2IBW	X-ray	1.90	A/B/C/D	35-427	[»]
2IBY	X-ray	1.85	A/B/C/D	35-427	[»]

ModBase

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Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases