P13437 · THIM_RAT

  • Protein
    3-ketoacyl-CoA thiolase, mitochondrial
  • Gene
    Acaa2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

In the production of energy from fats, this is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA (Probable). Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain unbranched 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms (Probable). Also catalyzes the condensation of two acetyl-CoA molecules into acetoacetyl-CoA and could be involved in the production of ketone bodies (Probable). Also displays hydrolase activity on various fatty acyl-CoAs (PubMed:16476568).
Thereby, could be responsible for the production of acetate in a side reaction to beta-oxidation (Probable). Abolishes BNIP3-mediated apoptosis and mitochondrial damage (By similarity).

Catalytic activity

  • acetyl-CoA + an acyl-CoA = a 3-oxoacyl-CoA + CoA
    This reaction proceeds in the forward
    and the backward
    directions.
    EC:2.3.1.16 (UniProtKB | ENZYME | Rhea)
  • 2 acetyl-CoA = acetoacetyl-CoA + CoA
    This reaction proceeds in the forward
    and the backward
    directions.
    EC:2.3.1.9 (UniProtKB | ENZYME | Rhea)
  • acetyl-CoA + H2O = acetate + CoA + H+
    This reaction proceeds in the forward direction.
    EC:3.1.2.1 (UniProtKB | ENZYME | Rhea)
  • H2O + propanoyl-CoA = CoA + H+ + propanoate
    This reaction proceeds in the forward direction.
  • butanoyl-CoA + H2O = butanoate + CoA + H+
    This reaction proceeds in the forward direction.
  • H2O + hexanoyl-CoA = CoA + H+ + hexanoate
    This reaction proceeds in the forward direction.
  • H2O + octanoyl-CoA = CoA + H+ + octanoate
    This reaction proceeds in the forward direction.
  • decanoyl-CoA + H2O = CoA + decanoate + H+
    This reaction proceeds in the forward direction.
  • dodecanoyl-CoA + H2O = CoA + dodecanoate + H+
    This reaction proceeds in the forward direction.
  • H2O + tetradecanoyl-CoA = CoA + H+ + tetradecanoate
    This reaction proceeds in the forward direction.
  • H2O + hexadecanoyl-CoA = CoA + H+ + hexadecanoate
    This reaction proceeds in the forward direction.
    EC:3.1.2.2 (UniProtKB | ENZYME | Rhea)

Activity regulation

The 3-oxoacetyl-CoA thiolase activity is inhibited by acetyl-CoA while the acetyl-CoA hydrolase activity is inhibited by acetoacetyl-CoA.

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
11.4 μMacetoacetyl-CoA
0.71 mMacetyl-CoA

Pathway

Lipid metabolism; fatty acid beta-oxidation.

Features

Showing features for active site, binding site, site.

TypeIDPosition(s)Description
Active site92Acyl-thioester intermediate
Binding site224CoA (UniProtKB | ChEBI)
Binding site227CoA (UniProtKB | ChEBI)
Binding site251CoA (UniProtKB | ChEBI)
Site352Increases nucleophilicity of active site Cys
Active site382Proton donor/acceptor

GO annotations

AspectTerm
Cellular Componentmitochondrial matrix
Cellular Componentmitochondrion
Molecular Functionacetyl-CoA C-acetyltransferase activity
Molecular Functionacetyl-CoA C-acyltransferase activity
Molecular Functionacetyl-CoA hydrolase activity
Molecular Functionfatty acyl-CoA hydrolase activity
Biological Processacetyl-CoA metabolic process
Biological Processcellular response to hypoxia
Biological Processfatty acid beta-oxidation
Biological Processnegative regulation of mitochondrial membrane permeability involved in apoptotic process
Biological Processnegative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway

Keywords

Enzyme and pathway databases

Chemistry

Names & Taxonomy

Protein names

  • Recommended name
    3-ketoacyl-CoA thiolase, mitochondrial
  • EC number
  • Alternative names
    • Acetyl-CoA acetyltransferase
      (EC:2.3.1.9
      ) . EC:2.3.1.9 (UniProtKB | ENZYME | Rhea)
    • Acetyl-CoA acyltransferase
    • Acyl-CoA hydrolase, mitochondrial
      (EC:3.1.2.-
      , EC:3.1.2.1
      , EC:3.1.2.2
      ) . EC:3.1.2.- (UniProtKB | ENZYME | Rhea)
      , EC:3.1.2.1 (UniProtKB | ENZYME | Rhea)
      , EC:3.1.2.2 (UniProtKB | ENZYME | Rhea)
    • Beta-ketothiolase
    • Mitochondrial 3-oxoacyl-CoA thiolase

Gene names

    • Name
      Acaa2

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    P13437

Proteomes

Organism-specific databases

Subcellular Location

Keywords

PTM/Processing

Features

Showing features for transit peptide, chain, modified residue.

TypeIDPosition(s)Description
Transit peptide1-16Mitochondrion; not cleaved
ChainPRO_00002233011-3973-ketoacyl-CoA thiolase, mitochondrial
Modified residue25N6-acetyllysine; alternate
Modified residue25N6-succinyllysine; alternate
Modified residue45N6-succinyllysine
Modified residue119Phosphothreonine
Modified residue121Phosphoserine
Modified residue127Phosphotyrosine
Modified residue136Phosphothreonine
Modified residue137N6-acetyllysine; alternate
Modified residue137N6-succinyllysine; alternate
Modified residue143N6-acetyllysine; alternate
Modified residue143N6-succinyllysine; alternate
Modified residue158N6-acetyllysine; alternate
Modified residue158N6-succinyllysine; alternate
Modified residue171N6-acetyllysine; alternate
Modified residue171N6-succinyllysine; alternate
Modified residue191N6-acetyllysine; alternate
Modified residue191N6-succinyllysine; alternate
Modified residue209N6-acetyllysine; alternate
Modified residue209N6-succinyllysine; alternate
Modified residue211N6-succinyllysine
Modified residue212N6-succinyllysine
Modified residue214N6-succinyllysine
Modified residue240N6-succinyllysine
Modified residue241N6-acetyllysine
Modified residue269N6-acetyllysine
Modified residue270N6-acetyllysine
Modified residue305N6-acetyllysine; alternate
Modified residue305N6-succinyllysine; alternate
Modified residue310Phosphoserine
Modified residue312N6-acetyllysine; alternate
Modified residue312N6-succinyllysine; alternate
Modified residue333Phosphoserine
Modified residue340N6-acetyllysine
Modified residue344Phosphoserine
Modified residue375N6-acetyllysine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed in liver, brown adipose tissue and heart (at protein level).

Induction

Up-regulated in liver, brown adipose tissue, heart, intestine and kidney by DEHP/bis(2-ethylhexyl)phthalate (at protein level).

Interaction

Subunit

Homotetramer. Interacts with BNIP3 (By similarity).

Protein-protein interaction databases

Structure

Family & Domains

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    397
  • Mass (Da)
    41,871
  • Last updated
    1990-01-01 v1
  • Checksum
    8344FB7271C3E2E1
MALLRGVFIVAAKRTPFGAYGGLLKDFTATDLTEFAARAALSAGKVPPETIDSVIVGNVMQSSSDAAYLARHVGLRVGVPTETGALTLNRLCGSGFQSIVSGCQEICSKDAEVVLCGGTESMSQSPYSVRNVRFGTKFGLDLKLEDTLWAGLTDQHVKLPMGMTAENLAAKYNISREDCDRYALQSQQRWKAANEAGYFNEEMAPIEVKTKKGKQTMQVDEHARPQTTLEQLQNLPPVFKKEGTVTAGNASGMSDGAGVVIIASEDAVKKHNFTPLARVVGYFVSGCDPAIMGIGPVPAITGALKKAGLSLKDMDLIDVNEAFAPQFLAVQKSLDLDPSKTNVSGGAIALGHPLGGSGSRITAHLVHELRRRGGKYAVGSACIGGGQGISLIIQNTA

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A0G2K642A0A0G2K642_RATAcaa2401
G3V9U2G3V9U2_RATAcaa2397

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
X05341
EMBL· GenBank· DDBJ
CAA28952.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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