P13437 · THIM_RAT
- Protein3-ketoacyl-CoA thiolase, mitochondrial
- GeneAcaa2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids397 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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 + CoAThis reaction proceeds in the forward and the backward directions.
- H2O + propanoyl-CoA = CoA + H+ + propanoateThis reaction proceeds in the forward direction.
- butanoyl-CoA + H2O = butanoate + CoA + H+This reaction proceeds in the forward direction.
- H2O + hexanoyl-CoA = CoA + H+ + hexanoateThis reaction proceeds in the forward direction.
- H2O + octanoyl-CoA = CoA + H+ + octanoateThis 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+ + tetradecanoateThis reaction proceeds in the forward direction.
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 μM | acetoacetyl-CoA | |||||
0.71 mM | acetyl-CoA |
Pathway
Lipid metabolism; fatty acid beta-oxidation.
Features
Showing features for active site, binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 92 | Acyl-thioester intermediate | ||||
Sequence: C | ||||||
Binding site | 224 | CoA (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 227 | CoA (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 251 | CoA (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Site | 352 | Increases nucleophilicity of active site Cys | ||||
Sequence: H | ||||||
Active site | 382 | Proton donor/acceptor | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrion | |
Molecular Function | acetyl-CoA C-acetyltransferase activity | |
Molecular Function | acetyl-CoA C-acyltransferase activity | |
Molecular Function | acetyl-CoA hydrolase activity | |
Molecular Function | fatty acyl-CoA hydrolase activity | |
Biological Process | acetyl-CoA metabolic process | |
Biological Process | cellular response to hypoxia | |
Biological Process | fatty acid beta-oxidation | |
Biological Process | negative regulation of mitochondrial membrane permeability involved in apoptotic process | |
Biological Process | negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended name3-ketoacyl-CoA thiolase, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP13437
Proteomes
Organism-specific databases
Subcellular Location
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-16 | Mitochondrion; not cleaved | ||||
Sequence: MALLRGVFIVAAKRTP | ||||||
Chain | PRO_0000223301 | 1-397 | 3-ketoacyl-CoA thiolase, mitochondrial | |||
Sequence: MALLRGVFIVAAKRTPFGAYGGLLKDFTATDLTEFAARAALSAGKVPPETIDSVIVGNVMQSSSDAAYLARHVGLRVGVPTETGALTLNRLCGSGFQSIVSGCQEICSKDAEVVLCGGTESMSQSPYSVRNVRFGTKFGLDLKLEDTLWAGLTDQHVKLPMGMTAENLAAKYNISREDCDRYALQSQQRWKAANEAGYFNEEMAPIEVKTKKGKQTMQVDEHARPQTTLEQLQNLPPVFKKEGTVTAGNASGMSDGAGVVIIASEDAVKKHNFTPLARVVGYFVSGCDPAIMGIGPVPAITGALKKAGLSLKDMDLIDVNEAFAPQFLAVQKSLDLDPSKTNVSGGAIALGHPLGGSGSRITAHLVHELRRRGGKYAVGSACIGGGQGISLIIQNTA | ||||||
Modified residue | 25 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 25 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 45 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 119 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 121 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 127 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 136 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 137 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 137 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 143 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 143 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 158 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 158 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 171 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 171 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 191 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 191 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 209 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 209 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 211 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 212 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 214 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 240 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 241 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 269 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 270 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 305 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 305 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 310 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 312 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 312 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 333 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 340 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 344 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 375 | N6-acetyllysine | ||||
Sequence: K |
Keywords
- PTM
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).
Structure
Sequence
- Sequence statusComplete
- Length397
- Mass (Da)41,871
- Last updated1990-01-01 v1
- Checksum8344FB7271C3E2E1
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0G2K642 | A0A0G2K642_RAT | Acaa2 | 401 | ||
G3V9U2 | G3V9U2_RAT | Acaa2 | 397 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X05341 EMBL· GenBank· DDBJ | CAA28952.1 EMBL· GenBank· DDBJ | mRNA |