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Overview

Uniprot IDP42765
Protein Name3-ketoacyl-CoA thiolase, mitochondrial
Gene NameACAA2
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
13 GVFVVAAKRTPFGAY
137 RNVRFGTKLGSDIKL
181 ISREECDKYALQSQQ
191 LQSQQRWKAANDAGY
209 EMAPIEVKTKKGKQT
214 EVKTKKGKQTMQVDE
234 TTLEQLQKLPPVFKK
241 KLPPVFKKDGTVTAG
270 ASEDAVKKHNFTPLA
305 PAISGALKKAGLSLK
340 SLDLDISKTNVNGGA
38 DLSEFAAKAALSAGK
81 GLRVGIPKETPALTI

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:25478839). Thereby, could be responsible for the production of acetate in a side reaction to beta-oxidation (Probable). Abolishes BNIP3-mediated apoptosis and mitochondrial damage (PubMed:18371312)

Protein Sequence

10 MALLRGVFVV 20 AAKRTPFGAY 30 GGLLKDFTAT 40 DLSEFAAKAA 50 LSAGKVSPET 60 VDSVIMGNVL 70 QSSSDAIYLA 80 RHVGLRVGIP 90 KETPALTINR 100 LCGSGFQSIV 110 NGCQEICVKE 120 AEVVLCGGTE 130 SMSQAPYCVR 140 NVRFGTKLGS 150 DIKLEDSLWV 160 SLTDQHVQLP 170 MAMTAENLAV 180 KHKISREECD 190 KYALQSQQRW 200 KAANDAGYFN 210 DEMAPIEVKT 220 KKGKQTMQVD 230 EHARPQTTLE 240 QLQKLPPVFK 250 KDGTVTAGNA 260 SGVADGAGAV 270 IIASEDAVKK 280 HNFTPLARIV 290 GYFVSGCDPS 300 IMGIGPVPAI 310 SGALKKAGLS 320 LKDMDLVEVN 330 EAFAPQYLAV 340 ERSLDLDISK 350 TNVNGGAIAL 360 GHPLGGSGSR 370 ITAHLVHELR 380 RRGGKYAVGS 390 ACIGGGQGIA VIIQSTA

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005759 mitochondrial matrix
Cellular Component GO:0005739 mitochondrion
Molecular Function GO:0003985 acetyl-CoA C-acetyltransferase activity
Molecular Function GO:0003988 acetyl-CoA C-acyltransferase activity
Molecular Function GO:0003986 acetyl-CoA hydrolase activity
Molecular Function GO:0047617 fatty acyl-CoA hydrolase activity
Molecular Function GO:0003723 RNA binding
Biological Process GO:0071456 cellular response to hypoxia
Biological Process GO:0006695 cholesterol biosynthetic process
Biological Process GO:0006635 fatty acid beta-oxidation
Biological Process GO:1902109 negative regulation of mitochondrial membrane permeability involved in apoptotic process
Biological Process GO:1901029 negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.