Search Results

Overview

Uniprot IDP55084
Protein NameTrifunctional enzyme subunit beta, mitochondrial
Gene NameHADHB
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
181 RHSRKMRKLMLDLNK
188 KLMLDLNKAKSMGQR
190 MLDLNKAKSMGQRLS
201 QRLSLISKFRFNFLA
254 RSHSLAKKAQDEGLL
272 VPFKVPGKDTVTKDN
277 PGKDTVTKDNGIRPS
291 SSLEQMAKLKPAFIK
334 LAMGYKPKAYLRDFM
361 GPTYATPKVLEKAGL
41 AAPAVQTKTKKTLAK
44 AVQTKTKKTLAKPNI
72 LLSGTSYKDLMPHDL

Function

Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway (PubMed:1550553, PubMed:16423905, PubMed:26474213, PubMed:29915090, PubMed:30850536, PubMed:8135828). The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through cycles of four consecutive reactions (PubMed:26474213, PubMed:29915090). Each beta-oxidation cycle shortens the fatty acyl-CoA by two carbons, yielding one acetyl-CoA (for the citric acid cycle), one FADH(2), and one NADH (which donate electrons to the respiratory chain for ATP production) (PubMed:26474213, PubMed:29915090). These cycles repeat until the chain is fully degraded to acetyl-CoA units (PubMed:26474213, PubMed:29915090). Among the enzymes involved in this pathway, the trifunctional protein, responsible for the hydration, dehydrogenation, and thiolysis steps, shows specificity for long-chain fatty acids, such as those from dietary and stored fats (PubMed:30850536). Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities while the trifunctional enzyme subunit beta/HADHB described here bears the 3-ketoacyl-CoA thiolase activity (PubMed:16423905, PubMed:26474213, PubMed:29915090, PubMed:30850536, PubMed:38372965, PubMed:8135828). These activities have been experimentally confirmed on a few substrates derived from beta-oxidation of long-chain saturated fatty acids such as palmitate (hexadecanoate) and laurate (dodecanoate) (PubMed:1550553, PubMed:8135828, PubMed:8163672, PubMed:8651282). In addition, based on its established catalytic mechanism, and combined genetic interaction or mutant phenotype evidence, it is predicted to act also on other substrates, including long-chain unsaturated fatty acids such as oleate (9Z-octadecenoate), linoleate (9Z,12Z-octadecadienoate), linolenate (9Z,12Z,15Z-octadecatrienoate), and others (Probable) (PubMed:26474213)

Protein Sequence

10 MTILTYPFKN 20 LPTASKWALR 30 FSIRPLSCSS 40 QLRAAPAVQT 50 KTKKTLAKPN 60 IRNVVVVDGV 70 RTPFLLSGTS 80 YKDLMPHDLA 90 RAALTGLLHR 100 TSVPKEVVDY 110 IIFGTVIQEV 120 KTSNVAREAA 130 LGAGFSDKTP 140 AHTVTMACIS 150 ANQAMTTGVG 160 LIASGQCDVI 170 VAGGVELMSD 180 VPIRHSRKMR 190 KLMLDLNKAK 200 SMGQRLSLIS 210 KFRFNFLAPE 220 LPAVSEFSTS 230 ETMGHSADRL 240 AAAFAVSRLE 250 QDEYALRSHS 260 LAKKAQDEGL 270 LSDVVPFKVP 280 GKDTVTKDNG 290 IRPSSLEQMA 300 KLKPAFIKPY 310 GTVTAANSSF 320 LTDGASAMLI 330 MAEEKALAMG 340 YKPKAYLRDF 350 MYVSQDPKDQ 360 LLLGPTYATP 370 KVLEKAGLTM 380 NDIDAFEFHE 390 AFSGQILANF 400 KAMDSDWFAE 410 NYMGRKTKVG 420 LPPLEKFNNW 430 GGSLSLGHPF 440 GATGCRLVMA 450 AANRLRKEGG 460 QYGLVAACAA 470 GGQGHAMIVE AYPK

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005783 endoplasmic reticulum
Cellular Component GO:0005743 mitochondrial inner membrane
Cellular Component GO:0042645 mitochondrial nucleoid
Cellular Component GO:0005741 mitochondrial outer membrane
Cellular Component GO:0005739 mitochondrion
Molecular Function GO:0003857 (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
Molecular Function GO:0003985 acetyl-CoA C-acetyltransferase activity
Molecular Function GO:0003988 acetyl-CoA C-acyltransferase activity
Molecular Function GO:0050633 acetyl-CoA C-myristoyltransferase activity
Molecular Function GO:0004300 enoyl-CoA hydratase activity
Molecular Function GO:0106222 lncRNA binding
Molecular Function GO:0044877 protein-containing complex binding
Molecular Function GO:0003723 RNA binding
Biological Process GO:0071222 cellular response to lipopolysaccharide
Biological Process GO:0006635 fatty acid beta-oxidation
Biological Process GO:0010467 gene expression
Cellular Component GO:0005740 mitochondrial envelope
Cellular Component GO:0016507 mitochondrial fatty acid beta-oxidation multienzyme complex

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.