Search Results

Overview

Uniprot IDQ8BMS1
Protein NameTrifunctional enzyme subunit alpha, mitochondrial
Gene NameHadha
OrganismMus musculus

Kla Sites from experimental identification

Position Flanking peptide
129 EGQRMFEKLEKSPKP
135 EKLEKSPKPVVAAIS
166 RIATKDRKTVLGVPE
214 IRADRAKKMGLVDQL
262 KVSAKQSKGLVEKLT
284 FVRQQVYKTVEEKVK
289 VYKTVEEKVKKQTKG
295 EKVKKQTKGLYPAPL
303 GLYPAPLKIIDAVKA
309 LKIIDAVKAGLEQGS
326 GYLAESQKFGELALT
334 FGELALTKESKALMG
337 LALTKESKALMGLYN
350 YNGQVLCKKNKFGAP
353 QVLCKKNKFGAPQKN
390 KGLKTLLKDTTVTGL
406 RGQQQVFKGLNDKVK
411 VFKGLNDKVKKKALT
415 LNDKVKKKALTSFER
46 THINYGVKGDVAVIR
489 NQIAAVSKRPEKVIG
493 AVSKRPEKVIGMHYF
516 LEIITTDKTSKDTTA
519 ITTDKTSKDTTASAV
540 GKVIIVVKDGPGFYT
569 LQEGVDPKKLDALTT
60 RINSPNSKVNTLNKE
620 GGSVELLKQMVSKGF
625 LLKQMVSKGFLGRKS
631 SKGFLGRKSGKGFYI
634 FLGRKSGKGFYIYQE
644 YIYQEGSKNKSLNSE
646 YQEGSKNKSLNSEMD
664 ANLRLPAKPEVSSDE
728 VDLYGAQKVVDRLRK
759 DHANNSSKKFYQ***

Function

Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway. The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through cycles of four consecutive reactions. 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). These cycles repeat until the chain is fully degraded to acetyl-CoA units. 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. Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA described here carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities while the trifunctional enzyme subunit beta/HADHB bears the 3-ketoacyl-CoA thiolase activity. 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). 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. Independently of subunit beta, HADHA also exhibits a cardiolipin acyltransferase activity that participates in cardiolipin remodeling; cardiolipin is a major mitochondrial membrane phospholipid. HADHA may act downstream of Tafazzin/TAZ, that remodels monolysocardiolipin (MLCL) to a cardiolipin intermediate, and then HADHA may continue to remodel this species into mature tetralinoleoyl-cardiolipin. Has also been proposed to act directly on MLCL; capable of acylating MLCL using different acyl-CoA substrates, with highest activity for oleoyl-CoA

Protein Sequence

10 MVASRAIGSL 20 SRFSAFRILR 30 SRGCICRSFT 40 TSSALLTRTH 50 INYGVKGDVA 60 VIRINSPNSK 70 VNTLNKEVQS 80 EFIEVMNEIW 90 ANDQIRSAVL 100 ISSKPGCFVA 110 GADINMLSSC 120 TTPQEATRIS 130 QEGQRMFEKL 140 EKSPKPVVAA 150 ISGSCLGGGL 160 ELAIACQYRI 170 ATKDRKTVLG 180 VPEVLLGILP 190 GAGGTQRLPK 200 MVGVPAAFDM 210 MLTGRNIRAD 220 RAKKMGLVDQ 230 LVEPLGPGIK 240 SPEERTIEYL 250 EEVAVNFAKG 260 LADRKVSAKQ 270 SKGLVEKLTT 280 YAMTVPFVRQ 290 QVYKTVEEKV 300 KKQTKGLYPA 310 PLKIIDAVKA 320 GLEQGSDAGY 330 LAESQKFGEL 340 ALTKESKALM 350 GLYNGQVLCK 360 KNKFGAPQKN 370 VQQLAILGAG 380 LMGAGIAQVS 390 VDKGLKTLLK 400 DTTVTGLGRG 410 QQQVFKGLND 420 KVKKKALTSF 430 ERDSIFSNLI 440 GQLDYKGFEK 450 ADMVIEAVFE 460 DLGVKHKVLK 470 EVESVTPEHC 480 IFASNTSALP 490 INQIAAVSKR 500 PEKVIGMHYF 510 SPVDKMQLLE 520 IITTDKTSKD 530 TTASAVAVGL 540 RQGKVIIVVK 550 DGPGFYTTRC 560 LAPMMSEVMR 570 ILQEGVDPKK 580 LDALTTGFGF 590 PVGAATLADE 600 VGVDVAQHVA 610 EDLGKAFGER 620 FGGGSVELLK 630 QMVSKGFLGR 640 KSGKGFYIYQ 650 EGSKNKSLNS 660 EMDNILANLR 670 LPAKPEVSSD 680 EDVQYRVITR 690 FVNEAVLCLQ 700 EGILATPAEG 710 DIGAVFGLGF 720 PPCLGGPFRF 730 VDLYGAQKVV 740 DRLRKYESAY 750 GTQFTPCQLL 760 LDHANNSSKK FYQ

Gene Ontology

Classification GO ID Description
Cellular Component GO:0016507 mitochondrial fatty acid beta-oxidation multienzyme complex
Cellular Component GO:0005743 mitochondrial inner membrane
Cellular Component GO:0042645 mitochondrial nucleoid
Cellular Component GO:0005739 mitochondrion
Molecular Function GO:0003857 (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
Molecular Function GO:0018812 3-hydroxyacyl-CoA dehydratase activity
Molecular Function GO:0003988 acetyl-CoA C-acyltransferase activity
Molecular Function GO:0004300 enoyl-CoA hydratase activity
Molecular Function GO:0000062 fatty-acyl-CoA binding
Molecular Function GO:0016509 long-chain (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
Molecular Function GO:0052816 long-chain fatty acyl-CoA hydrolase activity
Molecular Function GO:0051287 NAD binding
Molecular Function GO:0070403 NAD+ binding
Molecular Function GO:0044877 protein-containing complex binding
Biological Process GO:0035965 cardiolipin acyl-chain remodeling
Biological Process GO:0006635 fatty acid beta-oxidation
Biological Process GO:0032868 response to insulin
Biological Process GO:0009410 response to xenobiotic stimulus

Reference

[1] Chang J, Wu W, Qian P, Lu Z, He X et al.. Multi-omics study on the effect of moderate-intensity exercise on protein lactylation in mouse muscle tissue.. Front Cell Dev Biol 12:1472338. 2024. PMID: 39935788.

[2] Zhuo W, Zhang M, Tan J, Gao Y, Wang Y et al.. Lysine lactylation analysis of proteins in the heart of the Kawasaki disease mouse model.. Front Cell Dev Biol 13:1550220. 2025. PMID: 40114965.

[3] Wu D, Tang Y, Li X, Xiong S, Zhang Z et al.. Characterization of protein lactylation in healthy and ischemic mouse hearts.. Front Cardiovasc Med 12:1644886. 2025. PMID: 41089239.