Search Results

Overview

Uniprot IDP49748
Protein NameVery long-chain acyl-CoA dehydrogenase, mitochondrial
Gene NameACADVL
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
195 GILLFGTKAQKEKYL
204 QKEKYLPKLASGETV
239 AVPSPCGKYYTLNGS
276 DPATGAVKEKITAFV
278 ATGAVKEKITAFVVE
298 ITHGPPEKKMGIKAS
358 TMRGIIAKAVDHATN
372 NRTQFGEKIHNFGLI
382 NFGLIQEKLARMVML
482 QGCMDKGKELSGLGS
550 FATVVEAKLIKHKKG
556 AKLIKHKKGIVNEQF
639 RNFKSISKALVERGG

Function

Catalyzes the first of the four reactions of the mitochondrial fatty acid beta-oxidation (FAO) pathway, which consists in the proR-proR stereospecific alpha, beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physiologic electron acceptor, resulting in the formation of trans-2-enoyl-CoA ((2E)-enoyl-CoA) (PubMed:17564966, PubMed:18227065, PubMed:26474213, PubMed:7668252, PubMed:9461620, PubMed:9599005, PubMed:9839948). The mitochondrial FAO pathway is the major energy-producing process in tissues and is performed through cycles of four consecutive reactions (PubMed:26474213, PubMed:7668252). Each FAO 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:7668252). Among the different mitochondrial acyl-CoA dehydrogenases, very long-chain specific acyl-CoA dehydrogenase acts specifically on fatty acyl-CoAs with saturated 12 to 24 carbons long primary chains (PubMed:17564966, PubMed:21237683, PubMed:9839948), but can also catalyze monounsaturated fatty acids such as oleate ((9Z)-octadecenoate), (9Z)-hexadecenoate, and others (PubMed:17564966). Can use (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate as substrate in vitro (which is not primarily used for energy but mainly beta-oxidized in the peroxisomes) (PubMed:17564966, PubMed:26474213). In addition, based on its established catalytic mechanism, and combined genetic interaction or mutant phenotype evidence, it is predicted to act also on substrates that have not been tested experimentally but are metabolized by mitochondrial FAO, including long-chain unsaturated fatty acids such as linoleate (9Z,12Z-octadecadienoate), linolenate (9Z,12Z,15Z-octadecatrienoate), and others (PubMed:26474213). Among the different mitochondrial acyl-CoA dehydrogenases, its FAO activity overlaps with that of ACAD9 and ACADL, but plays a primary role in tissues where it is the main long-chain ACAD expressed, such as the heart and skeletal muscle (PubMed:17564966)

Protein Sequence

10 MQAARMAASL 20 GRQLLRLGGG 30 SSRLTALLGQ 40 PRPGPARRPY 50 AGGAAQLALD 60 KSDSHPSDAL 70 TRKKPAKAES 80 KSFAVGMFKG 90 QLTTDQVFPY 100 PSVLNEEQTQ 110 FLKELVEPVS 120 RFFEEVNDPA 130 KNDALEMVEE 140 TTWQGLKELG 150 AFGLQVPSEL 160 GGVGLCNTQY 170 ARLVEIVGMH 180 DLGVGITLGA 190 HQSIGFKGIL 200 LFGTKAQKEK 210 YLPKLASGET 220 VAAFCLTEPS 230 SGSDAASIRT 240 SAVPSPCGKY 250 YTLNGSKLWI 260 SNGGLADIFT 270 VFAKTPVTDP 280 ATGAVKEKIT 290 AFVVERGFGG 300 ITHGPPEKKM 310 GIKASNTAEV 320 FFDGVRVPSE 330 NVLGEVGSGF 340 KVAMHILNNG 350 RFGMAAALAG 360 TMRGIIAKAV 370 DHATNRTQFG 380 EKIHNFGLIQ 390 EKLARMVMLQ 400 YVTESMAYMV 410 SANMDQGATD 420 FQIEAAISKI 430 FGSEAAWKVT 440 DECIQIMGGM 450 GFMKEPGVER 460 VLRDLRIFRI 470 FEGTNDILRL 480 FVALQGCMDK 490 GKELSGLGSA 500 LKNPFGNAGL 510 LLGEAGKQLR 520 RRAGLGSGLS 530 LSGLVHPELS 540 RSGELAVRAL 550 EQFATVVEAK 560 LIKHKKGIVN 570 EQFLLQRLAD 580 GAIDLYAMVV 590 VLSRASRSLS 600 EGHPTAQHEK 610 MLCDTWCIEA 620 AARIREGMAA 630 LQSDPWQQEL 640 YRNFKSISKA 650 LVERGGVVTS NPLGF

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005743 mitochondrial inner membrane
Cellular Component GO:0005759 mitochondrial matrix
Cellular Component GO:0031966 mitochondrial membrane
Cellular Component GO:0042645 mitochondrial nucleoid
Cellular Component GO:0005739 mitochondrion
Molecular Function GO:0003995 acyl-CoA dehydrogenase activity
Molecular Function GO:0000062 fatty-acyl-CoA binding
Molecular Function GO:0050660 flavin adenine dinucleotide binding
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0004466 long-chain fatty acyl-CoA dehydrogenase activity
Molecular Function GO:0017099 very-long-chain fatty acyl-CoA dehydrogenase activity
Biological Process GO:0015980 energy derivation by oxidation of organic compounds
Biological Process GO:0030855 epithelial cell differentiation
Biological Process GO:0033539 fatty acid beta-oxidation using acyl-CoA dehydrogenase
Biological Process GO:0045717 negative regulation of fatty acid biosynthetic process
Biological Process GO:0046322 negative regulation of fatty acid oxidation
Biological Process GO:0090181 regulation of cholesterol metabolic process
Biological Process GO:0001659 temperature homeostasis

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] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.

[4] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.

[5] 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.

[6] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.