Search Results

Overview

Uniprot IDQ8JZN5
Protein NameComplex I assembly factor ACAD9, mitochondrial
Gene NameAcad9
OrganismMus musculus

Kla Sites from experimental identification

Position Flanking peptide
104 IPVDTLEKLKSLGLF
206 RATLSEDKKYFILNG
242 VVDSDGSKTDKMTAF
460 TSRIKELKSGNVTTV
525 TLLLRFGKNIVEEQL
96 RKIDQEGKIPVDTLE

Function

Together with NDUFAF1 and ECSIT, forms part of the mitochondrial complex I (MCIA),which is required for the biogenesis of respiratory Complex I (CI) and is therefore crucial for the activation of the oxidative phosphorylation system. ECSIT binding triggers a large conformational change, switching ACAD9 from a fatty acid oxidation (FAO) enzyme to a CI assembly factor. The function in CI assembly is independent of the fatty acid oxidation (FAO) activity of the protein. As FAO enzyme, it catalyzes the first step in mitochondrial FAO, 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). Its preferred substrates are both saturated and unsaturated long-chain acyl-CoA substrates, with optimum activity toward the latter. 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. Among the different mitochondrial acyl-CoA dehydrogenases, its FAO activity overlaps with that of ACADV and ACADL, but plays a primary role in tissues where it is the main long-chain ACAD expressed. It differs significantly from ACADVL in the use of polyunsaturated substrates in vitro, especially docosahexaenoic acid (which is not primarily used for energy but mainly beta-oxidized in the peroxisomes)

Protein Sequence

10 MSGCVLLSRG 20 ATAAAAAARA 30 SRVLREFTAR 40 RRPLHTSLQS 50 CSFAKELFLG 60 NIEQKGVFPF 70 PEVSQHELSE 80 INQFVGPLEK 90 FFTEEVDSRK 100 IDQEGKIPVD 110 TLEKLKSLGL 120 FGIQVPEEYG 130 GLGLSNTMYA 140 RLGEIISLDA 150 SITVTLAAHQ 160 AIGLKGIILV 170 GNEEQKAKYL 180 PKLSSGEHIA 190 AFCLTEPASG 200 SDAASIQTRA 210 TLSEDKKYFI 220 LNGSKVWITN 230 GGLANIFTVF 240 AKTEVVDSDG 250 SKTDKMTAFI 260 VERDFGGITN 270 GKPEDKLGIR 280 GSNTCEVHFE 290 NTRVPVENVL 300 GEVGGGFKVA 310 MNILNSGRFS 320 MGSAVAGMLK 330 KLIELTAEYA 340 CTRKQFNRNL 350 SEFGLIQEKF 360 ALMAQKAYVM 370 ESMAYLTSGM 380 LDQPGFPDCS 390 IEAAMVKVFS 400 SEAAWQCVSE 410 ALQILGGSGY 420 MKDYPYERML 430 RDARILLIFE 440 GTNEILRLFI 450 ALTGLQHAGR 460 ILTSRIKELK 470 SGNVTTVMET 480 IGRKLRDSLG 490 RTVDLGLTGD 500 LGVVHPSLGD 510 SANKLEENVH 520 YFGRTVETLL 530 LRFGKNIVEE 540 QLVLKRVANI 550 LINLYGMTAV 560 LSRASRSIRI 570 GLRNHDHEVL 580 LANMFCVEAY 590 FQNLFSLSQL 600 DKNAPENLDE 610 QIKKVSRQIL 620 EKRAYICAHP LDRAS

Gene Ontology

Classification GO ID Description
Cellular Component GO:0030425 dendrite
Cellular Component GO:0160295 mitochondrial complex I intermediate assembly complex
Cellular Component GO:0031966 mitochondrial membrane
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005634 nucleus
Molecular Function GO:0003995 acyl-CoA dehydrogenase activity
Molecular Function GO:0050660 flavin adenine dinucleotide binding
Molecular Function GO:0004466 long-chain fatty acyl-CoA dehydrogenase activity
Molecular Function GO:0070991 medium-chain fatty acyl-CoA dehydrogenase activity
Molecular Function GO:0030674 protein-macromolecule adaptor activity
Molecular Function GO:0017099 very-long-chain fatty acyl-CoA dehydrogenase activity
Biological Process GO:0046395 carboxylic acid catabolic process
Biological Process GO:0001676 long-chain fatty acid metabolic process
Biological Process GO:0051791 medium-chain fatty acid metabolic process
Biological Process GO:0032981 mitochondrial respiratory chain complex I assembly

Reference

[1] 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.

[2] 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.