Search Results

Overview

Uniprot ID	B1WC61
Protein Name	Complex I assembly factor ACAD9, mitochondrial
Gene Name	Acad9
Organism	Rattus norvegicus

Kla Sites from experimental identification

Position	Flanking peptide
243	VDSDGSIKDKMTAFI
96	RKIDQEGKIPADTLA

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 MSGYVLFSRG 20 ATAAAAAARA 30 SRVLRVFTER 40 RRTLHTSLQS 50 CSFAKELFLG 60 HIQQKGVFPF 70 PEVSQEELSE 80 INQFVGPLEK 90 FFNEEVDSRK 100 IDQEGKIPAD 110 TLAKLKSLGL 120 FGIQVPEEYG 130 GLGLSNTMYA 140 RLGEIISMDA 150 SITVTLAAHQ 160 AIGLKGIILV 170 GNEEQKAKYL 180 PKLSSGEHIA 190 AFCLTEPASG 200 SDAASIQTRA 210 TLSEDKKYFV 220 LNGSKVWITN 230 GGLANIFTVF 240 AKTEVVDSDG 250 SIKDKMTAFI 260 VERDFGGITN 270 GKPEDKLGIR 280 GSNTCEVHFE 290 NTRVPVENVL 300 GEVGGGFKVA 310 MNILNSGRFS 320 MGSAVAGMLK 330 KLIEQTAEYA 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 RTVDLGLSSN 500 IAVVHPSLGD 510 SANKLEENVH 520 YFGRTVETLL 530 LRFGKTIVEE 540 QLVLKRVANI 550 LINLYGMTAV 560 LSRASRSIRI 570 GLKNHDHEIL 580 LANMFCVEAY 590 FQNLFSLSQL 600 DKYAPENLDE 610 QIKKVSQQIL 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
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] Yao Y, Bade R, Li G, Zhang A, Zhao H et al.. Global-Scale Profiling of Differential Expressed Lysine-Lactylated Proteins in the Cerebral Endothelium of Cerebral Ischemia-Reperfusion Injury Rats.. Cell Mol Neurobiol 43(5):1989-2004. 2023 Jul. PMID: 36030297.

[2] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.