Search Results

Overview

Uniprot ID	Q9H845
Protein Name	Complex I assembly factor ACAD9, mitochondrial
Gene Name	ACAD9
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
239	VDSDGSVKDKITAFI
41	PPVRAFAKELFLGKI
47	AKELFLGKIKKKEVF
608	VSQQILEKRAYICAH

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 (PubMed:20816094, PubMed:24158852, PubMed:32320651, PubMed:38086790). ECSIT binding triggers a large conformational change, switching ACAD9 from a fatty acid oxidation (FAO) enzyme to a CI assembly factor (PubMed:38086790). The function in CI assembly is independent of the fatty acid oxidation (FAO) activity of the protein (PubMed:24158852). 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) (PubMed:12359260, PubMed:16020546, PubMed:17564966, PubMed:21237683, PubMed:24158852). Its preferred substrates are both saturated and unsaturated long-chain acyl-CoA substrates, with optimum activity toward the latter (PubMed:12359260, PubMed:16020546, PubMed:17564966, PubMed:21237683, PubMed:24158852). 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 ACADV and ACADL, but plays a primary role in tissues where it is the main long-chain ACAD expressed, such as the central nervous system (PubMed:16020546, PubMed:17564966, PubMed:24158852, PubMed:25721401, PubMed:26474213). 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) (PubMed:16020546, PubMed:17564966)

Protein Sequence

10 MSGCGLFLRT 20 TAAARACRGL 30 VVSTANRRLL 40 RTSPPVRAFA 50 KELFLGKIKK 60 KEVFPFPEVS 70 QDELNEINQF 80 LGPVEKFFTE 90 EVDSRKIDQE 100 GKIPDETLEK 110 LKSLGLFGLQ 120 VPEEYGGLGF 130 SNTMYSRLGE 140 IISMDGSITV 150 TLAAHQAIGL 160 KGIILAGTEE 170 QKAKYLPKLA 180 SGEHIAAFCL 190 TEPASGSDAA 200 SIRSRATLSE 210 DKKHYILNGS 220 KVWITNGGLA 230 NIFTVFAKTE 240 VVDSDGSVKD 250 KITAFIVERD 260 FGGVTNGKPE 270 DKLGIRGSNT 280 CEVHFENTKI 290 PVENILGEVG 300 DGFKVAMNIL 310 NSGRFSMGSV 320 VAGLLKRLIE 330 MTAEYACTRK 340 QFNKRLSEFG 350 LIQEKFALMA 360 QKAYVMESMT 370 YLTAGMLDQP 380 GFPDCSIEAA 390 MVKVFSSEAA 400 WQCVSEALQI 410 LGGLGYTRDY 420 PYERILRDTR 430 ILLIFEGTNE 440 ILRMYIALTG 450 LQHAGRILTT 460 RIHELKQAKV 470 STVMDTVGRR 480 LRDSLGRTVD 490 LGLTGNHGVV 500 HPSLADSANK 510 FEENTYCFGR 520 TVETLLLRFG 530 KTIMEEQLVL 540 KRVANILINL 550 YGMTAVLSRA 560 SRSIRIGLRN 570 HDHEVLLANT 580 FCVEAYLQNL 590 FSLSQLDKYA 600 PENLDEQIKK 610 VSQQILEKRA 620 YICAHPLDRT C

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0030425	dendrite
Cellular Component	GO:0160295	mitochondrial complex I intermediate assembly complex
Cellular Component	GO:0005743	mitochondrial inner membrane
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: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] 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.