ID ACAD9_HUMAN Reviewed; 621 AA. AC Q9H845; D3DNB8; Q8WXX3; DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 02-OCT-2024, entry version 194. DE RecName: Full=Complex I assembly factor ACAD9, mitochondrial {ECO:0000303|PubMed:24158852}; DE AltName: Full=Acyl-CoA dehydrogenase family member 9 {ECO:0000303|PubMed:12359260}; DE Short=ACAD-9 {ECO:0000303|PubMed:12359260}; DE EC=1.3.8.- {ECO:0000269|PubMed:12359260, ECO:0000269|PubMed:16020546, ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:24158852}; DE Flags: Precursor; GN Name=ACAD9 {ECO:0000312|HGNC:HGNC:21497}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE RP SPECIFICITY. RC TISSUE=Dendritic cell; RX PubMed=12359260; DOI=10.1016/s0006-291x(02)02336-7; RA Zhang J., Zhang W., Zou D., Chen G., Wan T., Zhang M., Cao X.; RT "Cloning and functional characterization of ACAD-9, a novel member of human RT acyl-CoA dehydrogenase family."; RL Biochem. Biophys. Res. Commun. 297:1033-1042(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, SUBSTRATE SPECIFICITY, CATALYTIC ACTIVITY, COFACTOR, RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND CLEAVAGE RP OF TRANSIT PEPTIDE AFTER ARG-37. RX PubMed=16020546; DOI=10.1074/jbc.m504460200; RA Ensenauer R., He M., Willard J.M., Goetzman E.S., Corydon T.J., RA Vandahl B.B., Mohsen A.W., Isaya G., Vockley J.; RT "Human acyl-CoA dehydrogenase-9 plays a novel role in the mitochondrial RT beta-oxidation of unsaturated fatty acids."; RL J. Biol. Chem. 280:32309-32316(2005). RN [6] RP INVOLVEMENT IN MC1DN20. RX PubMed=17564966; DOI=10.1086/519219; RA He M., Rutledge S.L., Kelly D.R., Palmer C.A., Murdoch G., Majumder N., RA Nicholls R.D., Pei Z., Watkins P.A., Vockley J.; RT "A new genetic disorder in mitochondrial fatty acid beta-oxidation: ACAD9 RT deficiency."; RL Am. J. Hum. Genet. 81:87-103(2007). RN [7] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-41, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NDUFAF1 AND ECSIT, RP INVOLVEMENT IN MC1DN20, AND VARIANTS MC1DN20 LYS-413 AND HIS-518. RX PubMed=20816094; DOI=10.1016/j.cmet.2010.08.002; RA Nouws J., Nijtmans L., Houten S.M., van den Brand M., Huynen M., RA Venselaar H., Hoefs S., Gloerich J., Kronick J., Hutchin T., Willems P., RA Rodenburg R., Wanders R., van den Heuvel L., Smeitink J., Vogel R.O.; RT "Acyl-CoA dehydrogenase 9 is required for the biogenesis of oxidative RT phosphorylation complex I."; RL Cell Metab. 12:283-294(2010). RN [9] RP INVOLVEMENT IN MC1DN20, AND VARIANTS MC1DN20 ILE-44; TRP-193; PHE-234; RP GLN-266; SER-303; THR-326; CYS-417 AND TRP-532. RX PubMed=21057504; DOI=10.1038/ng.706; RA Haack T.B., Danhauser K., Haberberger B., Hoser J., Strecker V., Boehm D., RA Uziel G., Lamantea E., Invernizzi F., Poulton J., Rolinski B., Iuso A., RA Biskup S., Schmidt T., Mewes H.W., Wittig I., Meitinger T., Zeviani M., RA Prokisch H.; RT "Exome sequencing identifies ACAD9 mutations as a cause of complex I RT deficiency."; RL Nat. Genet. 42:1131-1134(2010). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY. RX PubMed=21237683; DOI=10.1016/j.ymgme.2010.12.005; RA He M., Pei Z., Mohsen A.W., Watkins P., Murdoch G., Van Veldhoven P.P., RA Ensenauer R., Vockley J.; RT "Identification and characterization of new long chain acyl-CoA RT dehydrogenases."; RL Mol. Genet. Metab. 102:418-429(2011). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF GLU-426. RX PubMed=24158852; DOI=10.1093/hmg/ddt521; RA Nouws J., Te Brinke H., Nijtmans L.G., Houten S.M.; RT "ACAD9, a complex I assembly factor with a moonlighting function in fatty RT acid oxidation deficiencies."; RL Hum. Mol. Genet. 23:1311-1319(2014). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [15] RP IDENTIFICATION IN THE MCIA COMPLEX, AND FUNCTION. RX PubMed=32320651; DOI=10.1016/j.celrep.2020.107541; RA Formosa L.E., Muellner-Wong L., Reljic B., Sharpe A.J., Jackson T.D., RA Beilharz T.H., Stojanovski D., Lazarou M., Stroud D.A., Ryan M.T.; RT "Dissecting the Roles of Mitochondrial Complex I Intermediate Assembly RT Complex Factors in the Biogenesis of Complex I."; RL Cell Rep. 31:107541-107541(2020). RN [16] RP INTERACTION WITH TMEM70 AND TMEM242. RX PubMed=33753518; DOI=10.1073/pnas.2100558118; RA Carroll J., He J., Ding S., Fearnley I.M., Walker J.E.; RT "TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase RT and interact with assembly factors for complex I."; RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021). RN [17] RP VARIANTS MC1DN20 LYS-127; TRP-469 AND TRP-532. RX PubMed=20929961; DOI=10.1093/brain/awq273; RA Gerards M., van den Bosch B.J., Danhauser K., Serre V., van Weeghel M., RA Wanders R.J., Nicolaes G.A., Sluiter W., Schoonderwoerd K., Scholte H.R., RA Prokisch H., Rotig A., de Coo I.F., Smeets H.J.; RT "Riboflavin-responsive oxidative phosphorylation complex I deficiency RT caused by defective ACAD9: new function for an old gene."; RL Brain 134:210-219(2011). RN [18] RP VARIANT MC1DN20 TRP-532. RX PubMed=22499348; DOI=10.1136/jmedgenet-2012-100846; RA Haack T.B., Haberberger B., Frisch E.M., Wieland T., Iuso A., Gorza M., RA Strecker V., Graf E., Mayr J.A., Herberg U., Hennermann J.B., Klopstock T., RA Kuhn K.A., Ahting U., Sperl W., Wilichowski E., Hoffmann G.F., Tesarova M., RA Hansikova H., Zeman J., Plecko B., Zeviani M., Wittig I., Strom T.M., RA Schuelke M., Freisinger P., Meitinger T., Prokisch H.; RT "Molecular diagnosis in mitochondrial complex I deficiency using exome RT sequencing."; RL J. Med. Genet. 49:277-283(2012). RN [19] RP VARIANT MC1DN20 CYS-414. RX PubMed=23836383; DOI=10.1001/jamaneurol.2013.3197; RA Garone C., Donati M.A., Sacchini M., Garcia-Diaz B., Bruno C., Calvo S., RA Mootha V.K., Dimauro S.; RT "Mitochondrial encephalomyopathy due to a novel mutation in ACAD9."; RL JAMA Neurol. 70:1177-1179(2013). RN [20] RP VARIANT MC1DN20 VAL-220. RX PubMed=23996478; DOI=10.1007/8904_2013_242; RA Nouws J., Wibrand F., van den Brand M., Venselaar H., Duno M., Lund A.M., RA Trautner S., Nijtmans L., Ostergard E.; RT "A patient with complex I deficiency caused by a novel ACAD9 mutation not RT responding to riboflavin treatment."; RL JIMD Rep. 12:37-45(2014). RN [21] RP VARIANTS MC1DN20 GLY-271; MET-384 AND HIS-606. RX PubMed=26741492; DOI=10.1371/journal.pgen.1005679; RA Kohda M., Tokuzawa Y., Kishita Y., Nyuzuki H., Moriyama Y., Mizuno Y., RA Hirata T., Yatsuka Y., Yamashita-Sugahara Y., Nakachi Y., Kato H., RA Okuda A., Tamaru S., Borna N.N., Banshoya K., Aigaki T., Sato-Miyata Y., RA Ohnuma K., Suzuki T., Nagao A., Maehata H., Matsuda F., Higasa K., RA Nagasaki M., Yasuda J., Yamamoto M., Fushimi T., Shimura M., RA Kaiho-Ichimoto K., Harashima H., Yamazaki T., Mori M., Murayama K., RA Ohtake A., Okazaki Y.; RT "A comprehensive genomic analysis reveals the genetic landscape of RT mitochondrial respiratory chain complex deficiencies."; RL PLoS Genet. 12:E1005679-E1005679(2016). CC -!- FUNCTION: As part of the MCIA complex, primarily participates in the CC assembly of the mitochondrial complex I and therefore plays a role in CC oxidative phosphorylation (PubMed:20816094, PubMed:24158852, CC PubMed:32320651). This moonlighting protein has also a dehydrogenase CC activity toward a broad range of substrates with greater specificity CC for long-chain unsaturated acyl-CoAs (PubMed:12359260, PubMed:16020546, CC PubMed:21237683, PubMed:24158852). However, in vivo, it does not seem CC to play a primary role in fatty acid oxidation (PubMed:20816094, CC PubMed:24158852). In addition, the function in complex I assembly is CC independent of the dehydrogenase activity of the protein CC (PubMed:24158852). {ECO:0000269|PubMed:12359260, CC ECO:0000269|PubMed:16020546, ECO:0000269|PubMed:20816094, CC ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:24158852, CC ECO:0000269|PubMed:32320651}. CC -!- CATALYTIC ACTIVITY: CC Reaction=eicosanoyl-CoA + H(+) + oxidized [electron-transfer CC flavoprotein] = (2E)-eicosenoyl-CoA + reduced [electron-transfer CC flavoprotein]; Xref=Rhea:RHEA:47236, Rhea:RHEA-COMP:10685, Rhea:RHEA- CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57380, ChEBI:CHEBI:57692, CC ChEBI:CHEBI:58307, ChEBI:CHEBI:74691; CC Evidence={ECO:0000269|PubMed:16020546, ECO:0000269|PubMed:21237683}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47237; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + octadecanoyl-CoA + oxidized [electron-transfer CC flavoprotein] = (2E)-octadecenoyl-CoA + reduced [electron-transfer CC flavoprotein]; Xref=Rhea:RHEA:47240, Rhea:RHEA-COMP:10685, Rhea:RHEA- CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57394, ChEBI:CHEBI:57692, CC ChEBI:CHEBI:58307, ChEBI:CHEBI:71412; CC Evidence={ECO:0000269|PubMed:12359260, ECO:0000269|PubMed:16020546, CC ECO:0000269|PubMed:21237683}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47241; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + hexadecanoyl-CoA + oxidized [electron-transfer CC flavoprotein] = (2E)-hexadecenoyl-CoA + reduced [electron-transfer CC flavoprotein]; Xref=Rhea:RHEA:43448, Rhea:RHEA-COMP:10685, Rhea:RHEA- CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57379, ChEBI:CHEBI:57692, CC ChEBI:CHEBI:58307, ChEBI:CHEBI:61526; CC Evidence={ECO:0000269|PubMed:12359260, ECO:0000269|PubMed:16020546, CC ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:24158852}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43449; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- CATALYTIC ACTIVITY: CC Reaction=decanoyl-CoA + H(+) + oxidized [electron-transfer CC flavoprotein] = (2E)-decenoyl-CoA + reduced [electron-transfer CC flavoprotein]; Xref=Rhea:RHEA:48176, Rhea:RHEA-COMP:10685, Rhea:RHEA- CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, CC ChEBI:CHEBI:61406, ChEBI:CHEBI:61430; CC Evidence={ECO:0000269|PubMed:16020546}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48177; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + nonanoyl-CoA + oxidized [electron-transfer CC flavoprotein] = (2E)-nonenoyl-CoA + reduced [electron-transfer CC flavoprotein]; Xref=Rhea:RHEA:48208, Rhea:RHEA-COMP:10685, Rhea:RHEA- CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, CC ChEBI:CHEBI:76291, ChEBI:CHEBI:76292; CC Evidence={ECO:0000269|PubMed:16020546}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48209; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + oxidized [electron-transfer flavoprotein] + CC pentadecanoyl-CoA = (2E)-pentadecenoyl-CoA + reduced [electron- CC transfer flavoprotein]; Xref=Rhea:RHEA:48204, Rhea:RHEA-COMP:10685, CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, CC ChEBI:CHEBI:58307, ChEBI:CHEBI:74309, ChEBI:CHEBI:77545; CC Evidence={ECO:0000269|PubMed:16020546}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48205; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + oxidized [electron-transfer flavoprotein] + undecanoyl- CC CoA = reduced [electron-transfer flavoprotein] + trans-2-undecenoyl- CC CoA; Xref=Rhea:RHEA:48200, Rhea:RHEA-COMP:10685, Rhea:RHEA- CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, CC ChEBI:CHEBI:77547, ChEBI:CHEBI:77548; CC Evidence={ECO:0000269|PubMed:16020546}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48201; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(9Z)-hexadecenoyl-CoA + H(+) + oxidized [electron-transfer CC flavoprotein] = (2E,9Z)-hexadecadienoyl-CoA + reduced [electron- CC transfer flavoprotein]; Xref=Rhea:RHEA:47304, Rhea:RHEA-COMP:10685, CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, CC ChEBI:CHEBI:58307, ChEBI:CHEBI:61540, ChEBI:CHEBI:77549; CC Evidence={ECO:0000269|PubMed:16020546}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47305; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + heptadecanoyl-CoA + oxidized [electron-transfer CC flavoprotein] = reduced [electron-transfer flavoprotein] + trans-2- CC heptadecenoyl-CoA; Xref=Rhea:RHEA:48196, Rhea:RHEA-COMP:10685, CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, CC ChEBI:CHEBI:58307, ChEBI:CHEBI:74307, ChEBI:CHEBI:77551; CC Evidence={ECO:0000269|PubMed:16020546}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48197; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(9E)-octadecenoyl-CoA + H(+) + oxidized [electron-transfer CC flavoprotein] = (2E,9E)-octadecadienoyl-CoA + reduced [electron- CC transfer flavoprotein]; Xref=Rhea:RHEA:48192, Rhea:RHEA-COMP:10685, CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, CC ChEBI:CHEBI:58307, ChEBI:CHEBI:77537, ChEBI:CHEBI:77552; CC Evidence={ECO:0000269|PubMed:16020546}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48193; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(9Z)-octadecenoyl-CoA + H(+) + oxidized [electron-transfer CC flavoprotein] = (2E,9Z)-octadecadienoyl-CoA + reduced [electron- CC transfer flavoprotein]; Xref=Rhea:RHEA:47300, Rhea:RHEA-COMP:10685, CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57387, CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:77553; CC Evidence={ECO:0000269|PubMed:16020546}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47301; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(9Z,12Z)-octadecadienoyl-CoA + H(+) + oxidized [electron- CC transfer flavoprotein] = (2E,9Z,12Z)-octadecatrienoyl-CoA + reduced CC [electron-transfer flavoprotein]; Xref=Rhea:RHEA:48188, Rhea:RHEA- CC COMP:10685, Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57383, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, CC ChEBI:CHEBI:77558; Evidence={ECO:0000269|PubMed:16020546}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48189; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + H(+) + oxidized CC [electron-transfer flavoprotein] = (2E,4Z,7Z,10Z,13Z,16Z,19Z)- CC docosaheptaenoyl-CoA + reduced [electron-transfer flavoprotein]; CC Xref=Rhea:RHEA:48184, Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, CC ChEBI:CHEBI:74298, ChEBI:CHEBI:77559; CC Evidence={ECO:0000269|PubMed:16020546}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48185; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + oxidized [electron-transfer flavoprotein] + CC tetradecanoyl-CoA = (2E)-tetradecenoyl-CoA + reduced [electron- CC transfer flavoprotein]; Xref=Rhea:RHEA:47316, Rhea:RHEA-COMP:10685, CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57385, CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:61405; CC Evidence={ECO:0000269|PubMed:21237683}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47317; CC Evidence={ECO:0000305|PubMed:24158852}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000305|PubMed:16020546}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=2.8 uM for hexadecanoyl-CoA {ECO:0000269|PubMed:16020546}; CC KM=0.7 uM for (9Z)-hexadecenoyl-CoA {ECO:0000269|PubMed:16020546}; CC KM=2.1 uM for (9Z,12Z)-octadecadienoyl-CoA CC {ECO:0000269|PubMed:16020546}; CC -!- SUBUNIT: Homodimer (PubMed:16020546). Interacts with NDUFAF1 and ECSIT CC (PubMed:20816094). Part of the mitochondrial complex I assembly/MCIA CC complex that comprises at least the core subunits TMEM126B, NDUFAF1, CC ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186 CC (PubMed:32320651). Interacts with TMEM70 and TMEM242 (PubMed:33753518). CC {ECO:0000269|PubMed:16020546, ECO:0000269|PubMed:20816094, CC ECO:0000269|PubMed:32320651, ECO:0000269|PubMed:33753518}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:16020546, ECO:0000269|PubMed:20816094}; Peripheral CC membrane protein {ECO:0000269|PubMed:16020546}; Matrix side CC {ECO:0000269|PubMed:16020546}. Note=Essentially associated with CC membranes. {ECO:0000269|PubMed:16020546}. CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in most normal human tissues CC and cancer cell lines with high level of expression in heart, skeletal CC muscles, brain, kidney and liver (PubMed:12359260). In the cerebellum CC uniquely expressed in the granular layer (at protein level) CC (PubMed:21237683). {ECO:0000269|PubMed:12359260, CC ECO:0000269|PubMed:21237683}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 20 (MC1DN20) CC [MIM:611126]: An autosomal recessive metabolic disorder associated with CC mitochondrial complex I deficiency, resulting in multisystemic and CC variable manifestations. Clinical features include infantile onset of CC acute metabolic acidosis, Reye-like episodes (brain edema and vomiting CC that may rapidly progress to seizures, coma and death), exercise CC intolerance, hypertrophic cardiomyopathy, liver failure, muscle CC weakness, and neurologic dysfunction. {ECO:0000269|PubMed:17564966, CC ECO:0000269|PubMed:20816094, ECO:0000269|PubMed:20929961, CC ECO:0000269|PubMed:21057504, ECO:0000269|PubMed:22499348, CC ECO:0000269|PubMed:23836383, ECO:0000269|PubMed:23996478, CC ECO:0000269|PubMed:26741492}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF327351; AAL56011.1; -; mRNA. DR EMBL; AK024012; BAB14775.1; -; mRNA. DR EMBL; CH471052; EAW79295.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79296.1; -; Genomic_DNA. DR EMBL; BC013354; AAH13354.1; -; mRNA. DR EMBL; BC007970; AAH07970.1; -; mRNA. DR CCDS; CCDS3053.1; -. DR PIR; JC7892; JC7892. DR RefSeq; NP_054768.2; NM_014049.4. DR PDB; 8PHE; EM; 3.10 A; A/B=38-621. DR PDB; 8PHF; EM; 3.60 A; A/B=38-621. DR PDBsum; 8PHE; -. DR PDBsum; 8PHF; -. DR AlphaFoldDB; Q9H845; -. DR EMDB; EMD-17659; -. DR EMDB; EMD-17660; -. DR EMDB; EMD-17661; -. DR SASBDB; Q9H845; -. DR SMR; Q9H845; -. DR BioGRID; 118799; 448. DR ComplexPortal; CPX-6322; Mitochondrial complex I intermediate assembly (MCIA) complex. DR DIP; DIP-53699N; -. DR IntAct; Q9H845; 120. DR MINT; Q9H845; -. DR STRING; 9606.ENSP00000312618; -. DR SwissLipids; SLP:000000619; -. DR GlyGen; Q9H845; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q9H845; -. DR MetOSite; Q9H845; -. DR PhosphoSitePlus; Q9H845; -. DR SwissPalm; Q9H845; -. DR BioMuta; ACAD9; -. DR DMDM; 32469596; -. DR jPOST; Q9H845; -. DR MassIVE; Q9H845; -. DR PaxDb; 9606-ENSP00000312618; -. DR PeptideAtlas; Q9H845; -. DR ProteomicsDB; 81177; -. DR Pumba; Q9H845; -. DR Antibodypedia; 33213; 202 antibodies from 25 providers. DR DNASU; 28976; -. DR Ensembl; ENST00000308982.12; ENSP00000312618.7; ENSG00000177646.20. DR Ensembl; ENST00000681583.1; ENSP00000506340.1; ENSG00000177646.20. DR GeneID; 28976; -. DR KEGG; hsa:28976; -. DR MANE-Select; ENST00000308982.12; ENSP00000312618.7; NM_014049.5; NP_054768.2. DR UCSC; uc003ela.5; human. DR AGR; HGNC:21497; -. DR CTD; 28976; -. DR DisGeNET; 28976; -. DR GeneCards; ACAD9; -. DR HGNC; HGNC:21497; ACAD9. DR HPA; ENSG00000177646; Low tissue specificity. DR MalaCards; ACAD9; -. DR MIM; 611103; gene. DR MIM; 611126; phenotype. DR neXtProt; NX_Q9H845; -. DR OpenTargets; ENSG00000177646; -. DR Orphanet; 99901; Acyl-CoA dehydrogenase 9 deficiency. DR PharmGKB; PA134900655; -. DR VEuPathDB; HostDB:ENSG00000177646; -. DR eggNOG; KOG0137; Eukaryota. DR GeneTree; ENSGT00940000157312; -. DR HOGENOM; CLU_018204_11_2_1; -. DR InParanoid; Q9H845; -. DR OMA; CLGPSNF; -. DR OrthoDB; 275353at2759; -. DR PhylomeDB; Q9H845; -. DR TreeFam; TF105053; -. DR PathwayCommons; Q9H845; -. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SABIO-RK; Q9H845; -. DR SignaLink; Q9H845; -. DR BioGRID-ORCS; 28976; 103 hits in 1173 CRISPR screens. DR GeneWiki; ACAD9; -. DR GenomeRNAi; 28976; -. DR Pharos; Q9H845; Tbio. DR PRO; PR:Q9H845; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q9H845; protein. DR Bgee; ENSG00000177646; Expressed in upper arm skin and 178 other cell types or tissues. DR ExpressionAtlas; Q9H845; baseline and differential. DR GO; GO:0030425; C:dendrite; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome. DR GO; GO:0031966; C:mitochondrial membrane; IDA:BHF-UCL. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003995; F:acyl-CoA dehydrogenase activity; IBA:GO_Central. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro. DR GO; GO:0004466; F:long-chain fatty acyl-CoA dehydrogenase activity; IDA:BHF-UCL. DR GO; GO:0070991; F:medium-chain fatty acyl-CoA dehydrogenase activity; IDA:BHF-UCL. DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IDA:BHF-UCL. DR GO; GO:0051791; P:medium-chain fatty acid metabolic process; IDA:BHF-UCL. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR CDD; cd01161; VLCAD; 1. DR Gene3D; 1.10.540.10; Acyl-CoA dehydrogenase/oxidase, N-terminal domain; 1. DR Gene3D; 2.40.110.10; Butyryl-CoA Dehydrogenase, subunit A, domain 2; 1. DR Gene3D; 1.20.140.10; Butyryl-CoA Dehydrogenase, subunit A, domain 3; 2. DR InterPro; IPR049448; ACAD9/ACADV-like_C. DR InterPro; IPR006089; Acyl-CoA_DH_CS. DR InterPro; IPR006091; Acyl-CoA_Oxase/DH_mid-dom. DR InterPro; IPR046373; Acyl-CoA_Oxase/DH_mid-dom_sf. DR InterPro; IPR036250; AcylCo_DH-like_C. DR InterPro; IPR009075; AcylCo_DH/oxidase_C. DR InterPro; IPR013786; AcylCoA_DH/ox_N. DR InterPro; IPR037069; AcylCoA_DH/ox_N_sf. DR InterPro; IPR009100; AcylCoA_DH/oxidase_NM_dom_sf. DR PANTHER; PTHR43884; ACYL-COA DEHYDROGENASE; 1. DR PANTHER; PTHR43884:SF12; COMPLEX I ASSEMBLY FACTOR ACAD9, MITOCHONDRIAL-RELATED; 1. DR Pfam; PF21343; ACAD9-ACADV_C; 1. DR Pfam; PF00441; Acyl-CoA_dh_1; 1. DR Pfam; PF02770; Acyl-CoA_dh_M; 1. DR Pfam; PF02771; Acyl-CoA_dh_N; 1. DR SUPFAM; SSF47203; Acyl-CoA dehydrogenase C-terminal domain-like; 2. DR SUPFAM; SSF56645; Acyl-CoA dehydrogenase NM domain-like; 1. DR PROSITE; PS00072; ACYL_COA_DH_1; 1. DR PROSITE; PS00073; ACYL_COA_DH_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Disease variant; FAD; Flavoprotein; Membrane; KW Mitochondrion; Mitochondrion inner membrane; Oxidoreductase; KW Phosphoprotein; Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Transit peptide. FT TRANSIT 1..37 FT /note="Mitochondrion" FT /evidence="ECO:0000269|PubMed:16020546" FT CHAIN 38..621 FT /note="Complex I assembly factor ACAD9, mitochondrial" FT /id="PRO_0000000524" FT ACT_SITE 426 FT /note="Proton acceptor" FT /evidence="ECO:0000305|PubMed:24158852" FT MOD_RES 41 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 92 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8JZN5" FT MOD_RES 478 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q8JZN5" FT MOD_RES 521 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8JZN5" FT MOD_RES 521 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8JZN5" FT VARIANT 44 FT /note="F -> I (in MC1DN20; dbSNP:rs387907041)" FT /evidence="ECO:0000269|PubMed:21057504" FT /id="VAR_071892" FT VARIANT 127 FT /note="R -> K (in MC1DN20)" FT /evidence="ECO:0000269|PubMed:20929961" FT /id="VAR_071893" FT VARIANT 193 FT /note="R -> W (in MC1DN20; uncertain significance; FT dbSNP:rs377547811)" FT /evidence="ECO:0000269|PubMed:21057504" FT /id="VAR_071894" FT VARIANT 220 FT /note="A -> V (in MC1DN20)" FT /evidence="ECO:0000269|PubMed:23996478" FT /id="VAR_071895" FT VARIANT 234 FT /note="S -> F (in MC1DN20; uncertain significance)" FT /evidence="ECO:0000269|PubMed:21057504" FT /id="VAR_071896" FT VARIANT 266 FT /note="R -> Q (in MC1DN20; dbSNP:rs387907042)" FT /evidence="ECO:0000269|PubMed:21057504" FT /id="VAR_071897" FT VARIANT 271 FT /note="C -> G (in MC1DN20)" FT /evidence="ECO:0000269|PubMed:26741492" FT /id="VAR_076177" FT VARIANT 303 FT /note="G -> S (in MC1DN20; uncertain significance; FT dbSNP:rs143383023)" FT /evidence="ECO:0000269|PubMed:21057504" FT /id="VAR_071898" FT VARIANT 326 FT /note="A -> T (in MC1DN20; uncertain significance; FT dbSNP:rs115532916)" FT /evidence="ECO:0000269|PubMed:21057504" FT /id="VAR_071899" FT VARIANT 384 FT /note="V -> M (in MC1DN20; dbSNP:rs1447947184)" FT /evidence="ECO:0000269|PubMed:26741492" FT /id="VAR_076178" FT VARIANT 413 FT /note="E -> K (in MC1DN20; uncertain significance; FT dbSNP:rs149753643)" FT /evidence="ECO:0000269|PubMed:20816094" FT /id="VAR_071900" FT VARIANT 414 FT /note="R -> C (in MC1DN20; dbSNP:rs777282696)" FT /evidence="ECO:0000269|PubMed:23836383" FT /id="VAR_071901" FT VARIANT 417 FT /note="R -> C (in MC1DN20; dbSNP:rs368949613)" FT /evidence="ECO:0000269|PubMed:21057504" FT /id="VAR_071902" FT VARIANT 469 FT /note="R -> W (in MC1DN20; dbSNP:rs139145143)" FT /evidence="ECO:0000269|PubMed:20929961" FT /id="VAR_071903" FT VARIANT 477 FT /note="R -> Q (in dbSNP:rs4494951)" FT /id="VAR_033459" FT VARIANT 518 FT /note="R -> H (in MC1DN20; dbSNP:rs781149699)" FT /evidence="ECO:0000269|PubMed:20816094" FT /id="VAR_071904" FT VARIANT 532 FT /note="R -> W (in MC1DN20; dbSNP:rs377022708)" FT /evidence="ECO:0000269|PubMed:20929961, FT ECO:0000269|PubMed:21057504, ECO:0000269|PubMed:22499348" FT /id="VAR_071905" FT VARIANT 606 FT /note="L -> H (in MC1DN20)" FT /evidence="ECO:0000269|PubMed:26741492" FT /id="VAR_076179" FT MUTAGEN 426 FT /note="E->Q: Loss of long-chain-acyl-CoA dehydrogenase FT activity. Does not affect mitochondrial complex I FT assembly." FT /evidence="ECO:0000269|PubMed:24158852" FT CONFLICT 397 FT /note="A -> V (in Ref. 1; AAL56011)" FT /evidence="ECO:0000305" FT HELIX 40..43 FT /evidence="ECO:0007829|PDB:8PHE" FT TURN 44..46 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 52..55 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 61..70 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 75..80 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 84..90 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 95..104 FT /evidence="ECO:0007829|PDB:8PHE" FT TURN 105..107 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 108..111 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 113..115 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 122..132 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 135..137 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 138..146 FT /evidence="ECO:0007829|PDB:8PHE" FT TURN 147..150 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 151..156 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 159..170 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 176..179 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 185..191 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 195..198 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 202..215 FT /evidence="ECO:0007829|PDB:8PHE" FT TURN 216..219 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 221..230 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 240..248 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 249..251 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 254..256 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 262..264 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 270..281 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 285..288 FT /evidence="ECO:0007829|PDB:8PHE" FT TURN 289..292 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 293..302 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 307..327 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 330..335 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 336..338 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 340..367 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 369..371 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 376..400 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 402..404 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 413..418 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 419..423 FT /evidence="ECO:0007829|PDB:8PHE" FT STRAND 425..427 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 429..452 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 492..494 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 495..519 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 520..524 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 527..556 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 561..584 FT /evidence="ECO:0007829|PDB:8PHE" FT HELIX 596..608 FT /evidence="ECO:0007829|PDB:8PHE" SQ SEQUENCE 621 AA; 68760 MW; 064BCE0378877F54 CRC64; MSGCGLFLRT TAAARACRGL VVSTANRRLL RTSPPVRAFA KELFLGKIKK KEVFPFPEVS QDELNEINQF LGPVEKFFTE EVDSRKIDQE GKIPDETLEK LKSLGLFGLQ VPEEYGGLGF SNTMYSRLGE IISMDGSITV TLAAHQAIGL KGIILAGTEE QKAKYLPKLA SGEHIAAFCL TEPASGSDAA SIRSRATLSE DKKHYILNGS KVWITNGGLA NIFTVFAKTE VVDSDGSVKD KITAFIVERD FGGVTNGKPE DKLGIRGSNT CEVHFENTKI PVENILGEVG DGFKVAMNIL NSGRFSMGSV VAGLLKRLIE MTAEYACTRK QFNKRLSEFG LIQEKFALMA QKAYVMESMT YLTAGMLDQP GFPDCSIEAA MVKVFSSEAA WQCVSEALQI LGGLGYTRDY PYERILRDTR ILLIFEGTNE ILRMYIALTG LQHAGRILTT RIHELKQAKV STVMDTVGRR LRDSLGRTVD LGLTGNHGVV HPSLADSANK FEENTYCFGR TVETLLLRFG KTIMEEQLVL KRVANILINL YGMTAVLSRA SRSIRIGLRN HDHEVLLANT FCVEAYLQNL FSLSQLDKYA PENLDEQIKK VSQQILEKRA YICAHPLDRT C //