ACAD9_HUMAN
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 03-AUG-2022, entry version 182.
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}.
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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 AlphaFoldDB; Q9H845; -.
DR SASBDB; Q9H845; -.
DR SMR; Q9H845; -.
DR BioGRID; 118799; 426.
DR ComplexPortal; CPX-6322; Mitochondrial complex I intermediate assembly (MCIA) complex.
DR DIP; DIP-53699N; -.
DR IntAct; Q9H845; 100.
DR MINT; Q9H845; -.
DR STRING; 9606.ENSP00000312618; -.
DR SwissLipids; SLP:000000619; -.
DR iPTMnet; Q9H845; -.
DR MetOSite; Q9H845; -.
DR PhosphoSitePlus; Q9H845; -.
DR SwissPalm; Q9H845; -.
DR BioMuta; ACAD9; -.
DR DMDM; 32469596; -.
DR EPD; Q9H845; -.
DR jPOST; Q9H845; -.
DR MassIVE; Q9H845; -.
DR MaxQB; Q9H845; -.
DR PaxDb; Q9H845; -.
DR PeptideAtlas; Q9H845; -.
DR PRIDE; Q9H845; -.
DR ProteomicsDB; 81177; -.
DR Antibodypedia; 33213; 176 antibodies from 24 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 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; KYLTGMS; -.
DR OrthoDB; 819314at2759; -.
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; 91 hits in 1089 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 176 other tissues.
DR ExpressionAtlas; Q9H845; baseline and differential.
DR Genevisible; Q9H845; HS.
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:0000062; F:fatty-acyl-CoA binding; IBA:GO_Central.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0004466; F:long-chain-acyl-CoA dehydrogenase activity; IDA:BHF-UCL.
DR GO; GO:0070991; F:medium-chain-acyl-CoA dehydrogenase activity; IDA:BHF-UCL.
DR GO; GO:0017099; F:very-long-chain-acyl-CoA dehydrogenase activity; IBA:GO_Central.
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 Gene3D; 1.10.540.10; -; 1.
DR Gene3D; 2.40.110.10; -; 1.
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.
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; SSF47203; 2.
DR SUPFAM; SSF56645; SSF56645; 1.
DR PROSITE; PS00072; ACYL_COA_DH_1; 1.
DR PROSITE; PS00073; ACYL_COA_DH_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Disease variant; FAD; Flavoprotein; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Oxidoreductase; Phosphoprotein;
KW Primary mitochondrial disease; 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; unknown pathological
FT significance; 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; unknown pathological
FT 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; unknown pathological
FT significance; dbSNP:rs143383023)"
FT /evidence="ECO:0000269|PubMed:21057504"
FT /id="VAR_071898"
FT VARIANT 326
FT /note="A -> T (in MC1DN20; unknown pathological
FT significance; 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; unknown pathological
FT significance; 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"
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
