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   07-OCT-2020, entry version 174.
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   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   [16]
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   [17]
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   [18]
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   [19]
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). This
CC       moonlighting protein has also a dehydrogenase activity toward a broad
CC       range of substrates with greater specificity for long-chain unsaturated
CC       acyl-CoAs (PubMed:12359260, PubMed:16020546, PubMed:21237683,
CC       PubMed:24158852). However, in vivo, it does not seem to play a primary
CC       role in fatty acid oxidation (PubMed:20816094, PubMed:24158852). In
CC       addition, the function in complex I assembly is independent of the
CC       dehydrogenase activity of the protein (PubMed:24158852).
CC       {ECO:0000269|PubMed:12359260, ECO:0000269|PubMed:16020546,
CC       ECO:0000269|PubMed:20816094, ECO:0000269|PubMed:21237683,
CC       ECO:0000269|PubMed:24158852}.
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). Part of the mitochondrial complex
CC       I assembly/MCIA complex that comprises at least TMEM126B, NDUFAF1,
CC       ECSIT, and ACAD9 (By similarity). Interacts with NDUFAF1 and ECSIT
CC       (PubMed:20816094). {ECO:0000250|UniProtKB:B1WC61,
CC       ECO:0000269|PubMed:16020546}.
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 mutations
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   SMR; Q9H845; -.
DR   BioGRID; 118799; 100.
DR   DIP; DIP-53699N; -.
DR   IntAct; Q9H845; 90.
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; 151 antibodies.
DR   DNASU; 28976; -.
DR   Ensembl; ENST00000308982; ENSP00000312618; ENSG00000177646.
DR   GeneID; 28976; -.
DR   KEGG; hsa:28976; -.
DR   UCSC; uc003ela.5; human.
DR   CTD; 28976; -.
DR   DisGeNET; 28976; -.
DR   EuPathDB; HostDB:ENSG00000177646.17; -.
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   eggNOG; KOG0137; Eukaryota.
DR   GeneTree; ENSGT00940000157312; -.
DR   HOGENOM; CLU_018204_11_2_1; -.
DR   InParanoid; Q9H845; -.
DR   KO; K15980; -.
DR   OMA; PIGKMEG; -.
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   BioGRID-ORCS; 28976; 72 hits in 874 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 zone of skin and 212 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: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   InterPro; IPR006089; Acyl-CoA_DH_CS.
DR   InterPro; IPR006091; Acyl-CoA_Oxase/DH_cen-dom.
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 mutation; FAD; Flavoprotein; Membrane; Mitochondrion;
KW   Mitochondrion inner membrane; Oxidoreductase; Phosphoprotein; Polymorphism;
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:0000244|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
//