ACADL_HUMAN
ID ACADL_HUMAN Reviewed; 430 AA.
AC P28330; B2R8T3; Q8IUN8;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Long-chain specific acyl-CoA dehydrogenase, mitochondrial;
DE Short=LCAD;
DE EC=1.3.8.8 {ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:8155643, ECO:0000269|PubMed:8823175};
DE Flags: Precursor;
GN Name=ACADL {ECO:0000312|HGNC:HGNC:88};
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].
RX PubMed=1774065; DOI=10.1016/0888-7543(91)90068-p;
RA Indo Y., Yang-Feng T., Glassberg R., Tanaka K.;
RT "Molecular cloning and nucleotide sequence of cDNAs encoding human long-
RT chain acyl-CoA dehydrogenase and assignment of the location of its gene
RT (ACADL) to chromosome 2.";
RL Genomics 11:609-620(1991).
RN [2]
RP ERRATUM OF PUBMED:1774065.
RX PubMed=1559716; DOI=10.1016/0888-7543(92)90462-2;
RA Indo Y., Yang-Feng T., Glassberg R., Tanaka K.;
RL Genomics 12:626-626(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-333.
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Colon;
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 [7]
RP CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF GLU-291.
RX PubMed=8155643; DOI=10.1021/bi00180a021;
RA Djordjevic S., Dong Y., Paschke R., Frerman F.E., Strauss A.W., Kim J.J.;
RT "Identification of the catalytic base in long chain acyl-CoA
RT dehydrogenase.";
RL Biochemistry 33:4258-4264(1994).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
RP SPECIFICITY.
RX PubMed=8823175; DOI=10.1021/bi960785e;
RA Nandy A., Kieweg V., Kraeutle F.G., Vock P., Kuechler B., Bross P.,
RA Kim J.J., Rasched I., Ghisla S.;
RT "Medium-long-chain chimeric human Acyl-CoA dehydrogenase: medium-chain
RT enzyme with the active center base arrangement of long-chain Acyl-CoA
RT dehydrogenase.";
RL Biochemistry 35:12402-12411(1996).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE 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 [10]
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 [11]
RP VARIANTS THR-303 AND GLN-333.
RA Kelly D., Ogden M., Hale D., Hainline B., Strauss A.;
RT "The molecular basis of human long chain acyl-CoA dehydrogenase
RT deficiency.";
RL Am. J. Hum. Genet. 49:409-409(1991).
CC -!- FUNCTION: Long-chain specific acyl-CoA dehydrogenase is one of the
CC acyl-CoA dehydrogenases that catalyze the first step of mitochondrial
CC fatty acid beta-oxidation, an aerobic process breaking down fatty acids
CC into acetyl-CoA and allowing the production of energy from fats (By
CC similarity). The first step of fatty acid beta-oxidation consists in
CC the removal of one hydrogen from C-2 and C-3 of the straight-chain
CC fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-
CC CoA (By similarity). Among the different mitochondrial acyl-CoA
CC dehydrogenases, long-chain specific acyl-CoA dehydrogenase can act on
CC saturated and unsaturated acyl-CoAs with 6 to 24 carbons with a
CC preference for 8 to 18 carbons long primary chains (PubMed:8823175,
CC PubMed:21237683). {ECO:0000250|UniProtKB:P15650,
CC ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:8823175}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a long-chain 2,3-saturated fatty acyl-CoA + H(+) + oxidized
CC [electron-transfer flavoprotein] = a long-chain (2E)-enoyl-CoA +
CC reduced [electron-transfer flavoprotein]; Xref=Rhea:RHEA:17721,
CC Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:83721,
CC ChEBI:CHEBI:83727; EC=1.3.8.8; Evidence={ECO:0000269|PubMed:21237683,
CC ECO:0000269|PubMed:8155643, ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17722;
CC Evidence={ECO:0000305|PubMed:8823175};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexanoyl-CoA + oxidized [electron-transfer
CC flavoprotein] = (2E)-hexenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:43464, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:62077, ChEBI:CHEBI:62620;
CC Evidence={ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43465;
CC Evidence={ECO:0000305|PubMed:8823175};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + octanoyl-CoA + oxidized [electron-transfer
CC flavoprotein] = (2E)-octenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:48180, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57386, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:62242;
CC Evidence={ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:8155643,
CC ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48181;
CC Evidence={ECO:0000305|PubMed:8823175};
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:21237683, ECO:0000269|PubMed:8155643,
CC ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48177;
CC Evidence={ECO:0000305|PubMed:8823175};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-dodecenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:47296, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57330, ChEBI:CHEBI:57375,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307;
CC Evidence={ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47297;
CC Evidence={ECO:0000305|PubMed:8823175};
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, ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47317;
CC Evidence={ECO:0000305|PubMed:8823175};
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:21237683, ECO:0000269|PubMed:8155643,
CC ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43449;
CC Evidence={ECO:0000305|PubMed:8823175};
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:21237683, ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47241;
CC Evidence={ECO:0000305|PubMed:8823175};
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:21237683};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47237;
CC Evidence={ECO:0000305|PubMed:21237683};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=docosanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-docosenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:47228, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:65059, ChEBI:CHEBI:74692;
CC Evidence={ECO:0000269|PubMed:21237683};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47229;
CC Evidence={ECO:0000305|PubMed:21237683};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxidized [electron-transfer flavoprotein] +
CC tetracosanoyl-CoA = (2E)-tetracosenoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:47232, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:65052, ChEBI:CHEBI:74693;
CC Evidence={ECO:0000269|PubMed:21237683};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47233;
CC Evidence={ECO:0000305|PubMed:21237683};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5E)-tetradecenoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E,5E)-tetradecadienoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:49828, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:131943, ChEBI:CHEBI:131944;
CC Evidence={ECO:0000250|UniProtKB:P15650};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49829;
CC Evidence={ECO:0000250|UniProtKB:P15650};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z)-tetradecenoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E,5Z)-tetradecadienoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:47448, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:84650, ChEBI:CHEBI:87701;
CC Evidence={ECO:0000250|UniProtKB:P15650};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47449;
CC Evidence={ECO:0000250|UniProtKB:P15650};
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:0000250|UniProtKB:P15650};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47301;
CC Evidence={ECO:0000250|UniProtKB:P15650};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P15650};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=29 uM for hexanoyl-CoA {ECO:0000269|PubMed:8823175};
CC KM=8 uM for octanoyl-CoA {ECO:0000269|PubMed:8823175};
CC KM=10 uM for decanoyl-CoA {ECO:0000269|PubMed:8823175};
CC KM=7 uM for dodecanoyl-CoA {ECO:0000269|PubMed:8823175};
CC KM=10 uM for tetradecanoyl-CoA {ECO:0000269|PubMed:8823175};
CC KM=14 uM for hexadecanoyl-CoA {ECO:0000269|PubMed:8823175};
CC KM=8 uM for octadecanoyl-CoA {ECO:0000269|PubMed:8823175};
CC -!- PATHWAY: Lipid metabolism; mitochondrial fatty acid beta-oxidation.
CC {ECO:0000250|UniProtKB:P15650}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P15650}.
CC -!- INTERACTION:
CC P28330; P22735: TGM1; NbExp=3; IntAct=EBI-12059321, EBI-2562368;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P15650}.
CC -!- PTM: Acetylation at Lys-318 and Lys-322 in proximity of the cofactor-
CC binding sites strongly reduces catalytic activity. These sites are
CC deacetylated by SIRT3. {ECO:0000250|UniProtKB:P51174}.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; M74096; AAA51565.1; -; mRNA.
DR EMBL; AK313498; BAG36280.1; -; mRNA.
DR EMBL; AC006994; AAY14881.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70481.1; -; Genomic_DNA.
DR EMBL; BC039063; AAH39063.1; -; mRNA.
DR EMBL; BC064549; AAH64549.1; -; mRNA.
DR CCDS; CCDS2389.1; -.
DR PIR; A40559; A40559.
DR RefSeq; NP_001599.1; NM_001608.3.
DR AlphaFoldDB; P28330; -.
DR SMR; P28330; -.
DR BioGRID; 106551; 17.
DR IntAct; P28330; 8.
DR STRING; 9606.ENSP00000233710; -.
DR SwissLipids; SLP:000001327; -.
DR iPTMnet; P28330; -.
DR PhosphoSitePlus; P28330; -.
DR SwissPalm; P28330; -.
DR BioMuta; ACADL; -.
DR DMDM; 223590148; -.
DR MassIVE; P28330; -.
DR MaxQB; P28330; -.
DR PaxDb; P28330; -.
DR PeptideAtlas; P28330; -.
DR PRIDE; P28330; -.
DR ProteomicsDB; 54469; -.
DR Antibodypedia; 1641; 331 antibodies from 33 providers.
DR DNASU; 33; -.
DR Ensembl; ENST00000233710.4; ENSP00000233710.3; ENSG00000115361.8.
DR GeneID; 33; -.
DR KEGG; hsa:33; -.
DR MANE-Select; ENST00000233710.4; ENSP00000233710.3; NM_001608.4; NP_001599.1.
DR UCSC; uc002vdz.5; human.
DR CTD; 33; -.
DR DisGeNET; 33; -.
DR GeneCards; ACADL; -.
DR HGNC; HGNC:88; ACADL.
DR HPA; ENSG00000115361; Tissue enhanced (liver, pancreas).
DR MalaCards; ACADL; -.
DR MIM; 609576; gene.
DR neXtProt; NX_P28330; -.
DR OpenTargets; ENSG00000115361; -.
DR PharmGKB; PA24424; -.
DR VEuPathDB; HostDB:ENSG00000115361; -.
DR eggNOG; KOG0141; Eukaryota.
DR GeneTree; ENSGT00940000157652; -.
DR HOGENOM; CLU_018204_0_3_1; -.
DR InParanoid; P28330; -.
DR OMA; QWEKDGI; -.
DR OrthoDB; 589058at2759; -.
DR PhylomeDB; P28330; -.
DR TreeFam; TF105054; -.
DR BioCyc; MetaCyc:HS03876-MON; -.
DR PathwayCommons; P28330; -.
DR Reactome; R-HSA-77285; Beta oxidation of myristoyl-CoA to lauroyl-CoA.
DR Reactome; R-HSA-77288; mitochondrial fatty acid beta-oxidation of unsaturated fatty acids.
DR Reactome; R-HSA-77310; Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA.
DR SABIO-RK; P28330; -.
DR SignaLink; P28330; -.
DR UniPathway; UPA00660; -.
DR BioGRID-ORCS; 33; 11 hits in 1066 CRISPR screens.
DR ChiTaRS; ACADL; human.
DR GenomeRNAi; 33; -.
DR Pharos; P28330; Tbio.
DR PRO; PR:P28330; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P28330; protein.
DR Bgee; ENSG00000115361; Expressed in body of pancreas and 135 other tissues.
DR Genevisible; P28330; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0003995; F:acyl-CoA dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; IEA:Ensembl.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0004466; F:long-chain-acyl-CoA dehydrogenase activity; ISS:BHF-UCL.
DR GO; GO:0016401; F:palmitoyl-CoA oxidase activity; ISS:BHF-UCL.
DR GO; GO:0042413; P:carnitine catabolic process; ISS:BHF-UCL.
DR GO; GO:0019254; P:carnitine metabolic process, CoA-linked; ISS:BHF-UCL.
DR GO; GO:0044242; P:cellular lipid catabolic process; ISS:BHF-UCL.
DR GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; ISS:BHF-UCL.
DR GO; GO:0042758; P:long-chain fatty acid catabolic process; IBA:GO_Central.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0046322; P:negative regulation of fatty acid oxidation; ISS:BHF-UCL.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0090181; P:regulation of cholesterol metabolic process; ISS:BHF-UCL.
DR GO; GO:0001659; P:temperature homeostasis; ISS:BHF-UCL.
DR CDD; cd01160; LCAD; 1.
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 InterPro; IPR034179; LCAD.
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; 1.
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; FAD; Fatty acid metabolism; Flavoprotein; Lipid metabolism;
KW Mitochondrion; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..30
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P15650"
FT CHAIN 31..430
FT /note="Long-chain specific acyl-CoA dehydrogenase,
FT mitochondrial"
FT /id="PRO_0000000509"
FT ACT_SITE 291
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:8155643"
FT BINDING 170..179
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 179
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 203..205
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 227..228
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 282
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 289..292
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 317
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 328
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 385..389
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 412..413
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 414..416
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT MOD_RES 42
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15650"
FT MOD_RES 66
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 66
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 81
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 81
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 92
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 95
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 165
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 240
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 254
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 254
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 279
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 279
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 318
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 322
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 322
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 358
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51174"
FT VARIANT 303
FT /note="S -> T (in dbSNP:rs1801204)"
FT /evidence="ECO:0000269|Ref.11"
FT /id="VAR_000328"
FT VARIANT 333
FT /note="K -> Q (in dbSNP:rs2286963)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.11"
FT /id="VAR_000329"
FT MUTAGEN 291
FT /note="E->Q: Loss of long-chain-acyl-CoA dehydrogenase
FT activity. No effect on protein abundance. No effect on
FT solubility. No effect on substrate binding."
FT /evidence="ECO:0000269|PubMed:8155643"
SQ SEQUENCE 430 AA; 47656 MW; 72F9803685406DF9 CRC64;
MAARLLRGSL RVLGGHRAPR QLPAARCSHS GGEERLETPS AKKLTDIGIR RIFSPEHDIF
RKSVRKFFQE EVIPHHSEWE KAGEVSREVW EKAGKQGLLG VNIAEHLGGI GGDLYSAAIV
WEEQAYSNCS GPGFSIHSGI VMSYITNHGS EEQIKHFIPQ MTAGKCIGAI AMTEPGAGSD
LQGIKTNAKK DGSDWILNGS KVFISNGSLS DVVIVVAVTN HEAPSPAHGI SLFLVENGMK
GFIKGRKLHK MGLKAQDTAE LFFEDIRLPA SALLGEENKG FYYIMKELPQ ERLLIADVAI
SASEFMFEET RNYVKQRKAF GKTVAHLQTV QHKLAELKTH ICVTRAFVDN CLQLHEAKRL
DSATACMAKY WASELQNSVA YDCVQLHGGW GYMWEYPIAK AYVDARVQPI YGGTNEIMKE
LIAREIVFDK
