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 27-MAR-2024, entry version 207. 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}. 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; 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; 9606-ENSP00000233710; -. DR PeptideAtlas; P28330; -. DR ProteomicsDB; 54469; -. DR Pumba; P28330; -. DR Antibodypedia; 1641; 349 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 AGR; HGNC:88; -. 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; MWEYPVA; -. DR OrthoDB; 275353at2759; -. DR PhylomeDB; P28330; -. DR TreeFam; TF105054; -. DR BioCyc; MetaCyc:HS03876-MONOMER; -. 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; 12 hits in 1147 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 137 other cell types or tissues. 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: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; 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; 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_sf. DR InterPro; IPR034179; LCAD. DR PANTHER; PTHR43884; ACYL-COA DEHYDROGENASE; 1. DR PANTHER; PTHR43884:SF12; COMPLEX I ASSEMBLY FACTOR ACAD9, MITOCHONDRIAL-RELATED; 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; 1. 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. DR Genevisible; P28330; HS. 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 //