ACADL_MACFA
ID ACADL_MACFA Reviewed; 430 AA.
AC Q60HI0;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Long-chain specific acyl-CoA dehydrogenase, mitochondrial;
DE Short=LCAD;
DE EC=1.3.8.8 {ECO:0000250|UniProtKB:P28330};
DE Flags: Precursor;
GN Name=ACADL {ECO:0000250|UniProtKB:P28330}; ORFNames=QtrA-17450;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Temporal cortex;
RA Kusuda J., Osada N., Tanuma R., Hirata M., Sugano S., Hashimoto K.;
RT "Isolation and characterization of cDNA for macaque neurological disease
RT genes.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
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. The
CC first step of fatty acid beta-oxidation consists in the removal of one
CC hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA
CC thioester, resulting in the formation of trans-2-enoyl-CoA (By
CC similarity). Among the different mitochondrial acyl-CoA dehydrogenases,
CC long-chain specific acyl-CoA dehydrogenase can act on saturated and
CC unsaturated acyl-CoAs with 6 to 24 carbons with a preference for 8 to
CC 18 carbons long primary chains (By similarity).
CC {ECO:0000250|UniProtKB:P15650, ECO:0000250|UniProtKB:P28330}.
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;
CC Evidence={ECO:0000250|UniProtKB:P28330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17722;
CC Evidence={ECO:0000250|UniProtKB:P28330};
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:0000250|UniProtKB:P28330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43465;
CC Evidence={ECO:0000250|UniProtKB:P28330};
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:0000250|UniProtKB:P28330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48181;
CC Evidence={ECO:0000250|UniProtKB:P28330};
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:0000250|UniProtKB:P28330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48177;
CC Evidence={ECO:0000250|UniProtKB:P28330};
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:0000250|UniProtKB:P28330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47297;
CC Evidence={ECO:0000250|UniProtKB:P28330};
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:0000250|UniProtKB:P28330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47317;
CC Evidence={ECO:0000250|UniProtKB:P28330};
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:0000250|UniProtKB:P28330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43449;
CC Evidence={ECO:0000250|UniProtKB:P28330};
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:0000250|UniProtKB:P28330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47241;
CC Evidence={ECO:0000250|UniProtKB:P28330};
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:0000250|UniProtKB:P28330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47237;
CC Evidence={ECO:0000250|UniProtKB:P28330};
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:0000250|UniProtKB:P28330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47229;
CC Evidence={ECO:0000250|UniProtKB:P28330};
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:0000250|UniProtKB:P28330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47233;
CC Evidence={ECO:0000250|UniProtKB:P28330};
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 -!- PATHWAY: Lipid metabolism; mitochondrial fatty acid beta-oxidation.
CC {ECO:0000250|UniProtKB:P15650}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P15650}.
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; AB125147; BAD51935.1; -; mRNA.
DR RefSeq; NP_001272752.1; NM_001285823.1.
DR AlphaFoldDB; Q60HI0; -.
DR SMR; Q60HI0; -.
DR STRING; 9541.XP_005574217.1; -.
DR GeneID; 102134056; -.
DR CTD; 33; -.
DR VEuPathDB; HostDB:ENSMFAG00000003569; -.
DR eggNOG; KOG0141; Eukaryota.
DR OMA; QWEKDGI; -.
DR UniPathway; UPA00660; -.
DR Proteomes; UP000233100; Chromosome 12.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0004466; F:long-chain-acyl-CoA dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0042758; P:long-chain fatty acid catabolic process; IEA:InterPro.
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 2: Evidence at transcript 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_0000000510"
FT ACT_SITE 291
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P26440"
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 55
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51174"
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"
SQ SEQUENCE 430 AA; 47838 MW; 0EA455DD1CF1EC29 CRC64;
MAARLLRGSL RFLGGHCAAR PLPALRCSHS GGEERLETPS AKNLTDIGIR RIFSSEHDIF
RKSIRKFFQE EVIPHHSEWE KAGEVSREVW EKAGKQGLLG VNIAEHLGGI GGDLYYAAVV
WEEQAYSNCS GPGFSVHSGI VMSYITNYGS EEQIKHFIPQ MTAGKCIGAI AMTELGAGSD
LQGIKTNAKK DGSDWILNGS KVFISNGWLS DVVIVVAVTN HEAPSPARGI SLFLVENGMK
GFIKGRKLHK MGLKAQDTAE LFFEDVRLPA SALLGEENKG FYYIMKELPQ ERLLIADMAV
SASEFMFEET RNYVKQRKAF GKTVAHLQTV QHKLAELKTH ICVTRAFVDN CLQLHEAKRL
DSATACMAKY WASELQNSVA YDCVQLHGGW GYMWEYPIAK AYVDARVQPI YGGTNEIMKE
LIAREIVFDK
