ACADV_RAT
ID ACADV_RAT Reviewed; 655 AA.
AC P45953;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Very long-chain specific acyl-CoA dehydrogenase, mitochondrial {ECO:0000305|PubMed:1730632};
DE Short=VLCAD {ECO:0000303|PubMed:8034667};
DE EC=1.3.8.9 {ECO:0000269|PubMed:1730632, ECO:0000269|PubMed:8034667};
DE Flags: Precursor;
GN Name=Acadvl {ECO:0000312|RGD:2014};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC
RP ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=8034667; DOI=10.1016/s0021-9258(17)32278-0;
RA Aoyama T., Ueno I., Kamijo T., Hashimoto T.;
RT "Rat very-long-chain acyl-CoA dehydrogenase, a novel mitochondrial acyl-CoA
RT dehydrogenase gene product, is a rate-limiting enzyme in long-chain fatty
RT acid beta-oxidation system. cDNA and deduced amino acid sequence and
RT distinct specificities of the cDNA-expressed protein.";
RL J. Biol. Chem. 269:19088-19094(1994).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PATHWAY, SUBSTRATE SPECIFICITY,
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=1730632; DOI=10.1016/s0021-9258(18)48390-1;
RA Izai K., Uchida Y., Orii T., Yamamoto S., Hashimoto T.;
RT "Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. I.
RT Purification and properties of very-long-chain acyl-coenzyme A
RT dehydrogenase.";
RL J. Biol. Chem. 267:1027-1033(1992).
CC -!- FUNCTION: Very 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
CC (PubMed:8034667, PubMed:1730632). The first step of fatty acid beta-
CC oxidation consists in the removal of one hydrogen from C-2 and C-3 of
CC the straight-chain fatty acyl-CoA thioester, resulting in the formation
CC of trans-2-enoyl-CoA (PubMed:8034667, PubMed:1730632). Among the
CC different mitochondrial acyl-CoA dehydrogenases, very long-chain
CC specific acyl-CoA dehydrogenase acts specifically on acyl-CoAs with
CC saturated 12 to 24 carbons long primary chains (PubMed:1730632).
CC {ECO:0000269|PubMed:1730632, ECO:0000269|PubMed:8034667}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a very-long-chain 2,3-saturated fatty acyl-CoA + H(+) +
CC oxidized [electron-transfer flavoprotein] = a very-long-chain (2E)-
CC enoyl-CoA + reduced [electron-transfer flavoprotein];
CC Xref=Rhea:RHEA:19181, Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:83724, ChEBI:CHEBI:83728; EC=1.3.8.9;
CC Evidence={ECO:0000269|PubMed:1730632, ECO:0000269|PubMed:8034667};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19182;
CC Evidence={ECO:0000305|PubMed:1730632};
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:1730632};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47297;
CC Evidence={ECO:0000305|PubMed:1730632};
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:1730632};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47317;
CC Evidence={ECO:0000305|PubMed:1730632};
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:1730632, ECO:0000269|PubMed:8034667};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43449;
CC Evidence={ECO:0000305|PubMed:1730632};
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:1730632, ECO:0000269|PubMed:8034667};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47241;
CC Evidence={ECO:0000305|PubMed:1730632};
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:1730632};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47237;
CC Evidence={ECO:0000305|PubMed:1730632};
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:1730632};
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:1730632};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47233;
CC Evidence={ECO:0000305|PubMed:1730632};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:1730632};
CC -!- PATHWAY: Lipid metabolism; mitochondrial fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:1730632, ECO:0000269|PubMed:8034667}.
CC -!- SUBUNIT: Homodimer (PubMed:1730632). Homodimerizes after import into
CC the mitochondrion (By similarity). {ECO:0000250|UniProtKB:P49748,
CC ECO:0000269|PubMed:1730632}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:1730632, ECO:0000269|PubMed:8034667}; Peripheral
CC membrane protein {ECO:0000250|UniProtKB:P49748}.
CC -!- TISSUE SPECIFICITY: Widely expressed (at protein level).
CC {ECO:0000269|PubMed:8034667}.
CC -!- PTM: S-nitrosylation at Cys-237 in liver improves catalytic efficiency.
CC {ECO:0000250|UniProtKB:P50544}.
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; D30647; BAA06331.1; -; mRNA.
DR PIR; A54872; A54872.
DR RefSeq; NP_037023.1; NM_012891.2.
DR AlphaFoldDB; P45953; -.
DR SMR; P45953; -.
DR BioGRID; 247402; 2.
DR STRING; 10116.ENSRNOP00000024973; -.
DR ChEMBL; CHEMBL2176830; -.
DR SwissLipids; SLP:000001587; -.
DR CarbonylDB; P45953; -.
DR iPTMnet; P45953; -.
DR PhosphoSitePlus; P45953; -.
DR jPOST; P45953; -.
DR PaxDb; P45953; -.
DR PRIDE; P45953; -.
DR GeneID; 25363; -.
DR KEGG; rno:25363; -.
DR UCSC; RGD:2014; rat.
DR CTD; 37; -.
DR RGD; 2014; Acadvl.
DR eggNOG; KOG0137; Eukaryota.
DR InParanoid; P45953; -.
DR OrthoDB; 819314at2759; -.
DR PhylomeDB; P45953; -.
DR Reactome; R-RNO-77305; Beta oxidation of palmitoyl-CoA to myristoyl-CoA.
DR UniPathway; UPA00660; -.
DR PRO; PR:P45953; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0031314; C:extrinsic component of mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:RGD.
DR GO; GO:0031966; C:mitochondrial membrane; ISO:RGD.
DR GO; GO:0042645; C:mitochondrial nucleoid; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0003995; F:acyl-CoA dehydrogenase activity; IDA:RGD.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; IDA:RGD.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0004466; F:long-chain-acyl-CoA dehydrogenase activity; IDA:RGD.
DR GO; GO:0017099; F:very-long-chain-acyl-CoA dehydrogenase activity; IDA:RGD.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IDA:RGD.
DR GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; ISS:UniProtKB.
DR GO; GO:0009062; P:fatty acid catabolic process; ISO:RGD.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; ISO:RGD.
DR GO; GO:0046322; P:negative regulation of fatty acid oxidation; ISO:RGD.
DR GO; GO:0090181; P:regulation of cholesterol metabolic process; ISO:RGD.
DR GO; GO:0009409; P:response to cold; ISO:RGD.
DR GO; GO:0001659; P:temperature homeostasis; ISO:RGD.
DR Gene3D; 1.10.540.10; -; 1.
DR Gene3D; 2.40.110.10; -; 1.
DR InterPro; IPR006089; Acyl-CoA_DH_CS.
DR InterPro; IPR006091; Acyl-CoA_Oxase/DH_mid-dom.
DR InterPro; IPR046373; Acyl-CoA_Oxase/DH_mid-dom_sf.
DR InterPro; IPR036250; AcylCo_DH-like_C.
DR InterPro; IPR009075; AcylCo_DH/oxidase_C.
DR InterPro; IPR013786; AcylCoA_DH/ox_N.
DR InterPro; IPR037069; AcylCoA_DH/ox_N_sf.
DR InterPro; IPR009100; AcylCoA_DH/oxidase_NM_dom.
DR Pfam; PF00441; Acyl-CoA_dh_1; 1.
DR Pfam; PF02770; Acyl-CoA_dh_M; 1.
DR Pfam; PF02771; Acyl-CoA_dh_N; 1.
DR SUPFAM; SSF47203; SSF47203; 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; Direct protein sequencing; FAD; Fatty acid metabolism;
KW Flavoprotein; Lipid metabolism; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Oxidoreductase; Phosphoprotein;
KW Reference proteome; S-nitrosylation; Transit peptide.
FT TRANSIT 1..40
FT /note="Mitochondrion"
FT CHAIN 41..655
FT /note="Very long-chain specific acyl-CoA dehydrogenase,
FT mitochondrial"
FT /id="PRO_0000000518"
FT REGION 1..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 41..482
FT /note="Catalytic"
FT /evidence="ECO:0000250|UniProtKB:P49748"
FT REGION 483..516
FT /note="Membrane-anchoring"
FT /evidence="ECO:0000250|UniProtKB:P49748"
FT COMPBIAS 23..42
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 462
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P49748"
FT BINDING 214..223
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P49748"
FT BINDING 249..251
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P49748"
FT BINDING 461..463
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P49748"
FT BINDING 464..466
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P49748"
FT BINDING 562
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P49748"
FT MOD_RES 51
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 71
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 71
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 127
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 127
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 195
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 237
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 239
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P49748"
FT MOD_RES 239
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 268
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 276
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 276
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 278
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 278
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 298
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 316
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 331
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P49748"
FT MOD_RES 331
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 372
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 482
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 482
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 517
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49748"
FT MOD_RES 522
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49748"
FT MOD_RES 550
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 556
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 556
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50544"
FT MOD_RES 639
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50544"
SQ SEQUENCE 655 AA; 70749 MW; E808EDEB0E4595D7 CRC64;
MQSARMTPSV GRQLLRLGAR SSRSAALQGQ PRPTSAQRLY ASEATQAVLE KPETLSSDAS
TREKPARAES KSFAVGMFKG QLTTDQVFPY PSVLNEGQTQ FLKELVGPVA RFFEEVNDPA
KNDSLEKVEE DTLQGLKELG AFGLQVPSEL GGLGLSNTQY ARLAEIVGMH DLGVSVTLGA
HQSIGFKGIL LYGTKAQKEK YLPRVASGQA LAAFCLTEPS SGSDVASIRS SAVPSPCGKY
YTLNGSKIWI SNGGLADIFT VFAKTPIKDA ATGAVKEKIT AFVVERSFGG VTHGLPEKKM
GIKASNTSEV YFDGVKVPAE NVLGEVGDGF KVAVNILNNG RFGMAATLAG TMKAIIAKAV
DHATNRTQFG DKIHNFGVIQ EKLARMAILQ YVTESMAYML SANMDQGFKD FQIEAAISKI
FGSEAAWKVT DECIQIMGGM GFMKEPGVER VLRDIRIFRI FEGTNDILRL FVALQGCMDK
GKELTGLGNA LKNPLGNVGL LIGEASKQLR RRTGIGSGLS LSGIVHPELS RSGELAVQAL
EQFATVVEAK LMKHKKGIVN EQFLLQRLAD GAIDLYAMVV VLSRASRSLS EGYPTAQHEK
MLCDSWCIEA ATRIRENMAS LQSNPQQQEL FRNFRSISKA MVENGGLVTS NPLRV
