ACDSB_RAT
ID ACDSB_RAT Reviewed; 432 AA.
AC P70584;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial {ECO:0000305|PubMed:6874697};
DE Short=SBCAD {ECO:0000303|PubMed:8660691};
DE EC=1.3.8.5 {ECO:0000269|PubMed:6874697, ECO:0000269|PubMed:8660691};
DE AltName: Full=2-methyl branched chain acyl-CoA dehydrogenase;
DE Short=2-MEBCAD;
DE AltName: Full=2-methylbutyryl-coenzyme A dehydrogenase;
DE Short=2-methylbutyryl-CoA dehydrogenase;
DE Flags: Precursor;
GN Name=Acadsb {ECO:0000312|RGD:2013};
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], PROTEIN SEQUENCE OF 51-59, FUNCTION, CATALYTIC
RP ACTIVITY, PATHWAY, SUBSTRATE SPECIFICITY, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=8660691; DOI=10.1006/abbi.1996.0290;
RA Willard J., Vicanek C., Battaile K.P., van Veldhoven P.P., Fauq A.H.,
RA Rozen R., Vockley J.;
RT "Cloning of a cDNA for short/branched chain acyl-Coenzyme A dehydrogenase
RT from rat and characterization of its tissue expression and substrate
RT specificity.";
RL Arch. Biochem. Biophys. 331:127-133(1996).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=6874697; DOI=10.1016/s0021-9258(17)44692-8;
RA Ikeda Y., Tanaka K.;
RT "Purification and characterization of 2-methyl-branched chain acyl coenzyme
RT A dehydrogenase, an enzyme involved in the isoleucine and valine
RT metabolism, from rat liver mitochondria.";
RL J. Biol. Chem. 258:9477-9487(1983).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
RP SPECIFICITY.
RX PubMed=12855692; DOI=10.1074/jbc.m306882200;
RA He M., Burghardt T.P., Vockley J.;
RT "A novel approach to the characterization of substrate specificity in
RT short/branched chain Acyl-CoA dehydrogenase.";
RL J. Biol. Chem. 278:37974-37986(2003).
CC -!- FUNCTION: Short and branched chain specific acyl-CoA dehydrogenase that
CC catalyzes the removal of one hydrogen from C-2 and C-3 of the fatty
CC acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA
CC (PubMed:8660691, PubMed:6874697, PubMed:12855692). Among the different
CC mitochondrial acyl-CoA dehydrogenases, acts specifically on short and
CC branched chain acyl-CoA derivatives such as (S)-2-methylbutyryl-CoA as
CC well as short straight chain acyl-CoAs such as butyryl-CoA
CC (PubMed:8660691, PubMed:6874697, PubMed:12855692). Plays an important
CC role in the metabolism of L-isoleucine by catalyzing the
CC dehydrogenation of 2-methylbutyryl-CoA, one of the steps of the L-
CC isoleucine catabolic pathway (By similarity). Can also act on valproyl-
CC CoA, a metabolite of the valproic acid drug (PubMed:8660691).
CC {ECO:0000250|UniProtKB:P45954, ECO:0000269|PubMed:12855692,
CC ECO:0000269|PubMed:6874697, ECO:0000269|PubMed:8660691}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylbutanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-2-methylbut-2-enoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:43780, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57336,
CC ChEBI:CHEBI:57337, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307; EC=1.3.8.5;
CC Evidence={ECO:0000269|PubMed:6874697, ECO:0000269|PubMed:8660691};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43781;
CC Evidence={ECO:0000305|PubMed:8660691};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S)-2-methylbutanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-2-methylbut-2-enoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:48256, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57337,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:88166;
CC Evidence={ECO:0000269|PubMed:12855692, ECO:0000269|PubMed:6874697,
CC ECO:0000269|PubMed:8660691};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48257;
CC Evidence={ECO:0000305|PubMed:8660691};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-2-methylbutanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = ethylacryloyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:65296, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:156439, ChEBI:CHEBI:156440;
CC Evidence={ECO:0000269|PubMed:6874697, ECO:0000269|PubMed:8660691};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65297;
CC Evidence={ECO:0000305|PubMed:8660691};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=butanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-butenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:24004, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57332, ChEBI:CHEBI:57371,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307;
CC Evidence={ECO:0000269|PubMed:6874697, ECO:0000269|PubMed:8660691};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24005;
CC Evidence={ECO:0000305|PubMed:8660691};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylpropanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-2-methylpropenoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:44180, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57338,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:62500;
CC Evidence={ECO:0000269|PubMed:12855692, ECO:0000269|PubMed:6874697,
CC ECO:0000269|PubMed:8660691};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44181;
CC Evidence={ECO:0000305|PubMed:8660691};
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:12855692};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43465;
CC Evidence={ECO:0000305|PubMed:12855692};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxidized [electron-transfer flavoprotein] + valproyl-
CC CoA = (2E)-2-propylpent-2-enoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:65344, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:156457, ChEBI:CHEBI:156458;
CC Evidence={ECO:0000269|PubMed:8660691};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65345;
CC Evidence={ECO:0000305|PubMed:8660691};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:6874697};
CC -!- ACTIVITY REGULATION: Inhibited by N-ethylmaleimide,
CC hydroxymercuribenzoate, methyl mercury iodide and heavy metals such as
CC Hg2+, Cu2+, and Ag2+. {ECO:0000269|PubMed:6874697}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=89 uM for 2-methylpropanoyl-CoA {ECO:0000269|PubMed:6874697};
CC KM=20 uM for (2S)-2-methylbutanoyl-CoA {ECO:0000269|PubMed:6874697};
CC KM=3.9 uM for (2S)-2-methylbutanoyl-CoA (at 32 degrees Celsius)
CC {ECO:0000269|PubMed:12855692};
CC KM=44 uM for hexanoyl-CoA (at 32 degrees Celsius)
CC {ECO:0000269|PubMed:12855692};
CC KM=110 uM for 2-methylpropanoyl-CoA (at 32 degrees Celsius)
CC {ECO:0000269|PubMed:12855692};
CC Vmax=2 umol/min/mg enzyme with 2-methylpropanoyl-CoA as substrate
CC {ECO:0000269|PubMed:6874697};
CC Vmax=2.2 umol/min/mg enzyme with (2S)-2-methylbutanoyl-CoA as
CC substrate {ECO:0000269|PubMed:6874697};
CC Note=kcat is 30000 sec(-1) for the dehydrogenation of (2S)-2-
CC methylbutanoyl-CoA (PubMed:12855692). kcat is 1800 sec(-1) for the
CC dehydrogenation of hexanoyl-CoA (PubMed:12855692). kcat is 8500 sec(-
CC 1) for the dehydrogenation of hexanoyl-CoA (PubMed:12855692).
CC {ECO:0000269|PubMed:12855692};
CC pH dependence:
CC Optimum pH is 8.0. {ECO:0000269|PubMed:6874697};
CC -!- PATHWAY: Lipid metabolism; mitochondrial fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:6874697, ECO:0000269|PubMed:8660691}.
CC -!- PATHWAY: Amino-acid degradation; L-isoleucine degradation.
CC {ECO:0000250|UniProtKB:P45954}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:6874697}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:6874697}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:8660691}.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; U64451; AAB17136.1; -; mRNA.
DR PIR; S71321; S71321.
DR RefSeq; NP_037216.1; NM_013084.2.
DR AlphaFoldDB; P70584; -.
DR SMR; P70584; -.
DR STRING; 10116.ENSRNOP00000027999; -.
DR SwissLipids; SLP:000001390; -.
DR iPTMnet; P70584; -.
DR PhosphoSitePlus; P70584; -.
DR PaxDb; P70584; -.
DR PRIDE; P70584; -.
DR DNASU; 25618; -.
DR Ensembl; ENSRNOT00000112423; ENSRNOP00000092354; ENSRNOG00000020624.
DR GeneID; 25618; -.
DR KEGG; rno:25618; -.
DR UCSC; RGD:2013; rat.
DR CTD; 36; -.
DR RGD; 2013; Acadsb.
DR eggNOG; KOG0139; Eukaryota.
DR GeneTree; ENSGT00940000156525; -.
DR InParanoid; P70584; -.
DR OrthoDB; 589058at2759; -.
DR PhylomeDB; P70584; -.
DR TreeFam; TF105055; -.
DR BioCyc; MetaCyc:MON-11692; -.
DR Reactome; R-RNO-70895; Branched-chain amino acid catabolism.
DR SABIO-RK; P70584; -.
DR UniPathway; UPA00364; -.
DR UniPathway; UPA00660; -.
DR PRO; PR:P70584; -.
DR Proteomes; UP000002494; Chromosome 1.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0047119; F:2-methyl-branched-chain-enoyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0003853; F:2-methylacyl-CoA dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0003995; F:acyl-CoA dehydrogenase activity; IDA:RGD.
DR GO; GO:0009055; F:electron transfer activity; IDA:RGD.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0102035; F:isobutyryl-CoA:FAD oxidoreductase activity; IEA:UniProtKB-EC.
DR GO; GO:0016937; F:short-branched-chain-acyl-CoA dehydrogenase activity; IDA:MGI.
DR GO; GO:0006637; P:acyl-CoA metabolic process; IDA:MGI.
DR GO; GO:0006635; P:fatty acid beta-oxidation; TAS:RGD.
DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0006550; P:isoleucine catabolic process; ISS:UniProtKB.
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; Mitochondrion; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..33
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT CHAIN 34..432
FT /note="Short/branched chain specific acyl-CoA
FT dehydrogenase, mitochondrial"
FT /id="PRO_0000000521"
FT ACT_SITE 414
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT BINDING 174..183
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT BINDING 183
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT BINDING 207..209
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT BINDING 229
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT BINDING 283
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT BINDING 291..294
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT BINDING 319
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT BINDING 330
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT BINDING 387..391
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT BINDING 416..418
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT MOD_RES 70
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBL1"
FT MOD_RES 70
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBL1"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT MOD_RES 278
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBL1"
FT MOD_RES 284
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P45954"
FT MOD_RES 284
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBL1"
FT MOD_RES 426
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBL1"
SQ SEQUENCE 432 AA; 47824 MW; D35380C6DE3FC7DA CRC64;
MAVSAFQLWR AGGLLRRNFL THSSSWKIPP RVLKSSQPEA LLSVTNNALC FAPLQTFTDE
DIMMQKAVKK FAQEQIAPLV STMDENSKME KSVIQGLFQQ GMMGIEVEAK YGGTEASFLC
SVLVIEELAK VDASVALLCD IQNTVINKLF RKHGTEEQKA TYLPKLVTEK LGSFCLSEAG
AGSDSFALKT RADKSGNYYV INGSKMWISN AEHAELFLVF ANVDPPSGYR GITCFLVDRD
TEGFQIGRRE NKMGIRASST CQLTFENVKV PETSVLGKIG HGYKYAIGSL NEGRIGIAAQ
MLGLAQGCFD YTIPYIKERM QFGKRIFDFQ GLQHQVAHVA TQLEAARLLT YNAARLVEAG
RPFIKEASMA KYYASEVAGL TTSKCIEWMG GVGYTKDYPV EKFFRDAKIG TIYEGTSNIQ
LNTIAKHIDA EY
