ID   ACADM_MACFA             Reviewed;         421 AA.
AC   Q8HXY8;
DT   12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   24-JAN-2024, entry version 89.
DE   RecName: Full=Medium-chain specific acyl-CoA dehydrogenase, mitochondrial {ECO:0000250|UniProtKB:P11310};
DE            Short=MCAD {ECO:0000250|UniProtKB:P11310};
DE            EC=1.3.8.7 {ECO:0000250|UniProtKB:P11310};
DE   Flags: Precursor;
GN   Name=ACADM {ECO:0000250|UniProtKB:P11310};
GN   ORFNames=QtrA-12403 {ECO:0000312|EMBL:BAC20580.1};
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., Hida M., Sugano S., Hashimoto K.;
RT   "Isolation and characterization of cDNA for macaque neurological disease
RT   genes.";
RL   Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Medium-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. Electron
CC       transfer flavoprotein (ETF) is the electron acceptor that transfers
CC       electrons to the main mitochondrial respiratory chain via ETF-
CC       ubiquinone oxidoreductase (ETF dehydrogenase). Among the different
CC       mitochondrial acyl-CoA dehydrogenases, medium-chain specific acyl-CoA
CC       dehydrogenase acts specifically on acyl-CoAs with saturated 6 to 12
CC       carbons long primary chains. {ECO:0000250|UniProtKB:P11310}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a medium-chain 2,3-saturated fatty acyl-CoA + H(+) + oxidized
CC         [electron-transfer flavoprotein] = a medium-chain (2E)-enoyl-CoA +
CC         reduced [electron-transfer flavoprotein]; Xref=Rhea:RHEA:14477,
CC         Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:83723,
CC         ChEBI:CHEBI:83726; EC=1.3.8.7;
CC         Evidence={ECO:0000250|UniProtKB:P11310};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14478;
CC         Evidence={ECO:0000250|UniProtKB:P11310};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H(+) + oxidized [electron-transfer flavoprotein] + pentanoyl-
CC         CoA = (2E)-pentenoyl-CoA + reduced [electron-transfer flavoprotein];
CC         Xref=Rhea:RHEA:43456, Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57389, ChEBI:CHEBI:57692,
CC         ChEBI:CHEBI:58307, ChEBI:CHEBI:86160;
CC         Evidence={ECO:0000250|UniProtKB:P08503};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43457;
CC         Evidence={ECO:0000250|UniProtKB:P08503};
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:P11310};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43465;
CC         Evidence={ECO:0000250|UniProtKB:P11310};
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:P11310};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48181;
CC         Evidence={ECO:0000250|UniProtKB:P11310};
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:P11310};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48177;
CC         Evidence={ECO:0000250|UniProtKB:P11310};
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:P11310};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47297;
CC         Evidence={ECO:0000250|UniProtKB:P11310};
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:P11310};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47317;
CC         Evidence={ECO:0000250|UniProtKB:P11310};
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:P11310};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43449;
CC         Evidence={ECO:0000250|UniProtKB:P11310};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000250|UniProtKB:P11310};
CC   -!- PATHWAY: Lipid metabolism; mitochondrial fatty acid beta-oxidation.
CC       {ECO:0000250|UniProtKB:P11310}.
CC   -!- SUBUNIT: Homotetramer. Interacts with the heterodimeric electron
CC       transfer flavoprotein ETF. {ECO:0000250|UniProtKB:P11310}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC       {ECO:0000250|UniProtKB:P08503}.
CC   -!- PTM: Acetylated. Could occur at proximity of the cofactor-binding sites
CC       and reduce the catalytic activity. Could be deacetylated by SIRT3.
CC       {ECO:0000250|UniProtKB:P11310}.
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; AB083301; BAC20580.1; -; mRNA.
DR   AlphaFoldDB; Q8HXY8; -.
DR   SMR; Q8HXY8; -.
DR   STRING; 9541.ENSMFAP00000019385; -.
DR   eggNOG; KOG0140; Eukaryota.
DR   UniPathway; UPA00660; -.
DR   Proteomes; UP000233100; Unplaced.
DR   GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR   GO; GO:0003995; F:acyl-CoA dehydrogenase activity; ISS:UniProtKB.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR   GO; GO:0070991; F:medium-chain-acyl-CoA dehydrogenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006635; P:fatty acid beta-oxidation; ISS:UniProtKB.
DR   GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; ISS:UniProtKB.
DR   CDD; cd01157; MCAD; 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; IPR034180; MCAD.
DR   PANTHER; PTHR48083:SF2; MEDIUM-CHAIN SPECIFIC ACYL-COA DEHYDROGENASE, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR48083; MEDIUM-CHAIN SPECIFIC ACYL-COA DEHYDROGENASE, 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   PIRSF; PIRSF016578; HsaA; 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.
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..25
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250|UniProtKB:P08503"
FT   CHAIN           26..421
FT                   /note="Medium-chain specific acyl-CoA dehydrogenase,
FT                   mitochondrial"
FT                   /id="PRO_0000000503"
FT   ACT_SITE        401
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P41367"
FT   BINDING         158..167
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:P41367"
FT   BINDING         167
FT                   /ligand="octanoyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57386"
FT                   /evidence="ECO:0000250|UniProtKB:P41367"
FT   BINDING         191..193
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:P41367"
FT   BINDING         278
FT                   /ligand="octanoyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57386"
FT                   /evidence="ECO:0000250|UniProtKB:P41367"
FT   BINDING         281
FT                   /ligand="octanoyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57386"
FT                   /evidence="ECO:0000250|UniProtKB:P41367"
FT   BINDING         306..308
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:P41367"
FT   BINDING         316..317
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:P41367"
FT   BINDING         349
FT                   /ligand="octanoyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57386"
FT                   /evidence="ECO:0000250|UniProtKB:P41367"
FT   BINDING         351
FT                   /ligand="octanoyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57386"
FT                   /evidence="ECO:0000250|UniProtKB:P41367"
FT   BINDING         374..378
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:P41367"
FT   BINDING         401
FT                   /ligand="octanoyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57386"
FT                   /evidence="ECO:0000250|UniProtKB:P41367"
FT   BINDING         402..405
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:P41367"
FT   MOD_RES         69
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P45952"
FT   MOD_RES         69
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P45952"
FT   MOD_RES         179
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P45952"
FT   MOD_RES         212
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P45952"
FT   MOD_RES         212
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P45952"
FT   MOD_RES         217
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P45952"
FT   MOD_RES         217
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P45952"
FT   MOD_RES         259
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P45952"
FT   MOD_RES         259
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P45952"
FT   MOD_RES         271
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P45952"
FT   MOD_RES         271
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P45952"
FT   MOD_RES         279
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P11310"
FT   MOD_RES         301
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P11310"
FT   MOD_RES         351
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P45952"
SQ   SEQUENCE   421 AA;  46626 MW;  DDA2F825B5AF9CC0 CRC64;
     MAAAFGRCCR VLRSISRFHW RSQHTKADRQ REPGLGFSFE FTEQQKEFQA TARKFAREEI
     IPVAAEYDKT GEYPVPLIRR AWELGLMNPH IPQNCGGLGL GTFDACLISE ELAYGCTGVQ
     TAIEGNSLGQ MPIIIAGNEQ QKKKYLGRMT EEPLMCAYCV TEPGAGSDVA GIKTKAEKKG
     DEYIINGQKM WITNGGKASW YFLLARSDPD PKAPANKAFT GFIVEADTPG IQIGRKELNM
     GQRCSDTRGI VFEDVKVLKE NVLIGDGAGF KIAMGAFDKT RPTVSSGAVG LAQRALDEAT
     KYALERKTFG KLLIEHQAIS FMLAEMAMKV ELARMSYQRA AWEVDSGRRN TYYASIAKAF
     AGDIANQLAT DAVQIFGGNG FNTEYPVEKL MRDAKIYQIY EGTSQIQRLI IAREHIGKYK
     S
//