ID   B7Z9I1_HUMAN            Unreviewed;       385 AA.
AC   B7Z9I1;
DT   03-MAR-2009, integrated into UniProtKB/TrEMBL.
DT   03-MAR-2009, sequence version 1.
DT   24-JAN-2024, entry version 119.
DE   RecName: Full=Medium-chain specific acyl-CoA dehydrogenase, mitochondrial {ECO:0000256|ARBA:ARBA00019125};
DE            EC=1.3.8.7 {ECO:0000256|ARBA:ARBA00012033};
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 {ECO:0000313|EMBL:BAH14317.1};
RN   [1] {ECO:0000313|EMBL:BAH14317.1}
RP   NUCLEOTIDE SEQUENCE.
RC   TISSUE=Alzheimer cortex {ECO:0000313|EMBL:BAH14317.1};
RA   Wakamatsu A., Yamamoto J., Kimura K., Ishii S., Watanabe K., Sugiyama A.,
RA   Murakawa K., Kaida T., Tsuchiya K., Fukuzumi Y., Kumagai A., Oishi Y.,
RA   Yamamoto S., Ono Y., Komori Y., Yamazaki M., Kisu Y., Nishikawa T.,
RA   Sugano S., Nomura N., Isogai T.;
RT   "NEDO human cDNA sequencing project.";
RL   Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases.
RN   [2] {ECO:0007829|PubMed:19608861}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [3] {ECO:0007829|PubMed:21269460}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Burckstummer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [4] {ECO:0007829|PubMed:24275569}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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   [5] {ECO:0007829|PubMed:25944712}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
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:0000256|ARBA:ARBA00001337};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43449;
CC         Evidence={ECO:0000256|ARBA:ARBA00001337};
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:0000256|ARBA:ARBA00001483};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43465;
CC         Evidence={ECO:0000256|ARBA:ARBA00001483};
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:0000256|ARBA:ARBA00001547};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48181;
CC         Evidence={ECO:0000256|ARBA:ARBA00001547};
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:0000256|ARBA:ARBA00023695};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43457;
CC         Evidence={ECO:0000256|ARBA:ARBA00023695};
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:0000256|ARBA:ARBA00001236};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47317;
CC         Evidence={ECO:0000256|ARBA:ARBA00001236};
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:0000256|ARBA:ARBA00034058};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14478;
CC         Evidence={ECO:0000256|ARBA:ARBA00034058};
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:0000256|ARBA:ARBA00000121};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48177;
CC         Evidence={ECO:0000256|ARBA:ARBA00000121};
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:0000256|ARBA:ARBA00001486};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47297;
CC         Evidence={ECO:0000256|ARBA:ARBA00001486};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000256|ARBA:ARBA00001974,
CC         ECO:0000256|PIRSR:PIRSR634180-3, ECO:0000256|RuleBase:RU362125};
CC   -!- PATHWAY: Lipid metabolism; mitochondrial fatty acid beta-oxidation.
CC       {ECO:0000256|ARBA:ARBA00005198}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC       {ECO:0000256|ARBA:ARBA00004305}.
CC   -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC       {ECO:0000256|ARBA:ARBA00009347, ECO:0000256|RuleBase:RU362125}.
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DR   EMBL; AK315946; BAH14317.1; -; mRNA.
DR   RefSeq; NP_001272971.1; NM_001286042.1.
DR   AlphaFoldDB; B7Z9I1; -.
DR   SMR; B7Z9I1; -.
DR   IntAct; B7Z9I1; 1.
DR   EPD; B7Z9I1; -.
DR   MassIVE; B7Z9I1; -.
DR   MaxQB; B7Z9I1; -.
DR   PeptideAtlas; B7Z9I1; -.
DR   ProteomicsDB; 7032; -.
DR   Antibodypedia; 1642; 521 antibodies from 38 providers.
DR   DNASU; 34; -.
DR   GeneID; 34; -.
DR   UCSC; uc010ore.4; human.
DR   CTD; 34; -.
DR   VEuPathDB; HostDB:ENSG00000117054; -.
DR   HOGENOM; CLU_018204_0_2_1; -.
DR   OrthoDB; 275353at2759; -.
DR   UniPathway; UPA00660; -.
DR   BioGRID-ORCS; 34; 15 hits in 1160 CRISPR screens.
DR   ChiTaRS; ACADM; human.
DR   GenomeRNAi; 34; -.
DR   ExpressionAtlas; B7Z9I1; baseline and differential.
DR   GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0070991; F:medium-chain-acyl-CoA dehydrogenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006635; P:fatty acid beta-oxidation; IEA:InterPro.
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; 2.
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   1: Evidence at protein level;
KW   Acetylation {ECO:0000256|ARBA:ARBA00022990};
KW   FAD {ECO:0000256|ARBA:ARBA00022827, ECO:0000256|PIRSR:PIRSR634180-3};
KW   Flavoprotein {ECO:0000256|ARBA:ARBA00022630,
KW   ECO:0000256|RuleBase:RU362125};
KW   Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW   ECO:0000256|RuleBase:RU362125};
KW   Transit peptide {ECO:0000256|ARBA:ARBA00022946}.
FT   DOMAIN          6..115
FT                   /note="Acyl-CoA dehydrogenase/oxidase N-terminal"
FT                   /evidence="ECO:0000259|Pfam:PF02771"
FT   DOMAIN          121..219
FT                   /note="Acyl-CoA oxidase/dehydrogenase middle"
FT                   /evidence="ECO:0000259|Pfam:PF02770"
FT   DOMAIN          231..378
FT                   /note="Acyl-CoA dehydrogenase/oxidase C-terminal"
FT                   /evidence="ECO:0000259|Pfam:PF00441"
FT   ACT_SITE        365
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR634180-1"
FT   BINDING         122..131
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:0000256|PIRSR:PIRSR634180-3"
FT   BINDING         131
FT                   /ligand="octanoyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57386"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR634180-2"
FT   BINDING         155..157
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:0000256|PIRSR:PIRSR634180-3"
FT   BINDING         180
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR634180-2"
FT   BINDING         242..245
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR634180-2"
FT   BINDING         270..272
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:0000256|PIRSR:PIRSR634180-3"
FT   BINDING         280..281
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:0000256|PIRSR:PIRSR634180-3"
FT   BINDING         338..342
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:0000256|PIRSR:PIRSR634180-3"
FT   BINDING         366
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR634180-2"
FT   BINDING         367..369
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:0000256|PIRSR:PIRSR634180-3"
FT   BINDING         377
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR634180-2"
SQ   SEQUENCE   385 AA;  42427 MW;  73DDC14C91A62D6D CRC64;
     MLQEFTEQQK EFQATARKFA REEIIPVAAE YDKTGEYPVP LIRRAWELGL MNTHIPENCG
     GLGLGTFDAC LISEELAYGC TGVQTAIEGN SLGQMPIIIA GNDQQKKKYL GRMTEEPLMC
     AYCVTEPGAG SDVAGIKTKA EKKGDEYIIN GQKMWITNGG KANWYFLLAR SDPDPKAPAN
     KAFTGFIVEA DTPGIQIGRK ELNMGQRCSD TRGIVFEDVK VPKENVLIGD GAGFKVAMGA
     FDKTRPVVAA GAVGLAQRAL DEATKYALER KTFGKLLVEH QAISFMLAEM AMKVELARMS
     YQRAAWEVDS GRRNTYYASI AKAFAGDIAN QLATDAVQIL GGNGFNTEYP VEKLMRDAKI
     YQIYEGTSQI QRLIVAREHI DKYKN
//