DCMC_HUMAN
ID DCMC_HUMAN Reviewed; 493 AA.
AC O95822; Q9UNU5; Q9Y3F2;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 3.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Malonyl-CoA decarboxylase, mitochondrial {ECO:0000305};
DE Short=MCD;
DE EC=4.1.1.9 {ECO:0000269|PubMed:10417274, ECO:0000269|PubMed:10455107, ECO:0000269|PubMed:15003260, ECO:0000269|PubMed:23482565, ECO:0000269|PubMed:9869665};
DE Flags: Precursor;
GN Name=MLYCD {ECO:0000312|HGNC:HGNC:7150};
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC+PEROXISOMAL), CATALYTIC
RP ACTIVITY, SUBCELLULAR LOCATION, AND INVOLVEMENT IN MLYCD DEFICIENCY.
RX PubMed=10417274; DOI=10.1086/302492;
RA FitzPatrick D.R., Hill A., Tolmie J.L., Thorburn D.R., Christodoulou J.;
RT "The molecular basis of malonyl-CoA decarboxylase deficiency.";
RL Am. J. Hum. Genet. 65:318-326(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC+PEROXISOMAL), FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=10455107; DOI=10.1074/jbc.274.35.24461;
RA Sacksteder K.A., Morrell J.C., Wanders R.J.A., Matalon R., Gould S.J.;
RT "MCD encodes peroxisomal and cytoplasmic forms of malonyl-CoA decarboxylase
RT and is mutated in malonyl-CoA decarboxylase deficiency.";
RL J. Biol. Chem. 274:24461-24468(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MITOCHONDRIAL), AND CATALYTIC ACTIVITY.
RX PubMed=9869665;
RA Gao J., Waber L., Bennett M.J., Gibson K.M., Cohen J.C.;
RT "Cloning and mutational analysis of human malonyl-coenzyme A
RT decarboxylase.";
RL J. Lipid Res. 40:178-182(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS MITOCHONDRIAL AND
RP CYTOPLASMIC+PEROXISOMAL).
RC TISSUE=Eye, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=15003260; DOI=10.1016/j.pep.2003.11.023;
RA Zhou D., Yuen P., Chu D., Thon V., McConnell S., Brown S., Tsang A.,
RA Pena M., Russell A., Cheng J.F., Nadzan A.M., Barbosa M.S., Dyck J.R.,
RA Lopaschuk G.D., Yang G.;
RT "Expression, purification, and characterization of human malonyl-CoA
RT decarboxylase.";
RL Protein Expr. Purif. 34:261-269(2004).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18314420; DOI=10.2337/db07-0583;
RA Bouzakri K., Austin R., Rune A., Lassman M.E., Garcia-Roves P.M.,
RA Berger J.P., Krook A., Chibalin A.V., Zhang B.B., Zierath J.R.;
RT "Malonyl CoenzymeA decarboxylase regulates lipid and glucose metabolism in
RT human skeletal muscle.";
RL Diabetes 57:1508-1516(2008).
RN [8]
RP ASSOCIATION WITH PEX5.
RX PubMed=20178365; DOI=10.1021/ja9109049;
RA Ghosh D., Berg J.M.;
RT "A proteome-wide perspective on peroxisome targeting signal 1(PTS1)-Pex5p
RT affinities.";
RL J. Am. Chem. Soc. 132:3973-3979(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
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).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 39-493 IN COMPLEX WITH LIGAND
RP REPRESENTING COENZYME A, CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, DISULFIDE BONDS, MUTAGENESIS OF
RP CYS-206; CYS-243 AND GLU-302, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23482565; DOI=10.1074/jbc.m112.443846;
RA Aparicio D., Perez R., Carpena X., Diaz M., Ferrer J.C., Loewen P.C.,
RA Fita I.;
RT "Structural asymmetry and disulphide bridges among subunits modulate the
RT activity of human Malonyl-CoA Decarboxylase.";
RL J. Biol. Chem. 288:11907-11919(2013).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 40-490, SUBUNIT, ACTIVE SITE, AND
RP MUTAGENESIS OF SER-290; SER-329; HIS-423 AND TYR-456.
RX PubMed=23791943; DOI=10.1016/j.str.2013.05.001;
RA Froese D.S., Forouhar F., Tran T.H., Vollmar M., Kim Y.S., Lew S.,
RA Neely H., Seetharaman J., Shen Y., Xiao R., Acton T.B., Everett J.K.,
RA Cannone G., Puranik S., Savitsky P., Krojer T., Pilka E.S., Kiyani W.,
RA Lee W.H., Marsden B.D., von Delft F., Allerston C.K., Spagnolo L.,
RA Gileadi O., Montelione G.T., Oppermann U., Yue W.W., Tong L.;
RT "Crystal structures of malonyl-coenzyme A decarboxylase provide insights
RT into its catalytic mechanism and disease-causing mutations.";
RL Structure 21:1182-1192(2013).
CC -!- FUNCTION: Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In the
CC fatty acid biosynthesis MCD selectively removes malonyl-CoA and thus
CC assures that methyl-malonyl-CoA is the only chain elongating substrate
CC for fatty acid synthase and that fatty acids with multiple methyl side
CC chains are produced. In peroxisomes it may be involved in degrading
CC intraperoxisomal malonyl-CoA, which is generated by the peroxisomal
CC beta-oxidation of odd chain-length dicarboxylic fatty acids. Plays a
CC role in the metabolic balance between glucose and lipid oxidation in
CC muscle independent of alterations in insulin signaling. May play a role
CC in controlling the extent of ischemic injury by promoting glucose
CC oxidation. {ECO:0000269|PubMed:10455107, ECO:0000269|PubMed:15003260,
CC ECO:0000269|PubMed:18314420, ECO:0000269|PubMed:23482565}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + malonyl-CoA = acetyl-CoA + CO2; Xref=Rhea:RHEA:18781,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:57384; EC=4.1.1.9; Evidence={ECO:0000269|PubMed:10417274,
CC ECO:0000269|PubMed:10455107, ECO:0000269|PubMed:15003260,
CC ECO:0000269|PubMed:23482565, ECO:0000269|PubMed:9869665};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18782;
CC Evidence={ECO:0000305|PubMed:23482565};
CC -!- ACTIVITY REGULATION: Malonyl-CoA decarboxylase activity does not
CC require any cofactors or divalent metal ions. Formation of interchain
CC disulfide bonds leads to positive cooperativity between active sites
CC and increases the affinity for malonyl-CoA and the catalytic efficiency
CC (in vitro). {ECO:0000269|PubMed:15003260, ECO:0000269|PubMed:23482565}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.36 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial
CC form) {ECO:0000269|PubMed:15003260};
CC KM=0.83 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial
CC form) {ECO:0000269|PubMed:23482565};
CC KM=0.22 mM for malonyl-CoA (Malonyl-CoA decarboxylase
CC cytoplasmic+peroxisomal form) {ECO:0000269|PubMed:10455107};
CC KM=0.33 mM for malonyl-CoA (Malonyl-CoA decarboxylase
CC cytoplasmic+peroxisomal form) {ECO:0000269|PubMed:15003260};
CC Note=kcat is 19 sec(-1) with malonyl-CoA for malonyl-CoA
CC decarboxylase mitochondrial form (PubMed:15003260). kcat is 28 sec(-
CC 1) with malonyl-CoA for Malonyl-CoA decarboxylase
CC cytoplasmic+peroxisomal form (PubMed:15003260). The catalytic
CC efficiency for malonyl-CoA is at least 1.09-fold higher with the
CC malonyl-CoA decarboxylase cytoplasmic+peroxisomal form
CC (PubMed:15003260). {ECO:0000269|PubMed:15003260};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; acetyl-CoA biosynthesis;
CC acetyl-CoA from malonyl-CoA: step 1/1.
CC -!- SUBUNIT: Homotetramer. Dimer of dimers. The two subunits within a dimer
CC display conformational differences suggesting that at any given moment,
CC only one of the two subunits is competent for malonyl-CoA binding and
CC catalytic activity. Under oxidizing conditions, can form disulfide-
CC linked homotetramers (in vitro). Associates with the peroxisomal
CC targeting signal receptor PEX5. {ECO:0000269|PubMed:23482565,
CC ECO:0000269|PubMed:23791943}.
CC -!- INTERACTION:
CC O95822; O95822: MLYCD; NbExp=4; IntAct=EBI-10714916, EBI-10714916;
CC O95822-2; P52756: RBM5; NbExp=4; IntAct=EBI-13315321, EBI-714003;
CC O95822-2; Q8TB05: UBALD1; NbExp=3; IntAct=EBI-13315321, EBI-725656;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10417274}.
CC Mitochondrion matrix {ECO:0000269|PubMed:10417274}. Peroxisome
CC {ECO:0000269|PubMed:10417274}. Peroxisome matrix
CC {ECO:0000250|UniProtKB:Q920F5}. Note=Enzymatically active in all three
CC subcellular compartments. {ECO:0000250|UniProtKB:Q920F5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Comment=A single transcription start site has been demonstrated in
CC Rat.;
CC Name=Mitochondrial;
CC IsoId=O95822-1; Sequence=Displayed;
CC Name=Cytoplasmic+peroxisomal;
CC IsoId=O95822-2; Sequence=VSP_047649;
CC -!- TISSUE SPECIFICITY: Expressed in fibroblasts and hepatoblastoma cells
CC (at protein level). Expressed strongly in heart, liver, skeletal
CC muscle, kidney and pancreas. Expressed in myotubes. Expressed weakly in
CC brain, placenta, spleen, thymus, testis, ovary and small intestine.
CC {ECO:0000269|PubMed:10455107, ECO:0000269|PubMed:18314420}.
CC -!- PTM: Acetylation at Lys-472 activates malonyl-CoA decarboxylase
CC activity. Deacetylation at Lys-472 by SIRT4 represses activity, leading
CC to promote lipogenesis (By similarity). {ECO:0000250|UniProtKB:Q99J39}.
CC -!- PTM: Interchain disulfide bonds may form in peroxisomes (Potential).
CC Interchain disulfide bonds are not expected to form in the reducing
CC environment of the cytoplasm and mitochondria. {ECO:0000305}.
CC -!- DISEASE: Malonyl-CoA decarboxylase deficiency (MLYCD deficiency)
CC [MIM:248360]: Autosomal recessive disease characterized by abdominal
CC pain, chronic constipation, episodic vomiting, metabolic acidosis and
CC malonic aciduria. {ECO:0000269|PubMed:10417274}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform Cytoplasmic+peroxisomal]: May be produced by
CC alternative initiation at Met-40 of isoform mitochondrial.
CC Alternatively, represents a proteolytic processed form of the
CC mitochondrial form. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD16177.2; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF097832; AAD16177.2; ALT_FRAME; mRNA.
DR EMBL; AF153679; AAD34631.1; -; mRNA.
DR EMBL; AF090834; AAD48994.1; -; mRNA.
DR EMBL; AC009119; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000286; AAH00286.1; -; mRNA.
DR EMBL; BC052592; AAH52592.1; -; mRNA.
DR CCDS; CCDS42206.1; -. [O95822-1]
DR RefSeq; NP_036345.2; NM_012213.2. [O95822-1]
DR PDB; 2YGW; X-ray; 2.80 A; A/B=40-490.
DR PDB; 4F0X; X-ray; 3.29 A; A/B/C/D/E/F/G/H=39-493.
DR PDBsum; 2YGW; -.
DR PDBsum; 4F0X; -.
DR AlphaFoldDB; O95822; -.
DR SMR; O95822; -.
DR BioGRID; 116989; 29.
DR DIP; DIP-60405N; -.
DR IntAct; O95822; 18.
DR STRING; 9606.ENSP00000262430; -.
DR BindingDB; O95822; -.
DR ChEMBL; CHEMBL4698; -.
DR GuidetoPHARMACOLOGY; 1275; -.
DR SwissLipids; SLP:000000251; -.
DR iPTMnet; O95822; -.
DR PhosphoSitePlus; O95822; -.
DR BioMuta; MLYCD; -.
DR EPD; O95822; -.
DR jPOST; O95822; -.
DR MassIVE; O95822; -.
DR MaxQB; O95822; -.
DR PaxDb; O95822; -.
DR PeptideAtlas; O95822; -.
DR PRIDE; O95822; -.
DR ProteomicsDB; 51071; -. [O95822-1]
DR Antibodypedia; 30519; 109 antibodies from 21 providers.
DR DNASU; 23417; -.
DR Ensembl; ENST00000262430.6; ENSP00000262430.4; ENSG00000103150.7. [O95822-1]
DR GeneID; 23417; -.
DR KEGG; hsa:23417; -.
DR MANE-Select; ENST00000262430.6; ENSP00000262430.4; NM_012213.3; NP_036345.2.
DR UCSC; uc002fgz.4; human. [O95822-1]
DR CTD; 23417; -.
DR DisGeNET; 23417; -.
DR GeneCards; MLYCD; -.
DR HGNC; HGNC:7150; MLYCD.
DR HPA; ENSG00000103150; Tissue enhanced (tongue).
DR MalaCards; MLYCD; -.
DR MIM; 248360; phenotype.
DR MIM; 606761; gene.
DR neXtProt; NX_O95822; -.
DR OpenTargets; ENSG00000103150; -.
DR Orphanet; 943; Malonic aciduria.
DR PharmGKB; PA30861; -.
DR VEuPathDB; HostDB:ENSG00000103150; -.
DR eggNOG; KOG3018; Eukaryota.
DR GeneTree; ENSGT00390000005410; -.
DR HOGENOM; CLU_023433_0_0_1; -.
DR InParanoid; O95822; -.
DR OMA; PIDWSTP; -.
DR OrthoDB; 1436590at2759; -.
DR PhylomeDB; O95822; -.
DR TreeFam; TF312959; -.
DR BRENDA; 4.1.1.9; 2681.
DR PathwayCommons; O95822; -.
DR Reactome; R-HSA-390247; Beta-oxidation of very long chain fatty acids. [O95822-2]
DR Reactome; R-HSA-9033241; Peroxisomal protein import. [O95822-2]
DR SABIO-RK; O95822; -.
DR SignaLink; O95822; -.
DR UniPathway; UPA00340; UER00710.
DR BioGRID-ORCS; 23417; 8 hits in 1075 CRISPR screens.
DR ChiTaRS; MLYCD; human.
DR GenomeRNAi; 23417; -.
DR Pharos; O95822; Tchem.
DR PRO; PR:O95822; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O95822; protein.
DR Bgee; ENSG00000103150; Expressed in skeletal muscle tissue of rectus abdominis and 161 other tissues.
DR ExpressionAtlas; O95822; baseline and differential.
DR Genevisible; O95822; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005782; C:peroxisomal matrix; ISS:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050080; F:malonyl-CoA decarboxylase activity; IDA:UniProtKB.
DR GO; GO:0006085; P:acetyl-CoA biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006637; P:acyl-CoA metabolic process; TAS:Reactome.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0019395; P:fatty acid oxidation; IEA:Ensembl.
DR GO; GO:2001294; P:malonyl-CoA catabolic process; IDA:UniProtKB.
DR GO; GO:0046321; P:positive regulation of fatty acid oxidation; IMP:UniProtKB.
DR GO; GO:0031998; P:regulation of fatty acid beta-oxidation; IEA:Ensembl.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IMP:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; ISS:UniProtKB.
DR Gene3D; 1.20.140.90; -; 1.
DR Gene3D; 3.40.630.150; -; 1.
DR InterPro; IPR038917; Malonyl_CoA_deC.
DR InterPro; IPR007956; Malonyl_CoA_deC_C.
DR InterPro; IPR042303; Malonyl_CoA_deC_C_sf.
DR InterPro; IPR035372; MCD_N.
DR InterPro; IPR038351; MCD_N_sf.
DR PANTHER; PTHR28641; PTHR28641; 1.
DR Pfam; PF05292; MCD; 1.
DR Pfam; PF17408; MCD_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative initiation; Cytoplasm;
KW Decarboxylase; Disulfide bond; Fatty acid biosynthesis;
KW Fatty acid metabolism; Lipid biosynthesis; Lipid metabolism; Lyase;
KW Mitochondrion; Peroxisome; Reference proteome; Transit peptide.
FT TRANSIT 1..39
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 40..493
FT /note="Malonyl-CoA decarboxylase, mitochondrial"
FT /id="PRO_0000021088"
FT REGION 40..190
FT /note="Alpha-helical domain"
FT REGION 191..493
FT /note="Catalytic domain"
FT MOTIF 491..493
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 329
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:23791943"
FT ACT_SITE 423
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:23791943"
FT BINDING 299..305
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000305"
FT BINDING 329
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000305"
FT BINDING 423
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000305"
FT SITE 211
FT /note="Essential for catalytic activity"
FT /evidence="ECO:0000250"
FT MOD_RES 59
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99J39"
FT MOD_RES 168
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99J39"
FT MOD_RES 168
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99J39"
FT MOD_RES 211
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99J39"
FT MOD_RES 222
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99J39"
FT MOD_RES 389
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99J39"
FT MOD_RES 472
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99J39"
FT DISULFID 206
FT /note="Interchain"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..39
FT /note="Missing (in isoform Cytoplasmic+peroxisomal)"
FT /evidence="ECO:0000303|PubMed:10417274,
FT ECO:0000303|PubMed:10455107, ECO:0000303|PubMed:15489334"
FT /id="VSP_047649"
FT MUTAGEN 206
FT /note="C->S: Abolishes formation of disulfide-linked
FT homotetramers. Abolishes the cooperative enzyme kinetics
FT that are seen under oxidative conditions."
FT /evidence="ECO:0000269|PubMed:23482565"
FT MUTAGEN 243
FT /note="C->S: Does not abolish formation of disulfide-linked
FT homotetramers. No effect on development of cooperative
FT enzyme kinetics in response to oxidative conditions."
FT /evidence="ECO:0000269|PubMed:23482565"
FT MUTAGEN 290
FT /note="S->F: 2-fold reduction in catalytic activity."
FT /evidence="ECO:0000269|PubMed:23791943"
FT MUTAGEN 302
FT /note="E->G: Decreases catalytic activity. Increases
FT affinity for malonyl-CoA."
FT /evidence="ECO:0000269|PubMed:23482565"
FT MUTAGEN 329
FT /note="S->A: 110-fold reduction in catalytic activity."
FT /evidence="ECO:0000269|PubMed:23791943"
FT MUTAGEN 423
FT /note="H->N: 7-fold reduction in catalytic activity."
FT /evidence="ECO:0000269|PubMed:23791943"
FT MUTAGEN 456
FT /note="Y->S: 3.5-fold reduction in catalytic activity."
FT /evidence="ECO:0000269|PubMed:23791943"
FT CONFLICT 82
FT /note="A -> D (in Ref. 1; AAD16177)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="A -> S (in Ref. 3; AAD48994)"
FT /evidence="ECO:0000305"
FT CONFLICT 127
FT /note="D -> V (in Ref. 3; AAD48994)"
FT /evidence="ECO:0000305"
FT CONFLICT 192
FT /note="S -> P (in Ref. 2; AAD34631)"
FT /evidence="ECO:0000305"
FT HELIX 40..47
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 67..76
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 81..94
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 99..112
FT /evidence="ECO:0007829|PDB:2YGW"
FT TURN 114..116
FT /evidence="ECO:0007829|PDB:4F0X"
FT HELIX 119..132
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 138..145
FT /evidence="ECO:0007829|PDB:2YGW"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:4F0X"
FT HELIX 150..166
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 173..189
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:2YGW"
FT STRAND 195..200
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 206..214
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 224..230
FT /evidence="ECO:0007829|PDB:2YGW"
FT STRAND 235..242
FT /evidence="ECO:0007829|PDB:2YGW"
FT STRAND 250..260
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 266..269
FT /evidence="ECO:0007829|PDB:2YGW"
FT STRAND 285..294
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:2YGW"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:4F0X"
FT HELIX 303..318
FT /evidence="ECO:0007829|PDB:2YGW"
FT STRAND 324..327
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 334..341
FT /evidence="ECO:0007829|PDB:2YGW"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:4F0X"
FT HELIX 357..367
FT /evidence="ECO:0007829|PDB:4F0X"
FT HELIX 374..379
FT /evidence="ECO:0007829|PDB:2YGW"
FT TURN 380..382
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 383..386
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 388..393
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 395..407
FT /evidence="ECO:0007829|PDB:2YGW"
FT STRAND 414..417
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 418..425
FT /evidence="ECO:0007829|PDB:2YGW"
FT STRAND 429..434
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 441..447
FT /evidence="ECO:0007829|PDB:2YGW"
FT STRAND 451..455
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 458..460
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 461..471
FT /evidence="ECO:0007829|PDB:2YGW"
FT HELIX 478..486
FT /evidence="ECO:0007829|PDB:2YGW"
SQ SEQUENCE 493 AA; 55003 MW; 8F061CA38908E8FC CRC64;
MRGFGPGLTA RRLLPLRLPP RPPGPRLASG QAAGALERAM DELLRRAVPP TPAYELREKT
PAPAEGQCAD FVSFYGGLAE TAQRAELLGR LARGFGVDHG QVAEQSAGVL HLRQQQREAA
VLLQAEDRLR YALVPRYRGL FHHISKLDGG VRFLVQLRAD LLEAQALKLV EGPDVREMNG
VLKGMLSEWF SSGFLNLERV TWHSPCEVLQ KISEAEAVHP VKNWMDMKRR VGPYRRCYFF
SHCSTPGEPL VVLHVALTGD ISSNIQAIVK EHPPSETEEK NKITAAIFYS ISLTQQGLQG
VELGTFLIKR VVKELQREFP HLGVFSSLSP IPGFTKWLLG LLNSQTKEHG RNELFTDSEC
KEISEITGGP INETLKLLLS SSEWVQSEKL VRALQTPLMR LCAWYLYGEK HRGYALNPVA
NFHLQNGAVL WRINWMADVS LRGITGSCGL MANYRYFLEE TGPNSTSYLG SKIIKASEQV
LSLVAQFQKN SKL
