ID   ACEB_YARLI              Reviewed;         565 AA.
AC   Q6BZP5;
DT   24-JUN-2015, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2004, sequence version 1.
DT   25-MAY-2022, entry version 94.
DE   RecName: Full=2-methylisocitrate lyase, mitochondrial {ECO:0000303|PubMed:7117251, ECO:0000303|Ref.2, ECO:0000303|Ref.3, ECO:0000303|Ref.4};
DE            EC=4.1.3.30 {ECO:0000269|PubMed:7117251, ECO:0000269|Ref.2, ECO:0000269|Ref.3, ECO:0000269|Ref.4};
DE   Flags: Precursor;
GN   OrderedLocusNames=YALI0F31999g;
OS   Yarrowia lipolytica (strain CLIB 122 / E 150) (Yeast) (Candida lipolytica).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Dipodascaceae; Yarrowia.
OX   NCBI_TaxID=284591;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=CLIB 122 / E 150;
RX   PubMed=15229592; DOI=10.1038/nature02579;
RA   Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I.,
RA   de Montigny J., Marck C., Neuveglise C., Talla E., Goffard N., Frangeul L.,
RA   Aigle M., Anthouard V., Babour A., Barbe V., Barnay S., Blanchin S.,
RA   Beckerich J.-M., Beyne E., Bleykasten C., Boisrame A., Boyer J.,
RA   Cattolico L., Confanioleri F., de Daruvar A., Despons L., Fabre E.,
RA   Fairhead C., Ferry-Dumazet H., Groppi A., Hantraye F., Hennequin C.,
RA   Jauniaux N., Joyet P., Kachouri R., Kerrest A., Koszul R., Lemaire M.,
RA   Lesur I., Ma L., Muller H., Nicaud J.-M., Nikolski M., Oztas S.,
RA   Ozier-Kalogeropoulos O., Pellenz S., Potier S., Richard G.-F.,
RA   Straub M.-L., Suleau A., Swennen D., Tekaia F., Wesolowski-Louvel M.,
RA   Westhof E., Wirth B., Zeniou-Meyer M., Zivanovic Y., Bolotin-Fukuhara M.,
RA   Thierry A., Bouchier C., Caudron B., Scarpelli C., Gaillardin C.,
RA   Weissenbach J., Wincker P., Souciet J.-L.;
RT   "Genome evolution in yeasts.";
RL   Nature 430:35-44(2004).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   DOI=10.1271/bbb1961.40.1863;
RA   Tabuchi T., Satoh T.;
RT   "Distinction between isocitrate lyase and methylisocitrate lyase in Candida
RT   lipolytica.";
RL   Agric. Biol. Chem. 40:1863-1869(1976).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND
RP   ACTIVITY REGULATION.
RX   DOI=10.1271/bbb1961.41.169;
RA   Tabuchi T., Satoh T.;
RT   "Purification and properties of methylisocitrate lyase, a key enzyme in
RT   propionate metabolism, from Candida lipolytica.";
RL   Agric. Biol. Chem. 41:169-174(1977).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
RX   DOI=10.1271/bbb1961.42.2381;
RA   Tabuchi T., Igoshi K.;
RT   "Regulation of enzyme synthesis of the glycolate, the citric acid, and the
RT   methylcitric acid cycles in Candida lipolytica.";
RL   Agric. Biol. Chem. 42:2381-2386(1978).
RN   [5]
RP   SUBCELLULAR LOCATION, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=7117251; DOI=10.1111/j.1432-1033.1982.tb06713.x;
RA   Uchiyama H., Ando M., Toyonaka Y., Tabuchi T.;
RT   "Subcellular localization of the methylcitric-acid-cycle enzymes in
RT   propionate metabolism of Yarrowia lipolytica.";
RL   Eur. J. Biochem. 125:523-527(1982).
CC   -!- FUNCTION: Component of the methylcitrate cycle that catalyzes the
CC       formation of pyruvate and succinate from 2-methylisocitrate during the
CC       metabolism of endogenous propionyl-CoA. {ECO:0000269|PubMed:7117251,
CC       ECO:0000269|Ref.2, ECO:0000269|Ref.3, ECO:0000269|Ref.4}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = pyruvate +
CC         succinate; Xref=Rhea:RHEA:16809, ChEBI:CHEBI:15361,
CC         ChEBI:CHEBI:30031, ChEBI:CHEBI:57429; EC=4.1.3.30;
CC         Evidence={ECO:0000269|PubMed:7117251, ECO:0000269|Ref.2,
CC         ECO:0000269|Ref.3, ECO:0000269|Ref.4};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|Ref.3};
CC   -!- ACTIVITY REGULATION: Inhibited in the presence of NADH and NADPH. When
CC       Mg(2+) is present, Cu(2+), Hg(2+) and Zn(2+) inhibit the enzyme
CC       activity in some extent. {ECO:0000269|Ref.3}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.77 mM for (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate
CC         {ECO:0000269|Ref.3};
CC         KM=0.6 mM for magnesium chloride (MgCl(2)) {ECO:0000269|Ref.3};
CC         KM=0.43 mM for cysteine {ECO:0000269|Ref.3};
CC       pH dependence:
CC         Optimum pH is 7.3-7.8. {ECO:0000269|Ref.2, ECO:0000269|Ref.3};
CC       Temperature dependence:
CC         Optimum temperature is 40 degrees Celsius. {ECO:0000269|Ref.3};
CC   -!- PATHWAY: Organic acid metabolism; propanoate degradation.
CC       {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000305}.
CC   -!- INDUCTION: Repressed by glucose. {ECO:0000269|Ref.4}.
CC   -!- SIMILARITY: Belongs to the isocitrate lyase/PEP mutase superfamily.
CC       Isocitrate lyase family. {ECO:0000305}.
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DR   EMBL; CR382132; CAG78931.1; -; Genomic_DNA.
DR   RefSeq; XP_506117.1; XM_506117.1.
DR   AlphaFoldDB; Q6BZP5; -.
DR   SMR; Q6BZP5; -.
DR   STRING; 4952.CAG78931; -.
DR   EnsemblFungi; CAG78931; CAG78931; YALI0_F31999g.
DR   GeneID; 2908123; -.
DR   KEGG; yli:YALI0F31999g; -.
DR   VEuPathDB; FungiDB:YALI0_F31999g; -.
DR   HOGENOM; CLU_019214_2_2_1; -.
DR   InParanoid; Q6BZP5; -.
DR   OMA; ARFQWDM; -.
DR   UniPathway; UPA00946; -.
DR   Proteomes; UP000001300; Chromosome F.
DR   GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR   GO; GO:0004451; F:isocitrate lyase activity; IEA:InterPro.
DR   GO; GO:0046421; F:methylisocitrate lyase activity; IBA:GO_Central.
DR   GO; GO:0019629; P:propionate catabolic process, 2-methylcitrate cycle; IBA:GO_Central.
DR   CDD; cd00377; ICL_PEPM; 1.
DR   Gene3D; 3.20.20.60; -; 1.
DR   InterPro; IPR039556; ICL/PEPM.
DR   InterPro; IPR006254; Isocitrate_lyase.
DR   InterPro; IPR018523; Isocitrate_lyase_ph_CS.
DR   InterPro; IPR015813; Pyrv/PenolPyrv_Kinase-like_dom.
DR   InterPro; IPR040442; Pyrv_Kinase-like_dom_sf.
DR   PANTHER; PTHR21631; PTHR21631; 1.
DR   Pfam; PF00463; ICL; 1.
DR   PIRSF; PIRSF001362; Isocit_lyase; 1.
DR   SUPFAM; SSF51621; SSF51621; 1.
DR   TIGRFAMs; TIGR01346; isocit_lyase; 1.
DR   PROSITE; PS00161; ISOCITRATE_LYASE; 1.
PE   1: Evidence at protein level;
KW   Lyase; Mitochondrion; Reference proteome; Transit peptide.
FT   TRANSIT         1..19
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           20..565
FT                   /note="2-methylisocitrate lyase, mitochondrial"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000433360"
FT   ACT_SITE        238
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10119"
SQ   SEQUENCE   565 AA;  63005 MW;  A8E2FF6730819F14 CRC64;
     MLRTRFINSV NSARAMSRNI NTLSQFPYPT LQQEESFFKS QVEDIEKWWA SPRYEGIKRP
     YTAEKVAIHR GTLPQTYASS VQAEKLFNIF TERGKQGLPV HTTGSVDPVQ MTQSAPHQEV
     VYISGWACSS LLTTTNEVSP DFGDYPYDTV PNQVDRIFRA QGLHDKKAWH EWMSLSHEER
     VKRDQEGKGR IDYLRPIIAD ADTGHGGLSA VMKLAKLFAE RGAAAIHLED QLHGGKKCGH
     LAGKVIVPTG SHISRLNATR MQWDIMGCSN LVIARTDSES AKLLSSAADP SDHEYILGVV
     KPIKPLAEVL LTAEANGATA DMVNKLELEW TKEAEMMTYD EAVQRALTEA GKSDKIEEYL
     TKAKGKSNFE ARQIADELAG KHIFFDWDAP KTREGHYHVQ CGIEPAIKRA LAFAPYADLI
     WLETKTPDLA QAQAFAKRIR EKFPGKWLVY NLSPSFNWSA HGYSDEQLKS FVWDLAKSGF
     VMQLISLAGL HSNAVATHEL STRFKTEGMK AYVDLVQRKE KELGCDVLTH QKWSGANYLD
     SIISTVQSGS SGTSSTGGDS TENQF