ID   ACEA1_MYCTE             Reviewed;         428 AA.
AC   H8EVV4;
DT   01-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT   16-MAY-2012, sequence version 1.
DT   03-AUG-2022, entry version 53.
DE   RecName: Full=Isocitrate lyase 1 {ECO:0000303|PubMed:16689789};
DE            Short=ICL1 {ECO:0000303|PubMed:16689789};
DE            EC=4.1.3.1 {ECO:0000269|PubMed:16689789};
DE   AltName: Full=Isocitrase {ECO:0000303|PubMed:16689789};
DE   AltName: Full=Isocitratase {ECO:0000303|PubMed:16689789};
DE   AltName: Full=Methylisocitrate lyase {ECO:0000303|PubMed:16689789};
DE            Short=MICA {ECO:0000303|PubMed:16689789};
DE            EC=4.1.3.30 {ECO:0000269|PubMed:16689789};
GN   Name=icl1; OrderedLocusNames=ERDMAN_0512; ORFNames=Q643_00485;
OS   Mycobacterium tuberculosis (strain ATCC 35801 / TMC 107 / Erdman).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium; Mycobacterium tuberculosis complex.
OX   NCBI_TaxID=652616;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX   PubMed=22535945; DOI=10.1128/jb.00353-12;
RA   Miyoshi-Akiyama T., Matsumura K., Iwai H., Funatogawa K., Kirikae T.;
RT   "Complete annotated genome sequence of Mycobacterium tuberculosis Erdman.";
RL   J. Bacteriol. 194:2770-2770(2012).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 35801 / TMC 107 / Erdman;
RG   The Broad Institute Genomics Platform;
RG   The Broad Institute Genome Sequencing Center for Infectious Disease;
RA   Earl A.M., Hung D., Gomez D., Hsueh P.R., Rozo J.C., Zambrano M.M.,
RA   Desjardins C., Abeel T., Young S., Zeng Q., Gargeya S., Abouelleil A.,
RA   Alvarado L., Chapman S.B., Gainer-Dewar J., Goldberg J., Griggs A.,
RA   Gujja S., Hansen M., Howarth C., Imamovic A., Larimer J., Murphy C.,
RA   Naylor J., Pearson M., Poon T.W., Priest M., Roberts A., Saif S., Shea T.,
RA   Sykes S., Wortman J., Nusbaum C., Birren B.;
RT   "The genome sequence of Mycobacterium tuberculosis Erdman.";
RL   Submitted (APR-2014) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RC   STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX   PubMed=16689789; DOI=10.1111/j.1365-2958.2006.05155.x;
RA   Munoz-Elias E.J., Upton A.M., Cherian J., McKinney J.D.;
RT   "Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism,
RT   intracellular growth, and virulence.";
RL   Mol. Microbiol. 60:1109-1122(2006).
CC   -!- FUNCTION: Involved in the persistence and virulence of M.tuberculosis.
CC       Catalyzes the reversible formation of succinate and glyoxylate from
CC       isocitrate, a key step of the glyoxylate cycle, which operates as an
CC       anaplerotic route for replenishing the tricarboxylic acid cycle during
CC       growth on fatty acid substrates. It also catalyzes the formation of
CC       pyruvate and succinate from 2-methylisocitrate, a key step in the
CC       methylcitrate cycle (propionate degradation route).
CC       {ECO:0000269|PubMed:16689789}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-threo-isocitrate = glyoxylate + succinate;
CC         Xref=Rhea:RHEA:13245, ChEBI:CHEBI:15562, ChEBI:CHEBI:30031,
CC         ChEBI:CHEBI:36655; EC=4.1.3.1;
CC         Evidence={ECO:0000269|PubMed:16689789};
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:16689789};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P9WKK7};
CC   -!- PATHWAY: Carbohydrate metabolism; glyoxylate cycle; (S)-malate from
CC       isocitrate: step 1/2. {ECO:0000305|PubMed:16689789}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P9WKK7}.
CC   -!- DISRUPTION PHENOTYPE: Deletion of icl1 in cells growing on 0.1%
CC       propionate shows 10 and 8-fold decrease of isocitrate and
CC       methylisocitrate lyase activity, respectively.
CC       {ECO:0000269|PubMed:16689789}.
CC   -!- MISCELLANEOUS: Cell growing on 0.2% glucose show barely detectable
CC       isocitrate and methylisocitrate lyase activities. On 0.1% and 0.2%
CC       propionate, the lyase activities increase more than 10 and 100-fold,
CC       respectively. {ECO:0000269|PubMed:16689789}.
CC   -!- SIMILARITY: Belongs to the isocitrate lyase/PEP mutase superfamily.
CC       Isocitrate lyase family. {ECO:0000305}.
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DR   EMBL; AP012340; BAL64328.1; -; Genomic_DNA.
DR   EMBL; JLBG01000002; KBK18542.1; -; Genomic_DNA.
DR   RefSeq; WP_003402316.1; NZ_KK339487.1.
DR   AlphaFoldDB; H8EVV4; -.
DR   SMR; H8EVV4; -.
DR   PRIDE; H8EVV4; -.
DR   EnsemblBacteria; BAL64328; BAL64328; ERDMAN_0512.
DR   GeneID; 45424429; -.
DR   KEGG; mtn:ERDMAN_0512; -.
DR   PATRIC; fig|652616.3.peg.519; -.
DR   HOGENOM; CLU_019214_2_0_11; -.
DR   UniPathway; UPA00703; UER00719.
DR   Proteomes; UP000007568; Chromosome.
DR   GO; GO:0004451; F:isocitrate lyase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0046421; F:methylisocitrate lyase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006097; P:glyoxylate cycle; IEA:UniProtKB-UniPathway.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR   Gene3D; 3.20.20.60; -; 1.
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; 2.
DR   PIRSF; PIRSF001362; Isocit_lyase; 1.
DR   SUPFAM; SSF51621; SSF51621; 1.
DR   TIGRFAMs; TIGR01346; isocit_lyase; 2.
DR   PROSITE; PS00161; ISOCITRATE_LYASE; 1.
PE   1: Evidence at protein level;
KW   Glyoxylate bypass; Lyase; Magnesium; Metal-binding;
KW   Tricarboxylic acid cycle.
FT   CHAIN           1..428
FT                   /note="Isocitrate lyase 1"
FT                   /id="PRO_0000432564"
FT   ACT_SITE        191
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT   BINDING         91..93
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT   BINDING         153
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT   BINDING         192..193
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT   BINDING         228
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT   BINDING         313..317
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT   BINDING         347
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
SQ   SEQUENCE   428 AA;  47087 MW;  E5223F38CB5D9E8B CRC64;
     MSVVGTPKSA EQIQQEWDTN PRWKDVTRTY SAEDVVALQG SVVEEHTLAR RGAEVLWEQL
     HDLEWVNALG ALTGNMAVQQ VRAGLKAIYL SGWQVAGDAN LSGHTYPDQS LYPANSVPQV
     VRRINNALQR ADQIAKIEGD TSVENWLAPI VADGEAGFGG ALNVYELQKA LIAAGVAGSH
     WEDQLASEKK CGHLGGKVLI PTQQHIRTLT SARLAADVAD VPTVVIARTD AEAATLITSD
     VDERDQPFIT GERTREGFYR TKNGIEPCIA RAKAYAPFAD LIWMETGTPD LEAARQFSEA
     VKAEYPDQML AYNCSPSFNW KKHLDDATIA KFQKELAAMG FKFQFITLAG FHALNYSMFD
     LAYGYAQNQM SAYVELQERE FAAEERGYTA TKHQREVGAG YFDRIATTVD PNSSTTALTG
     STEEGQFH