ACEA_ECOLI
ID ACEA_ECOLI Reviewed; 434 AA.
AC P0A9G6; P05313; Q2M6T9;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Isocitrate lyase {ECO:0000303|Ref.9};
DE Short=ICL {ECO:0000303|Ref.9};
DE EC=4.1.3.1 {ECO:0000269|PubMed:3281659, ECO:0000269|PubMed:7826335, ECO:0000269|Ref.9};
DE AltName: Full=Isocitrase {ECO:0000303|Ref.9};
DE AltName: Full=Isocitratase {ECO:0000303|Ref.9};
GN Name=aceA {ECO:0000303|PubMed:3050899}; Synonyms=icl;
GN OrderedLocusNames=b4015, JW3975;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=3050899; DOI=10.1093/nar/16.19.9342;
RA Byrne C.R., Stokes H.W., Ward K.A.;
RT "Nucleotide sequence of the aceB gene encoding malate synthase A in
RT Escherichia coli.";
RL Nucleic Acids Res. 16:9342-9342(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=3060852; DOI=10.1093/nar/16.22.10924;
RA Byrne C.R., Stokes H.W., Ward K.A.;
RT "Nucleotide sequence of the aceB gene encoding malate synthase A in
RT Escherichia coli.";
RL Nucleic Acids Res. 16:10924-10924(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=3290857; DOI=10.1093/nar/16.12.5689;
RA Rieul C., Bleicher F., Duclos B., Cortay J.-C., Cozzone A.J.;
RT "Nucleotide sequence of the aceA gene coding for isocitrate lyase in
RT Escherichia coli.";
RL Nucleic Acids Res. 16:5689-5689(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-17, AND SUBUNIT.
RX PubMed=3049537; DOI=10.1128/jb.170.10.4528-4536.1988;
RA Matsuoka M., McFadden B.A.;
RT "Isolation, hyperexpression, and sequencing of the aceA gene encoding
RT isocitrate lyase in Escherichia coli.";
RL J. Bacteriol. 170:4528-4536(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=8265357; DOI=10.1093/nar/21.23.5408;
RA Blattner F.R., Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L.;
RT "Analysis of the Escherichia coli genome. IV. DNA sequence of the region
RT from 89.2 to 92.8 minutes.";
RL Nucleic Acids Res. 21:5408-5417(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 293-434.
RX PubMed=2836370; DOI=10.1128/jb.170.6.2763-2769.1988;
RA Klumpp D.J., Plank D.W., Bowdin L.J., Stueland C.S., Chung T.,
RA Laporte D.C.;
RT "Nucleotide sequence of aceK, the gene encoding isocitrate dehydrogenase
RT kinase/phosphatase.";
RL J. Bacteriol. 170:2763-2769(1988).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RA Robertson E.F., Reeves H.C.;
RT "Purification and characterization of isocitrate lyase from Escherichia
RT coli.";
RL Curr. Microbiol. 14:347-359(1986).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND SUBUNIT.
RC STRAIN=ML308;
RX PubMed=3281659; DOI=10.1042/bj2500025;
RA MacKintosh C., Nimmo H.G.;
RT "Purification and regulatory properties of isocitrate lyase from
RT Escherichia coli ML308.";
RL Biochem. J. 250:25-31(1988).
RN [11]
RP PHOSPHORYLATION, AND ACTIVITY REGULATION.
RX PubMed=3276689; DOI=10.1016/s0021-9258(18)69231-2;
RA Robertson E.F., Hoyt J.C., Reeves H.C.;
RT "Evidence of histidine phosphorylation in isocitrate lyase from Escherichia
RT coli.";
RL J. Biol. Chem. 263:2477-2482(1988).
RN [12]
RP FUNCTION, ACTIVITY REGULATION, AND COFACTOR.
RX PubMed=3291954; DOI=10.1016/0304-4165(88)90125-0;
RA Hoyt J.C., Robertson E.F., Berlyn K.A., Reeves H.C.;
RT "Escherichia coli isocitrate lyase: properties and comparisons.";
RL Biochim. Biophys. Acta 966:30-35(1988).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF
RP CYS-195, AND ACTIVE SITE.
RC STRAIN=ML308;
RX PubMed=7826335; DOI=10.1042/bj3050239;
RA Robertson A.G., Nimmo H.G.;
RT "Site-directed mutagenesis of cysteine-195 in isocitrate lyase from
RT Escherichia coli ML308.";
RL Biochem. J. 305:239-244(1995).
RN [14]
RP FUNCTION, AND PATHWAY.
RX PubMed=15748982; DOI=10.1016/j.resmic.2004.09.004;
RA Prasad Maharjan R., Yu P.L., Seeto S., Ferenci T.;
RT "The role of isocitrate lyase and the glyoxylate cycle in Escherichia coli
RT growing under glucose limitation.";
RL Res. Microbiol. 156:178-183(2005).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF MUTANT CYS-219 IN COMPLEX WITH
RP MAGNESIUM AND SUBSTRATE, MUTAGENESIS OF ALA-219, AND SUBUNIT.
RX PubMed=11526312; DOI=10.1107/s0907444901008642;
RA Britton K.L., Abeysinghe I.S., Baker P.J., Barynin V., Diehl P.,
RA Langridge S.J., McFadden B.A., Sedelnikova S.E., Stillman T.J.,
RA Weeradechapon K., Rice D.W.;
RT "The structure and domain organization of Escherichia coli isocitrate
RT lyase.";
RL Acta Crystallogr. D 57:1209-1218(2001).
CC -!- FUNCTION: Involved in the metabolic adaptation in response to
CC environmental changes. Catalyzes the reversible formation of succinate
CC and glyoxylate from isocitrate, a key step of the glyoxylate cycle,
CC which operates as an anaplerotic route for replenishing the
CC tricarboxylic acid cycle during growth on fatty acid substrates.
CC {ECO:0000269|PubMed:15748982, ECO:0000269|PubMed:3281659,
CC ECO:0000269|PubMed:3291954, ECO:0000269|PubMed:7826335,
CC ECO:0000269|Ref.9}.
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; Evidence={ECO:0000269|PubMed:3281659,
CC ECO:0000269|PubMed:7826335, ECO:0000269|Ref.9};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:3291954};
CC Note=Divalent metal cations. Can also use Mn(2+) ion.
CC {ECO:0000269|PubMed:3291954};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on histidine.
CC Competitively inhibited by 3-phosphosglycerate, oxalate, malate,
CC chloride, phosphate and sulfate ions, and uncompetitively inhibited by
CC succinate and phosphoenolpyruvate (PEP). {ECO:0000269|PubMed:3276689,
CC ECO:0000269|PubMed:3281659, ECO:0000269|PubMed:3291954}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.076 uM for threo-D-isocitrate (at pH 7.3)
CC {ECO:0000269|PubMed:7826335};
CC KM=8 uM for threo-D-isocitrate (at pH 7.5 and 25 degrees Celsius)
CC {ECO:0000269|Ref.9};
CC KM=32 uM for isocitrate (at pH 6.8) {ECO:0000269|PubMed:3281659};
CC KM=63 uM for isocitrate (at pH 7.3) {ECO:0000269|PubMed:3281659};
CC KM=130 uM for glyoxylate (at pH 7.3) {ECO:0000269|PubMed:3281659};
CC KM=590 uM for succinate (at pH 7.3) {ECO:0000269|PubMed:3281659};
CC Note=kcat is 28.5 sec(-1) for isocitrate lyase activity with threo-D-
CC isocitrate as substrate (at pH 7.3). {ECO:0000269|PubMed:7826335};
CC pH dependence:
CC Optimum pH is 7.3. {ECO:0000269|Ref.9};
CC -!- PATHWAY: Carbohydrate metabolism; glyoxylate cycle; (S)-malate from
CC isocitrate: step 1/2. {ECO:0000305|PubMed:15748982}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:11526312,
CC ECO:0000269|PubMed:3049537, ECO:0000269|PubMed:3281659,
CC ECO:0000269|Ref.9}.
CC -!- SIMILARITY: Belongs to the isocitrate lyase/PEP mutase superfamily.
CC Isocitrate lyase family. {ECO:0000305}.
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DR EMBL; X12431; CAA30974.1; -; Genomic_DNA.
DR EMBL; X07543; CAA30416.1; -; Genomic_DNA.
DR EMBL; M22621; AAC13650.1; -; Genomic_DNA.
DR EMBL; U00006; AAC43109.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76985.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE78017.1; -; Genomic_DNA.
DR EMBL; M20714; AAA24009.1; -; Genomic_DNA.
DR PIR; S05692; WZECIC.
DR RefSeq; NP_418439.1; NC_000913.3.
DR RefSeq; WP_000857856.1; NZ_STEB01000022.1.
DR PDB; 1IGW; X-ray; 2.10 A; A/B/C/D=1-434.
DR PDBsum; 1IGW; -.
DR AlphaFoldDB; P0A9G6; -.
DR SMR; P0A9G6; -.
DR BioGRID; 4263469; 7.
DR DIP; DIP-35893N; -.
DR IntAct; P0A9G6; 3.
DR STRING; 511145.b4015; -.
DR SWISS-2DPAGE; P0A9G6; -.
DR jPOST; P0A9G6; -.
DR PaxDb; P0A9G6; -.
DR PRIDE; P0A9G6; -.
DR EnsemblBacteria; AAC76985; AAC76985; b4015.
DR EnsemblBacteria; BAE78017; BAE78017; BAE78017.
DR GeneID; 66672074; -.
DR GeneID; 948517; -.
DR KEGG; ecj:JW3975; -.
DR KEGG; eco:b4015; -.
DR PATRIC; fig|1411691.4.peg.2698; -.
DR EchoBASE; EB0021; -.
DR eggNOG; COG2224; Bacteria.
DR HOGENOM; CLU_019214_2_0_6; -.
DR InParanoid; P0A9G6; -.
DR OMA; LEKDWAE; -.
DR PhylomeDB; P0A9G6; -.
DR BioCyc; EcoCyc:ISOCIT-LYASE-MON; -.
DR BioCyc; MetaCyc:ISOCIT-LYASE-MON; -.
DR BRENDA; 4.1.3.1; 2026.
DR SABIO-RK; P0A9G6; -.
DR UniPathway; UPA00703; UER00719.
DR EvolutionaryTrace; P0A9G6; -.
DR PRO; PR:P0A9G6; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:UniProtKB.
DR GO; GO:0043169; F:cation binding; IDA:EcoliWiki.
DR GO; GO:0004451; F:isocitrate lyase activity; IDA:EcoliWiki.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006097; P:glyoxylate cycle; IC:EcoliWiki.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
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; 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 3D-structure; Direct protein sequencing; Glyoxylate bypass; Lyase;
KW Magnesium; Manganese; Metal-binding; Phosphoprotein; Reference proteome;
KW Tricarboxylic acid cycle.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:3049537"
FT CHAIN 2..434
FT /note="Isocitrate lyase"
FT /id="PRO_0000068774"
FT ACT_SITE 195
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:7826335"
FT BINDING 91..93
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11526312"
FT BINDING 157
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:11526312"
FT BINDING 196..197
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT BINDING 232
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11526312"
FT BINDING 317..321
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT BINDING 351
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT MUTAGEN 195
FT /note="C->A: Large decrease in activity."
FT /evidence="ECO:0000269|PubMed:7826335"
FT MUTAGEN 195
FT /note="C->S: Large decrease in activity."
FT /evidence="ECO:0000269|PubMed:7826335"
FT MUTAGEN 219
FT /note="A->C: Isocitrate lyase activity is reduced compared
FT to the wild-type."
FT /evidence="ECO:0000269|PubMed:11526312"
FT CONFLICT 101..117
FT /note="LAASMYPDQSLYPANSV -> WRPACIRISRSIRQTRC (in Ref. 3;
FT CAA30416)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="A -> P (in Ref. 3; CAA30416)"
FT /evidence="ECO:0000305"
FT CONFLICT 293
FT /note="P -> R (in Ref. 8; AAA24009)"
FT /evidence="ECO:0000305"
FT CONFLICT 338
FT /note="Q -> E (in Ref. 3; CAA30416)"
FT /evidence="ECO:0000305"
FT CONFLICT 419..434
FT /note="TSSVTALTGSTEESQF -> DVFSHRADRLH (in Ref. 4)"
FT /evidence="ECO:0000305"
FT HELIX 4..14
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 18..20
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 29..34
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 44..57
FT /evidence="ECO:0007829|PDB:1IGW"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:1IGW"
FT STRAND 61..70
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 74..83
FT /evidence="ECO:0007829|PDB:1IGW"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 92..98
FT /evidence="ECO:0007829|PDB:1IGW"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 116..137
FT /evidence="ECO:0007829|PDB:1IGW"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:1IGW"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 165..177
FT /evidence="ECO:0007829|PDB:1IGW"
FT STRAND 181..188
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 206..223
FT /evidence="ECO:0007829|PDB:1IGW"
FT STRAND 228..233
FT /evidence="ECO:0007829|PDB:1IGW"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:1IGW"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 247..252
FT /evidence="ECO:0007829|PDB:1IGW"
FT STRAND 253..257
FT /evidence="ECO:0007829|PDB:1IGW"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 269..279
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:1IGW"
FT STRAND 284..288
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 295..308
FT /evidence="ECO:0007829|PDB:1IGW"
FT STRAND 313..317
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 330..334
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 336..343
FT /evidence="ECO:0007829|PDB:1IGW"
FT STRAND 345..350
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 353..371
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 374..381
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 383..390
FT /evidence="ECO:0007829|PDB:1IGW"
FT TURN 391..393
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 399..402
FT /evidence="ECO:0007829|PDB:1IGW"
FT HELIX 405..415
FT /evidence="ECO:0007829|PDB:1IGW"
SQ SEQUENCE 434 AA; 47522 MW; F66449CCD1E168E9 CRC64;
MKTRTQQIEE LQKEWTQPRW EGITRPYSAE DVVKLRGSVN PECTLAQLGA AKMWRLLHGE
SKKGYINSLG ALTGGQALQQ AKAGIEAVYL SGWQVAADAN LAASMYPDQS LYPANSVPAV
VERINNTFRR ADQIQWSAGI EPGDPRYVDY FLPIVADAEA GFGGVLNAFE LMKAMIEAGA
AAVHFEDQLA SVKKCGHMGG KVLVPTQEAI QKLVAARLAA DVTGVPTLLV ARTDADAADL
ITSDCDPYDS EFITGERTSE GFFRTHAGIE QAISRGLAYA PYADLVWCET STPDLELARR
FAQAIHAKYP GKLLAYNCSP SFNWQKNLDD KTIASFQQQL SDMGYKFQFI TLAGIHSMWF
NMFDLANAYA QGEGMKHYVE KVQQPEFAAA KDGYTFVSHQ QEVGTGYFDK VTTIIQGGTS
SVTALTGSTE ESQF
