ID   FUMA_ECOLI              Reviewed;         548 AA.
AC   P0AC33; P00923; P76889;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   24-JAN-2024, entry version 131.
DE   RecName: Full=Fumarate hydratase class I, aerobic {ECO:0000303|PubMed:3282546};
DE            EC=4.2.1.2 {ECO:0000269|PubMed:1329945, ECO:0000269|PubMed:23405168, ECO:0000269|PubMed:8422384};
DE   AltName: Full=Fumarase A {ECO:0000303|PubMed:1329945};
DE   AltName: Full=Oxaloacetate keto--enol-isomerase {ECO:0000303|PubMed:8422384};
DE            Short=OAAKE isomerase {ECO:0000303|PubMed:8422384};
DE   AltName: Full=Oxaloacetate tautomerase {ECO:0000305|PubMed:8422384};
DE            EC=5.3.2.2 {ECO:0000269|PubMed:8422384};
GN   Name=fumA {ECO:0000303|PubMed:6328431};
GN   OrderedLocusNames=b1612, JW1604;
OS   Escherichia coli (strain K12).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=83333;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6328431; DOI=10.1093/nar/12.8.3631;
RA   Miles J.S., Guest J.R.;
RT   "Complete nucleotide sequence of the fumarase gene fumA, of Escherichia
RT   coli.";
RL   Nucleic Acids Res. 12:3631-3642(1984).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=9097039; DOI=10.1093/dnares/3.6.363;
RA   Aiba H., Baba T., Fujita K., Hayashi K., Inada T., Isono K., Itoh T.,
RA   Kasai H., Kashimoto K., Kimura S., Kitakawa M., Kitagawa M., Makino K.,
RA   Miki T., Mizobuchi K., Mori H., Mori T., Motomura K., Nakade S.,
RA   Nakamura Y., Nashimoto H., Nishio Y., Oshima T., Saito N., Sampei G.,
RA   Seki Y., Sivasundaram S., Tagami H., Takeda J., Takemoto K., Takeuchi Y.,
RA   Wada C., Yamamoto Y., Horiuchi T.;
RT   "A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT   the 28.0-40.1 min region on the linkage map.";
RL   DNA Res. 3:363-377(1996).
RN   [3]
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   [4]
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   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
RC   STRAIN=W / ATCC 11105 / DSM 1900;
RX   PubMed=1917897; DOI=10.1093/oxfordjournals.jbchem.a123448;
RA   Ueda Y., Yumoto N., Tokushige M., Fukui K., Ohya-Nishiguchi H.;
RT   "Purification and characterization of two types of fumarase from
RT   Escherichia coli.";
RL   J. Biochem. 109:728-733(1991).
RN   [6]
RP   PROTEIN SEQUENCE OF 2-12.
RC   STRAIN=K12 / EMG2;
RX   PubMed=9298646; DOI=10.1002/elps.1150180807;
RA   Link A.J., Robison K., Church G.M.;
RT   "Comparing the predicted and observed properties of proteins encoded in the
RT   genome of Escherichia coli K-12.";
RL   Electrophoresis 18:1259-1313(1997).
RN   [7]
RP   FUNCTION, AND INDUCTION.
RX   DOI=10.1111/j.1574-6968.1987.tb02545.x;
RA   Woods S.A., Guest J.R.;
RT   "Differential roles of the Escherichia coli fumarases and fnr-dependent
RT   expression of fumarase B and aspartase.";
RL   FEMS Microbiol. Lett. 48:219-224(1987).
RN   [8]
RP   FUNCTION, AND SUBUNIT.
RC   STRAIN=K12;
RX   PubMed=3282546; DOI=10.1016/0167-4838(88)90050-7;
RA   Woods S.A., Shwartzbach S.D., Guest J.R.;
RT   "Two biochemically distinct classes of fumarase in Escherichia coli.";
RL   Biochim. Biophys. Acta 954:14-26(1988).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP   ACTIVITY REGULATION, AND SUBUNIT.
RC   STRAIN=K12;
RX   PubMed=1329945; DOI=10.1021/bi00157a022;
RA   Flint D.H., Emptage M.H., Guest J.R.;
RT   "Fumarase a from Escherichia coli: purification and characterization as an
RT   iron-sulfur cluster containing enzyme.";
RL   Biochemistry 31:10331-10337(1992).
RN   [10]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP   REGULATION.
RC   STRAIN=K12;
RX   PubMed=8422384; DOI=10.1021/bi00054a009;
RA   Flint D.H.;
RT   "Escherichia coli fumarase A catalyzes the isomerization of enol and keto
RT   oxalacetic acid.";
RL   Biochemistry 32:799-805(1993).
RN   [11]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE SPECIFICITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RC   STRAIN=K12;
RX   PubMed=23405168; DOI=10.1371/journal.pone.0055549;
RA   van Vugt-Lussenburg B.M., van der Weel L., Hagen W.R., Hagedoorn P.L.;
RT   "Biochemical similarities and differences between the catalytic [4Fe-4S]
RT   cluster containing fumarases FumA and FumB from Escherichia coli.";
RL   PLoS ONE 8:E55549-E55549(2013).
CC   -!- FUNCTION: Catalyzes the reversible hydration of fumarate to (S)-malate.
CC       Functions as an aerobic enzyme in the direction of malate formation as
CC       part of the citric acid cycle. Accounts for about 80% of the fumarase
CC       activity when the bacteria grow aerobically. To a lesser extent, also
CC       displays D-tartrate dehydratase activity in vitro, but is not able to
CC       convert (R)-malate, L-tartrate or meso-tartrate. Can also catalyze the
CC       isomerization of enol- to keto-oxaloacetate.
CC       {ECO:0000269|PubMed:1329945, ECO:0000269|PubMed:23405168,
CC       ECO:0000269|PubMed:3282546, ECO:0000269|PubMed:8422384,
CC       ECO:0000269|Ref.7}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15589, ChEBI:CHEBI:29806; EC=4.2.1.2;
CC         Evidence={ECO:0000269|PubMed:1329945, ECO:0000269|PubMed:23405168,
CC         ECO:0000269|PubMed:8422384};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=oxaloacetate = enol-oxaloacetate; Xref=Rhea:RHEA:16021,
CC         ChEBI:CHEBI:16452, ChEBI:CHEBI:17479; EC=5.3.2.2;
CC         Evidence={ECO:0000269|PubMed:8422384};
CC   -!- COFACTOR:
CC       Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC         Evidence={ECO:0000269|PubMed:1329945, ECO:0000269|PubMed:23405168};
CC       Note=Binds 1 [4Fe-4S] cluster per subunit. {ECO:0000269|PubMed:1329945,
CC       ECO:0000269|PubMed:23405168};
CC   -!- ACTIVITY REGULATION: Is inactivated by oxygen, due to oxidation of the
CC       Fe-S cluster to its [3Fe-4S] form. Both the fumarase and the isomerase
CC       reactions are competitively inhibited by 3-hydroxy-2-nitropropionate.
CC       The isomerase reaction is also inhibited by fumarate and malate.
CC       {ECO:0000269|PubMed:1329945, ECO:0000269|PubMed:23405168,
CC       ECO:0000269|PubMed:8422384}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.7 mM for (S)-malate {ECO:0000269|PubMed:1329945,
CC         ECO:0000269|PubMed:23405168};
CC         KM=0.6 mM for fumarate {ECO:0000269|PubMed:8422384};
CC         KM=0.46 mM for fumarate {ECO:0000269|PubMed:23405168};
CC         KM=0.8 mM for D-tartrate {ECO:0000269|PubMed:23405168};
CC         KM=0.1 mM for enol-oxaloacetate {ECO:0000269|PubMed:8422384};
CC         Vmax=720 umol/min/mg enzyme for (S)-malate dehydration
CC         {ECO:0000269|PubMed:23405168};
CC         Vmax=1900 umol/min/mg enzyme for fumarate hydration
CC         {ECO:0000269|PubMed:23405168};
CC         Vmax=2.3 umol/min/mg enzyme for D-tartrate dehydration
CC         {ECO:0000269|PubMed:23405168};
CC         Note=kcat is 3000 sec(-1) for the hydration of fumarate and 300
CC         sec(-1) for the isomerization of enol-oxaloacetate.
CC         {ECO:0000269|PubMed:8422384};
CC   -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; (S)-malate
CC       from fumarate: step 1/1. {ECO:0000303|PubMed:1329945,
CC       ECO:0000303|PubMed:3282546}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:1329945,
CC       ECO:0000269|PubMed:3282546}.
CC   -!- INTERACTION:
CC       P0AC33; P0AC33: fumA; NbExp=2; IntAct=EBI-549075, EBI-549075;
CC   -!- INDUCTION: Is expressed under aerobic conditions. Is repressed by
CC       glucose and anaerobiosis. {ECO:0000269|Ref.7}.
CC   -!- SIMILARITY: Belongs to the class-I fumarase family. {ECO:0000305}.
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DR   EMBL; X00522; CAA25204.1; -; Genomic_DNA.
DR   EMBL; AP009048; BAA15360.1; -; Genomic_DNA.
DR   EMBL; U00096; AAC74684.1; -; Genomic_DNA.
DR   PIR; A03531; UFECAQ.
DR   RefSeq; NP_416129.1; NC_000913.3.
DR   RefSeq; WP_000066639.1; NZ_STEB01000003.1.
DR   AlphaFoldDB; P0AC33; -.
DR   SMR; P0AC33; -.
DR   BioGRID; 4263122; 17.
DR   BioGRID; 851167; 1.
DR   DIP; DIP-36200N; -.
DR   IntAct; P0AC33; 5.
DR   STRING; 511145.b1612; -.
DR   jPOST; P0AC33; -.
DR   PaxDb; 511145-b1612; -.
DR   EnsemblBacteria; AAC74684; AAC74684; b1612.
DR   GeneID; 75204456; -.
DR   GeneID; 946826; -.
DR   KEGG; ecj:JW1604; -.
DR   KEGG; eco:b1612; -.
DR   PATRIC; fig|1411691.4.peg.650; -.
DR   EchoBASE; EB0351; -.
DR   eggNOG; COG1838; Bacteria.
DR   eggNOG; COG1951; Bacteria.
DR   HOGENOM; CLU_026758_0_0_6; -.
DR   InParanoid; P0AC33; -.
DR   OMA; AGVLPMC; -.
DR   OrthoDB; 9798978at2; -.
DR   PhylomeDB; P0AC33; -.
DR   BioCyc; EcoCyc:FUMA-MONOMER; -.
DR   BioCyc; MetaCyc:FUMA-MONOMER; -.
DR   BRENDA; 4.2.1.2; 2026.
DR   BRENDA; 4.2.1.34; 2026.
DR   SABIO-RK; P0AC33; -.
DR   UniPathway; UPA00223; UER01007.
DR   PRO; PR:P0AC33; -.
DR   Proteomes; UP000000318; Chromosome.
DR   Proteomes; UP000000625; Chromosome.
DR   GO; GO:0005829; C:cytosol; HDA:UniProtKB.
DR   GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:EcoCyc.
DR   GO; GO:0004333; F:fumarate hydratase activity; IDA:EcoliWiki.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0050163; F:oxaloacetate tautomerase activity; IDA:EcoCyc.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:EcoCyc.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IMP:EcoCyc.
DR   Gene3D; 3.20.130.10; Fe-S hydro-lyase, tartrate dehydratase beta-type, catalytic domain; 1.
DR   InterPro; IPR004646; Fe-S_hydro-lyase_TtdA-typ_cat.
DR   InterPro; IPR004647; Fe-S_hydro-lyase_TtdB-typ_cat.
DR   InterPro; IPR036660; Fe-S_hydroAse_TtdB_cat_sf.
DR   InterPro; IPR011167; Fe_dep_fumarate_hydratase.
DR   InterPro; IPR020557; Fumarate_lyase_CS.
DR   NCBIfam; TIGR00722; ttdA_fumA_fumB; 1.
DR   NCBIfam; TIGR00723; ttdB_fumA_fumB; 1.
DR   PANTHER; PTHR30389:SF0; FUMARATE HYDRATASE CLASS I, AEROBIC; 1.
DR   PANTHER; PTHR30389; FUMARATE HYDRATASE-RELATED; 1.
DR   Pfam; PF05681; Fumerase; 1.
DR   Pfam; PF05683; Fumerase_C; 1.
DR   PIRSF; PIRSF001394; Fe_dep_fumar_hy; 1.
DR   SUPFAM; SSF117457; FumA C-terminal domain-like; 1.
DR   PROSITE; PS00163; FUMARATE_LYASES; 1.
PE   1: Evidence at protein level;
KW   4Fe-4S; Direct protein sequencing; Iron; Iron-sulfur; Isomerase; Lyase;
KW   Metal-binding; Reference proteome; Tricarboxylic acid cycle.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:9298646"
FT   CHAIN           2..548
FT                   /note="Fumarate hydratase class I, aerobic"
FT                   /id="PRO_0000195656"
FT   BINDING         105
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000250|UniProtKB:E9AE57"
FT   BINDING         224
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000250|UniProtKB:E9AE57"
FT   BINDING         318
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000250|UniProtKB:E9AE57"
SQ   SEQUENCE   548 AA;  60299 MW;  6082744088C64603 CRC64;
     MSNKPFHYQA PFPLKKDDTE YYLLTSEHVS VSEFEGQEIL KVAPEALTLL ARQAFHDASF
     MLRPAHQQQV ADILRDPEAS ENDKYVALQF LRNSDIAAKG VLPTCQDTGT AIIVGKKGQR
     VWTGGGDEAA LARGVYNTYI EDNLRYSQNA PLDMYKEVNT GTNLPAQIDL YAVDGDEYKF
     LCIAKGGGSA NKTYLYQETK ALLTPGKLKN YLVEKMRTLG TAACPPYHIA FVIGGTSAET
     NLKTVKLASA KYYDELPTEG NEHGQAFRDV ELEKELLIEA QNLGLGAQFG GKYFAHDIRV
     IRLPRHGASC PVGMGVSCSA DRNIKAKINR QGIWIEKLEH NPGKYIPEEL RKAGEGEAVR
     VDLNRPMKEI LAQLSQYPVS TRLSLNGTII VGRDIAHAKL KERMDNGEGL PQYIKDHPIY
     YAGPAKTPEG YASGSLGPTT AGRMDSYVDQ LQAQGGSMIM LAKGNRSQQV TDACKKHGGF
     YLGSIGGPAA VLAQGSIKSL ECVEYPELGM EAIWKIEVED FPAFILVDDK GNDFFQQIQL
     TQCTRCVK
//