ID   FUMH_DICDI              Reviewed;         485 AA.
AC   Q54VA2; Q54VA1;
DT   29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   24-MAY-2005, sequence version 1.
DT   27-MAR-2024, entry version 115.
DE   RecName: Full=Fumarate hydratase, mitochondrial {ECO:0000250|UniProtKB:P07954};
DE            Short=Fumarase {ECO:0000250|UniProtKB:P07954};
DE            EC=4.2.1.2 {ECO:0000250|UniProtKB:P07954};
DE   Flags: Precursor;
GN   Name=fumH {ECO:0000312|dictyBase:DDB_G0280495}; ORFNames=DDB_G0280495;
OS   Dictyostelium discoideum (Social amoeba).
OC   Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC   Dictyosteliaceae; Dictyostelium.
OX   NCBI_TaxID=44689;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AX4;
RX   PubMed=15875012; DOI=10.1038/nature03481;
RA   Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA   Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA   Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA   Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA   Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA   Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA   Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA   Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA   Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA   Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA   Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA   Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA   Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA   Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA   Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA   Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA   Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT   "The genome of the social amoeba Dictyostelium discoideum.";
RL   Nature 435:43-57(2005).
CC   -!- FUNCTION: Catalyzes the reversible stereospecific interconversion of
CC       fumarate to L-malate. {ECO:0000250|UniProtKB:P07954}.
CC   -!- FUNCTION: [Isoform Mitochondrial]: Catalyzes the hydration of fumarate
CC       to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a
CC       transition step in the production of energy in the form of NADH.
CC       {ECO:0000250|UniProtKB:P10173}.
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:0000250|UniProtKB:P07954};
CC   -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; (S)-malate
CC       from fumarate: step 1/1. {ECO:0000250|UniProtKB:P10173}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P07954}.
CC   -!- SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion
CC       {ECO:0000250|UniProtKB:P07954}.
CC   -!- SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm
CC       {ECO:0000250|UniProtKB:P07954}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=Mitochondrial;
CC         IsoId=Q54VA2-1; Sequence=Displayed;
CC       Name=Cytoplasmic;
CC         IsoId=Q54VA2-2; Sequence=VSP_033185;
CC   -!- MISCELLANEOUS: There are 2 substrate-binding sites: the catalytic A
CC       site, and the non-catalytic B site that may play a role in the transfer
CC       of substrate or product between the active site and the solvent.
CC       Alternatively, the B site may bind allosteric effectors.
CC       {ECO:0000250|UniProtKB:P05042, ECO:0000250|UniProtKB:P9WN93}.
CC   -!- SIMILARITY: Belongs to the class-II fumarase/aspartase family. Fumarase
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AAFI02000036; EAL67226.1; -; Genomic_DNA.
DR   EMBL; AAFI02000036; EAL67227.1; -; Genomic_DNA.
DR   RefSeq; XP_001134561.1; XM_001134561.1.
DR   RefSeq; XP_641207.1; XM_636115.1.
DR   AlphaFoldDB; Q54VA2; -.
DR   SMR; Q54VA2; -.
DR   STRING; 44689.Q54VA2; -.
DR   PaxDb; 44689-DDB0231397; -.
DR   EnsemblProtists; EAL67226; EAL67226; DDB_G0280495.
DR   EnsemblProtists; EAL67227; EAL67227; DDB_G0280495.
DR   GeneID; 8622588; -.
DR   KEGG; ddi:DDB_G0280495; -.
DR   dictyBase; DDB_G0280495; fumH.
DR   eggNOG; KOG1317; Eukaryota.
DR   InParanoid; Q54VA2; -.
DR   OMA; AKWRAQT; -.
DR   PhylomeDB; Q54VA2; -.
DR   Reactome; R-DDI-71403; Citric acid cycle (TCA cycle).
DR   UniPathway; UPA00223; UER01007.
DR   PRO; PR:Q54VA2; -.
DR   Proteomes; UP000002195; Chromosome 3.
DR   GO; GO:0005737; C:cytoplasm; ISS:dictyBase.
DR   GO; GO:0005739; C:mitochondrion; ISS:dictyBase.
DR   GO; GO:0045335; C:phagocytic vesicle; HDA:dictyBase.
DR   GO; GO:0045239; C:tricarboxylic acid cycle enzyme complex; IEA:InterPro.
DR   GO; GO:0004333; F:fumarate hydratase activity; IBA:GO_Central.
DR   GO; GO:0006106; P:fumarate metabolic process; IBA:GO_Central.
DR   GO; GO:0006108; P:malate metabolic process; IBA:GO_Central.
DR   GO; GO:0009617; P:response to bacterium; HEP:dictyBase.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR   CDD; cd01362; Fumarase_classII; 1.
DR   Gene3D; 1.10.40.30; Fumarase/aspartase (C-terminal domain); 1.
DR   Gene3D; 1.20.200.10; Fumarase/aspartase (Central domain); 1.
DR   Gene3D; 1.10.275.10; Fumarase/aspartase (N-terminal domain); 1.
DR   HAMAP; MF_00743; FumaraseC; 1.
DR   InterPro; IPR005677; Fum_hydII.
DR   InterPro; IPR024083; Fumarase/histidase_N.
DR   InterPro; IPR018951; Fumarase_C_C.
DR   InterPro; IPR020557; Fumarate_lyase_CS.
DR   InterPro; IPR000362; Fumarate_lyase_fam.
DR   InterPro; IPR022761; Fumarate_lyase_N.
DR   InterPro; IPR008948; L-Aspartase-like.
DR   NCBIfam; TIGR00979; fumC_II; 1.
DR   PANTHER; PTHR11444; ASPARTATEAMMONIA/ARGININOSUCCINATE/ADENYLOSUCCINATE LYASE; 1.
DR   PANTHER; PTHR11444:SF1; FUMARATE HYDRATASE, MITOCHONDRIAL; 1.
DR   Pfam; PF10415; FumaraseC_C; 1.
DR   Pfam; PF00206; Lyase_1; 1.
DR   PRINTS; PR00149; FUMRATELYASE.
DR   SUPFAM; SSF48557; L-aspartase-like; 1.
DR   PROSITE; PS00163; FUMARATE_LYASES; 1.
PE   3: Inferred from homology;
KW   Alternative initiation; Cytoplasm; Lyase; Mitochondrion;
KW   Reference proteome; Transit peptide; Tricarboxylic acid cycle.
FT   TRANSIT         1..19
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           20..485
FT                   /note="Fumarate hydratase, mitochondrial"
FT                   /id="PRO_0000331360"
FT   ACT_SITE        209
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   ACT_SITE        339
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   BINDING         118..120
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   BINDING         150..153
FT                   /ligand="substrate"
FT                   /note="in site B"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   BINDING         160..162
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   BINDING         208
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   BINDING         340
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   BINDING         345..347
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   SITE            352
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   VAR_SEQ         1..19
FT                   /note="Missing (in isoform Cytoplasmic)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_033185"
SQ   SEQUENCE   485 AA;  52963 MW;  A70941925A48FBBE CRC64;
     MLSASRKLNN QQFLKTIRNM TTFRSEFDTF GEVKVNDEKY WGAQTQRSLE NFDIGGESEK
     MPLMVVRSFG ILKRCAAIVN KKYGLDATIA DNIAKAATEV VEGKLDDQFP LVVFQTGSGT
     QSNMNANEVI SNRAIELMTG KRDFSKKLVH PNDHVNKSQS SNDTFPTCMH IAAAISINEK
     LVPALEMLLA AMRTKQNEFN HIIKIGRTHL QDATPLTLGQ EFSGYCTQIE YGIQRIKDTL
     PRLYNLAQGG TAVGTGLNTP VGFDVDIASE VAKFTGLPFK TAPNKFEALA AHDAMVEVSG
     ALNTVAVSLM KIANDIRFLG SGPRCGLGEL ILPENEPGSS IMPGKVNPTQ CEAMTMVCAQ
     VMGNNTTVSI AGSNGHFELN VFKPVIIKNV LSSIRLIADA SVSFTKHCVV GIKADEKRID
     QLLHESLMLV TALNPYIGYD KAAKAAKKAH KEKTTLKEAC LSLGFTTSEE FDKWVDPSKM
     IGSMK
//