FUMH_DICDI
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 03-AUG-2022, entry version 109.
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 (Slime mold).
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.DDB0231397; -.
DR PaxDb; Q54VA2; -.
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; HDSMGEV; -.
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; 1.10.275.10; -; 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 PANTHER; PTHR11444; PTHR11444; 1.
DR Pfam; PF10415; FumaraseC_C; 1.
DR Pfam; PF00206; Lyase_1; 1.
DR PRINTS; PR00149; FUMRATELYASE.
DR SUPFAM; SSF48557; SSF48557; 1.
DR TIGRFAMs; TIGR00979; fumC_II; 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
