ID   FUMH_SCHPO              Reviewed;         520 AA.
AC   O94552; O74868;
DT   28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT   22-SEP-2009, sequence version 3.
DT   27-MAR-2024, entry version 144.
DE   RecName: Full=Fumarate hydratase, mitochondrial;
DE            Short=Fumarase;
DE            EC=4.2.1.2 {ECO:0000250|UniProtKB:P08417};
DE   Flags: Precursor;
GN   Name=fum1; ORFNames=SPCC18.18c, SPCC290.01c;
OS   Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC   Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC   Schizosaccharomyces.
OX   NCBI_TaxID=284812;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=972 / ATCC 24843;
RX   PubMed=11859360; DOI=10.1038/nature724;
RA   Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA   Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA   Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA   Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA   Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA   Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA   Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA   Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA   O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA   Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA   Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA   Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA   Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA   Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA   Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA   Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA   Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA   Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA   Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA   Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA   del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA   Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA   Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA   Nurse P.;
RT   "The genome sequence of Schizosaccharomyces pombe.";
RL   Nature 415:871-880(2002).
CC   -!- FUNCTION: Catalyzes the reversible stereospecific interconversion of
CC       fumarate to L-malate. In mitochondrion, catalyzes the hydration of
CC       fumarate to L-malate in the tricarboxylic acid (TCA) cycle to
CC       facilitate a transition step in the production of energy in the form of
CC       NADH. In cytoplasm and nucleus, involved in DNA repair in response to
CC       DNA damage: following DNA double-strand breaks (DSBs), translocates
CC       from the cytosol to the nucleus and promotes DNA repair by catalyzing
CC       the dehydration of L-malate to fumarate.
CC       {ECO:0000250|UniProtKB:P08417}.
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:P08417};
CC   -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; (S)-malate
CC       from fumarate: step 1/1. {ECO:0000250|UniProtKB:P08417}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P08417}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC       {ECO:0000250|UniProtKB:P08417}. Cytoplasm
CC       {ECO:0000250|UniProtKB:P08417}. Nucleus {ECO:0000250|UniProtKB:P08417}.
CC       Note=Translocates from the cytosol to the nucleus in response to DNA
CC       damage. {ECO:0000250|UniProtKB:P08417}.
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 (By
CC       similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the class-II fumarase/aspartase family. Fumarase
CC       subfamily. {ECO:0000305}.
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DR   EMBL; CU329672; CAA21432.3; -; Genomic_DNA.
DR   PIR; T41265; T41265.
DR   RefSeq; NP_588397.3; NM_001023388.3.
DR   AlphaFoldDB; O94552; -.
DR   SMR; O94552; -.
DR   BioGRID; 275911; 2.
DR   STRING; 284812.O94552; -.
DR   iPTMnet; O94552; -.
DR   SwissPalm; O94552; -.
DR   MaxQB; O94552; -.
DR   PaxDb; 4896-SPCC18-18c-1; -.
DR   EnsemblFungi; SPCC18.18c.1; SPCC18.18c.1:pep; SPCC18.18c.
DR   GeneID; 2539345; -.
DR   KEGG; spo:SPCC18.18c; -.
DR   PomBase; SPCC18.18c; fum1.
DR   VEuPathDB; FungiDB:SPCC18.18c; -.
DR   eggNOG; KOG1317; Eukaryota.
DR   HOGENOM; CLU_021594_4_1_1; -.
DR   InParanoid; O94552; -.
DR   OMA; AKWRAQT; -.
DR   PhylomeDB; O94552; -.
DR   Reactome; R-SPO-71403; Citric acid cycle (TCA cycle).
DR   UniPathway; UPA00223; UER01007.
DR   PRO; PR:O94552; -.
DR   Proteomes; UP000002485; Chromosome III.
DR   GO; GO:0005829; C:cytosol; HDA:PomBase.
DR   GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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:0006974; P:DNA damage response; ISS:UniProtKB.
DR   GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
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: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   Cytoplasm; DNA damage; DNA repair; Lyase; Mitochondrion; Nucleus;
KW   Reference proteome; Transit peptide; Tricarboxylic acid cycle.
FT   TRANSIT         1..39
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           40..520
FT                   /note="Fumarate hydratase, mitochondrial"
FT                   /id="PRO_0000010332"
FT   ACT_SITE        243
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   ACT_SITE        373
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   BINDING         153..155
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   BINDING         184..187
FT                   /ligand="substrate"
FT                   /note="in site B"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   BINDING         194..196
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   BINDING         242
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   BINDING         374
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   BINDING         379..381
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   SITE            386
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
SQ   SEQUENCE   520 AA;  56322 MW;  4AF0DA8BF5E14AE8 CRC64;
     MASVAHISTA KAIFRAGGLP CRRLITPTLT GLPLKTHRMN STTPTYHLIP KGGKHGEFRQ
     ESDTFGPIQV PAEKYWGAQT QRSLQNFRIG GEKERLPLPL VRAFGVLKRA AASVNREFGL
     DPKLADAIEQ AAQEVIDGRL DDNFPLVVFQ TGSGTQSNMN SNEVIANRAI EILGGTLGSK
     KPVHPNDHVN MSQSSNDTFP TVMHIASVLQ IHTHLLPAMK HLHRALKGKE EEFKNIIKIG
     RTHMQDATPL SLGQEFSGYV TQVGYGIERI NNALPRLCLL AQGGTAVGTG LNTFEGFDVK
     VAEKVSKLTN IEFKTAPNKF EALAAHDAIV EMSGALNVIA CSLMKIANDI RQLGSGPRCG
     LGELILPANE PGSSIMPGKV NPTQCEALTM VCAQVMGNHA TITVAGASGH CELNVFKPLL
     AKNILSSIRL LGDACESFTD HCVVGIEPNY EGIARHLRDS LMLVTALNPH IGYDNCAKIA
     KTALKNKSTL KHEFVTLGFG TPEQFDEWVR PELMISAKKV
//