FUMH_SCHPO
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 03-AUG-2022, entry version 137.
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; 4896.SPCC18.18c.1; -.
DR SwissPalm; O94552; -.
DR MaxQB; O94552; -.
DR PaxDb; O94552; -.
DR PRIDE; O94552; -.
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; HDSMGEV; -.
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; ISS:PomBase.
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; ISS:PomBase.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0006106; P:fumarate metabolic process; ISS:PomBase.
DR GO; GO:0006108; P:malate metabolic process; IBA:GO_Central.
DR GO; GO:0006099; P:tricarboxylic acid cycle; ISS:PomBase.
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 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
