ID   FUM1_ARATH              Reviewed;         492 AA.
AC   P93033; O24649;
DT   15-DEC-2003, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-2003, sequence version 2.
DT   27-MAR-2024, entry version 164.
DE   RecName: Full=Fumarate hydratase 1, mitochondrial {ECO:0000303|PubMed:20202172};
DE            Short=AtFUM1 {ECO:0000303|PubMed:29688630};
DE            Short=Fumarase 1 {ECO:0000303|PubMed:20202172};
DE            EC=4.2.1.2 {ECO:0000269|PubMed:29688630};
DE   Flags: Precursor;
GN   Name=FUM1 {ECO:0000303|PubMed:20202172}; OrderedLocusNames=At2g47510;
GN   ORFNames=T30B22.19;
OS   Arabidopsis thaliana (Mouse-ear cress).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX   NCBI_TaxID=3702;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Behal R.H., Oliver D.J.;
RL   Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=cv. Columbia;
RX   PubMed=10617197; DOI=10.1038/45471;
RA   Lin X., Kaul S., Rounsley S.D., Shea T.P., Benito M.-I., Town C.D.,
RA   Fujii C.Y., Mason T.M., Bowman C.L., Barnstead M.E., Feldblyum T.V.,
RA   Buell C.R., Ketchum K.A., Lee J.J., Ronning C.M., Koo H.L., Moffat K.S.,
RA   Cronin L.A., Shen M., Pai G., Van Aken S., Umayam L., Tallon L.J.,
RA   Gill J.E., Adams M.D., Carrera A.J., Creasy T.H., Goodman H.M.,
RA   Somerville C.R., Copenhaver G.P., Preuss D., Nierman W.C., White O.,
RA   Eisen J.A., Salzberg S.L., Fraser C.M., Venter J.C.;
RT   "Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana.";
RL   Nature 402:761-768(1999).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=cv. Columbia;
RX   PubMed=27862469; DOI=10.1111/tpj.13415;
RA   Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA   Town C.D.;
RT   "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT   genome.";
RL   Plant J. 89:789-804(2017).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=cv. Columbia;
RX   PubMed=14593172; DOI=10.1126/science.1088305;
RA   Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA   Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA   Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA   Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA   Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA   Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA   Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA   Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA   Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA   Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA   Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA   Ecker J.R.;
RT   "Empirical analysis of transcriptional activity in the Arabidopsis
RT   genome.";
RL   Science 302:842-846(2003).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE SCALE
RP   ANALYSIS].
RC   STRAIN=cv. Landsberg erecta;
RX   PubMed=14671022; DOI=10.1105/tpc.016055;
RA   Heazlewood J.L., Tonti-Filippini J.S., Gout A.M., Day D.A., Whelan J.,
RA   Millar A.H.;
RT   "Experimental analysis of the Arabidopsis mitochondrial proteome highlights
RT   signaling and regulatory components, provides assessment of targeting
RT   prediction programs, and indicates plant-specific mitochondrial proteins.";
RL   Plant Cell 16:241-256(2004).
RN   [6]
RP   SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX   PubMed=20202172; DOI=10.1111/j.1365-313x.2010.04189.x;
RA   Pracharoenwattana I., Zhou W., Keech O., Francisco P.B., Udomchalothorn T.,
RA   Tschoep H., Stitt M., Gibon Y., Smith S.M.;
RT   "Arabidopsis has a cytosolic fumarase required for the massive allocation
RT   of photosynthate into fumaric acid and for rapid plant growth on high
RT   nitrogen.";
RL   Plant J. 62:785-795(2010).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND CLEAVAGE OF TRANSIT PEPTIDE AFTER
RP   TYR-28.
RX   PubMed=25732537; DOI=10.1093/jxb/erv064;
RA   Carrie C., Venne A.S., Zahedi R.P., Soll J.;
RT   "Identification of cleavage sites and substrate proteins for two
RT   mitochondrial intermediate peptidases in Arabidopsis thaliana.";
RL   J. Exp. Bot. 66:2691-2708(2015).
RN   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP   REGULATION, AND SUBUNIT.
RX   PubMed=29688630; DOI=10.1111/febs.14483;
RA   Zubimendi J.P., Martinatto A., Valacco M.P., Moreno S., Andreo C.S.,
RA   Drincovich M.F., Tronconi M.A.;
RT   "The complex allosteric and redox regulation of the fumarate hydratase and
RT   malate dehydratase reactions of Arabidopsis thaliana Fumarase 1 and 2 gives
RT   clues for understanding the massive accumulation of fumarate.";
RL   FEBS J. 285:2205-2224(2018).
CC   -!- FUNCTION: Catalyzes the reversible stereospecific interconversion of
CC       fumarate to L-malate (PubMed:29688630). 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 (By similarity). {ECO:0000250|UniProtKB:P08417,
CC       ECO:0000250|UniProtKB:P10173, ECO:0000269|PubMed:29688630}.
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:29688630};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12461;
CC         Evidence={ECO:0000269|PubMed:29688630};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:12462;
CC         Evidence={ECO:0000269|PubMed:29688630};
CC   -!- ACTIVITY REGULATION: Fumarate hydratase activity (fumarate to L-malate)
CC       is strongly inhibited by phosphoenolpyruvate, citrate, oxaloacetate,
CC       ATP and ADP (PubMed:29688630). Malate dehydratase activity (malate to
CC       fumarate) is activated by oxaloacetate, pyruvate, Asn and Gln
CC       (PubMed:29688630). Malate dehydratase activity (malate to fumarate) is
CC       inhibited by citrate, succinate, ADP, ATP, glucose-6P and
CC       phosphoenolpyruvate (PubMed:29688630). {ECO:0000269|PubMed:29688630}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.7 mM for fumarate (at pH 8.0) {ECO:0000269|PubMed:29688630};
CC         KM=1.8 mM for (S)-malate (at pH 8.0) {ECO:0000269|PubMed:29688630};
CC         Note=kcat is 21 sec(-1) for fumarate (at pH 8.0) (PubMed:29688630).
CC         kcat is 15.3 sec(-1) for (S)-malate (at pH 8.0) (PubMed:29688630).
CC         {ECO:0000269|PubMed:29688630};
CC   -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; (S)-malate
CC       from fumarate: step 1/1. {ECO:0000250|UniProtKB:P08417,
CC       ECO:0000250|UniProtKB:P10173}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:29688630}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14671022,
CC       ECO:0000269|PubMed:20202172, ECO:0000305|PubMed:25732537}.
CC   -!- DISRUPTION PHENOTYPE: Embryonic lethality.
CC       {ECO:0000269|PubMed:20202172}.
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; U82202; AAB39989.1; -; mRNA.
DR   EMBL; AC002535; AAC62859.1; -; Genomic_DNA.
DR   EMBL; CP002685; AEC10852.1; -; Genomic_DNA.
DR   EMBL; CP002685; AEC10853.1; -; Genomic_DNA.
DR   EMBL; CP002685; ANM62150.1; -; Genomic_DNA.
DR   EMBL; AF020303; AAB71399.1; -; Genomic_DNA.
DR   EMBL; AY054252; AAL06911.1; -; mRNA.
DR   EMBL; AY062460; AAL32538.1; -; mRNA.
DR   EMBL; BT003361; AAO29979.1; -; mRNA.
DR   PIR; T00433; T00433.
DR   RefSeq; NP_001078075.1; NM_001084606.2.
DR   RefSeq; NP_001324328.1; NM_001337266.1.
DR   RefSeq; NP_182273.1; NM_130319.4.
DR   AlphaFoldDB; P93033; -.
DR   SMR; P93033; -.
DR   BioGRID; 4699; 5.
DR   IntAct; P93033; 2.
DR   STRING; 3702.P93033; -.
DR   iPTMnet; P93033; -.
DR   MetOSite; P93033; -.
DR   SwissPalm; P93033; -.
DR   PaxDb; 3702-AT2G47510-1; -.
DR   ProteomicsDB; 230004; -.
DR   EnsemblPlants; AT2G47510.1; AT2G47510.1; AT2G47510.
DR   EnsemblPlants; AT2G47510.2; AT2G47510.2; AT2G47510.
DR   EnsemblPlants; AT2G47510.3; AT2G47510.3; AT2G47510.
DR   GeneID; 819364; -.
DR   Gramene; AT2G47510.1; AT2G47510.1; AT2G47510.
DR   Gramene; AT2G47510.2; AT2G47510.2; AT2G47510.
DR   Gramene; AT2G47510.3; AT2G47510.3; AT2G47510.
DR   KEGG; ath:AT2G47510; -.
DR   Araport; AT2G47510; -.
DR   TAIR; AT2G47510; FUM1.
DR   eggNOG; KOG1317; Eukaryota.
DR   HOGENOM; CLU_021594_4_1_1; -.
DR   InParanoid; P93033; -.
DR   OMA; AKWRAQT; -.
DR   OrthoDB; 1341425at2759; -.
DR   PhylomeDB; P93033; -.
DR   BRENDA; 4.2.1.2; 399.
DR   SABIO-RK; P93033; -.
DR   UniPathway; UPA00223; UER01007.
DR   PRO; PR:P93033; -.
DR   Proteomes; UP000006548; Chromosome 2.
DR   ExpressionAtlas; P93033; baseline and differential.
DR   GO; GO:0005829; C:cytosol; HDA:TAIR.
DR   GO; GO:0005739; C:mitochondrion; HDA:TAIR.
DR   GO; GO:0045239; C:tricarboxylic acid cycle enzyme complex; IEA:InterPro.
DR   GO; GO:0004333; F:fumarate hydratase activity; IDA:UniProtKB.
DR   GO; GO:0006106; P:fumarate metabolic process; IDA:UniProtKB.
DR   GO; GO:0006108; P:malate metabolic process; IDA:UniProtKB.
DR   GO; GO:0048868; P:pollen tube development; IMP:TAIR.
DR   GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-UniPathway.
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.
DR   Genevisible; P93033; AT.
PE   1: Evidence at protein level;
KW   Lyase; Mitochondrion; Reference proteome; Transit peptide;
KW   Tricarboxylic acid cycle.
FT   TRANSIT         1..28
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000269|PubMed:25732537"
FT   CHAIN           29..492
FT                   /note="Fumarate hydratase 1, mitochondrial"
FT                   /id="PRO_0000010329"
FT   ACT_SITE        216
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   ACT_SITE        346
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   BINDING         127..129
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   BINDING         157..160
FT                   /ligand="substrate"
FT                   /note="in site B"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   BINDING         167..169
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   BINDING         215
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   BINDING         347
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   BINDING         352..354
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   SITE            359
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   CONFLICT        8..9
FT                   /note="RR -> A (in Ref. 1; AAB39989)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        197
FT                   /note="S -> R (in Ref. 1; AAB39989)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        393..394
FT                   /note="IA -> TS (in Ref. 1; AAB39989)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        442
FT                   /note="P -> R (in Ref. 1; AAB39989)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        446
FT                   /note="Y -> C (in Ref. 1; AAB39989)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   492 AA;  53000 MW;  DF07D2D393966B3E CRC64;
     MSIYVASRRL SGGTTVTALR YATSLRSYST SFREERDTFG PIQVPSDKLW GAQTQRSLQN
     FEIGGERERM PEPIVRAFGV LKKCAAKVNM EYGLDPTIGK AIMQAAQEVA EGKLNDHFPL
     VVWQTGSGTQ SNMNANEVIA NRAAEILGRK RGEKCVHPND HVNRSQSSND TFPTVMHIAA
     ATEINSRLIP SLKTLHSTLE SKSFEFKDIV KIGRTHTQDA TPLTLGQEFG GYATQVKYGL
     NRVTCTLPRL YQLAQGGTAV GTGLNTKKGF DVKIAAAVAE ETNLPFVTAE NKFEALAAHD
     ACVETSGSLN TIATSLMKIA NDIRFLGSGP RCGLGELVLP ENEPGSSIMP GKVNPTQCEA
     LTMVCAQVMG NHVAVTVGGS NGHFELNVFK PVIASALLHS VRLIADASAS FEKNCVRGIE
     ANRERISKLL HESLMLVTSL NPKIGYDNAA AVAKKAHKEG CTLKEAALNL GVLTAEEFDT
     LVVPEKMIGP SD
//