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Information on EC 4.2.1.2 - fumarate hydratase and Organism(s) Saccharomyces cerevisiae and UniProt Accession P08417
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4.2.1.2 fumarate hydrataseSpecify your search results
Word Map
- 4.2.1.2
- succinate
- leiomyomatosis
- hereditary
-
tricarboxylic
- uterine
- leiomyoma
-
hlrcc
-
germline
- isocitrate
- citrate
- tca
-
papillary
-
krebs
- aconitase
- carboxylase
-
citric
-
predisposition
- fibroids
- phosphoenolpyruvate
- succinyl-coa
- nucleoli
-
l-malic
-
halo
- alpha-ketoglutarate
- leiomyosarcoma
-
oncometabolite
- paragangliomas
- aspartase
-
pseudohypoxic
-
reed
- oxalacetate
-
perinucleolar
-
hippel-lindau
-
hysterectomy
-
chromophobe
-
1.1.1.37
- analysis
- 2-hydroxyglutarate
- synthesis
-
papules
- oncocytomas
- medicine
- industry
The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
fumarase, fumarate hydratase, fumarase c, class ii fumarase, lmfh-2, scfumc, slfumc, mmcbc, lmfh-1, stfumc, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
fumarase
hydratase, fumarate
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-
-
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L-malate hydro-lyase
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-
-
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fumarase
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
elimination
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-
-
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PATHWAY SOURCE
PATHWAYS
KEGG
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-, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
(S)-malate hydro-lyase (fumarate-forming)
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CAS REGISTRY NUMBER
COMMENTARY
9032-88-6
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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mitochondrial and cytosolic isoforms are derivatives of a single translation product and have identical amino termini
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translation product of the FUM1 gene, distribution can be affected by hsp70 molecular chaperones
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mitochondrial and cytosolic isoforms are derivatives of a single translation product and have identical amino termini
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translation product of the FUM1 gene, distribution can be affected by hsp70 molecular chaperones
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the presequence of fumarase is exposed to the cytosol during import into mitochondria
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
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increased sensitivity (10-100fold) of the FUM1 mutant strain to ionizing radiation, to the presence of hydroxyurea and to double-strand breaks when compared to the wild-type. Cytosolic absence of fumarase in yeast with a DELTAfum1 chromosomal deletion can be complemented by human fumarase. Fumaric acid (25 mM) complements the phenotype of fumarase cytosolic absence. FUM1 mutant strain sensitivity to double-strand breaks can be complemented by catalytically active pDELTAMTS-FUM1 but not by the corresponding H153R mutant
physiological function
physiological function
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cytosolic fumarase plays a role in the cellular response to double-strand breaks. Fumarase enzymatic activity is required for its DNA damage protective function. Fumarase activity is also required for the extra-mitochondrial function of fumarase
physiological function
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metabolites of the glyoxylate shunt act as nanosensors for fumarase subcellular targeting and distribution. Glyoxylate shunt deletion mutants exhibit an altered fumarase dual distribution. Expression levels of Cit2 affect dual targeting of fumarase. Amount of cytosolic fumarase is drastically reduced in the DELTAcit2 strain, when compared with the wild-type strain. Proportion of fumarase activity is very low in the cytosolic versus mitochondrial fractions obtained from DELTAcit2 and wild-type plus pCit2 strains when compared with the wild-type or DELTAcit2 plus pCit2 strains, in which the fumarase activity is divided equally between the corresponding subcellular fractions
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native and recombinant enzyme, native fumarase is crystallized in the presence of the competitive inhibitor meso-tartrate
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H153R
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is catalytically inactive since it does not complement a fumarase knockout strain with respect to its TCA cycle function. Yeast strains expressing the mutant protein do not grow on glycerol as the sole energy and carbon source
additional information
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isolation of fumarase mutants in which dual targeting (to cytosol and mitochondria) is abolished because of perturbation of its conformation
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
mitochondrially targeted fumarase harboring a tobacco etch virus protease recognition sequence is efficiently cleaved by the mitochondrial but not by the cytosolic tobacco etch virus protease. Fumarase is readily cleaved by cytosolic tobacco etch virus when its import into mitochondria is slowed down by either disrupting the activity of the TOMcomplex, lowering the growth temperature, or reducing the inner membrane electrochemical potential
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
mutant fumarase derivative lacking the MTS expressed in the FUM1 mutant strain, expressing the site-specific HO double-stranded DNA endonuclease
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plasmid encoding fumarase lacking an MTS transformed into the wild-type, DELTAcit2 and R strains
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
level of fumarase mRNA is upregulated both in the DELTacit2 and wild-type plus pCit2 strains. Approximately 2fold higher Fum1 mRNA level in a DELTAcit2 strain when compared with the wild-type strain. Significant increase in fumarase expression and cellular enzymatic activity in the glyoxylate deletion strains: DELTAmls1, DELTAicl1, DELTAaco1and DELTAcit2. Succinic acid in the growth medium affects fumarase dual distribution, succinic acid directly interacts with fumarase and slows down its folding thereby causing more fumarase to be fully imported into mitochondria
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Alberty, R.A.
Fumarase
The Enzymes, 2nd Ed (Boyer, P. D. , Lardy, H. , Myrbck, K. , eds. )
5
531-544
1961
Azotobacter vinelandii, Saccharomyces cerevisiae, Sus scrofa
-
Wu, M.; Tzagoloff, A.
Mitochondrial and cytoplasmic fumarases in Saccharomyces cerevisiae are encoded by a single nuclear gene FUM1
J. Biol. Chem.
262
12275-12282
1987
Saccharomyces cerevisiae
Weaver, T.; Lees, M.; Zaitsev, V.; Zaitseva, I.; Duke, E.; Lindley, P.; McSweeny, S.; Svensson, A.; Keruchenko, J.; Keruchenko, I.; Gladilin, K.; Banaszak, L.
Crystal structures of native and recombinant yeast fumarase
J. Mol. Biol.
280
431-442
1998
Saccharomyces cerevisiae (P08417), Saccharomyces cerevisiae
Keruchenko, J.S.; Keruchenko, I.D.; Gladilin, K.L.; Zaitsev, V.; Chiragadze, N.Y.
Purification, characterization and preliminary X-ray study of fumarase from Saccharomyces cerevisiae
Biochim. Biophys. Acta
1122
85-92
1992
Saccharomyces cerevisiae
Mizobata, T.; Fujioka, T.; Yamasaki, F.; Hidaka, M.; Nagai, J.; Kawata, Y.
Purification and characterization of a thermostable class II fumarase from Thermus thermophilus
Arch. Biochem. Biophys.
355
49-55
1998
Saccharomyces cerevisiae, Thermus thermophilus
Sass, E.; Blachinsky, E.; Karniely, S.; Pines, O.
Mitochondrial and cytosolic isoforms of yeast fumarase are derivatives of a single translation product and have identical amino termini
J. Biol. Chem.
276
46111-46117
2001
Saccharomyces cerevisiae
Sass, E.; Karniely, S.; Pines, O.
Folding of fumarase during mitochondrial import determines its dual targeting in yeast
J. Biol. Chem.
278
45109-45116
2003
Saccharomyces cerevisiae
Singh, B.; Gupta, R.S.
Mitochondrial import of human and yeast fumarase in live mammalian cells: retrograde translocation of the yeast enzyme is mainly caused by its poor targeting sequence
Biochem. Biophys. Res. Commun.
346
911-918
2006
Homo sapiens (P07954), Homo sapiens, Saccharomyces cerevisiae (P08417), Saccharomyces cerevisiae
Yogev, O.; Karniely, S.; Pines, O.
Translation-coupled translocation of yeast fumarase into mitochondria in vivo
J. Biol. Chem.
282
29222-29229
2007
Saccharomyces cerevisiae
Karniely, S.; Regev-Rudzki, N.; Pines, O.
The presequence of fumarase is exposed to the cytosol during import into mitochondria
J. Mol. Biol.
358
396-405
2006
Saccharomyces cerevisiae
Regev-Rudzki, N.; Yogev, O.; Pines, O.
The mitochondrial targeting sequence tilts the balance between mitochondrial and cytosolic dual localization
J. Cell Sci.
121
2423-2431
2008
Saccharomyces cerevisiae
Regev-Rudzki, N.; Battat, E.; Goldberg, I.; Pines, O.
Dual localization of fumarase is dependent on the integrity of the glyoxylate shunt
Mol. Microbiol.
72
297-306
2009
Saccharomyces cerevisiae
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