Details of Protein

General Information of Protein (ID: PRT01037)
Name Fumarate hydratase (FH)
Synonyms   Click to Show/Hide Synonyms of This Protein
Fumarase; EF-3; Fh; Fh1
Gene Name Fh Gene ID
14194
UniProt ID
P97807
Family Lyases (EC 4)
EC Number   EC: 4.2.1.2  (Click to Show/Hide the Complete EC Tree)
Lyases
Carbon-oxygen lyase
Hydro-lyase
EC: 4.2.1.2
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MYRALRLLARSRRLLRVPSAGAAVSGEATTLPRCAPNVARMASQNSFRVEFDTFGELKVP
TDKYYGAQTVRSTMNFKIGGATERMPIPVIQAFGILKRAAAEVNQEYGLDPKIASAIMKA
ADEVAEGKLNDHFPLVVWQTGSGTQTNMNVNEVISNRAIEMLGGELGSKKPVHPNDHVNK
SQSSNDTFPTAMHIAAAVEVHKVLLPGLQKLHDALSAKSKEFAQVIKIGRTHTQDAVPLT
LGQEFSGYVQQVQYAMVRIKAAMPRIYELAAGGTAVGTGLNTRIGFAEKVAAKVAALTGL
PFVTAPNKFEALAAHDALVELSGAMNTAACSLMKIANDIRFLGSGPRSGLGELILPENEP
GSSIMPGKVNPTQCEAMTMVAAQVMGNHVAVTVGGSNGHFELNVFKPMMIKNVLHSARLL
GDASVSFTDNCVVGIQANTERINKLMNESLMLVTALNPHIGYDKAAKIAKTAHKNGSTLK
ETAIELGYLTAEQFDEWVKPKDMLGPK
Function Catalyzes the reversible stereospecific interconversion of fumarate to L-malate. Experiments in different species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the other (Probable).; [Isoform Mitochondrial]: Catalyzes the hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a transition step in the production of energy in the form of NADH.; [Isoform Cytoplasmic]: Catalyzes the dehydration of L-malate to fumarate. Fumarate metabolism in the cytosol plays a role during urea cycle and arginine metabolism; fumarate being a by-product of the urea cycle and amino-acid catabolism. Also plays a role in DNA repair by promoting non-homologous end-joining (NHEJ). In response to DNA damage and phosphorylation by PRKDC, translocates to the nucleus and accumulates at DNA double-strand breaks (DSBs): acts by catalyzing formation of fumarate, an inhibitor of KDM2B histone demethylase activity, resulting in enhanced dimethylation of histone H3 'Lys-36' (H3K36me2).
Regulatory Network
Full List of Metabolite(s) Regulated by This Protein
      Organic acids and derivatives
            Argininosuccinic acid Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Knockout of Fh
                      Induced Change Argininosuccinic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of Fh leads to the increase of argininosuccinic acid levels compared with control group.
            Aspartic acid Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of Fh
                      Induced Change Aspartic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status hydronephrosis [ICD-11: GB56]
                      Details It is reported that knockout of FLNB leads to the increase of aspartic acid levels compared with control group.
            Citrulline Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of Fh
                      Induced Change Citrulline concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status hydronephrosis [ICD-11: GB56]
                      Details It is reported that knockout of FLNB leads to the increase of citrulline levels compared with control group.
      Organic oxygen compounds
            Glycerol Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2], [1]
                      Introduced Variation Knockout of Fh
                      Induced Change Glycerol concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual ...
                      Details It is reported that knockout of FLNB leads to the increase of glycerol levels compared with control group.
References
1 Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells. Cancer Metab. 2013 Mar 21;1(1):12.
2 A role for cytosolic fumarate hydratase in urea cycle metabolism and renal neoplasia. Cell Rep. 2013 May 30;3(5):1440-8.

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