Details of Protein

General Information of Protein (ID: PRT01036)
Name Fumarate hydratase (FH)
Synonyms   Click to Show/Hide Synonyms of This Protein
Fumarase; HsFH; FH
Gene Name FH Gene ID
2271
UniProt ID
P07954
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
MYRALRLLARSRPLVRAPAAALASAPGLGGAAVPSFWPPNAARMASQNSFRIEYDTFGEL
KVPNDKYYGAQTVRSTMNFKIGGVTERMPTPVIKAFGILKRAAAEVNQDYGLDPKIANAI
MKAADEVAEGKLNDHFPLVVWQTGSGTQTNMNVNEVISNRAIEMLGGELGSKIPVHPNDH
VNKSQSSNDTFPTAMHIAAAIEVHEVLLPGLQKLHDALDAKSKEFAQIIKIGRTHTQDAV
PLTLGQEFSGYVQQVKYAMTRIKAAMPRIYELAAGGTAVGTGLNTRIGFAEKVAAKVAAL
TGLPFVTAPNKFEALAAHDALVELSGAMNTTACSLMKIANDIRFLGSGPRSGLGELILPE
NEPGSSIMPGKVNPTQCEAMTMVAAQVMGNHVAVTVGGSNGHFELNVFKPMMIKNVLHSA
RLLGDASVSFTENCVVGIQANTERINKLMNESLMLVTALNPHIGYDKAAKIAKTAHKNGS
TLKETAIELGYLTAEQFDEWVKPKDMLGPK
Structure
3E04 ; 5D6B ; 5UPP ; 6EBT ; 6V8F ; 6VBE
Function Catalyzes the reversible stereospecific interconversion of fumarate to L-malate. Experiments in other 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
            Succinic 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 Mutation (AAAins435/R58X; P131R/exon 2 splice variant; R190H/R190H; K187R/K187R) of FH
                      Induced Change Succinic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (AAAins435/R58X; P131R/exon 2 splice variant; R190H/R190H; K187R/K187R) of FH leads to the increase of succinic acid 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 [1]
                      Introduced Variation Mutation (AAAins435/R58X; R190H/R190H; K187R/K187R) of FH
                      Induced Change Glycerol concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutant of FH leads to the increase of glycerol levels compared with control group.
References
1 Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations. Hum Mol Genet. 2005 Aug 1;14(15):2231-9.

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