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Details on Person UniProt:P07954 FH
| Class:Id | ReferenceGeneProduct:55030 |
|---|---|
| _chainChangeLog | transit peptide:1-44 added on Sat February 7 2015;chain:45-510 added on Sat February 7 2015;initiator methionine: for 55030 added on Sun February 16 2020;initiator methionine: for 55030 removed on Fri Aug 15 2025;initiator methionine:1 for 55030 added on Fri Aug 15 2025 |
| _displayName | UniProt:P07954 FH |
| _timestamp | 2025-08-15 21:14:52 |
| chain | transit peptide:1-44 chain:45-510 initiator methionine:1 |
| checksum | 86F91F95DC046F64 |
| comment | FUNCTION Catalyzes the reversible stereospecific interconversion of fumarate to L-malate (PubMed:30761759). Experiments in other species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the other (Probable).FUNCTION 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.FUNCTION Catalyzes the dehydration of L-malate to fumarate (By similarity). 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 (By similarity). Also plays a role in DNA repair by promoting non-homologous end-joining (NHEJ) (PubMed:20231875, PubMed:26237645). 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) (PubMed:26237645).CATALYTIC ACTIVITY (S)-malate = fumarate + H2OCATALYTIC ACTIVITY (S)-malate = fumarate + H2OCATALYTIC ACTIVITY (S)-malate = fumarate + H2OBIOPHYSICOCHEMICAL PROPERTIES kcat is 280 sec(-1) with L-malate (at pH 8.5) (PubMed:30761759). kcat is 170 sec(-1) with fumarate (at pH 8.5) (PubMed:30761759).PATHWAY Carbohydrate metabolism; tricarboxylic acid cycle; (S)-malate from fumarate: step 1/1.SUBUNIT Homotetramer (PubMed:21445611, PubMed:30761759). Interacts with H2AZ1 (PubMed:26237645).INTERACTION Translocates to the nucleus in response to DNA damage: localizes to DNA double-strand breaks (DSBs) following phosphorylation by PRKDC.ALTERNATIVE PRODUCTS Expressed in red blood cells; underexpressed in red blood cells (cytoplasm) of patients with hereditary non-spherocytic hemolytic anemia of unknown etiology.PTM Phosphorylation at Thr-236 by PRKDC in response to DNA damage promotes translocation to the nucleus and recruitment to DNA double-strand breaks (DSBs).DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry. Isoform Cytoplasmic: HLRCC is probably caused by an accumulation of fumarate (PubMed:30718813). Accumulation of fumarate coupled with protonation promotes the formation of non-enzymatic post-translational modification cysteine S-succination (S-(2-succinyl)cysteine) on proteins, such as SMARCC1 (PubMed:30718813).MISCELLANEOUS There are 2 substrate-binding sites: the catalytic A site, and the non-catalytic B site that may play a role in the transfer of substrate or product between the active site and the solvent. Alternatively, the B site may bind allosteric effectors.SIMILARITY Belongs to the class-II fumarase/aspartase family. Fumarase subfamily. |
| description | recommendedName: fullName evidence="16 18"Fumarate hydratase, mitochondrial shortName evidence="18 19 20"Fumarase shortName evidence="17"HsFH ecNumber evidence="12"4.2.1.2 |
| geneName | FH |
| identifier | P07954 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative initiation Chromosome Cytoplasm Direct protein sequencing Disease variant DNA damage DNA repair Lyase Mitochondrion Nucleus Phosphoprotein Proteomics identification Reference proteome Transit peptide Tricarboxylic acid cycle Tumor suppressor |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | FH |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8958402] ENSEMBL:ENSG00000091483 FH [Homo sapiens] |
| secondaryIdentifier | FUMH_HUMAN B1ANK7 |
| sequenceLength | 510 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:229980] UniProt:P07954-2 FH [Homo sapiens] [ReferenceIsoform:402563] UniProt:P07954-1 FH [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:70980] FH [mitochondrial matrix] [Homo sapiens] [EntityWithAccessionedSequence:8958513] FH [extracellular region] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P07954 FH (55030)
