FH
entrez
2271
canonical
uniprot
P07954
canonical
ensembl
ENSG00000091483
resolver
ensp
ENSP00000355518
resolver
genesymbol
FH
resolver
hgnc
HGNC:3700
resolver
uniprot
A0A0S2Z4C3
resolver
uniprot
B1ANK7
resolver
uniprot_entry
A0A0S2Z4C3_HUMAN
resolver
uniprot_entry
FUMH_HUMAN
resolver
uniprot_sec
B1ANK7
resolver
amino_acid_sequence
MYRALRLLARSRPLVRAPAAALASAPGLGGAAVPSFWPPNAARMASQNSFRIEYDTFGELKVPNDKYYGAQTVRSTMNFKIGGVTERMPTPVIKAFGILKRAAAEVNQDYGLDPKIANAIMKAADEVAEGKLNDHFPLVVWQTGSGTQTNMNVNEVISNRAIEMLGGELGSKIPVHPNDHVNKSQSSNDTFPTAMHIAAAIEVHEVLLPGLQKLHDALDAKSKEFAQIIKIGRTHTQDAVPLTLGQEFSGYVQQVKYAMTRIKAAMPRIYELAAGGTAVGTGLNTRIGFAEKVAAKVAALTGLPFVTAPNKFEALAAHDALVELSGAMNTTACSLMKIANDIRFLGSGPRSGLGELILPENEPGSSIMPGKVNPTQCEAMTMVAAQVMGNHVAVTVGGSNGHFELNVFKPMMIKNVLHSARLLGDASVSFTENCVVGIQANTERINKLMNESLMLVTALNPHIGYDKAAKIAKTAHKNGSTLKETAIELGYLTAEQFDEWVKPKDMLGPK
uniprot
proteins
disease_involvement
DISEASE: Fumarase deficiency (FMRD) [MIM:606812]: A severe autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound psychomotor retardation, and brain abnormalities, such as agenesis of the corpus callosum, gyral defects, and ventriculomegaly. Many patients show neonatal distress, metabolic acidosis, and/or encephalopathy. {ECO:0000269|PubMed:9635293, ECO:0000269|Ref.23}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: [Isoform Cytoplasmic]: Hereditary leiomyomatosis and renal cell cancer (HLRCC) [MIM:150800]: A disorder characterized by predisposition to cutaneous and uterine leiomyomas, and papillary type 2 renal cancer which occurs in about 20% of patients. {ECO:0000269|PubMed:11865300, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:8200987}. Note=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). {ECO:0000269|PubMed:30718813}.
uniprot
proteins
ec_number
4.2.1.2
uniprot
proteins
function
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). {ECO:0000269|PubMed:30761759, ECO:0000305}.; FUNCTION: [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. {ECO:0000250|UniProtKB:P10173}.; FUNCTION: [Isoform Cytoplasmic]: 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). {ECO:0000250|UniProtKB:P97807, ECO:0000269|PubMed:20231875, ECO:0000269|PubMed:26237645}.
uniprot
proteins
mass_dalton
54637
uniprot
proteins
mutagenesis
MUTAGEN 46; /note="S->A: Does not affect phosphorylation by PRKDC."; /evidence="ECO:0000269|PubMed:26237645"; MUTAGEN 147; /note="T->A: Does not affect phosphorylation by PRKDC."; /evidence="ECO:0000269|PubMed:26237645"; MUTAGEN 187; /note="S->A: Does not affect phosphorylation by PRKDC."; /evidence="ECO:0000269|PubMed:26237645"; MUTAGEN 236; /note="T->A: Abolished interaction with H2AZ1 and localization to chromatin in response to DNA damage."; /evidence="ECO:0000269|PubMed:26237645"; MUTAGEN 236; /note="T->D: Phosphomimetic mutant; promotes interaction with H2AZ1, leading to increased localization to chromatin in response to DNA damage."; /evidence="ECO:0000269|PubMed:26237645
uniprot
proteins
pathway_participation
PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; (S)-malate from fumarate: step 1/1. {ECO:0000250|UniProtKB:P10173}.
uniprot
proteins
post_translational_modification
PTM: [Isoform Cytoplasmic]: Phosphorylation at Thr-236 by PRKDC in response to DNA damage promotes translocation to the nucleus and recruitment to DNA double-strand breaks (DSBs). {ECO:0000269|PubMed:26237645}.
uniprot
proteins
protein_family
Class-II fumarase/aspartase family
uniprot
proteins
protein_family
Fumarase subfamily
uniprot
proteins
pubmed
11865300
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20231875
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21445611
uniprot
proteins
pubmed
22509282
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24419633
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26237645
uniprot
proteins
pubmed
27037871
uniprot
proteins
pubmed
30718813
uniprot
proteins
pubmed
30761759
uniprot
proteins
pubmed
3828494
uniprot
proteins
pubmed
8200987
uniprot
proteins
pubmed
9635293
uniprot
proteins
sequence_length
510
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion {ECO:0000269|PubMed:27037871}.; SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm, cytosol {ECO:0000269|PubMed:20231875, ECO:0000269|PubMed:22509282, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:27037871}. Nucleus {ECO:0000269|PubMed:20231875, ECO:0000269|PubMed:26237645}. Chromosome {ECO:0000269|PubMed:26237645}. Note=Translocates to the nucleus in response to DNA damage: localizes to DNA double-strand breaks (DSBs) following phosphorylation by PRKDC. {ECO:0000269|PubMed:26237645}.
uniprot
proteins