Mouse anti-Human/Mouse/Rat sapiens (Human) FH Monoclonal Antibody

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)

Subcellular Location

Cytoplasm, cytosol; Nucleus; Chromosome

Disease Association

Fumarase deficiency (FMRD) : 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. [The disease is caused by variants affecting the gene represented in this entry] | Hereditary leiomyomatosis and renal cell cancer (HLRCC) : A disorder characterized by predisposition to cutaneous and uterine leiomyomas, and papillary type 2 renal cancer which occurs in about 20% of patients. [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)]

Tissue Specificity

Expressed in red blood cells; underexpressed in red blood cells (cytoplasm) of patients with hereditary non-spherocytic hemolytic anemia of unknown etiology

Subunit

Homotetramer (PubMed:21445611, PubMed:30761759). Interacts with H2AZ1 (PubMed:26237645)

Pathway

Carbohydrate metabolism; tricarboxylic acid cycle; (S)-malate from fumarate: step 1/1

• Gellera C. et al. PubMed: CI-25H200T96USVP (MAY-)
• Bourgeron T. et al. Complete cDNA sequence of the human fumarase. (FEB-)
• Kalnine N. et al. Cloning of human full-length CDSs in BD Creator(TM) system donor vector. (AUG-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Mural R.J. et al. PubMed: CI-56FT96O07V0QG (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Kinsella B.T. et al. Nucleotide sequence of a cDNA coding for mitochondrial fumarase from human liver. — Biosci. Rep. (1986)
• Lubec G. et al. PubMed: CI-EJHB5D8BI36EI (MAR-)