FUMARIC ACID
Relevant Data
Food Additives Approved by WHO:
Flavouring Substances Approved by European Union:
Food Additives Approved by European Union:
General Information
| Mainterm | FUMARIC ACID |
| Doc Type | ASP |
| CAS Reg.No.(or other ID) | 110-17-8 |
| Regnum |
175.105 175.300 175.320 176.170 177.1200 177.2420 150.141 150.161 172.808 172.350 172.810 172.822 |
From www.fda.gov
Computed Descriptors
Download SDF| 2D Structure | |
| CID | 444972 |
| IUPAC Name | (E)-but-2-enedioic acid |
| InChI | InChI=1S/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1+ |
| InChI Key | VZCYOOQTPOCHFL-OWOJBTEDSA-N |
| Canonical SMILES | C(=CC(=O)O)C(=O)O |
| Molecular Formula | C4H4O4 |
| Wikipedia | fumaric acid |
From Pubchem
Computed Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 116.072 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 2 |
| Complexity | 119.0 |
| CACTVS Substructure Key Fingerprint | A A A D c Y B g O A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A G g A A C A A A C A C A g A A A C A A A A g C I A C D S C A A A A A A A A A A I C A A A A E A A B A A A A A A A E A A A A A A A E Y A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = = |
| Topological Polar Surface Area | 74.6 |
| Monoisotopic Mass | 116.011 |
| Exact Mass | 116.011 |
| Compound Is Canonicalized | True |
| Formal Charge | 0 |
| Heavy Atom Count | 8 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 1 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
From Pubchem
Food Additives Biosynthesis/Degradation
ADMET Predicted Profile --- Classification
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9017 |
| Human Intestinal Absorption | HIA+ | 0.8740 |
| Caco-2 Permeability | Caco2- | 0.6728 |
| P-glycoprotein Substrate | Non-substrate | 0.8006 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9850 |
| Non-inhibitor | 0.9808 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9583 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.7863 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8262 |
| CYP450 2D6 Substrate | Non-substrate | 0.9397 |
| CYP450 3A4 Substrate | Non-substrate | 0.8039 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9659 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9490 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9606 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9773 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9554 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9899 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9836 |
| Non-inhibitor | 0.9891 | |
| AMES Toxicity | Non AMES toxic | 0.9132 |
| Carcinogens | Non-carcinogens | 0.5130 |
| Fish Toxicity | High FHMT | 0.8398 |
| Tetrahymena Pyriformis Toxicity | Low TPT | 0.9808 |
| Honey Bee Toxicity | High HBT | 0.7308 |
| Biodegradation | Ready biodegradable | 0.7561 |
| Acute Oral Toxicity | III | 0.7762 |
| Carcinogenicity (Three-class) | Non-required | 0.7191 |
From admetSAR
ADMET Predicted Profile --- Regression
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -0.3321 | LogS |
| Caco-2 Permeability | 0.4098 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 1.6871 | LD50, mol/kg |
| Fish Toxicity | 0.9694 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | -0.6339 | pIGC50, ug/L |
From admetSAR
Toxicity Profile
| Route of Exposure | Endogenous, ingestion, contact (skin and eyes) |
|---|---|
| Mechanism of Toxicity | Acute Toxicity: Fumarate is also an endogenous electrophile and reacts spontaneously with cysteine residues in proteins by a Michael addition reaction to form S-(2-succinyl) cysteine, a process termed succination. Lachrymators such as fumarate are thought to act by attacking sulfhydryl functional groups in enzymes. One of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes, nose, mouth and lungs. Chronic Toxicity: Fumarate is increasingly being identified as an oncometabolite. Fumarase or fumarate hydratase (FH) is a tumor suppressor, whose mutation is associated with the development of leiomyomata, renal cysts, and tumors. Loss of FH enzymatic activity results in accumulation of intracellular fumarate which has been proposed to act as a competitive inhibitor of 2-oxoglutarate-dependent oxygenases including the hypoxia-inducible factor (HIF) hydroxylases, thus activating oncogenic HIF pathways. Mitochondrial dysfunction is also associated with FH deficiency. Fumarate hydratase-deficient cells and tumors have been shown to accumulate fumarate to very high levels with multiple consequences including the activation of oncogenic pathways . Fumarate (and succinate) inhibit the activity or function of other members of the 2-oxoglutarate-dependent oxygenase superfamily, including histone demethylase enzymes (HDMs) and the TET family of 5-methlycytosine (5mC) hydroxylases which are critical in epigenetic regulation of gene expression.. Fumarate accumulation may also affect cytosolic pathways by inhibiting the reactions involved in the biosynthesis of arginine and purine. More recently it has been found that fumarate promotes p65 phosphorylation and p65 accumulation at the HIF-1α promoter through non-canonical signaling via the upstream Tank Binding Kinase 1 (TBK1). Fumarate is also an endogenous electrophile and reacts spontaneously with cysteine residues in proteins by a Michael addition reaction to form S-(2-succinyl) cysteine, a process termed succination. Accumulation of cellular fumarate has been shown to correlate directly with an increase in succinated proteins. Targets for succination include the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, adiponectin, cytoskeletal proteins, and endoplasmic reticulum chaperone proteins. Furthermore, evidence suggests that succination of these proteins in cells may impair their functions. |
| Metabolism | Fumarate is an intermediate in the citric acid cycle used by cells to produce energy in the form of adenosine triphosphate (ATP) from food. It is formed by the oxidation of succinate by the enzyme succinate dehydrogenase. Fumarate is then converted by the enzyme fumarase (fumarate hydratase) to malate. |
| Toxicity Values | |
| Lethal Dose | |
| Carcinogenicity (IARC Classification) | Not listed by IARC. Has been implicated in oncogenesis . |
| Minimum Risk Level | |
| Health Effects | Acute exposure to fumaric acid can cause skin redness (skin contact), cough or sore throat (inhalation), abdominal cramps, nausea and diarrhea (ingestion). Chronically high levels of fumaric acid are associated with at least 3 inborn errors of metabolism including: 2-Ketoglutarate dehydrogenase complex deficiency, Fumarase deficiency and Pyruvate carboxylase deficiency. Fumarase deficiency causes encephalopathy, severe mental retardation, unusual facial features, brain malformation, and epileptic seizures. High intracellular fumaric acid levels are associated with the development of renal cancer, leiomyomata, renal cysts, and tumors. |
| Treatment | Acute exposure: EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. Chronic Exposure: There is no treatment for fumarase deficiencies. Only palliative care is possible. For cancers caused by intracellular fumarate excess, there are a wide variety of cancer treatments including drugs and surgery. |
| Reference |
|
From T3DB
Taxonomic Classification
| Kingdom | Organic compounds |
|---|---|
| Superclass | Organic acids and derivatives |
| Class | Carboxylic acids and derivatives |
| Subclass | Dicarboxylic acids and derivatives |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Dicarboxylic acids and derivatives |
| Alternative Parents | |
| Molecular Framework | Aliphatic acyclic compounds |
| Substituents | Fatty acyl - Fatty acid - Unsaturated fatty acid - Dicarboxylic acid or derivatives - Carboxylic acid - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Carbonyl group - Aliphatic acyclic compound |
| Description | This compound belongs to the class of organic compounds known as dicarboxylic acids and derivatives. These are organic compounds containing exactly two carboxylic acid groups. |
From ClassyFire
Targets
- General Function:
- Protein serine/threonine kinase activity
- Specific Function:
- Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes. Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus. Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy. Phosphorylates and activates AKT1. Seems to play a role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C. Phosphorylates Borna disease virus (BDV) P protein.
- Gene Name:
- TBK1
- Uniprot ID:
- Q9UHD2
- Molecular Weight:
- 83641.51 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for 5-hydroxymethylcytosine in CpG motifs. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT.
- Gene Name:
- TET2
- Uniprot ID:
- Q6N021
- Molecular Weight:
- 223809.995 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Peptidyl-proline 4-dioxygenase activity
- Specific Function:
- Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle. Also regulates susceptibility to normoxic oxidative neuronal death. Links oxygen sensing to cell cycle and primary cilia formation by hydroxylating the critical centrosome component CEP192 which promotes its ubiquitination and subsequent proteasomal degradation. Hydroxylates IKBKB, mediating NF-kappaB activation in hypoxic conditions. Target proteins are preferentially recognized via a LXXLAP motif.
- Gene Name:
- EGLN2
- Uniprot ID:
- Q96KS0
- Molecular Weight:
- 43650.03 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Peptidyl-proline dioxygenase activity
- Specific Function:
- Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif.
- Gene Name:
- EGLN1
- Uniprot ID:
- Q9GZT9
- Molecular Weight:
- 46020.585 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Peptidyl-proline 4-dioxygenase activity
- Specific Function:
- Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis. Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex. In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity. Also essential for hypoxic regulation of neutrophilic inflammation. Plays a crucial role in DNA damage response (DDR) by hydroxylating TELO2, promoting its interaction with ATR which is required for activation of the ATR/CHK1/p53 pathway. Target proteins are preferentially recognized via a LXXLAP motif.
- Gene Name:
- EGLN3
- Uniprot ID:
- Q9H6Z9
- Molecular Weight:
- 27261.06 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3.
- Gene Name:
- PHF8
- Uniprot ID:
- Q9UPP1
- Molecular Weight:
- 117862.955 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively.Isoform 2: Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain.
- Gene Name:
- KDM4A
- Uniprot ID:
- O75164
- Molecular Weight:
- 120661.265 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Only able to demethylate trimethylated H3 'Lys-9', with a weaker activity than KDM4A, KDM4C and KDM4D. Demethylation of Lys residue generates formaldehyde and succinate.
- Gene Name:
- KDM4B
- Uniprot ID:
- O94953
- Molecular Weight:
- 121895.515 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate.
- Gene Name:
- KDM4C
- Uniprot ID:
- Q9H3R0
- Molecular Weight:
- 119980.795 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Metal ion binding
- Specific Function:
- Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Demethylates both di- and trimethylated H3 'Lys-9' residue, while it has no activity on monomethylated residues. Demethylation of Lys residue generates formaldehyde and succinate.
- Gene Name:
- KDM4D
- Uniprot ID:
- Q6B0I6
- Molecular Weight:
- 58602.32 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Participates in transcriptional repression of neuronal genes by recruiting histone deacetylases and REST at neuron-restrictive silencer elements. Represses the CLOCK-ARNTL/BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2 (By similarity).
- Gene Name:
- KDM5C
- Uniprot ID:
- P41229
- Molecular Weight:
- 175718.565 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Lysine demethylase that demethylates both histones and non-histone proteins. Enzymatically inactive by itself, and becomes active following phosphorylation by PKA: forms a complex with ARID5B and mediates demethylation of methylated ARID5B. Demethylation of ARID5B leads to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. PHF2 is recruited to trimethylated 'Lys-4' of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA.
- Gene Name:
- PHF2
- Uniprot ID:
- O75151
- Molecular Weight:
- 120773.925 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, plays a more general role in chromatin regulation. Preferentially binds to CpG-rich sequences at promoters of both transcriptionally active and Polycomb-repressed genes. Involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT. Also involved in transcription repression of a subset of genes through recruitment of transcriptional repressors to promoters. Involved in the balance between pluripotency and lineage commitment of cells it plays a role in embryonic stem cells maintenance and inner cell mass cell specification.
- Gene Name:
- TET1
- Uniprot ID:
- Q8NFU7
- Molecular Weight:
- 235306.965 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors
- Specific Function:
- Catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates HIF1A at 'Pro-402' and 'Pro-564'. May function as a cellular oxygen sensor and, under normoxic conditions, may target HIF through the hydroxylation for proteasomal degradation via the von Hippel-Lindau ubiquitination complex.
- Gene Name:
- P4HTM
- Uniprot ID:
- Q9NXG6
- Molecular Weight:
- 56660.535 Da
References
- Yang M, Soga T, Pollard PJ, Adam J: The emerging role of fumarate as an oncometabolite. Front Oncol. 2012 Jul 31;2:85. doi: 10.3389/fonc.2012.00085. eCollection 2012. [22866264 ]
- General Function:
- Oxidative rna demethylase activity
- Specific Function:
- Dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. Has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. Has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine (PubMed:18775698, PubMed:20376003). Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:22002720, PubMed:26458103). Has no activity towards 1-methylguanine. Has no detectable activity towards double-stranded DNA. Requires molecular oxygen, alpha-ketoglutarate and iron. Contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. Contributes to the regulation of body size and body fat accumulation (PubMed:18775698, PubMed:20376003).
- Gene Name:
- FTO
- Uniprot ID:
- Q9C0B1
- Molecular Weight:
- 58281.53 Da
References
- Aik W, Demetriades M, Hamdan MK, Bagg EA, Yeoh KK, Lejeune C, Zhang Z, McDonough MA, Schofield CJ: Structural basis for inhibition of the fat mass and obesity associated protein (FTO). J Med Chem. 2013 May 9;56(9):3680-8. doi: 10.1021/jm400193d. Epub 2013 Apr 23. [23547775 ]
- General Function:
- Metal ion binding
- Specific Function:
- Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code.
- Gene Name:
- KDM4E
- Uniprot ID:
- B2RXH2
- Molecular Weight:
- 56803.925 Da
References
- Rose NR, Ng SS, Mecinovic J, Lienard BM, Bello SH, Sun Z, McDonough MA, Oppermann U, Schofield CJ: Inhibitor scaffolds for 2-oxoglutarate-dependent histone lysine demethylases. J Med Chem. 2008 Nov 27;51(22):7053-6. doi: 10.1021/jm800936s. [18942826 ]
- General Function:
- Temperature-gated cation channel activity
- Specific Function:
- Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
- Gene Name:
- TRPA1
- Uniprot ID:
- O75762
- Molecular Weight:
- 127499.88 Da
References
- Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]
- General Function:
- L-malate dehydrogenase activity
- Specific Function:
- Catalyzes the reversible oxidation of malate to oxaloacetate.
- Gene Name:
- mdh
- Uniprot ID:
- P80040
- Molecular Weight:
- 32750.54 Da
- General Function:
- Succinate dehydrogenase activity
- Specific Function:
- Catalyzes fumarate reduction using artificial electron donors such as methyl viologen. The physiological reductant is unknown, but evidence indicates that flavocytochrome c participates in electron transfer from formate to fumarate and possibly also to trimethylamine oxide (TMAO). This enzyme is essentially unidirectional.
- Gene Name:
- fccA
- Uniprot ID:
- P0C278
- Molecular Weight:
- 60620.95 Da
- General Function:
- Succinate dehydrogenase activity
- Specific Function:
- Catalyzes fumarate reduction using artificial electron donors such as methyl viologen. The physiological reductant is unknown, but evidence indicates that flavocytochrome c participates in electron transfer from formate to fumarate and possibly also to trimethylamine oxide (TMAO). This enzyme is essentially unidirectional (By similarity).
- Uniprot ID:
- P83223
- Molecular Weight:
- 62447.475 Da
- General Function:
- Oxaloacetate decarboxylase activity
- Gene Name:
- ME2
- Uniprot ID:
- P23368
- Molecular Weight:
- 65442.945 Da
- General Function:
- Metal ion binding
- Gene Name:
- FAH
- Uniprot ID:
- P16930
- Molecular Weight:
- 46373.97 Da
From T3DB