Succinic acid
Relevant Data
Food Additives Approved in the United States:
General Information
| Chemical name | Succinic acid |
| CAS number | 110-15-6 |
| COE number | 24 |
| Flavouring type | substances |
| FL No. | 08.024 |
| Mixture | No |
| Purity of the named substance at least 95% unless otherwise specified | |
| Reference body | CoE |
From webgate.ec.europa.eu
Computed Descriptors
Download SDF| 2D Structure | |
| CID | 1110 |
| IUPAC Name | butanedioic acid |
| InChI | InChI=1S/C4H6O4/c5-3(6)1-2-4(7)8/h1-2H2,(H,5,6)(H,7,8) |
| InChI Key | KDYFGRWQOYBRFD-UHFFFAOYSA-N |
| Canonical SMILES | C(CC(=O)O)C(=O)O |
| Molecular Formula | C4H6O4 |
| Wikipedia | succinic acid |
From Pubchem
Computed Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 118.088 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 3 |
| Complexity | 92.6 |
| 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 A I A A C Q C A A A A A A A A A A A A A E A A A A A A B A A A A A A Q A A E A A A A A A B D 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 | 118.027 |
| Exact Mass | 118.027 |
| 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 | 0 |
| 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+ | 0.8690 |
| Human Intestinal Absorption | HIA+ | 0.6680 |
| Caco-2 Permeability | Caco2- | 0.6480 |
| P-glycoprotein Substrate | Non-substrate | 0.7618 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9796 |
| Non-inhibitor | 0.9701 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9513 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.8485 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8535 |
| CYP450 2D6 Substrate | Non-substrate | 0.9161 |
| CYP450 3A4 Substrate | Non-substrate | 0.7794 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8848 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9759 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9713 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9856 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9679 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9951 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9622 |
| Non-inhibitor | 0.9771 | |
| AMES Toxicity | Non AMES toxic | 0.9587 |
| Carcinogens | Non-carcinogens | 0.7929 |
| Fish Toxicity | High FHMT | 0.5188 |
| Tetrahymena Pyriformis Toxicity | Low TPT | 0.9376 |
| Honey Bee Toxicity | High HBT | 0.6253 |
| Biodegradation | Ready biodegradable | 0.9399 |
| Acute Oral Toxicity | III | 0.7820 |
| Carcinogenicity (Three-class) | Non-required | 0.7537 |
From admetSAR
ADMET Predicted Profile --- Regression
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -0.1373 | LogS |
| Caco-2 Permeability | 0.3259 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 1.6866 | LD50, mol/kg |
| Fish Toxicity | 2.1341 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | -0.8148 | pIGC50, ug/L |
From admetSAR
Toxicity Profile
| Route of Exposure | Eye contact, Inhalation, Ingestion. |
|---|---|
| Mechanism of Toxicity | Succinate can inhibit the activities of α-KG–dependent oxygenases (KDMs) and the TET family of 5-methlycytosine (5mC) hydroxylases. Succinate also mediates allosteric inhibition of hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs). Inhibition of HIF PHDs leads to activation of HIF-mediated pseudohypoxic response, whereas inhibition of KDMs and TET family of 5mC hydroxylases causes epigenetic alterations that ultimately cause cancer. Succination of KEAP1 in FH deficiency results in the constitutive activation of the antioxidant defense pathway mediated by NRF2, conferring a reductive milieu that promotes cell proliferation. Succination of the Krebs cycle enzyme Aco2 impairs aconitase activity in Fh1-deficient MEFs. Succination also causes irreversible inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). |
| Metabolism | Succinic acid can be converted into fumaric acid by oxidation via succinate dehydrogenase. |
| Toxicity Values | Acute oral toxicity (LD50): 2260 mg/kg [Rat]. |
| Lethal Dose | |
| Carcinogenicity (IARC Classification) | Not listed by IARC. Has been implicated in oncogenesis . |
| Minimum Risk Level | |
| Health Effects | At acute doses or exposures succinic acid is a skin irritant. Chronically high doses of succinate can lead to succinylation or succination of a variety of enzymes. Partial succinate dehydrogenase deficiency (15% to 50% of normal reference enzyme activity) in skeletal muscle leads to elevated succinate levels and causes mitochondrial myopathy with various symptoms, for example, brain involvement, cardiomyopathy, and/or exercise intolerance. |
| Treatment | 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. INHALATION: supply fresh air. If required provide artificial respiration. |
| 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 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:
- Succinate transmembrane transporter activity
- Specific Function:
- High-affinity sodium-dicarboxylate cotransporter that accepts a range of substrates with 4-5 carbon atoms. The stoichiometry is probably 3 Na(+) for 1 divalent succinate.
- Gene Name:
- SLC13A3
- Uniprot ID:
- Q8WWT9
- Molecular Weight:
- 66840.355 Da
References
- Burckhardt BC, Drinkuth B, Menzel C, Konig A, Steffgen J, Wright SH, Burckhardt G: The renal Na(+)-dependent dicarboxylate transporter, NaDC-3, translocates dimethyl- and disulfhydryl-compounds and contributes to renal heavy metal detoxification. J Am Soc Nephrol. 2002 Nov;13(11):2628-38. [12397032 ]
- General Function:
- Succinate-semialdehyde dehydrogenase [nad(p)+] activity
- Specific Function:
- Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
- Gene Name:
- ALDH5A1
- Uniprot ID:
- P51649
- Molecular Weight:
- 57214.23 Da
References
- Chiribau CB, Mihasan M, Ganas P, Igloi GL, Artenie V, Brandsch R: Final steps in the catabolism of nicotine. FEBS J. 2006 Apr;273(7):1528-36. [16689938 ]
- General Function:
- Testosterone dehydrogenase (nad+) activity
- Specific Function:
- NAD-dependent oxidoreductase with broad substrate specificity that shows both oxidative and reductive activity (in vitro). Has 17-beta-hydroxysteroid dehydrogenase activity towards various steroids (in vitro). Converts 5-alpha-androstan-3-alpha,17-beta-diol to androsterone and estradiol to estrone (in vitro). Has 3-alpha-hydroxysteroid dehydrogenase activity towards androsterone (in vitro). Has retinol dehydrogenase activity towards all-trans-retinol (in vitro). Can convert androsterone to epi-androsterone. Androsterone is first oxidized to 5-alpha-androstane-3,17-dione and then reduced to epi-andosterone. Can act on both C-19 and C-21 3-alpha-hydroxysteroids.
- Gene Name:
- HSD17B6
- Uniprot ID:
- O14756
- Molecular Weight:
- 35965.41 Da
References
- Bayley JP, van Minderhout I, Weiss MM, Jansen JC, Oomen PH, Menko FH, Pasini B, Ferrando B, Wong N, Alpert LC, Williams R, Blair E, Devilee P, Taschner PE: Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma. BMC Med Genet. 2006 Jan 11;7:1. [16405730 ]
- General Function:
- Ubiquinone binding
- Specific Function:
- Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
- Gene Name:
- SDHD
- Uniprot ID:
- O14521
- Molecular Weight:
- 17042.82 Da
References
- Lehtonen HJ, Makinen MJ, Kiuru M, Laiho P, Herva R, van Minderhout I, Hogendoorn PC, Cornelisse C, Devilee P, Launonen V, Aaltonen LA: Increased HIF1 alpha in SDH and FH deficient tumors does not cause microsatellite instability. Int J Cancer. 2007 Sep 15;121(6):1386-9. [17520677 ]
- General Function:
- Succinate dehydrogenase activity
- Specific Function:
- Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). Can act as a tumor suppressor.
- Gene Name:
- SDHA
- Uniprot ID:
- P31040
- Molecular Weight:
- 72690.975 Da
References
- Ackrell BA: Cytopathies involving mitochondrial complex II. Mol Aspects Med. 2002 Oct;23(5):369-84. [12231007 ]
- General Function:
- Ubiquinone binding
- Specific Function:
- Iron-sulfur protein (IP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
- Gene Name:
- SDHB
- Uniprot ID:
- P21912
- Molecular Weight:
- 31629.365 Da
References
- Szeto SS, Reinke SN, Sykes BD, Lemire BD: Ubiquinone-binding site mutations in the Saccharomyces cerevisiae succinate dehydrogenase generate superoxide and lead to the accumulation of succinate. J Biol Chem. 2007 Sep 14;282(37):27518-26. Epub 2007 Jul 18. [17636259 ]
- General Function:
- Succinate dehydrogenase activity
- Specific Function:
- Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
- Gene Name:
- SDHC
- Uniprot ID:
- Q99643
- Molecular Weight:
- 18610.03 Da
References
- Kubo Y, Takagi H, Nakamori S: Effect of gene disruption of succinate dehydrogenase on succinate production in a sake yeast strain. J Biosci Bioeng. 2000;90(6):619-24. [16232921 ]
- General Function:
- Low-affinity sodium:dicarboxylate symporter activity
- Specific Function:
- Cotransport of sodium ions and dicarboxylates such as succinate and citrate.
- Gene Name:
- SLC13A2
- Uniprot ID:
- Q13183
- Molecular Weight:
- 64409.495 Da
References
- Hall JA, Pajor AM: Functional characterization of a Na(+)-coupled dicarboxylate carrier protein from Staphylococcus aureus. J Bacteriol. 2005 Aug;187(15):5189-94. [16030212 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Catalyzes the formation of L-carnitine from gamma-butyrobetaine.
- Gene Name:
- BBOX1
- Uniprot ID:
- O75936
- Molecular Weight:
- 44714.6 Da
References
- Yoshisue K, Yamamoto Y, Yoshida K, Saeki M, Minami Y, Esumi Y, Kawaguchi Y: Pharmacokinetics and biological fate of 3-(2,2, 2-trimethylhydrazinium)propionate dihydrate (MET-88), a novel cardioprotective agent, in rats. Drug Metab Dispos. 2000 Jun;28(6):687-94. [10820142 ]
- General Function:
- Sodium:sulfate symporter activity
- Specific Function:
- Sodium/sulfate cotransporter that mediates sulfate reabsorption in the kidney.
- Gene Name:
- SLC13A1
- Uniprot ID:
- Q9BZW2
- Molecular Weight:
- 66133.62 Da
References
- Lee A, Beck L, Markovich D: The human renal sodium sulfate cotransporter (SLC13A1; hNaSi-1) cDNA and gene: organization, chromosomal localization, and functional characterization. Genomics. 2000 Dec 15;70(3):354-63. [11161786 ]
- General Function:
- Succinate-coa ligase (adp-forming) activity
- Specific Function:
- Catalyzes the ATP-dependent ligation of succinate and CoA to form succinyl-CoA.
- Gene Name:
- SUCLA2
- Uniprot ID:
- Q9P2R7
- Molecular Weight:
- 50316.88 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
- General Function:
- Structural molecule activity
- Specific Function:
- Isoform 1: specifically hydroxylates an Asp or Asn residue in certain epidermal growth factor-like (EGF) domains of a number of proteins.Isoform 8: membrane-bound Ca(2+)-sensing protein, which is a structural component of the ER-plasma membrane junctions. Isoform 8 regulates the activity of Ca(+2) released-activated Ca(+2) (CRAC) channels in T-cells.
- Gene Name:
- ASPH
- Uniprot ID:
- Q12797
- Molecular Weight:
- 85862.095 Da
References
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
- General Function:
- Dicarboxylic acid transmembrane transporter activity
- Specific Function:
- Involved in translocation of malonate, malate and succinate in exchange for phosphate, sulfate, sulfite or thiosulfate across mitochondrial inner membrane.
- Gene Name:
- SLC25A10
- Uniprot ID:
- Q9UBX3
- Molecular Weight:
- 31282.21 Da
References
- Mizuarai S, Miki S, Araki H, Takahashi K, Kotani H: Identification of dicarboxylate carrier Slc25a10 as malate transporter in de novo fatty acid synthesis. J Biol Chem. 2005 Sep 16;280(37):32434-41. Epub 2005 Jul 15. [16027120 ]
- General Function:
- Procollagen-lysine 5-dioxygenase activity
- Specific Function:
- Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links.
- Gene Name:
- PLOD3
- Uniprot ID:
- O60568
- Molecular Weight:
- 84784.505 Da
References
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
- General Function:
- Protein complex binding
- Specific Function:
- Basement membrane-associated chondroitin sulfate proteoglycan (CSPG). Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens, especially types IV and V. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts.
- Gene Name:
- P3H1
- Uniprot ID:
- Q32P28
- Molecular Weight:
- 83393.195 Da
References
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
- General Function:
- Procollagen-proline 3-dioxygenase activity
- Specific Function:
- Shows prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly-sequences in collagens, especially types II, IV and V.
- Gene Name:
- P3H2
- Uniprot ID:
- Q8IVL5
- Molecular Weight:
- 80983.685 Da
References
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
- General Function:
- Procollagen-proline 3-dioxygenase activity
- Specific Function:
- Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly-sequences in collagens, especially types IV and V.
- Gene Name:
- P3H3
- Uniprot ID:
- Q8IVL6
- Molecular Weight:
- 81835.705 Da
References
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
- General Function:
- Procollagen-proline 4-dioxygenase activity
- Specific Function:
- Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
- Gene Name:
- P4HA1
- Uniprot ID:
- P13674
- Molecular Weight:
- 61048.775 Da
References
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
- General Function:
- Procollagen-proline 4-dioxygenase activity
- Specific Function:
- Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
- Gene Name:
- P4HA2
- Uniprot ID:
- O15460
- Molecular Weight:
- 60901.42 Da
References
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
- General Function:
- Succinate-coa ligase (gdp-forming) activity
- Specific Function:
- Catalyzes the GTP-dependent ligation of succinate and CoA to form succinyl-CoA.
- Gene Name:
- SUCLG2
- Uniprot ID:
- Q96I99
- Molecular Weight:
- 46510.215 Da
References
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
- General Function:
- 3-oxoacid coa-transferase activity
- Specific Function:
- Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate (By similarity).
- Gene Name:
- OXCT2
- Uniprot ID:
- Q9BYC2
- Molecular Weight:
- 56139.41 Da
References
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
- General Function:
- Trimethyllysine dioxygenase activity
- Specific Function:
- Converts trimethyllysine (TML) into hydroxytrimethyllysine (HTML).
- Gene Name:
- TMLHE
- Uniprot ID:
- Q9NVH6
- Molecular Weight:
- 49517.2 Da
References
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
- 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
- Leung IK, Flashman E, Yeoh KK, Schofield CJ, Claridge TD: Using NMR solvent water relaxation to investigate metalloenzyme-ligand binding interactions. J Med Chem. 2010 Jan 28;53(2):867-75. doi: 10.1021/jm901537q. [20025281 ]
- 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. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep 3;123(9):3652-8. doi: 10.1172/JCI67228. Epub 2013 Sep 3. [23999438 ]
- 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. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep 3;123(9):3652-8. doi: 10.1172/JCI67228. Epub 2013 Sep 3. [23999438 ]
- 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. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep 3;123(9):3652-8. doi: 10.1172/JCI67228. Epub 2013 Sep 3. [23999438 ]
- 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. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep 3;123(9):3652-8. doi: 10.1172/JCI67228. Epub 2013 Sep 3. [23999438 ]
- 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. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep 3;123(9):3652-8. doi: 10.1172/JCI67228. Epub 2013 Sep 3. [23999438 ]
- 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. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep 3;123(9):3652-8. doi: 10.1172/JCI67228. Epub 2013 Sep 3. [23999438 ]
- 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. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep 3;123(9):3652-8. doi: 10.1172/JCI67228. Epub 2013 Sep 3. [23999438 ]
- 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. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep 3;123(9):3652-8. doi: 10.1172/JCI67228. Epub 2013 Sep 3. [23999438 ]
- 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. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep 3;123(9):3652-8. doi: 10.1172/JCI67228. Epub 2013 Sep 3. [23999438 ]
- 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. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep 3;123(9):3652-8. doi: 10.1172/JCI67228. Epub 2013 Sep 3. [23999438 ]
- 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. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep 3;123(9):3652-8. doi: 10.1172/JCI67228. Epub 2013 Sep 3. [23999438 ]
- General Function:
- Peptidase activity
- Specific Function:
- Cleaves the GlcNAc-Asn bond which joins oligosaccharides to the peptide of asparagine-linked glycoproteins.
- Gene Name:
- AGA
- Uniprot ID:
- P20933
- Molecular Weight:
- 37207.955 Da
References
- Risley JM, Huang DH, Kaylor JJ, Malik JJ, Xia YQ: Glycosylasparaginase inhibition studies: competitive inhibitors, transition state mimics, noncompetitive inhibitors. J Enzyme Inhib. 2001;16(3):269-74. [11697047 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links.
- Gene Name:
- PLOD1
- Uniprot ID:
- Q02809
- Molecular Weight:
- 83549.55 Da
References
- Cudic M, Patel DA, Lauer-Fields JL, Brew K, Fields GB: Development of a convenient peptide-based assay for lysyl hydroxylase. Biopolymers. 2008;90(3):330-8. [17610258 ]
- General Function:
- G-protein coupled receptor activity
- Specific Function:
- Receptor for succinate.
- Gene Name:
- SUCNR1
- Uniprot ID:
- Q9BXA5
- Molecular Weight:
- 38697.395 Da
References
- Macaulay IC, Tijssen MR, Thijssen-Timmer DC, Gusnanto A, Steward M, Burns P, Langford CF, Ellis PD, Dudbridge F, Zwaginga JJ, Watkins NA, van der Schoot CE, Ouwehand WH: Comparative gene expression profiling of in vitro differentiated megakaryocytes and erythroblasts identifies novel activatory and inhibitory platelet membrane proteins. Blood. 2007 Apr 15;109(8):3260-9. Epub 2006 Dec 27. [17192395 ]
- General Function:
- Succinate-coa ligase (gdp-forming) activity
- Specific Function:
- Catalyzes the ATP- or GTP-dependent ligation of succinate and CoA to form succinyl-CoA. The nature of the beta subunit determines the nucleotide specificity (By similarity).
- Gene Name:
- SUCLG1
- Uniprot ID:
- P53597
- Molecular Weight:
- 36249.505 Da
References
- Ostergaard E, Christensen E, Kristensen E, Mogensen B, Duno M, Shoubridge EA, Wibrand F: Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion. Am J Hum Genet. 2007 Aug;81(2):383-7. Epub 2007 Jun 4. [17668387 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate.
- Gene Name:
- OXCT1
- Uniprot ID:
- P55809
- Molecular Weight:
- 56157.175 Da
References
- Coros AM, Swenson L, Wolodko WT, Fraser ME: Structure of the CoA transferase from pig heart to 1.7 A resolution. Acta Crystallogr D Biol Crystallogr. 2004 Oct;60(Pt 10):1717-25. Epub 2004 Sep 23. [15388917 ]
- 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. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep 3;123(9):3652-8. doi: 10.1172/JCI67228. Epub 2013 Sep 3. [23999438 ]
- 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 ]
From T3DB