Heparin
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Basic Info
| Common Name | Heparin(F04718) |
| 2D Structure | |
| Description | Heparin is a highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Unfractionated heparin (UH) is a heterogenous preparation of anionic, sulfated glycosaminoglycan polymers with weights ranging from 3000 to 30,000 Da. It is a naturally occurring anticoagulant released from mast cells. It binds reversibly to antithrombin III (ATIII) and greatly accelerates the rate at which ATIII inactivates coagulation enzymes thrombin (factor IIa) and factor Xa. UH is different from low molecular weight heparin (LMWH) in the following ways: the average molecular weight of LMWH is about 4.5 kDa whereas it is 15 kDa for UH; UH requires continuous infusions; activated partial prothrombin time (aPTT) monitoring is required when using UH; and UH has a higher risk of bleeding and higher risk of osteoporosis in long term use. Unfractionated heparin is more specific than LMWH for thrombin. Furthermore, the effects of UH can typically be reversed by using protamine sulfate. |
| FRCD ID | F04718 |
| CAS Number | 9005-49-6 |
| PubChem CID | 46507594 |
| Formula | C18H13FN2O4 |
| IUPAC Name | [(Z)-[3-[(3-fluorophenyl)carbamoyl]chromen-2-ylidene]amino] acetate |
| InChI Key | ZCEROSFTJOPMNK-UZYVYHOESA-N |
| InChI | InChI=1S/C18H13FN2O4/c1-11(22)25-21-18-15(9-12-5-2-3-8-16(12)24-18)17(23)20-14-7-4-6-13(19)10-14/h2-10H,1H3,(H,20,23)/b21-18- |
| Canonical SMILES | CC(=O)ON=C1C(=CC2=CC=CC=C2O1)C(=O)NC3=CC(=CC=C3)F |
| Isomeric SMILES | CC(=O)O/N=C\1/C(=CC2=CC=CC=C2O1)C(=O)NC3=CC(=CC=C3)F |
| Wikipedia | Heparin |
| Synonyms |
(2Z)-2-[(acetyloxy)imino]-N-(3-fluorophenyl)-2H-chromene-3-carboxamide
MolPort-007-599-302
STL134875
AKOS001776847
|
| Classifies |
Animal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 340.31 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 4 |
| Complexity | 590 |
| Monoisotopic Mass | 340.086 |
| Exact Mass | 340.086 |
| XLogP | 3.4 |
| Formal Charge | 0 |
| Heavy Atom Count | 25 |
| 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 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.8760 |
| Human Intestinal Absorption | HIA+ | 0.9705 |
| Caco-2 Permeability | Caco2- | 0.5416 |
| P-glycoprotein Substrate | Non-substrate | 0.6717 |
| P-glycoprotein Inhibitor | Inhibitor | 0.7289 |
| Inhibitor | 0.7457 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9222 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.4455 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7752 |
| CYP450 2D6 Substrate | Non-substrate | 0.8477 |
| CYP450 3A4 Substrate | Substrate | 0.5473 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.8385 |
| CYP450 2C9 Inhibitor | Inhibitor | 0.5402 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8589 |
| CYP450 2C19 Inhibitor | Inhibitor | 0.6430 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.7988 |
| CYP Inhibitory Promiscuity | High CYP Inhibitory Promiscuity | 0.8351 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9948 |
| Non-inhibitor | 0.8874 | |
| AMES Toxicity | AMES toxic | 0.5123 |
| Carcinogens | Non-carcinogens | 0.5369 |
| Fish Toxicity | High FHMT | 0.9206 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9414 |
| Honey Bee Toxicity | Low HBT | 0.8517 |
| Biodegradation | Not ready biodegradable | 1.0000 |
| Acute Oral Toxicity | III | 0.6264 |
| Carcinogenicity (Three-class) | Non-required | 0.5926 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.9159 | LogS |
| Caco-2 Permeability | 0.8965 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.4287 | LD50, mol/kg |
| Fish Toxicity | 0.7652 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.9207 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Dialysis Procedures Alter Metabolic Conditions. | Nutrients | 2017 May 27 | 28554992 |
| Antithrombotic activity of Batroxase, a metalloprotease from Bothrops atrox venom, in a model of venous thrombosis. | Int J Biol Macromol | 2017 Feb | 27876598 |
| Effect of pathological conditions on peritoneal macrophage glycosaminoglycans: Impact on cytoadherence. | Int J Biol Macromol | 2016 Nov | 27519294 |
| Heparanase Overexpression Reduces Hepcidin Expression, Affects Iron Homeostasis and Alters the Response to Inflammation. | PLoS One | 2016 | 27711215 |
| Bordetella pertussis fim3 gene regulation by BvgA: phosphorylation controls the formation of inactive vs. active transcription complexes. | Proc Natl Acad Sci U S A | 2015 Feb 10 | 25624471 |
| [THE DYNAMICS OF IMMUNOLOGICAL RESULTS OF PATIENTS WITH T-CELL SKIN LYMPHOMAS AND PSORIASIS BY THE THERAPY OF ACTIVATION MECHANISMS SANOGENESIS METHODS]. | Lik Sprava | 2015 Apr-Jun | 26827436 |
| Induced ablation of ghrelin cells in adult mice does not decrease food intake, body weight, or response to high-fat diet. | Cell Metab | 2014 Jul 1 | 24836560 |
| [The difference of conformation of apoB-100 in lipoproteins of low and very low density. The modified lipoproteins and destructive inflammation in intima of arteries: a lecture]. | Klin Lab Diagn | 2014 Feb | 25069231 |
| Preparation of affinity adsorbents and purification of lectins from natural sources. | Methods Mol Biol | 2014 | 25117224 |
| Functional profiling of immediate early gene Egr1 in an anorexic mouse model. | Mol Med Rep | 2013 Nov | 24002696 |
| Heat-stable components of wood ear mushroom, Auricularia polytricha (higher Basidiomycetes), inhibit in vitro activity of beta secretase (BACE1). | Int J Med Mushrooms | 2013 | 23662612 |
| Ablation of Sim1 neurons causes obesity through hyperphagia and reduced energy expenditure. | PLoS One | 2012 | 22558467 |
| The role of the hemostatic system in murine liver injury induced by coexposure to lipopolysaccharide and trovafloxacin, a drug with idiosyncratic liability. | Toxicol Appl Pharmacol | 2009 May 1 | 19367693 |
| Determination of oversulfated chondroitin sulfate and dermatan sulfate impurities in heparin by capillary electrophoresis. | J Chromatogr A | 2009 May 1 | 19272607 |
| Short communication: Attempts to identify Clostridium botulinum toxin in milk from three experimentally intoxicated Holstein cows. | J Dairy Sci | 2009 Jun | 19447984 |
| Silicate release from glass for pharmaceutical preparations. | Int J Pharm | 2008 May 1 | 18272302 |
| Coagulation-dependent gene expression and liver injury in rats given lipopolysaccharide with ranitidine but not with famotidine. | J Pharmacol Exp Ther | 2006 May | 16401727 |
| Coagulation-mediated hypoxia and neutrophil-dependent hepatic injury in rats given lipopolysaccharide and ranitidine. | J Pharmacol Exp Ther | 2005 Sep | 15933155 |
| Role of hepatic fibrin in idiosyncrasy-like liver injury from lipopolysaccharide-ranitidine coexposure in rats. | Hepatology | 2004 Dec | 15565632 |
| Augmentation of aflatoxin B1 hepatotoxicity by endotoxin: involvement of endothelium and the coagulation system. | Toxicol Sci | 2003 Mar | 12604847 |
Targets
- General Function:
- Serine-type endopeptidase inhibitor activity
- Specific Function:
- Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin, matriptase-3/TMPRSS7, as well as factors IXa, Xa and XIa. Its inhibitory activity is greatly enhanced in the presence of heparin.
- Gene Name:
- SERPINC1
- Uniprot ID:
- P01008
- Molecular Weight:
- 52601.935 Da
- Mechanism of Action:
- The mechanism of action of heparin is antithrombin-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Heparin interacts with antithrombin III, prothrombin and factor X.
References
- Lee S, Gibson CM: Enoxaparin in acute coronary syndromes. Expert Rev Cardiovasc Ther. 2007 May;5(3):387-99. [17489664 ]
- General Function:
- Serine-type endopeptidase activity
- Specific Function:
- Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
- Gene Name:
- F10
- Uniprot ID:
- P00742
- Molecular Weight:
- 54731.255 Da
- Mechanism of Action:
- The mechanism of action of heparin is antithrombin-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Heparin interacts with antithrombin III, prothrombin and factor X.
References
- Graff J, Picard-Willems B, Harder S: Monitoring effects of direct FXa-inhibitors with a new one-step prothrombinase-induced clotting time (PiCT) assay: comparative in vitro investigation with heparin, enoxaparin, fondaparinux and DX 9065a. Int J Clin Pharmacol Ther. 2007 Apr;45(4):237-43. [17474542 ]
- General Function:
- Sialic acid binding
- Specific Function:
- Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligand recognized is sialyl-Lewis X. Mediates rapid rolling of leukocyte rolling over vascular surfaces during the initial steps in inflammation through interaction with PSGL1.
- Gene Name:
- SELP
- Uniprot ID:
- P16109
- Molecular Weight:
- 90833.105 Da
- Mechanism of Action:
- The mechanism of action of heparin is antithrombin-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Heparin interacts with antithrombin III, prothrombin and factor X.
References
- Monzavi-Karbassi B, Stanley JS, Hennings L, Jousheghany F, Artaud C, Shaaf S, Kieber-Emmons T: Chondroitin sulfate glycosaminoglycans as major P-selectin ligands on metastatic breast cancer cell lines. Int J Cancer. 2007 Mar 15;120(6):1179-91. [17154173 ]
- General Function:
- Serine-type endopeptidase activity
- Specific Function:
- Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.
- Gene Name:
- F9
- Uniprot ID:
- P00740
- Molecular Weight:
- 51778.11 Da
- Mechanism of Action:
- The mechanism of action of heparin is antithrombin-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Heparin interacts with antithrombin III, prothrombin and factor X.
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- General Function:
- Fibroblast growth factor receptor binding
- Specific Function:
- Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. Stimulates glucose uptake in adipocytes. Activity requires the presence of KLB and FGFR4.
- Gene Name:
- FGF19
- Uniprot ID:
- O95750
- Molecular Weight:
- 24002.345 Da
References
- Harmer NJ, Pellegrini L, Chirgadze D, Fernandez-Recio J, Blundell TL: The crystal structure of fibroblast growth factor (FGF) 19 reveals novel features of the FGF family and offers a structural basis for its unusual receptor affinity. Biochemistry. 2004 Jan 27;43(3):629-40. [14730967 ]
- General Function:
- Ligand-dependent nuclear receptor transcription coactivator activity
- Specific Function:
- Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.
- Gene Name:
- FGF2
- Uniprot ID:
- P09038
- Molecular Weight:
- 30769.715 Da
References
- Rose K, Kriha D, Pallast S, Junker V, Klumpp S, Krieglstein J: Basic fibroblast growth factor: lysine 134 is essential for its neuroprotective activity. Neurochem Int. 2007 Jul;51(1):25-31. Epub 2007 Apr 19. [17524524 ]
- General Function:
- Heparin binding
- Specific Function:
- Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. Required for normal limb and cardiac valve development during embryogenesis.
- Gene Name:
- FGF4
- Uniprot ID:
- P08620
- Molecular Weight:
- 22047.355 Da
References
- Bellosta P, Iwahori A, Plotnikov AN, Eliseenkova AV, Basilico C, Mohammadi M: Identification of receptor and heparin binding sites in fibroblast growth factor 4 by structure-based mutagenesis. Mol Cell Biol. 2001 Sep;21(17):5946-57. [11486033 ]
- General Function:
- Protein tyrosine kinase activity
- Specific Function:
- Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.
- Gene Name:
- FGFR1
- Uniprot ID:
- P11362
- Molecular Weight:
- 91866.935 Da
References
- Ibrahimi OA, Zhang F, Hrstka SC, Mohammadi M, Linhardt RJ: Kinetic model for FGF, FGFR, and proteoglycan signal transduction complex assembly. Biochemistry. 2004 Apr 27;43(16):4724-30. [15096041 ]
- General Function:
- Protein tyrosine kinase activity
- Specific Function:
- Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.
- Gene Name:
- FGFR4
- Uniprot ID:
- P22455
- Molecular Weight:
- 87953.535 Da
References
- Loo BM, Kreuger J, Jalkanen M, Lindahl U, Salmivirta M: Binding of heparin/heparan sulfate to fibroblast growth factor receptor 4. J Biol Chem. 2001 May 18;276(20):16868-76. Epub 2001 Feb 21. [11278860 ]
- General Function:
- Heparin binding
- Specific Function:
- Released during platelet aggregation. Neutralizes the anticoagulant effect of heparin because it binds more strongly to heparin than to the chondroitin-4-sulfate chains of the carrier molecule. Chemotactic for neutrophils and monocytes. Inhibits endothelial cell proliferation, the short form is a more potent inhibitor than the longer form.
- Gene Name:
- PF4
- Uniprot ID:
- P02776
- Molecular Weight:
- 10844.78 Da
References
- Visentin GP, Ford SE, Scott JP, Aster RH: Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells. J Clin Invest. 1994 Jan;93(1):81-8. [8282825 ]
- General Function:
- Vascular endothelial growth factor receptor binding
- Specific Function:
- Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.
- Gene Name:
- VEGFA
- Uniprot ID:
- P15692
- Molecular Weight:
- 27042.205 Da
References
- Lee TY, Folkman J, Javaherian K: HSPG-binding peptide corresponding to the exon 6a-encoded domain of VEGF inhibits tumor growth by blocking angiogenesis in murine model. PLoS One. 2010 Apr 1;5(4):e9945. doi: 10.1371/journal.pone.0009945. [20376344 ]
- General Function:
- Thrombospondin receptor activity
- Specific Function:
- Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.
- Gene Name:
- F2
- Uniprot ID:
- P00734
- Molecular Weight:
- 70036.295 Da
- Mechanism of Action:
- The mechanism of action of heparin is antithrombin-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Heparin interacts with antithrombin III, prothrombin and factor X.
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- General Function:
- Syndecan binding
- Specific Function:
- Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extacellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis.
- Gene Name:
- HPSE
- Uniprot ID:
- Q9Y251
- Molecular Weight:
- 61148.17 Da
- Mechanism of Action:
- The mechanism of action of heparin is antithrombin-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Heparin interacts with antithrombin III, prothrombin and factor X.
References
- Zhao H, Liu H, Chen Y, Xin X, Li J, Hou Y, Zhang Z, Zhang X, Xie C, Geng M, Ding J: Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basic fibroblast growth factor, combats tumor angiogenesis and metastasis. Cancer Res. 2006 Sep 1;66(17):8779-87. [16951194 ]
- General Function:
- Protein tyrosine kinase activity
- Specific Function:
- Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.
- Gene Name:
- FGFR2
- Uniprot ID:
- P21802
- Molecular Weight:
- 92024.29 Da
References
- Robinson CJ, Harmer NJ, Goodger SJ, Blundell TL, Gallagher JT: Cooperative dimerization of fibroblast growth factor 1 (FGF1) upon a single heparin saccharide may drive the formation of 2:2:1 FGF1.FGFR2c.heparin ternary complexes. J Biol Chem. 2005 Dec 23;280(51):42274-82. Epub 2005 Oct 11. [16219767 ]