Tmic
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Record Information
Version2.0
Creation Date2014-08-28 20:09:03 UTC
Update Date2014-12-24 20:26:34 UTC
Accession NumberT3D3953
Identification
Common NameOxytetracycline
ClassSmall Molecule
DescriptionA tetracycline analog isolated from the actinomycete streptomyces rimosus and used in a wide variety of clinical conditions. [PubChem]
Compound Type
  • Drug
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Synthetic Compound
  • Tetracycline
Chemical Structure
Thumb
Synonyms
Synonym
2058-46-0 (Mono-hydrochloride)
5-Hydroxy-Tetracycline
5-Hydroxytetracycline
6153-64-6 (Di-hydrate)
6153-65-7 (Di-hydrochloride salt, di-hydrate)
7179-50-2 (Calcium (1:1) salt)
79-57-2 (ANHYDROUS)
Abbocin
Adamycin
Anglocycline
Antibiotic TM 25
Berkmycen
Biostat
Biostat pa
Bisolvomycin
Corsamycin
Dabicycline
Dalimycin
Embryostat
Fanterrin
Galsenomycin
Geomycin
Geotilin
Hydroxytetracycline
Hydroxytetracyclinum
Imperacin
Lenocycline
Liquamycin
Liquamycin LA 200
Macocyn
Medamycin
Mepatar
Mycoshield TMQTHC 20
NSC 9169
NSC9169 (HCL)
Oksisyklin
Ossitetraciclina
OTC
Oxacin
Oxacycline
Oxitetraciclina
Oxitetracyclin
Oxitetracyclinum
Oxy-kesso-tetra
Oxydon
Oxymycin
Oxymykoin
Oxypam
Oxypan
Oxysteclin
Oxyterracin
Oxyterracine
Oxyterracyna
Oxyterracyne
Oxytetracid
Oxytetracyclin
Oxytétracycline
Oxytetracycline (anhydrous)
Oxytetracycline amphoteric
Oxytetracycline anhydrous
Oxytetracycline calcium
Oxytetracyclinum
Pennox 200
Proteroxyna
Riomitsin
Ryomycin
Solkaciclina
Stecsolin
Stevacin
Tarocyn
Tarosin
Teravit
Terrados
Terrafungine
Terramitsin
Terramycin
Tetran
Tetrasona
Unimycin
Ursocyclin
Ursocycline
Vendarcin
Chemical FormulaC22H24N2O9
Average Molecular Mass460.434 g/mol
Monoisotopic Mass460.148 g/mol
CAS Registry Number79-57-2
IUPAC Name(4S,4aR,5S,5aR,6S,12aS)-4-(dimethylamino)-3,5,6,10,12,12a-hexahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
Traditional Nameoxytetracycline
SMILES[H][C@]1(O)[C@@]2([H])C(=C(O)[C@]3(O)C(=O)C(C(O)=N)=C(O)[C@@]([H])(N(C)C)[C@]13[H])C(=O)C1=C(C=CC=C1O)[C@@]2(C)O
InChI IdentifierInChI=1S/C22H24N2O9/c1-21(32)7-5-4-6-8(25)9(7)15(26)10-12(21)17(28)13-14(24(2)3)16(27)11(20(23)31)19(30)22(13,33)18(10)29/h4-6,12-14,17,25,27-29,32-33H,1-3H3,(H2,23,31)/t12-,13-,14+,17+,21-,22+/m1/s1
InChI KeyInChIKey=IWVCMVBTMGNXQD-PXOLEDIWSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as tetracyclines. These are polyketides having an octahydrotetracene-2-carboxamide skeleton, substituted with many hydroxy and other groups.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassTetracyclines
Sub ClassNot Available
Direct ParentTetracyclines
Alternative Parents
Substituents
  • Tetracycline
  • Naphthacene
  • Tetracene
  • Anthracene carboxylic acid or derivatives
  • Tetralin
  • Aryl ketone
  • 1-hydroxy-4-unsubstituted benzenoid
  • 1-hydroxy-2-unsubstituted benzenoid
  • Cyclohexenone
  • Aralkylamine
  • Benzenoid
  • Tertiary alcohol
  • Vinylogous acid
  • Tertiary aliphatic amine
  • Amino acid or derivatives
  • Tertiary amine
  • Carboxamide group
  • Secondary alcohol
  • Primary carboxylic acid amide
  • Ketone
  • Polyol
  • Carboxylic acid derivative
  • Enol
  • Amine
  • Organic oxygen compound
  • Organopnictogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Alcohol
  • Carbonyl group
  • Organic nitrogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Bone Marrow
  • Heart
  • Liver
Pathways
NameSMPDB LinkKEGG Link
Oxytetracycline Action PathwaySMP00293 Not Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point184.5°C
Boiling PointNot Available
Solubility313 mg/L (at 25°C)
LogP-0.9
Predicted Properties
PropertyValueSource
Water Solubility1.4 g/LALOGPS
logP-0.99ALOGPS
logP-4.6ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)0.24ChemAxon
pKa (Strongest Basic)7.75ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area201.85 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity115.4 m³·mol⁻¹ChemAxon
Polarizability43.4 ųChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-002f-0000900000-5672179671bb12c90e44View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004l-0000900000-50e9f5b99152f280cd90View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004i-1237900000-570a34d4c343b74d8b39View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0011900000-b4730d1729a6ab3c3527View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00ke-0357900000-f7d527caf2556638743bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000f-9175000000-36d7da806594f0c25f3fView in MoNA
Toxicity Profile
Route of ExposureReadily absorbed following oral administration.
Mechanism of ToxicityTetracyclines target the 28S small subunit of the mitochondrial ribosome thereby deactivation mitochondrial protein synthesis. As a result tetracyclines are cytotoxic to the most metabolically active cells or tissues including the heart, liver, thymus and bone-marrow. (5). The likely target of most tetracyclines is the 12S rRNA molecule in the mitochondrial ribosome, which is analogous to the 16S rRNA in bacterial ribosomes.
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesOxytetracycline is indicated for treatment of infections caused by a variety of Gram positive and Gram negative microorganisms including Mycoplasma pneumoniae, Pasteurella pestis, Escherichia coli, Haemophilus influenzae (respiratory infections), and Diplococcus pneumoniae.
Minimum Risk LevelNot Available
Health EffectsSide effects from normal doses of tetracyclines are relatively minimal, but of particular note is phototoxicity. Tetracylclines increase the risk of sunburn under exposure to light from the sun or other sources. Tetracyclines may also cause stomach or bowel upsets, and, on rare occasions, allergic reactions. Very rarely, severe headache and vision problems may be signs of dangerous secondary intracranial hypertension, also known as pseudotumor cerebri. Tetracyclines are teratogens and cause tooth discolouration and poor tooth mineralization in the fetus as they develop in infancy. Symptoms of tetracycline overdose include anorexia, nausea, diarrhea, glossitis, dysphagia, enterocolitis and inflammatory lesions, skin reactions such as maculopapular and erythematous rashes, exfoliative dermatitis, photosensitivity, hypersensitivity reactions such as urticaria, angioneurotic oedema, anaphylaxis, anaphyl-actoid purpura, pericarditis, and exacerbation of systemic lupus erythematosus, benign intracranial hypertension in adults disappearing on discontinuation of the medicine, haematologic abnormalities such as haemolytic anaemia, thrombocytopenia, neutropenia, and eosinophilia.
SymptomsSymptoms may include stomach or bowel upsets and rarely allergic reactions. Very rarely severe headache and vision problems may be signs of dangerous intracranial hypertenion.
TreatmentDrug therapy is discontinued immediately; exchange transfusion may be required to remove the drug. Sometimes, phenobarbital (UGT induction) is used.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00595
HMDB IDHMDB14733
PubChem Compound ID5280972
ChEMBL IDCHEMBL1517
ChemSpider ID4444458
KEGG IDC06624
UniProt IDNot Available
OMIM ID
ChEBI ID27701
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDOAQ
ACToR IDNot Available
Wikipedia LinkOxytetracycline
References
Synthesis Reference

Janos Balint, Laszlo Cseke, Ferenc Fabian, Lajos Kun, Miklos Szarvas, “Process for the preparation of an oxytetracycline-calcium silicate complex salt from fermentation broth.” U.S. Patent US4584135, issued April, 1951.

MSDSLink
General References
  1. Solis Y, Chavarria G, Garcia F, Rodriguez C: Exposure of a Tropical Soil to MG/KG of Oxytetracycline Elicits Hormetic Responses in the Catabolic Activities of Its Microbial Community. Dose Response. 2011;9(3):434-41. doi: 10.2203/dose-response.10-045.Rodriguez. Epub 2011 Apr 30. [22013404 ]
  2. Ci X, Chu X, Chen C, Li X, Yan S, Wang X, Yang Y, Deng X: Oxytetracycline attenuates allergic airway inflammation in mice via inhibition of the NF-kappaB pathway. J Clin Immunol. 2011 Apr;31(2):216-27. doi: 10.1007/s10875-010-9481-7. Epub 2010 Dec 7. [21136283 ]
  3. Sundell K, Wiklund T: Effect of biofilm formation on antimicrobial tolerance of Flavobacterium psychrophilum. J Fish Dis. 2011 May;34(5):373-83. doi: 10.1111/j.1365-2761.2011.01250.x. Epub 2011 Mar 24. [21488905 ]
  4. Le Breton MH, Savoy-Perroud MC, Diserens JM: Validation and comparison of the Copan Milk Test and Delvotest SP-NT for the detection of antimicrobials in milk. Anal Chim Acta. 2007 Mar 14;586(1-2):280-3. Epub 2006 Dec 2. [17386724 ]
  5. McKee EE, Ferguson M, Bentley AT, Marks TA: Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones. Antimicrob Agents Chemother. 2006 Jun;50(6):2042-9. [16723564 ]
  6. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
  7. Wikipedia. Oxytetracycline. Last updated on 13 March 2014 [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Identical protein binding
Specific Function:
Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
Gene Name:
B2M
Uniprot ID:
P61769
Molecular Weight:
13714.43 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5063 uMNot AvailableBindingDB 92401
References
  1. Giorgetti S, Raimondi S, Pagano K, Relini A, Bucciantini M, Corazza A, Fogolari F, Codutti L, Salmona M, Mangione P, Colombo L, De Luigi A, Porcari R, Gliozzi A, Stefani M, Esposito G, Bellotti V, Stoppini M: Effect of tetracyclines on the dynamics of formation and destructuration of beta2-microglobulin amyloid fibrils. J Biol Chem. 2011 Jan 21;286(3):2121-31. doi: 10.1074/jbc.M110.178376. Epub 2010 Nov 10. [21068391 ]
General Function:
Vascular endothelial growth factor-activated receptor activity
Specific Function:
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'.
Gene Name:
FLT4
Uniprot ID:
P35916
Molecular Weight:
152755.94 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.86 uMNVS_ENZ_hVEGFR3Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.84 uMNVS_NR_hPXRNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Sh3 domain binding
Specific Function:
Dephosphorylates cellular tyrosine kinases, including PTK2B/PYK2, and thereby regulates signaling via PTK2B/PYK2.
Gene Name:
PTPN12
Uniprot ID:
Q05209
Molecular Weight:
88105.665 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.20 uMNVS_ENZ_hPTPN12Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Sh3/sh2 adaptor activity
Specific Function:
Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity.
Gene Name:
PTPN11
Uniprot ID:
Q06124
Molecular Weight:
68436.0 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.63 uMNVS_ENZ_hPTPN11Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.41 uMNVS_ENZ_hFGFR1Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Transmembrane receptor protein tyrosine kinase activity
Specific Function:
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.
Gene Name:
EPHA2
Uniprot ID:
P29317
Molecular Weight:
108265.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.88 uMNVS_ENZ_hEphA2Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Transmembrane receptor protein tyrosine phosphatase activity
Specific Function:
Plays an important role in blood vessel remodeling and angiogenesis. Not necessary for the initial formation of blood vessels, but is essential for their maintenance and remodeling. Can induce dephosphorylation of TEK/TIE2, CDH5/VE-cadherin and KDR/VEGFR-2. Regulates angiopoietin-TIE2 signaling in endothelial cells. Acts as a negative regulator of TIE2, and controls TIE2 driven endothelial cell proliferation, which in turn affects blood vessel remodeling during embryonic development and determines blood vessel size during perinatal growth. Essential for the maintenance of endothelial cell contact integrity and for the adhesive function of VE-cadherin in endothelial cells and this requires the presence of plakoglobin (By similarity).
Gene Name:
PTPRB
Uniprot ID:
P23467
Molecular Weight:
224299.74 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.91 uMNVS_ENZ_hPTPRBNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Transmembrane receptor protein tyrosine kinase activity
Specific Function:
Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1.
Gene Name:
TEK
Uniprot ID:
Q02763
Molecular Weight:
125829.005 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC509.24 uMNVS_ENZ_hTie2Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis.
Gene Name:
RARA
Uniprot ID:
P10276
Molecular Weight:
50770.805 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC509.24 uMNVS_NR_hRAR_AntagonistNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Rac gtpase binding
Specific Function:
Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN.
Gene Name:
PAK4
Uniprot ID:
O96013
Molecular Weight:
64071.49 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC509.30 uMNVS_ENZ_hPAK4Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory2.00 uMNot AvailableNot Available