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T3D0052 - Di-n-butyl phthalate

Record Information
Version 1.0
Creation Date 2009-03-06 18:57:59 UTC
Update Date 2013-04-25 08:32:37 UTC
Accession Number T3D0052
Identification
Common Name Di-n-butyl phthalate
Description Di-n-butyl phthalate is a manufactured chemical that is added to plastics, paint, glue, hair spray, and other household products. It is commonly found in the environment, and most people are exposed to low levels in the air, water, and food. However, it is believed to have relativel low toxicity. (R258)
Compound Type
  • Organic Compound
  • Plasticizer
  • Aromatic Hydrocarbon
  • Phthalate
  • Cosmetic Toxin
Chemical Structure
Thumb
MOL SDF SMILES InChI
Synonyms
  1. 1,2-Benzenedicarboxylic Acid, dibutyl ester
  2. Benzene-o-dicarboxylic Acid di-n-butyl ester
  3. Benzenedicarboxylic Acid, dibutyl ester
  4. Butyl phthalate
  5. Celluflex DPB
  6. DBP
  7. Di-n-butyl phthalate
  8. Di-n-butylester kyseliny ftalove [czech]
  9. Di-n-butylorthophthalate
  10. Dibutyl 1,2-benzenedicarboxylate
  11. Dibutyl ester of 1,2-benzenedicarboxylic Acid
  12. Dibutyl o-phthalate
  13. Dibutyl phthalated
  14. Dibutyl-1,2-benzenedicarboxylate
  15. Dibutyl-o-phthalate
  16. Dibutyll phthalate
  17. Dibutylphthatlate
  18. Elaol
  19. Ergoplast FDB
  20. Hatcol DBP
  21. Kodaflex DBP
  22. Morflex 240
  23. N-butyl phthalate
  24. N-butylphthalate
  25. O-benzenedicarboxylic Acid, dibutyl ester
  26. Ortho-dibutyl phthalate
  27. Palatinol c
  28. Palatinol DBP
  29. Phthalate, butyl
  30. Phthalate, di-n-butyl
  31. Phthalate, dibutyl
  32. Phthalic Acid di-n-butyl ester
  33. Phthalic Acid dibutyl ester
  34. Phthalic Acid, dibutyl ester
  35. Staflex DBP
  36. Uniflex DBP
  37. Unimoll DB
  38. Uniplex 150
Chemical Formula C16H22O4
Average Molecular Weight 278.3435
Monoisotopic Molecular Weight 278.151809192
Chemical IUPAC Name
dibutyl phthalate
CAS Registry Number 84-74-2
SMILES
CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC
InChI Identifier
InChI=1S/C16H22O4/c1-3-5-11-19-15(17)13-9-7-8-10-14(13)16(18)20-12-6-4-2/h7-10H,3-6,11-12H2,1-2H3
InChI Key InChIKey=DOIRQSBPFJWKBE-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Benzenoids
Class Benzene and Substituted Derivatives
Sub Class Benzoic Acid and Derivatives
Direct Parent o-Phthalic Acid and Derivatives
Alternative Parents
  • Benzoic Acid Esters
  • Benzylethers
  • Benzoyl Derivatives
  • Dicarboxylic Acids and Derivatives
  • Carboxylic Acid Esters
  • Enolates
Molecular Framework Aromatic Homomonocyclic Compounds
Substituents
  • benzoate ester
  • benzylether
  • benzoyl
  • dicarboxylic acid derivative
  • carboxylic acid ester
  • enolate
External Descriptors
  • phthalate ester(ChEBI)
  • Phthalates(KEGG)
  • Insect repellents(KEGG)
DrugBank ID Not Available
PubChem Compound ID 3026 Link_out
KEGG ID Not Available
UniProt ID Not Available
OMIM ID Not Available
ChEBI ID 25520 Link_out
BioCyc ID Not Available
CTD ID D003993 Link_out
Stitch ID Di-n-butyl phthalate Link_out
PDB ID Not Available
ACToR ID 1740
Wikipedia Link http://en.wikipedia.org/wiki/Dibutyl_phthalate Link_out
Physical Properties
Appearance Colorless oily liquid.
Melting Point -35 C
Solubility 0.0112 mg/mL at 25 °C [HOWARD,PH et al. (1985)]
Predicted LogP 4.627997773333334
Toxicity Profile
Route of Exposure Oral (R258) ; inhalation (R258) ; dermal (R258)
Mechanism of Action The most characteristic effect of di-n-butyl phthalate is testicular atrophy. Di-n-butyl phthalate exposure causes both the release of iron from hemoglobin and/or transferrin in the liver and spleen, and the subsequent depletion of iron in the blood and testes. The decreased amount of available iron results in a decrease in succinate dehydrogenase activity in the Sertoli cells. This results in disturbances in the energy transfer system between Sertoli cells and germ cells, which is required for the differentiation of male germ cells and their progression through the seminiferous epithelium and release as mature spermatozoa. Di-n-butyl phthalate may also exhibit weak estrogenic activity. It has been shown to exhibit toxic effects in liver mitochondria by uncoupling energy-linked processes and inhibiting succinate dehydrogenase. (R258, R259)
Metabolism Di-n-butyl phthalate is absorbed via oral, inhalation, and dermal routes. It is rapidly distributed and cleared from the body. Metabolism of di-n-butyl phthalate proceeds mainly by nonspecific esterases in the gastrointestinal tract, which hydrolyze of one butyl ester bond to yield mono-n-butyl phthalate, the primary toxic metabolite. Mono-n-butyl phthalate is conjugated with glucuronic acid via glucuronosyltransferase and excreted in the urine. (R258)
Toxicity Values LD50: 3050 mg/kg (Intraperitoneal, Rat) (R261) LD50: 720 mg/kg (Intravenous, Mouse) (R261) LD50: 5289 mg/kg (Oral, Mouse) (R261) LC50: 25 g/m3 over 2 hours (Inhalation, Mouse) (R261)
Lethal Dose Not Available
Carcinogenicity (IARC Classification) Not Available
Uses/Sources Di-n-butyl phthalate is used to make plastics more flexible and is also in carpet backings, paints, glue, insect repellents, hair spray, nail polish, and rocket fuel. (R258)
Minimum Risk Level Not Available
Health Effects Adverse effects from di-n-butyl phthalate exposure have not yet been reported in humans. However, animals studies have shown that di-n-butyl phthalate can affect reproductive ability by decreasing sperm count and causing birth defects. (R258)
Symptoms Skin contact with di-n-butyl phthalate may cause mild irritation. (R258)
Treatment Not Available
References
General References
  • R258 — ATSDR - Agency for Toxic Substances and Disease Registry (2001). Toxicological profile for di-n-butyl phthalate. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  • R259 — Melnick RL, Schiller CM: Mitochondrial toxicity of phthalate esters. Environ Health Perspect. 1982 Nov;45:51-6. [7140696 Link_out]
  • R261 — Lewis RJ Sr. (ed) (2004). Sax's Dangerous Properties of Industrial Materials. 11th Edition. Hoboken, NJ: Wiley-Interscience, Wiley & Sons, Inc.

Targets

1. Succinate dehydrogenase cytochrome b560 subunit, mitochondrial

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).

Di-n-butyl phthalate has been shown to exhibit toxic effects in liver mitochondria by uncoupling energy-linked processes and inhibiting succinate dehydrogenase. (R259)
UniProt ID: Q99643 Link_out
Gene: SDHC Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • R259 — Melnick RL, Schiller CM: Mitochondrial toxicity of phthalate esters. Environ Health Perspect. 1982 Nov;45:51-6. [7140696 Link_out]

2. Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial

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) (By similarity).

Di-n-butyl phthalate has been shown to exhibit toxic effects in liver mitochondria by uncoupling energy-linked processes and inhibiting succinate dehydrogenase. (R259)
UniProt ID: O14521 Link_out
Gene: SDHD Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • R259 — Melnick RL, Schiller CM: Mitochondrial toxicity of phthalate esters. Environ Health Perspect. 1982 Nov;45:51-6. [7140696 Link_out]

3. Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial

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.

Di-n-butyl phthalate has been shown to exhibit toxic effects in liver mitochondria by uncoupling energy-linked processes and inhibiting succinate dehydrogenase. (R259)
UniProt ID: P31040 Link_out
Gene: SDHA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • R259 — Melnick RL, Schiller CM: Mitochondrial toxicity of phthalate esters. Environ Health Perspect. 1982 Nov;45:51-6. [7140696 Link_out]

4. Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial

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).

Di-n-butyl phthalate has been shown to exhibit toxic effects in liver mitochondria by uncoupling energy-linked processes and inhibiting succinate dehydrogenase. (R259)
UniProt ID: P21912 Link_out
Gene: SDHB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • R259 — Melnick RL, Schiller CM: Mitochondrial toxicity of phthalate esters. Environ Health Perspect. 1982 Nov;45:51-6. [7140696 Link_out]

5. Peroxisome proliferator-activated receptor alpha

Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety (By similarity). Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2.

Di-n-butyl phthalate causes peroxisome proliferation by activating peroxisome proliferator-activated receptors, which may lead to carcinogenic effects. (R262)
UniProt ID: Q07869 Link_out
Gene: PPARA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • R262 — Lapinskas PJ, Brown S, Leesnitzer LM, Blanchard S, Swanson C, Cattley RC, Corton JC: Role of PPARalpha in mediating the effects of phthalates and metabolites in the liver. Toxicology. 2005 Feb 1;207(1):149-63. [15590130 Link_out]

6. Peroxisome proliferator-activated receptor gamma

Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses.

Di-n-butyl phthalate causes peroxisome proliferation by activating peroxisome proliferator-activated receptors, which may lead to carcinogenic effects. (R262)
UniProt ID: P37231 Link_out
Gene: PPARG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • R262 — Lapinskas PJ, Brown S, Leesnitzer LM, Blanchard S, Swanson C, Cattley RC, Corton JC: Role of PPARalpha in mediating the effects of phthalates and metabolites in the liver. Toxicology. 2005 Feb 1;207(1):149-63. [15590130 Link_out]

7. C-C motif chemokine 2

Chemotactic factor that attracts monocytes and basophils but not neutrophils or eosinophils. Augments monocyte anti-tumor activity. Has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis or atherosclerosis. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis.

UniProt ID: P13500 Link_out
Gene: CCL2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

8. ADP-ribosyl cyclase 1

Synthesizes cyclic ADP-ribose, a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system.

UniProt ID: P28907 Link_out
Gene: CD38 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

9. Tumor necrosis factor receptor superfamily member 5

Receptor for TNFSF5/CD40LG.

UniProt ID: P25942 Link_out
Gene: CD40 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

10. Early activation antigen CD69

Involved in lymphocyte proliferation and functions as a signal transmitting receptor in lymphocytes, natural killer (NK) cells, and platelets.

UniProt ID: Q07108 Link_out
Gene: CD69 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

11. Collagen alpha-1(III) chain

Collagen type III occurs in most soft connective tissues along with type I collagen.

UniProt ID: P02461 Link_out
Gene: COL3A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

12. Macrophage colony-stimulating factor 1

Cytokine that plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone development. Required for normal male and female fertility. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration. Plays a role in lipoprotein clearance.

UniProt ID: P09603 Link_out
Gene: CSF1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

13. C-X-C motif chemokine 10

Chemotactic for monocytes and T-lymphocytes. Binds to CXCR3.

UniProt ID: P02778 Link_out
Gene: CXCL10 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

14. Cytochrome P450 1A1

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

15. Cytochrome P450 1A2

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.

UniProt ID: P05177 Link_out
Gene: CYP1A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

16. 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial

Catalyzes the conversion of 25-hydroxyvitamin D3 (25(OH)D) to 1-alpha,25-dihydroxyvitamin D3 (1,25(OH)2D) plays an important role in normal bone growth, calcium metabolism, and tissue differentiation.

UniProt ID: O15528 Link_out
Gene: CYP27B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

17. Cytochrome P450 2B6

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

18. Cytochrome P450 2C19

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

19. Cytochrome P450 3A4

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.

UniProt ID: P08684 Link_out
Gene: CYP3A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

20. Estrogen receptor

Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.

UniProt ID: P03372 Link_out
Gene: ESR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

21. Hypoxia-inducible factor 1-alpha

Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.

UniProt ID: Q16665 Link_out
Gene: HIF1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

22. Hepatocyte nuclear factor 4-alpha

Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.

UniProt ID: P41235 Link_out
Gene: HNF4A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

23. Interleukin-1 alpha

Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.

UniProt ID: P01583 Link_out
Gene: IL1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

24. Interleukin-8

IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to receptors CXCR1 and CXCR2 as compared to IL-8(1-77), respectively.

UniProt ID: P10145 Link_out
Gene: IL8 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

25. Transcription factor AP-1

Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.

UniProt ID: P05412 Link_out
Gene: JUN Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

26. Low-density lipoprotein receptor

Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.

UniProt ID: P01130 Link_out
Gene: LDLR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

27. Nuclear factor erythroid 2-related factor 2

Transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes. Important for the coordinated up-regulation of genes in response to oxidative stress. May be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region.

UniProt ID: Q16236 Link_out
Gene: NFE2L2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

28. Nuclear receptor subfamily 1 group I member 2

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.

UniProt ID: O75469 Link_out
Gene: NR1I2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

29. Nuclear receptor subfamily 1 group I member 3

Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element.

UniProt ID: Q14994 Link_out
Gene: NR1I3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

30. Tissue-type plasminogen activator

Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. Plays a direct role in facilitating neuronal migration.

UniProt ID: P00750 Link_out
Gene: PLAT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

31. Urokinase-type plasminogen activator

Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.

UniProt ID: P00749 Link_out
Gene: PLAU Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

32. Urokinase plasminogen activator surface receptor

Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.

UniProt ID: Q03405 Link_out
Gene: PLAUR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

33. Prostaglandin E2 receptor EP2 subtype

Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the relaxing effect of this receptor on smooth muscle.

UniProt ID: P43116 Link_out
Gene: PTGER2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

34. Nuclear receptor ROR-alpha

Orphan nuclear receptor. Binds DNA as a monomer to hormone response elements (HRE) containing a single core motif half-site preceded by a short A-T-rich sequence. This isomer binds to the consensus sequence 5'-[AT][TA]A[AT][CGT]TAGGTCA-3'. Regulates a number of genes involved in lipid metabolism such as apolipoproteins AI, APOA5, CIII, CYP71 and PPARgamma, in cerebellum and photoreceptor development including PCP2, OPN1SW, OPN1SM AND ARR3, in circadian rhythm with BMAL1, and skeletal muscle development with MYOD1. Possible receptor for cholesterol or one of its derivatives.

UniProt ID: P35398 Link_out
Gene: RORA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

35. E-selectin

Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with PSGL1/SELPLG. May have a role in capillary morphogenesis.

UniProt ID: P16581 Link_out
Gene: SELE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

36. Transforming growth factor beta-1

Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts.

UniProt ID: P01137 Link_out
Gene: TGFB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

37. Translocator protein

Responsible for the manifestation of peripheral-type benzodiazepine recognition sites and is most likely to comprise binding domains for benzodiazepines and isoquinoline carboxamides. May play a role in the transport of porphyrins and heme. Plays a role in the transport of cholesterol across mitochondrial membranes in steroidogenic cells (By similarity).

UniProt ID: P30536 Link_out
Gene: TSPO Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]

38. Vascular cell adhesion protein 1

Important in cell-cell recognition. Appears to function in leukocyte-endothelial cell adhesion. Interacts with the beta-1 integrin VLA4 on leukocytes, and mediates both adhesion and signal transduction. The VCAM1/VLA4 interaction may play a pathophysiologic role both in immune responses and in leukocyte emigration to sites of inflammation.

UniProt ID: P19320 Link_out
Gene: VCAM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • X003 — ToxCastDB (EPA, United States Environmental Protection Agency) [Link]