Insulin
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Basic Info
| Common Name | Insulin(F04701) |
| 2D Structure | |
| Description | Insulin is a hormone that has extensive effects on metabolism and other body functions, such as vascular compliance. It is a peptide hormone composed of 51 amino acid residues and has a molecular weight of 5808 Da. It is produced in the islets of Langerhans in the pancreas. When insulin is absent (or low), glucose is not taken up by body cells, and the body begins to use fat as an energy source (L1006). |
| FRCD ID | F04701 |
| CAS Number | 11061-68-0 |
| PubChem CID | 70678557 |
| Formula | C256H381N65O77S6 |
| IUPAC Name | None |
| InChI Key | YAJCHEVQCOHZDC-QMMNLEPNSA-N |
| InChI | InChI=1S/C256H381N65O77S6/c1-29-130(23)202(311-190(337)103-258)250(391)315-200(128(19)20)246(387)286-158(75-82-197(347)348)216(357)281-154(70-77-186(261)333)220(361)306-181-115-402-403-116-182-241(382)303-176(110-323)238(379)293-161(88-122(7)8)224(365)294-167(95-139-53-61-145(328)62-54-139)227(368)282-153(69-76-185(260)332)217(358)289-160(87-121(5)6)222(363)283-157(74-81-196(345)346)219(360)301-173(101-188(263)335)233(374)297-169(97-141-57-65-147(330)66-58-141)230(371)307-180(240(381)302-174(254(395)396)102-189(264)336)114-401-400-113-179(213(354)272-106-191(338)277-152(72-79-194(341)342)215(356)280-150(51-42-84-270-256(266)267)211(352)271-107-192(339)278-165(93-137-46-36-32-37-47-137)226(367)296-166(94-138-48-38-33-39-49-138)229(370)298-170(98-142-59-67-148(331)68-60-142)236(377)318-205(134(27)326)253(394)321-85-43-52-184(321)244(385)284-151(50-40-41-83-257)221(362)319-206(135(28)327)255(397)398)309-247(388)199(127(17)18)314-234(375)163(90-124(11)12)291-228(369)168(96-140-55-63-146(329)64-56-140)295-223(364)159(86-120(3)4)288-209(350)132(25)276-214(355)156(73-80-195(343)344)285-245(386)198(126(15)16)313-235(376)164(91-125(13)14)292-232(373)172(100-144-105-269-119-275-144)300-237(378)175(109-322)279-193(340)108-273-212(353)178(112-399-404-117-183(308-242(181)383)243(384)317-204(133(26)325)251(392)304-177(111-324)239(380)316-203(131(24)30-2)249(390)310-182)305-225(366)162(89-123(9)10)290-231(372)171(99-143-104-268-118-274-143)299-218(359)155(71-78-187(262)334)287-252(393)207(208(265)349)320-248(389)201(129(21)22)312-210(351)149(259)92-136-44-34-31-35-45-136/h31-39,44-49,53-68,104-105,118-135,149-184,198-207,322-331H,29-30,40-43,50-52,69-103,106-117,257-259H2,1-28H3,(H2,260,332)(H2,261,333)(H2,262,334)(H2,263,335)(H2,264,336)(H2,265,349)(H,268,274)(H,269,275)(H,271,352)(H,272,354)(H,273,353)(H,276,355)(H,277,338)(H,278,339)(H,279,340)(H,280,356)(H,281,357)(H,282,368)(H,283,363)(H,284,385)(H,285,386)(H,286,387)(H,287,393)(H,288,350)(H,289,358)(H,290,372)(H,291,369)(H,292,373)(H,293,379)(H,294,365)(H,295,364)(H,296,367)(H,297,374)(H,298,370)(H,299,359)(H,300,378)(H,301,360)(H,302,381)(H,303,382)(H,304,392)(H,305,366)(H,306,361)(H,307,371)(H,308,383)(H,309,388)(H,310,390)(H,311,337)(H,312,351)(H,313,376)(H,314,375)(H,315,391)(H,316,380)(H,317,384)(H,318,377)(H,319,362)(H,320,389)(H,341,342)(H,343,344)(H,345,346)(H,347,348)(H,395,396)(H,397,398)(H4,266,267,270)/t130-,131-,132+,133+,134+,135+,149+,150+,151+,152+,153+,154+,155+,156+,157+,158+,159+,160+,161+,162+,163+,164+,165+,166+,167+,168+,169+,170+,171+,172+,173+,174+,175+,176+,177+,178+,179+,180+,181+,182-,183+,184+,198+,199+,200+,201+,202+,203+,204+,205+,206+,207+/m1/s1 |
| Canonical SMILES | CCC(C)C1C(=O)NC2CSSCC(C(=O)NC(CSSCC(C(=O)NCC(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(CSSCC(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC2=O)CO)CC(C)C)CC3=CC=C(C=C3)O)CCC(=O)N)CC(C)C)CCC(=O)O)CC(=O)N)CC4=CC=C(C=C4)O)C(=O)NC(CC(=O)N)C(=O)O)C(=O)NCC(=O)NC(CCC(=O)O)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CC5=CC=CC=C5)C(=O)NC(CC6=CC=CC=C6)C(=O)NC(CC7=CC=C(C=C7)O)C(=O)NC(C(C)O)C(=O)N8CCCC8C(=O)NC(CCCCN)C(=O)NC(C(C)O)C(=O)O)C(C)C)CC(C)C)CC9=CC=C(C=C9)O)CC(C)C)C)CCC(=O)O)C(C)C)CC(C)C)CC2=CNC=N2)CO)NC(=O)C(CC(C)C)NC(=O)C(CC2=CNC=N2)NC(=O)C(CCC(=O)N)NC(=O)C(C(=O)N)NC(=O)C(C(C)C)NC(=O)C(CC2=CC=CC=C2)N)C(=O)NC(C(=O)NC(C(=O)N1)CO)C(C)O)NC(=O)C(CCC(=O)N)NC(=O)C(CCC(=O)O)NC(=O)C(C(C)C)NC(=O)C(C(C)CC)NC(=O)CN |
| Isomeric SMILES | CC[C@@H](C)[C@H]1C(=O)N[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC2=O)CO)CC(C)C)CC3=CC=C(C=C3)O)CCC(=O)N)CC(C)C)CCC(=O)O)CC(=O)N)CC4=CC=C(C=C4)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC5=CC=CC=C5)C(=O)N[C@@H](CC6=CC=CC=C6)C(=O)N[C@@H](CC7=CC=C(C=C7)O)C(=O)N[C@@H]([C@H](C)O)C(=O)N8CCC[C@H]8C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@H](C)O)C(=O)O)C(C)C)CC(C)C)CC9=CC=C(C=C9)O)CC(C)C)C)CCC(=O)O)C(C)C)CC(C)C)CC2=CNC=N2)CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(=O)N)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)N[C@H](C(=O)N[C@H](C(=O)N1)CO)[C@H](C)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H]([C@H](C)CC)NC(=O)CN |
| Wikipedia | Insulin |
| Synonyms |
Insulin recombinant
9004-10-8
Exubera
Endopancrine
Decurvon
Dermulin
Humilin
Insular
Insulyl
Iszilin
|
| Classifies |
Animal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organic Polymers |
| Class | Polypeptides |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Polypeptides |
| Alternative Parents |
|
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Polypeptide - Hexacarboxylic acid or derivatives - Cyclic alpha peptide - Tyrosine or derivatives - Arginine or derivatives - Phenylalanine or derivatives - Histidine or derivatives - Glutamic acid or derivatives - Glutamine or derivatives - Asparagine or derivatives - Isoleucine or derivatives - Leucine or derivatives - Valine or derivatives - N-acyl-alpha amino acid or derivatives - Proline or derivatives - N-acyl-alpha-amino acid - N-acyl-l-alpha-amino acid - Alpha-amino acid amide - Amphetamine or derivatives - Alpha-amino acid or derivatives - N-substituted-alpha-amino acid - N-acylpyrrolidine - Pyrrolidine carboxylic acid or derivatives - Pyrrolidine-2-carboxamide - 1-hydroxy-2-unsubstituted benzenoid - Phenol - Beta-hydroxy acid - Aralkylamine - Benzenoid - 1,3-dicarbonyl compound - Fatty amide - Hydroxy acid - N-acyl-amine - Monocyclic benzene moiety - Fatty acyl - Tertiary carboxylic acid amide - Heteroaromatic compound - Pyrrolidine - Azole - Imidazole - Amino acid or derivatives - Amino acid - Carboxamide group - Guanidine - Secondary carboxylic acid amide - Secondary alcohol - Primary carboxylic acid amide - Lactam - Organic disulfide - Azacycle - Carboxylic acid derivative - Carboxylic acid - Organoheterocyclic compound - Carboximidamide - Organooxygen compound - Organonitrogen compound - Organic oxygen compound - Carbonyl group - Organic nitrogen compound - Hydrocarbon derivative - Organic oxide - Imine - Primary aliphatic amine - Primary alcohol - Primary amine - Organopnictogen compound - Amine - Alcohol - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 5793.602 |
| Hydrogen Bond Donor Count | 78 |
| Hydrogen Bond Acceptor Count | 89 |
| Rotatable Bond Count | 178 |
| Complexity | 14600 |
| Monoisotopic Mass | 5789.622 |
| Exact Mass | 5791.629 |
| XLogP | -12.8 |
| Formal Charge | 0 |
| Heavy Atom Count | 404 |
| Defined Atom Stereocenter Count | 52 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB- | 0.9854 |
| Human Intestinal Absorption | HIA+ | 0.7564 |
| Caco-2 Permeability | Caco2- | 0.7587 |
| P-glycoprotein Substrate | Substrate | 0.8522 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.7638 |
| Non-inhibitor | 0.9767 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8376 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.4400 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7245 |
| CYP450 2D6 Substrate | Non-substrate | 0.7970 |
| CYP450 3A4 Substrate | Substrate | 0.5361 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8141 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.7774 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8683 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.7449 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.6597 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9167 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9212 |
| Inhibitor | 0.5255 | |
| AMES Toxicity | Non AMES toxic | 0.6834 |
| Carcinogens | Non-carcinogens | 0.7677 |
| Fish Toxicity | High FHMT | 0.9890 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9740 |
| Honey Bee Toxicity | Low HBT | 0.6804 |
| Biodegradation | Not ready biodegradable | 0.8847 |
| Acute Oral Toxicity | III | 0.4881 |
| Carcinogenicity (Three-class) | Non-required | 0.5558 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.4864 | LogS |
| Caco-2 Permeability | -0.2945 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 3.0697 | LD50, mol/kg |
| Fish Toxicity | 1.4210 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.4869 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Effects of supplemental calcium salts of palm oil and chromium-propionate oninsulin sensitivity and productive and reproductive traits of mid- tolate-lactating Holstein × Gir dairy cows consuming excessive energy. | J Dairy Sci | 2018 Jan | 29102132 |
| Short communication: Parameters of abomasal emptying and glucose-insulin dynamicsin Holstein-Friesian calves at 2 ages and 2 levels of milk replacer intake. | J Dairy Sci | 2017 Jun | 28434728 |
| Early High-Fat Feeding Induces Alteration of Trace Element Content in Tissues of Juvenile Male Wistar Rats. | Biol Trace Elem Res | 2017 Feb | 27311579 |
| A 12-week randomized clinical trial investigating the potential for sucralose to affect glucose homeostasis. | Regul Toxicol Pharmacol | 2017 Aug | 28502831 |
| Decreasing high postprandial stearic acid in impaired fasting glucose by dietary regulation. | Eur J Clin Nutr | 2016 Jul | 26733041 |
| Dietary patterns in men and women are simultaneously determinants of alteredglucose metabolism and bone metabolism. | Nutr Res | 2016 Apr | 27001278 |
| Zinc supplementation and the effects on metabolic status in gestational diabetes:A randomized, double-blind, placebo-controlled trial. | J Diabetes Complications | 2015 Nov-Dec | 26233572 |
| Association between Advanced Glycation End Products and Impaired Fasting Glucose:Results from the SALIA Study. | PLoS One | 2015 May 27 | 26018950 |
| Enzymatically Modified Starch Ameliorates Postprandial Serum Triglycerides andLipid Metabolome in Growing Pigs. | PLoS One | 2015 Jun 15 | 26076487 |
| Effects of sodium benzoate, a widely used food preservative, on glucosehomeostasis and metabolic profiles in humans. | Mol Genet Metab | 2015 Jan | 25497115 |
| Anti-Obesity Effects of the Mixture of Eriobotrya japonica and Nelumbo nuciferain Adipocytes and High-Fat Diet-Induced Obese Mice. | Am J Chin Med | 2015 | 26133751 |
| Development of an experimental diet model in rats to study hyperlipidemia andinsulin resistance, markers for coronary heart disease. | Indian J Pharmacol | 2014 May-Jun | 24987172 |
| Long-term intake of rice improves insulin sensitivity in mice fed a high-fatdiet. | Nutrition | 2014 Jul-Aug | 24985012 |
| Association between markers of glucose metabolism and risk of colorectal adenoma. | Gastroenterology | 2014 Jul | 24632359 |
| Therapeutic potential of octyl gallate isolated from fruits of Terminaliabellerica in streptozotocin-induced diabetic rats. | Pharm Biol | 2013 Jun | 23675839 |
| High-fructose corn syrup and sucrose have equivalent effects on energy-regulatinghormones at normal human consumption levels. | Nutr Res | 2013 Dec | 24267044 |
| Postprandial glucose, insulin, and free fatty acid responses to sucrose consumed with blackcurrants and lingonberries in healthy women. | Am J Clin Nutr | 2012 Sep | 22854401 |
| Dietary supplementation with short-chain fructo-oligosaccharides improves insulinsensitivity in obese horses. | J Anim Sci | 2011 Jan | 20870952 |
| Dietary amylose and amylopectin ratio and resistant starch content affects plasmaglucose, lactic acid, hormone levels and protein synthesis in splanchnic tissues. | J Anim Physiol Anim Nutr (Berl) | 2010 Apr | 19175452 |
| Influence of sourdough prefermentation, of steam cooking suppression and ofdecreased sucrose content during wheat flakes processing on the plasma glucoseand insulin responses and satiety of healthy subjects. | J Am Coll Nutr | 2009 Feb | 19571157 |
Targets
- General Function:
- Atp binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTG2
- Uniprot ID:
- P63267
- Molecular Weight:
- 41876.495 Da
- Mechanism of Action:
- Arsenic binds to actin.
References
- Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
- General Function:
- Ubiquitin protein ligase binding
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBA1B
- Uniprot ID:
- P68363
- Molecular Weight:
- 50151.24 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Ubiquitin protein ligase binding
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBB
- Uniprot ID:
- P07437
- Molecular Weight:
- 49670.515 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural molecule activity
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBA1C
- Uniprot ID:
- Q9BQE3
- Molecular Weight:
- 49894.93 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBA3C
- Uniprot ID:
- Q13748
- Molecular Weight:
- 49959.145 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Gene Name:
- TUBA3E
- Uniprot ID:
- Q6PEY2
- Molecular Weight:
- 49858.135 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBA4A
- Uniprot ID:
- P68366
- Molecular Weight:
- 49923.995 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Specific Function:
- Gtp binding
- Gene Name:
- TUBA8
- Uniprot ID:
- Q9NY65
- Molecular Weight:
- 50093.12 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Gene Name:
- TUBB1
- Uniprot ID:
- Q9H4B7
- Molecular Weight:
- 50326.56 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Gene Name:
- TUBB2A
- Uniprot ID:
- Q13885
- Molecular Weight:
- 49906.67 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Gene Name:
- TUBB8
- Uniprot ID:
- Q3ZCM7
- Molecular Weight:
- 49775.655 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTA1
- Uniprot ID:
- P68133
- Molecular Weight:
- 42050.67 Da
- Mechanism of Action:
- Arsenic binds to actin.
References
- Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
- General Function:
- Protein kinase binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTA2
- Uniprot ID:
- P62736
- Molecular Weight:
- 42008.57 Da
- Mechanism of Action:
- Arsenic binds to actin.
References
- Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
- General Function:
- Dihydrolipoyllysine-residue acetyltransferase activity
- Specific Function:
- The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
- Gene Name:
- DLAT
- Uniprot ID:
- P10515
- Molecular Weight:
- 68996.03 Da
- Mechanism of Action:
- Arsenic disrupts ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress.
References
- Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
- General Function:
- Tat protein binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTB
- Uniprot ID:
- P60709
- Molecular Weight:
- 41736.37 Da
- Mechanism of Action:
- Arsenic binds to actin.
References
- Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
- General Function:
- Ubiquitin protein ligase binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTG1
- Uniprot ID:
- P63261
- Molecular Weight:
- 41792.48 Da
- Mechanism of Action:
- Arsenic binds to actin.
References
- Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
- General Function:
- Aspartic-type endopeptidase activity
- Specific Function:
- Acid protease active in intracellular protein breakdown. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease.
- Gene Name:
- CTSD
- Uniprot ID:
- P07339
- Molecular Weight:
- 44551.845 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.(Microbial infection) The membrane-associated isoform acts as an entry receptor for varicella-zoster virus (VZV).
- Gene Name:
- IDE
- Uniprot ID:
- P14735
- Molecular Weight:
- 117967.49 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- Specific Function:
- Binds IGF-I and IGF-II with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion.
- Gene Name:
- IGFBP7
- Uniprot ID:
- Q16270
- Molecular Weight:
- 29130.055 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Calcium ion binding
- Specific Function:
- Acts together with cubilin to mediate HDL endocytosis (By similarity). May participate in regulation of parathyroid-hormone and para-thyroid-hormone-related protein release.
- Gene Name:
- LRP2
- Uniprot ID:
- P98164
- Molecular Weight:
- 521952.77 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Serine-type endopeptidase activity
- Specific Function:
- Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin, insulin and AGRP.
- Gene Name:
- PCSK1
- Uniprot ID:
- P29120
- Molecular Weight:
- 84150.92 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Serine-type endopeptidase activity
- Specific Function:
- Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Responsible for the release of glucagon from proglucagon in pancreatic A cells.
- Gene Name:
- PCSK2
- Uniprot ID:
- P16519
- Molecular Weight:
- 70564.735 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- Uniprot ID:
- A6NKZ8
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- Uniprot ID:
- Q99867
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Ubiquitin protein ligase binding
- Specific Function:
- Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity.
- Gene Name:
- RB1
- Uniprot ID:
- P06400
- Molecular Weight:
- 106158.335 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Modulates exocytosis of dense-core granules and secretion of hormones in the pancreas and the pituitary. Interacts with vesicles containing negatively charged phospholipids in a Ca(2+)-independent manner (By similarity).
- Gene Name:
- SYTL4
- Uniprot ID:
- Q96C24
- Molecular Weight:
- 76022.99 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Myosin binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTC1
- Uniprot ID:
- P68032
- Molecular Weight:
- 42018.6 Da
- Mechanism of Action:
- Arsenic binds to actin.
References
- Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Involved in DNA excision repair. Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Required for UV-induced CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation.
- Gene Name:
- XPA
- Uniprot ID:
- P23025
- Molecular Weight:
- 31367.71 Da
- Mechanism of Action:
- Arsenic binding of XPA is believed to induce carcinogenesis by affecting DNA repair.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Gene Name:
- TUBA4B
- Uniprot ID:
- Q9H853
- Molecular Weight:
- 27551.01 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
- Gene Name:
- NR3C1
- Uniprot ID:
- P04150
- Molecular Weight:
- 85658.57 Da
- Mechanism of Action:
- Arsenic binds to the glucocorticoid receptor.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Nadp binding
- Specific Function:
- Maintains high levels of reduced glutathione in the cytosol.
- Gene Name:
- GSR
- Uniprot ID:
- P00390
- Molecular Weight:
- 56256.565 Da
- Mechanism of Action:
- Arsenic binds glutathione reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity.
References
- ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). : http://www.atsdr.cdc.gov/toxprofiles/tp2.html
- General Function:
- Oxygen transporter activity
- Specific Function:
- Involved in oxygen transport from the lung to the various peripheral tissues.
- Gene Name:
- HBA1
- Uniprot ID:
- P69905
- Molecular Weight:
- 15257.405 Da
- Mechanism of Action:
- Arsenic binds to hemoglobin.
References
- Naranmandura H, Suzuki KT: Identification of the major arsenic-binding protein in rat plasma as the ternary dimethylarsinous-hemoglobin-haptoglobin complex. Chem Res Toxicol. 2008 Mar;21(3):678-85. doi: 10.1021/tx700383g. Epub 2008 Feb 2. [18247522 ]
- General Function:
- Oxygen transporter activity
- Specific Function:
- Involved in oxygen transport from the lung to the various peripheral tissues.LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.Spinorphin: functions as an endogenous inhibitor of enkephalin-degrading enzymes such as DPP3, and as a selective antagonist of the P2RX3 receptor which is involved in pain signaling, these properties implicate it as a regulator of pain and inflammation.
- Gene Name:
- HBB
- Uniprot ID:
- P68871
- Molecular Weight:
- 15998.34 Da
- Mechanism of Action:
- Arsenic binds to hemoglobin.
References
- Naranmandura H, Suzuki KT: Identification of the major arsenic-binding protein in rat plasma as the ternary dimethylarsinous-hemoglobin-haptoglobin complex. Chem Res Toxicol. 2008 Mar;21(3):678-85. doi: 10.1021/tx700383g. Epub 2008 Feb 2. [18247522 ]
- General Function:
- Transcription factor binding
- Specific Function:
- Acts as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome.
- Gene Name:
- KEAP1
- Uniprot ID:
- Q14145
- Molecular Weight:
- 69665.765 Da
- Mechanism of Action:
- Arsenic binds to kelch-like ECH-associated protein 1.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites.
- Gene Name:
- PARP1
- Uniprot ID:
- P09874
- Molecular Weight:
- 113082.945 Da
- Mechanism of Action:
- Arsenic binding of PARP-1 is believed to induce carcinogenesis by affecting DNA repair.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Pyruvate dehydrogenase (acetyl-transferring) activity
- Specific Function:
- The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
- Gene Name:
- PDHA2
- Uniprot ID:
- P29803
- Molecular Weight:
- 42932.855 Da
- Mechanism of Action:
- Arsenic disrupts ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress.
References
- Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
- General Function:
- Pyruvate dehydrogenase activity
- Specific Function:
- The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
- Gene Name:
- PDHB
- Uniprot ID:
- P11177
- Molecular Weight:
- 39233.1 Da
- Mechanism of Action:
- Arsenic disrupts ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress.
References
- Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
- General Function:
- Thioredoxin-disulfide reductase activity
- Specific Function:
- Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.
- Gene Name:
- TXNRD1
- Uniprot ID:
- Q16881
- Molecular Weight:
- 70905.58 Da
- Mechanism of Action:
- Arsenic binds thioredoxin reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity.
References
- ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). : http://www.atsdr.cdc.gov/toxprofiles/tp2.html
- General Function:
- Thioredoxin-disulfide reductase activity
- Specific Function:
- Maintains thioredoxin in a reduced state. Implicated in the defenses against oxidative stress. May play a role in redox-regulated cell signaling.
- Gene Name:
- TXNRD2
- Uniprot ID:
- Q9NNW7
- Molecular Weight:
- 56506.275 Da
- Mechanism of Action:
- Arsenic binds thioredoxin reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity.
References
- ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). : http://www.atsdr.cdc.gov/toxprofiles/tp2.html
- General Function:
- Thioredoxin-disulfide reductase activity
- Specific Function:
- Displays thioredoxin reductase, glutaredoxin and glutathione reductase activities. Catalyzes disulfide bond isomerization. Promotes disulfide bond formation between GPX4 and various sperm proteins and may play a role in sperm maturation by promoting formation of sperm structural components (By similarity).
- Gene Name:
- TXNRD3
- Uniprot ID:
- Q86VQ6
- Molecular Weight:
- 70682.52 Da
- Mechanism of Action:
- Arsenic binds thioredoxin reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity.
References
- ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). : http://www.atsdr.cdc.gov/toxprofiles/tp2.html
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Gene Name:
- TUBAL3
- Uniprot ID:
- A6NHL2
- Molecular Weight:
- 49908.305 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Specific Function:
- Gtp binding
- Gene Name:
- TUBA1A
- Uniprot ID:
- Q71U36
- Molecular Weight:
- 50135.25 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. TUBB3 plays a critical role in proper axon guidance and mantainance.
- Gene Name:
- TUBB3
- Uniprot ID:
- Q13509
- Molecular Weight:
- 50432.355 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBB4A
- Uniprot ID:
- P04350
- Molecular Weight:
- 49585.475 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Unfolded protein binding
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBB4B
- Uniprot ID:
- P68371
- Molecular Weight:
- 49830.72 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Gene Name:
- TUBB6
- Uniprot ID:
- Q9BUF5
- Molecular Weight:
- 49856.785 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Uniprot ID:
- A6NNZ2
- Molecular Weight:
- 49572.265 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Removes residual C-terminal Arg or Lys remaining after initial endoprotease cleavage during prohormone processing. Processes proinsulin.
- Gene Name:
- CPE
- Uniprot ID:
- P16870
- Molecular Weight:
- 53150.185 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Receptor signaling protein tyrosine kinase activity
- Specific Function:
- Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.
- Gene Name:
- INSR
- Uniprot ID:
- P06213
- Molecular Weight:
- 156331.465 Da
- Mechanism of Action:
- Insulin binds to its receptor, which then starts many protein activation cascades .
References
- Sacco A, Morcavallo A, Pandini G, Vigneri R, Belfiore A: Differential signaling activation by insulin and insulin-like growth factors I and II upon binding to insulin receptor isoform A. Endocrinology. 2009 Aug;150(8):3594-602. doi: 10.1210/en.2009-0377. Epub 2009 May 14. [19443570 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity). TUBB2B is implicated in neuronal migration.
- Gene Name:
- TUBB2B
- Uniprot ID:
- Q9BVA1
- Molecular Weight:
- 49952.76 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Protein tyrosine kinase activity
- Specific Function:
- Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.
- Gene Name:
- IGF1R
- Uniprot ID:
- P08069
- Molecular Weight:
- 154791.73 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Notch binding
- Specific Function:
- Immediate-early protein playing a role in various cellular processes including proliferation, adhesion, migration, differentiation and survival (PubMed:15181016, PubMed:15611078, PubMed:12695522, PubMed:21344378, PubMed:12050162). Acts by binding to integrins or membrane receptors such as NOTCH1 (PubMed:12695522, PubMed:21344378, PubMed:15611078). Essential regulator of hematopoietic stem and progenitor cell function (PubMed:17463287). Inhibits myogenic differentiation through the activation of Notch-signaling pathway (PubMed:12050162). Inhibits vascular smooth muscle cells proliferation by increasing expression of cell-cycle regulators such as CDKN2B or CDKN1A independently of TGFB1 signaling (PubMed:20139355). Ligand of integrins ITGAV:ITGB3 and ITGA5:ITGB1, acts directly upon endothelial cells to stimulate pro-angiogenic activities and induces angiogenesis. In endothelial cells, supports cell adhesion, induces directed cell migration (chemotaxis) and promotes cell survival (PubMed:12695522). Plays also a role in cutaneous wound healing acting as integrin receptor ligand. Supports skin fibroblast adhesion through ITGA5:ITGB1 and ITGA6:ITGB1 and induces fibroblast chemotaxis through ITGAV:ITGB5. Seems to enhance bFGF-induced DNA synthesis in fibroblasts (PubMed:15611078). Involved in bone regeneration as a negative regulator (By similarity). Enhances the articular chondrocytic phenotype, whereas it repressed the one representing endochondral ossification (PubMed:21871891). Impairs pancreatic beta-cell function, inhibits beta-cell proliferation and insulin secretion (By similarity). Plays a role as negative regulator of endothelial pro-inflammatory activation reducing monocyte adhesion, its anti-inflammatory effects occur secondary to the inhibition of NF-kappaB signaling pathway (PubMed:21063504). Contributes to the control and coordination of inflammatory processes in atherosclerosis (By similarity). Attenuates inflammatory pain through regulation of IL1B- and TNF-induced MMP9, MMP2 and CCL2 expression. Inhibits MMP9 expression through ITGB1 engagement (PubMed:21871891).
- Gene Name:
- NOV
- Uniprot ID:
- P48745
- Molecular Weight:
- 39161.82 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Zinc ion binding
- Specific Function:
- 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. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 Da
- Mechanism of Action:
- Arsenic binds to the estrogen receptor.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Serine-type endopeptidase activity
- Specific Function:
- As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an Antimicrobial; Antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidely cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway.Uncleaved haptoglogin, also known as zonulin, plays a role in intestinal permeability, allowing intercellular tight junction disassembly, and controlling the equilibrium between tolerance and immunity to non-self antigens.
- Gene Name:
- HP
- Uniprot ID:
- P00738
- Molecular Weight:
- 45205.065 Da
- Mechanism of Action:
- Arsenic binds to haptoglobin.
References
- Naranmandura H, Suzuki KT: Identification of the major arsenic-binding protein in rat plasma as the ternary dimethylarsinous-hemoglobin-haptoglobin complex. Chem Res Toxicol. 2008 Mar;21(3):678-85. doi: 10.1021/tx700383g. Epub 2008 Feb 2. [18247522 ]
- General Function:
- Pyruvate dehydrogenase activity
- Specific Function:
- The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
- Gene Name:
- PDHA1
- Uniprot ID:
- P08559
- Molecular Weight:
- 43295.255 Da
- Mechanism of Action:
- Arsenic disrupts ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress.
References
- Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
- General Function:
- Transferase activity, transferring acyl groups
- Specific Function:
- Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex.
- Gene Name:
- PDHX
- Uniprot ID:
- O00330
- Molecular Weight:
- 54121.76 Da
- Mechanism of Action:
- Arsenic disrupts ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress.
References
- Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.