Zinc
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Basic Info
| Common Name | Zinc(F03327) |
| 2D Structure | |
| Description | A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with anemia, short stature, hypogonadism, impaired wound healing, and geophagia. It is known by the symbol Zn. |
| FRCD ID | F03327 |
| CAS Number | 7440-66-6 |
| PubChem CID | 23994 |
| Formula | Zn |
| IUPAC Name | zinc |
| InChI Key | HCHKCACWOHOZIP-UHFFFAOYSA-N |
| InChI | InChI=1S/Zn |
| Canonical SMILES | [Zn] |
| Isomeric SMILES | [Zn] |
| Wikipedia | Zinc |
| Synonyms |
Rheinzink
Zinc
7440-66-6
Zinc dust
cinc
Merrillite
Jasad
Blue powder
Granular zinc
Zinc powder
|
| Classifies |
Pollutant
Metal
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Inorganic compounds |
| Superclass | Homogeneous metal compounds |
| Class | Homogeneous transition metal compounds |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Homogeneous transition metal compounds |
| Alternative Parents | |
| Molecular Framework | Not available |
| Substituents | Homogeneous transition metal |
| Description | This compound belongs to the class of inorganic compounds known as homogeneous transition metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a transition metal atom. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 65.38 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 0 |
| Rotatable Bond Count | 0 |
| Complexity | 0 |
| Monoisotopic Mass | 63.929 |
| Exact Mass | 63.929 |
| Formal Charge | 0 |
| Heavy Atom Count | 1 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9733 |
| Human Intestinal Absorption | HIA+ | 0.9838 |
| Caco-2 Permeability | Caco2+ | 0.7354 |
| P-glycoprotein Substrate | Non-substrate | 0.8810 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9787 |
| Non-inhibitor | 0.9858 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9110 |
| Distribution | ||
| Subcellular localization | Lysosome | 0.5856 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8466 |
| CYP450 2D6 Substrate | Non-substrate | 0.8259 |
| CYP450 3A4 Substrate | Non-substrate | 0.8158 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8584 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9241 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9638 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9452 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9834 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8820 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9547 |
| Non-inhibitor | 0.9746 | |
| AMES Toxicity | Non AMES toxic | 0.9633 |
| Carcinogens | Carcinogens | 0.6621 |
| Fish Toxicity | Low FHMT | 0.6181 |
| Tetrahymena Pyriformis Toxicity | Low TPT | 0.6631 |
| Honey Bee Toxicity | High HBT | 0.8277 |
| Biodegradation | Ready biodegradable | 0.7326 |
| Acute Oral Toxicity | III | 0.5846 |
| Carcinogenicity (Three-class) | Warning | 0.4769 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -1.0958 | LogS |
| Caco-2 Permeability | 1.6017 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.0135 | LD50, mol/kg |
| Fish Toxicity | 1.5413 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | -0.7156 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Effects of aged ZnO NPs and soil type on Zn availability, accumulation and toxicity to pea and beet in a greenhouse experiment. | Ecotoxicol Environ Saf | 2018 Sep 30 | 29807295 |
| Determination of macro, micro and trace elements in citrus fruits by inductively coupled plasma-optical emission spectrometry (ICP-OES), ICP-mass spectrometry and direct mercury analyzer. | J Sci Food Agric | 2018 Sep 27 | 30264403 |
| Identification of nicotianamine synthase genes in Triticum monococcum and theirexpression under different Fe and Zn concentrations. | Gene | 2018 Sep 25 | 29885462 |
| Evaluation of chemical extractants to assess metals phytoavailability in Brazilian municipal solid waste composts. | Environ Pollut | 2018 Sep 21 | 30267920 |
| Unconventional application of gold nanoclusters/Zn-MOF composite for fluorescenceturn-on sensitive detection of zinc ion. | Anal Chim Acta | 2018 Sep 18 | 29776540 |
| Long term insight into biodiversity of a smelter wasteland reclaimed with biosolids and by-product lime. | Sci Total Environ | 2018 Sep 15 | 29913567 |
| Concentration of heavy metals in seafood (fishes, shrimp, lobster and crabs) and human health assessment in Saint Martin Island, Bangladesh. | Ecotoxicol Environ Saf | 2018 Sep 15 | 29747150 |
| Source identification and spatial distribution of arsenic and heavy metals inagricultural soil around Hunan industrial estate by positive matrix factorizationmodel, principle components analysis and geo statistical analysis. | Ecotoxicol Environ Saf | 2018 Sep 15 | 29778047 |
| Food influence on lead relative bioavailability in contaminated soils: Mechanismsand health implications. | J Hazard Mater | 2018 Sep 15 | 30014932 |
| Biomass decaying and elemental release of aquatic macrophyte detritus inwaterways of the Indian River Lagoon basin, South Florida, USA. | Sci Total Environ | 2018 Sep 1 | 29710610 |
| A new perspective of using sequential extraction: To predict the deficiency oftrace elements during anaerobic digestion. | Water Res | 2018 Sep 1 | 29747126 |
| Development, validation and application of an ICP-MS/MS method to quantify minerals and (ultra-)trace elements in human serum. | J Trace Elem Med Biol | 2018 Sep | 29895367 |
| Arbuscular mycorrhizal fungi increase grain zinc concentration and modify the expression of root ZIP transporter genes in a modern barley (Hordeum vulgare) cultivar. | Plant Sci | 2018 Sep | 30080600 |
| Validation of a dilute and shoot method for quantification of 12 elements byinductively coupled plasma tandem mass spectrometry in human milk and in cow milkpreparations. | J Trace Elem Med Biol | 2018 Sep | 29895368 |
| Antioxidant responses of edible and model plant species subjected to subtoxiczinc concentrations. | J Trace Elem Med Biol | 2018 Sep | 29477361 |
| Changes in zinc status and zinc transporters expression in whole blood ofpatients with Systemic Inflammatory Response Syndrome (SIRS). | J Trace Elem Med Biol | 2018 Sep | 29199035 |
| Rice flakes produced from commercial wild rice: Chemical compositions, vitamin B compounds, mineral and trace element contents and their dietary intake evaluation. | Food Chem | 2018 Oct 30 | 29853391 |
| Phytotoxicity of polymetallic mine wastes from southern Tuscany and Saxony. | Ecotoxicol Environ Saf | 2018 Oct 30 | 30015197 |
| Organic cattle products: Authenticating production origin by analysis of serummineral content. | Food Chem | 2018 Oct 30 | 29853367 |
| Amending potential of organic and industrial by-products applied to heavymetal-rich mining soils. | Ecotoxicol Environ Saf | 2018 Oct 30 | 30031319 |
Targets
- General Function:
- Zinc ion binding
- Specific Function:
- Has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination.
- Gene Name:
- MID1
- Uniprot ID:
- O15344
- Molecular Weight:
- 75249.94 Da
References
- Massiah MA, Simmons BN, Short KM, Cox TC: Solution structure of the RBCC/TRIM B-box1 domain of human MID1: B-box with a RING. J Mol Biol. 2006 Apr 28;358(2):532-45. Epub 2006 Feb 20. [16529770 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Induces CD27-mediated apoptosis. Inhibits BCL2L1 isoform Bcl-x(L) anti-apoptotic activity. Inhibits activation of NF-kappa-B and promotes T-cell receptor-mediated apoptosis.
- Gene Name:
- SIVA1
- Uniprot ID:
- O15304
- Molecular Weight:
- 18694.45 Da
References
- Nestler M, Martin U, Hortschansky P, Saluz HP, Henke A, Munder T: The zinc containing pro-apoptotic protein siva interacts with the peroxisomal membrane protein pmp22. Mol Cell Biochem. 2006 Jul;287(1-2):147-55. Epub 2006 May 9. [16683188 ]
- General Function:
- Peptide binding
- Specific Function:
- This is a receptor for bradykinin. Could be a factor in chronic pain and inflammation.
- Gene Name:
- BDKRB1
- Uniprot ID:
- P46663
- Molecular Weight:
- 40494.29 Da
References
- Ignjatovic T, Tan F, Brovkovych V, Skidgel RA, Erdos EG: Novel mode of action of angiotensin I converting enzyme inhibitors: direct activation of bradykinin B1 receptor. J Biol Chem. 2002 May 10;277(19):16847-52. Epub 2002 Mar 5. [11880373 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.
- Gene Name:
- ADRB2
- Uniprot ID:
- P07550
- Molecular Weight:
- 46458.32 Da
References
- Elling CE, Frimurer TM, Gerlach LO, Jorgensen R, Holst B, Schwartz TW: Metal ion site engineering indicates a global toggle switch model for seven-transmembrane receptor activation. J Biol Chem. 2006 Jun 23;281(25):17337-46. Epub 2006 Mar 27. [16567806 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Delivers copper to copper zinc superoxide dismutase (SOD1).
- Gene Name:
- CCS
- Uniprot ID:
- O14618
- Molecular Weight:
- 29040.445 Da
References
- Stasser JP, Eisses JF, Barry AN, Kaplan JH, Blackburn NJ: Cysteine-to-serine mutants of the human copper chaperone for superoxide dismutase reveal a copper cluster at a domain III dimer interface. Biochemistry. 2005 Mar 8;44(9):3143-52. [15736924 ]
- 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
References
- Blessing H, Kraus S, Heindl P, Bal W, Hartwig A: Interaction of selenium compounds with zinc finger proteins involved in DNA repair. Eur J Biochem. 2004 Aug;271(15):3190-9. [15265038 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Binds heavy metals. Contains three zinc and three copper atoms per polypeptide chain and only a negligible amount of cadmium. Inhibits survival and neurite formation of cortical neurons in vitro.
- Gene Name:
- MT3
- Uniprot ID:
- P25713
- Molecular Weight:
- 6926.855 Da
References
- Palumaa P, Tammiste I, Kruusel K, Kangur L, Jornvall H, Sillard R: Metal binding of metallothionein-3 versus metallothionein-2: lower affinity and higher plasticity. Biochim Biophys Acta. 2005 Mar 14;1747(2):205-11. Epub 2004 Dec 19. [15698955 ]
- Specific Function:
- Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
- Gene Name:
- FBF1
- Uniprot ID:
- Q8TES7
- Molecular Weight:
- 125445.19 Da
References
- Enyedy EA, Horvath L, Gajda-Schrantz K, Galbacs G, Kiss T: An in vitro study of interactions between insulin-mimetic zinc(II) complexes and selected plasma components. J Inorg Biochem. 2006 Dec;100(12):1936-45. Epub 2006 Aug 30. [17034863 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer.
- Gene Name:
- HDAC4
- Uniprot ID:
- P56524
- Molecular Weight:
- 119038.875 Da
References
- Bhuiyan MP, Kato T, Okauchi T, Nishino N, Maeda S, Nishino TG, Yoshida M: Chlamydocin analogs bearing carbonyl group as possible ligand toward zinc atom in histone deacetylases. Bioorg Med Chem. 2006 May 15;14(10):3438-46. Epub 2006 Jan 24. [16439135 ]
- General Function:
- Transcription factor binding
- Specific Function:
- Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility.
- Gene Name:
- HDAC8
- Uniprot ID:
- Q9BY41
- Molecular Weight:
- 41757.29 Da
References
- Gantt SL, Gattis SG, Fierke CA: Catalytic activity and inhibition of human histone deacetylase 8 is dependent on the identity of the active site metal ion. Biochemistry. 2006 May 16;45(19):6170-8. [16681389 ]
- General Function:
- Protease binding
- Specific Function:
- Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.
- Gene Name:
- INS
- Uniprot ID:
- P01308
- Molecular Weight:
- 11980.795 Da
References
- Huus K, Havelund S, Olsen HB, van de Weert M, Frokjaer S: Chemical and thermal stability of insulin: effects of zinc and ligand binding to the insulin zinc-hexamer. Pharm Res. 2006 Nov;23(11):2611-20. Epub 2006 Sep 13. [16969698 ]
- General Function:
- Interleukin-3 receptor binding
- Specific Function:
- Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages.This CSF induces granulocytes, macrophages, mast cells, stem cells, erythroid cells, eosinophils and megakaryocytes.
- Gene Name:
- IL3
- Uniprot ID:
- P08700
- Molecular Weight:
- 17232.905 Da
References
- Smit V, van Veelen PA, Tjaden UR, van der Greef J, Haaijman JJ: Human interleukin-3 contains a discontinuous zinc binding domain. Biochem Biophys Res Commun. 1992 Sep 16;187(2):859-66. [1530641 ]
- General Function:
- Zinc ion binding
- Specific Function:
- May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.
- Gene Name:
- MMP9
- Uniprot ID:
- P14780
- Molecular Weight:
- 78457.51 Da
References
- Martens E, Leyssen A, Van Aelst I, Fiten P, Piccard H, Hu J, Descamps FJ, Van den Steen PE, Proost P, Van Damme J, Liuzzi GM, Riccio P, Polverini E, Opdenakker G: A monoclonal antibody inhibits gelatinase B/MMP-9 by selective binding to part of the catalytic domain and not to the fibronectin or zinc binding domains. Biochim Biophys Acta. 2007 Feb;1770(2):178-86. Epub 2006 Oct 26. [17137715 ]
- General Function:
- Zinc ion binding
- Specific Function:
- May play a scavenger role by digesting biologically active peptidoglycan (PGN) into biologically inactive fragments. Has no direct bacteriolytic activity.
- Gene Name:
- PGLYRP2
- Uniprot ID:
- Q96PD5
- Molecular Weight:
- 62216.365 Da
References
- Wang ZM, Li X, Cocklin RR, Wang M, Wang M, Fukase K, Inamura S, Kusumoto S, Gupta D, Dziarski R: Human peptidoglycan recognition protein-L is an N-acetylmuramoyl-L-alanine amidase. J Biol Chem. 2003 Dec 5;278(49):49044-52. Epub 2003 Sep 23. [14506276 ]
- General Function:
- Protein dimerization activity
- Specific Function:
- Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. May mediate Ca(2+)-regulated signals along the death pathway (By similarity). Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity. May inhibit KDR/VEGFR2-dependent angiogenesis; the function involves inhibition of VEGF-induced phosphoprylation of the Akt signaling pathway. Seems to play a role in the regulation of the distribution and function of MCOLN1 in the endosomal pathway. Isoform 2 has a lower Ca(2+) affinity than isoform 1. Isoform 1 and, to a lesser extend, isoform 2, can stabilize SHISA5.
- Gene Name:
- PDCD6
- Uniprot ID:
- O75340
- Molecular Weight:
- 21868.32 Da
References
- Suzuki H, Kawasaki M, Kakiuchi T, Shibata H, Wakatsuki S, Maki M: Crystallization and X-ray diffraction analysis of N-terminally truncated human ALG-2. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Nov 1;64(Pt 11):974-7. doi: 10.1107/S1744309108030297. Epub 2008 Oct 31. [18997320 ]
- General Function:
- Identical protein binding
- Specific Function:
- May function as calcium sensor and modulator, contributing to cellular calcium signaling. May function by interacting with other proteins, such as TPR-containing proteins, and indirectly play a role in many physiological processes. May also play a role in suppressing tumor cell growth.
- Gene Name:
- S100A2
- Uniprot ID:
- P29034
- Molecular Weight:
- 11116.695 Da
References
- Koch M, Bhattacharya S, Kehl T, Gimona M, Vasak M, Chazin W, Heizmann CW, Kroneck PM, Fritz G: Implications on zinc binding to S100A2. Biochim Biophys Acta. 2007 Mar;1773(3):457-70. Epub 2006 Dec 19. [17239974 ]
- General Function:
- Structural molecule activity
- Specific Function:
- Predominant protein in semen. It participates in the formation of a gel matrix entrapping the accessory gland secretions and ejaculated spermatozoa. Fragments of semenogelin and/or fragments of the related proteins may contribute to the activation of progressive sperm movements as the gel-forming proteins are fragmented by KLK3/PSA.Alpha-inhibin-92 and alpha-inhibin-31, derived from the proteolytic degradation of semenogelin, inhibit the secretion of pituitary follicle-stimulating hormone.
- Gene Name:
- SEMG1
- Uniprot ID:
- P04279
- Molecular Weight:
- 52130.885 Da
References
- Jonsson M, Lundwall A, Linse S, Frohm B, Malm J: Truncated semenogelin I binds zinc and is cleaved by prostate-specific antigen. J Androl. 2006 Jul-Aug;27(4):542-7. Epub 2006 Apr 1. [16582407 ]
- General Function:
- Transferrin receptor binding
- Specific Function:
- Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation.
- Gene Name:
- TF
- Uniprot ID:
- P02787
- Molecular Weight:
- 77063.195 Da
References
- Enyedy EA, Horvath L, Gajda-Schrantz K, Galbacs G, Kiss T: An in vitro study of interactions between insulin-mimetic zinc(II) complexes and selected plasma components. J Inorg Biochem. 2006 Dec;100(12):1936-45. Epub 2006 Aug 30. [17034863 ]
- General Function:
- Metal ion binding
- Specific Function:
- Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate. NAA occurs in high concentration in brain and its hydrolysis NAA plays a significant part in the maintenance of intact white matter. In other tissues it act as a scavenger of NAA from body fluids.
- Gene Name:
- ASPA
- Uniprot ID:
- P45381
- Molecular Weight:
- 35734.79 Da
References
- Herga S, Berrin JG, Perrier J, Puigserver A, Giardina T: Identification of the zinc binding ligands and the catalytic residue in human aspartoacylase, an enzyme involved in Canavan disease. FEBS Lett. 2006 Oct 30;580(25):5899-904. Epub 2006 Oct 2. [17027983 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
- Gene Name:
- MT1A
- Uniprot ID:
- P04731
- Molecular Weight:
- 6120.19 Da
References
- Sutherland DE, Willans MJ, Stillman MJ: Supermetalation of the beta domain of human metallothionein 1a. Biochemistry. 2010 May 4;49(17):3593-601. doi: 10.1021/bi1003537. [20329713 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
- Gene Name:
- MT2A
- Uniprot ID:
- P02795
- Molecular Weight:
- 6042.05 Da
References
- Palumaa P, Tammiste I, Kruusel K, Kangur L, Jornvall H, Sillard R: Metal binding of metallothionein-3 versus metallothionein-2: lower affinity and higher plasticity. Biochim Biophys Acta. 2005 Mar 14;1747(2):205-11. Epub 2004 Dec 19. [15698955 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
- Gene Name:
- SOD1
- Uniprot ID:
- P00441
- Molecular Weight:
- 15935.685 Da
- Mechanism of Action:
- Unbalanced levels of copper and zinc binding to Cu,Zn-superoxide dismutase has been linked to amyotrophic lateral sclerosis (ALS).
References
- Vonk WI, Klomp LW: Role of transition metals in the pathogenesis of amyotrophic lateral sclerosis. Biochem Soc Trans. 2008 Dec;36(Pt 6):1322-8. doi: 10.1042/BST0361322. [19021549 ]
- General Function:
- Transition metal ion binding
- Specific Function:
- Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).
- Gene Name:
- APP
- Uniprot ID:
- P05067
- Molecular Weight:
- 86942.715 Da
References
- Syme CD, Viles JH: Solution 1H NMR investigation of Zn2+ and Cd2+ binding to amyloid-beta peptide (Abeta) of Alzheimer's disease. Biochim Biophys Acta. 2006 Feb;1764(2):246-56. Epub 2005 Oct 14. [16266835 ]
- 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
References
- Payne JC, Rous BW, Tenderholt AL, Godwin HA: Spectroscopic determination of the binding affinity of zinc to the DNA-binding domains of nuclear hormone receptors. Biochemistry. 2003 Dec 9;42(48):14214-24. [14640689 ]
- General Function:
- Transcription regulatory region sequence-specific dna binding
- Specific Function:
- Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation.
- Gene Name:
- HDAC1
- Uniprot ID:
- Q13547
- Molecular Weight:
- 55102.615 Da
References
- Bhuiyan MP, Kato T, Okauchi T, Nishino N, Maeda S, Nishino TG, Yoshida M: Chlamydocin analogs bearing carbonyl group as possible ligand toward zinc atom in histone deacetylases. Bioorg Med Chem. 2006 May 15;14(10):3438-46. Epub 2006 Jan 24. [16439135 ]
- General Function:
- Methyltransferase activity
- Specific Function:
- Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated guanine in DNA by stoichiometrically transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.
- Gene Name:
- MGMT
- Uniprot ID:
- P16455
- Molecular Weight:
- 21645.83 Da
References
- Guengerich FP, Fang Q, Liu L, Hachey DL, Pegg AE: O6-alkylguanine-DNA alkyltransferase: low pKa and high reactivity of cysteine 145. Biochemistry. 2003 Sep 23;42(37):10965-70. [12974631 ]
- 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
References
- Mendes F, Groessl M, Nazarov AA, Tsybin YO, Sava G, Santos I, Dyson PJ, Casini A: Metal-based inhibition of poly(ADP-ribose) polymerase--the guardian angel of DNA. J Med Chem. 2011 Apr 14;54(7):2196-206. doi: 10.1021/jm2000135. Epub 2011 Mar 3. [21370912 ]