Zinc (T3D0074)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (28)XML
Targets (28)
Record Information
Version2.0
Creation Date2009-03-06 18:58:02 UTC
Update Date2014-12-24 20:21:03 UTC
Accession NumberT3D0074
Identification
Common NameZinc
ClassSmall Molecule
DescriptionA 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.
Compound Type
  • Drug
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Inorganic Compound
  • Metabolite
  • Metal
  • Natural Compound
  • Pollutant
  • Trace Element
  • Zinc Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Zinc (II) cation
Zinc ion
Zinc ion (Zn2+)
Zinc(2+)
Zinc(2+) ion
Zinc(II)
Zn
Zn(2+)
Zn2+
Chemical FormulaZn
Average Molecular Mass65.408 g/mol
Monoisotopic Mass63.928 g/mol
CAS Registry Number7440-66-6
IUPAC Namezinc(2+) ion
Traditional Namezinc(2+) ion
SMILES[Zn++]
InChI IdentifierInChI=1S/Zn/q+2
InChI KeyInChIKey=PTFCDOFLOPIGGS-UHFFFAOYSA-N
Chemical Taxonomy
Description 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.
KingdomInorganic compounds
Super ClassHomogeneous metal compounds
ClassHomogeneous transition metal compounds
Sub ClassNot Available
Direct ParentHomogeneous transition metal compounds
Alternative ParentsNot Available
Substituents
  • Homogeneous transition metal
Molecular FrameworkNot Available
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceBluish-white metallic solid.
Experimental Properties
PropertyValue
Melting Point419.5°C
Boiling Point908°C
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
logP0.16ChemAxon
pKa (Strongest Acidic)3.09ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity0 m³·mol⁻¹ChemAxon
Polarizability1.78 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-9000000000-0cd08967c771fb6453292015-09-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-9000000000-0cd08967c771fb6453292015-09-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03di-9000000000-0cd08967c771fb6453292015-09-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-9000000000-29976d3ebd17b2d11a4b2015-09-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-9000000000-29976d3ebd17b2d11a4b2015-09-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03di-9000000000-29976d3ebd17b2d11a4b2015-09-15View Spectrum
Toxicity Profile
Route of ExposureOral (4) ; inhalation (4) ; dermal (113)
Mechanism of ToxicityExcessive zinc intake alters copper and iron absorption, most likely through competitive binding in intestinal mucosal cells. Stomach acid dissolves metallic zinc, producing zinc chloride, which is a corrosive product damaging the stomach lining. Metal fume fever is thought to be an immune response to inhaled zinc. (3, 4, 1)
MetabolismZinc enters the body through the lungs, skin, and gastrointestinal tract. Intestinal absorption of zinc is controlled by zinc carrier protein CRIP and metallothioneins. Zinc is widely distributed in tissues and tissues fluids, and concentrated in the liver, gastrointestinal tract, kidney, skin, lung, brain, heart, and pancreas. Zinc binds to carbonic anhydrase in erythrocytes, and to albumin, α2-macroglobulin, and amino acids in the the plasma. Albumin and amino acid bound zinc can diffuse across tissue membranes. Zinc is excreted in the urine and faeces. (4)
Toxicity ValuesLD50: 630 mg/kg (Oral, Rat) (2)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesZinc has many commercial uses as coatings to prevent rust, in dry cell batteries, and can be mixed with other metals to produce alloys such as brass and bronze. Zinc compounds are widely used in industry to make paint, rubber, dyes, wood preservatives, and ointments. (4)
Minimum Risk LevelIntermediate Oral: 0.3 mg/kg/day (6) Chronic Oral: 0.3 mg/kg/day (6)
Health EffectsChronic exposure to zinc causes anemia, atazia, lethargy, and decreases the level of HDL (good) cholesterol in the body. It is also believed to cause pancreatic and reproductive damages. Unbalanced levels of copper and zinc binding to Cu,Zn-superoxide dismutase have been linked to amyotrophic lateral sclerosis (ALS). (4)
SymptomsIngestion of large doses of zinc causes stomach cramps, nausea, and vomiting. Acute inhalation of large amounts of zinc causes metal fume fever, which is characterized by chills, fever, headache, weakness, dryness of the nose and throat, chest pain, and coughing. Dermal contact with zinc results in skin irritation. (4)
TreatmentZinc poisoning is treated symptomatically, often by administering fluids such as water or milk, or with gastric lavage. (4)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01593
HMDB IDHMDB15532
PubChem Compound ID23994
ChEMBL IDNot Available
ChemSpider ID22430
KEGG IDC00038
UniProt IDNot Available
OMIM ID103600 , 110900 , 113705 , 121300 , 125270 , 137164 , 138750 , 150330 , 163729 , 165240 , 180200 , 184757 , 188840 , 190080 , 191170 , 191290 , 194470 , 300414 , 300473 , 314998 , 600140 , 600310 , 600871 , 600993 , 601487 , 601757 , 601758 , 602432 , 602575 , 602630 , 603693 , 604386 , 604485 , 606829 , 607035 , 607102 , 607818 , 608072 , 608118
ChEBI ID30185
BioCyc IDZN%2b2
CTD IDD015032
Stitch IDZinc
PDB IDNot Available
ACToR ID6568
Wikipedia LinkZinc
References
Synthesis Reference

Robert Nicaise, “Production of zinc powder for electrochemical batteries.” U.S. Patent US4104188, issued 1877.

MSDSLink
General References
  1. 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 ]
  2. Ullmann's Encyclopedia of Industrial Chemistry (2003). 6th ed. Vol 1. Federal Republic of Germany: Wiley-VCH Verlag GmbH & Co.
  3. Wikipedia. Zinc. Last Updated 24 March 2009. [Link]
  4. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for zinc. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  5. Wikipedia. Metallothionein. Last Updated 20 December 2008. [Link]
  6. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. Metallothionein-3
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
  1. Hasler DW, Jensen LT, Zerbe O, Winge DR, Vasak M: Effect of the two conserved prolines of human growth inhibitory factor (metallothionein-3) on its biological activity and structure fluctuation: comparison with a mutant protein. Biochemistry. 2000 Nov 28;39(47):14567-75. [11087412 ]
  2. Palumaa P, Eriste E, Njunkova O, Pokras L, Jornvall H, Sillard R: Brain-specific metallothionein-3 has higher metal-binding capacity than ubiquitous metallothioneins and binds metals noncooperatively. Biochemistry. 2002 May 14;41(19):6158-63. [11994011 ]
  3. Palumaa P, Njunkova O, Pokras L, Eriste E, Jornvall H, Sillard R: Evidence for non-isostructural replacement of Zn(2+) with Cd(2+) in the beta-domain of brain-specific metallothionein-3. FEBS Lett. 2002 Sep 11;527(1-3):76-80. [12220637 ]
  4. Roschitzki B, Vasak M: Redox labile site in a Zn4 cluster of Cu4,Zn4-metallothionein-3. Biochemistry. 2003 Aug 19;42(32):9822-8. [12911326 ]
  5. Eriste E, Kruusel K, Palumaa P, Jornvall H, Sillard R: Purification of recombinant human apometallothionein-3 and reconstitution with zinc. Protein Expr Purif. 2003 Sep;31(1):161-5. [12963354 ]
  6. Zheng WJ, Wu F, Zhuang HQ, Lu C, Yang F, Ma WL, Hua ZC: Expression of human metallothionein III and its metalloabsorption capability in Escherichia coli. Prep Biochem Biotechnol. 2004 Aug;34(3):265-78. [15461142 ]
  7. 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 ]
  8. Toriumi S, Saito T, Hosokawa T, Takahashi Y, Numata T, Kurasaki M: Metal binding ability of metallothionein-3 expressed in Escherichia coli. Basic Clin Pharmacol Toxicol. 2005 Apr;96(4):295-301. [15755312 ]
  9. Kameo S, Nakai K, Kurokawa N, Kanehisa T, Naganuma A, Satoh H: Metal components analysis of metallothionein-III in the brain sections of metallothionein-I and metallothionein-II null mice exposed to mercury vapor with HPLC/ICP-MS. Anal Bioanal Chem. 2005 Apr;381(8):1514-9. Epub 2005 Mar 22. [15782327 ]
Target Details
2. Amyloid beta A4 protein
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
  1. 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 ]
  2. Adlard PA, Bush AI: Metals and Alzheimer's disease. J Alzheimers Dis. 2006 Nov;10(2-3):145-63. [17119284 ]
Target Details
3. Aspartoacylase
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
  1. 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 ]
  2. Bitto E, Bingman CA, Wesenberg GE, McCoy JG, Phillips GN Jr: Structure of aspartoacylase, the brain enzyme impaired in Canavan disease. Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):456-61. Epub 2006 Dec 28. [17194761 ]
Target Details
4. Metallothionein-1A
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
  1. Aravindakumar CT, Ceulemans J, De Ley M: Nitric oxide induces Zn2+ release from metallothionein by destroying zinc-sulphur clusters without concomitant formation of S-nitrosothiol. Biochem J. 1999 Nov 15;344 Pt 1:253-8. [10548558 ]
  2. 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 ]
Target Details
5. Metallothionein-2
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
  1. 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 ]
  2. Yang F, Zhou M, He Z, Liu X, Sun L, Sun Y, Chen Z: High-yield expression in Escherichia coli of soluble human MT2A with native functions. Protein Expr Purif. 2007 May;53(1):186-94. Epub 2006 Dec 15. [17224279 ]
Target Details
6. Superoxide dismutase [Cu-Zn]
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
References
  1. 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 ]
  2. Huang YH, Shih CM, Huang CJ, Lin CM, Chou CM, Tsai ML, Liu TP, Chiu JF, Chen CT: Effects of cadmium on structure and enzymatic activity of Cu,Zn-SOD and oxidative status in neural cells. J Cell Biochem. 2006 Jun 1;98(3):577-89. [16440303 ]
Target Details
7. Apoptosis regulatory protein Siva
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
  1. 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 ]
Target Details
8. B1 bradykinin receptor
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
  1. 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 ]
Target Details
9. Beta-2 adrenergic receptor
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
  1. 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 ]
Target Details
10. Cellular tumor antigen p53
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
TP53
Uniprot ID:
P04637
Molecular Weight:
43652.79 Da
References
  1. Wang Y, Rosengarth A, Luecke H: Structure of the human p53 core domain in the absence of DNA. Acta Crystallogr D Biol Crystallogr. 2007 Mar;63(Pt 3):276-81. Epub 2007 Feb 21. [17327663 ]
Target Details
11. Copper chaperone for superoxide dismutase
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
  1. 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 ]
Target Details
12. DNA repair protein complementing XP-A cells
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
  1. 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 ]
Target Details
13. E3 ubiquitin-protein ligase Midline-1
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
  1. 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 ]
Target Details
14. Estrogen receptor
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
  1. 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 ]
Target Details
15. Fas-binding factor 1
General Function:
Not Available
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
  1. 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 ]
Target Details
16. Histone deacetylase 1
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
  1. 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 ]
Target Details
17. Histone deacetylase 4
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
  1. 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 ]
Target Details
18. Histone deacetylase 8
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
  1. 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 ]
Target Details
19. Insulin
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
  1. 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 ]
Target Details
20. Interleukin-3
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
  1. 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 ]
Target Details
21. Matrix metalloproteinase-9
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
  1. 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 ]
Target Details
22. Methylated-DNA--protein-cysteine methyltransferase
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
  1. 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 ]
Target Details
23. N-acetylmuramoyl-L-alanine amidase
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
  1. 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 ]
Target Details
24. Poly [ADP-ribose] polymerase 1
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
  1. 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 ]
Target Details
25. Programmed cell death protein 6
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
  1. 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 ]
Target Details
26. Protein S100-A2
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
  1. 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 ]
Target Details
27. Semenogelin-1
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
  1. 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 ]
Target Details
28. Serotransferrin
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
  1. 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 ]