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Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:03:56
Primary Accession Number DB01017
Secondary Accession Number
  • APRD00547
Name Minocycline
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description A tetracycline analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant staphylococcus infections. [PubChem]
Synonyms
  1. minocycline
Brand Names
  1. Alti-Minocycline
  2. Apo-Minocycline
  3. Arestin
  4. Dynacin
  5. Gen-Minocycline
  6. Klinomycin
  7. Minociclina [INN-Spanish]
  8. Minocin
  9. Minocyclin
  10. Minocycline HCl
  11. Minocyclinum [INN-Latin]
  12. Minocyn
  13. Minomycin
  14. Novo-Minocycline
  15. Solodyn
  16. Vectrin
Brand Mixtures Not Available
Chemical IUPAC Name (2Z,4S,4aS,5aR,12aS)-2-(amino-hydroxymethylidene)-4,7-bis(dimethylamino)-10,11,12a-trihydroxy-4a,5,5a,6-tetrahydro-4H-tetracene-1,3,12-trione
Chemical Formula C23H27N3O7
Chemical Structure Structure
CAS Registry Number 10118-90-8
InChI Identifier InChI=1/C23H27N3O7/c1-25(2)12-5-6-13(27)15-10(12)7-9-8-11-17(26(3)4)19(29)16(22(24)32)21(31)23(11,33)20(30)14(9)18(15)28/h5-6,9,11,17,27-28,32-33H,7-8,24H2,1-4H3/b22-16+/t9-,11-,17-,23-/m0/s1
InChI Key CUJCFMVUUMIFDR-XVLNIUNCBN
KEGG Drug D05045 Link Image
KEGG Compound C07225 Link Image
PubChem Compound 5281021 Link Image
PubChem Substance 167749 Link Image
ChEBI ID Not Available
PharmGKB ID PA450519 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02242080 Link Image
RxList Link http://www.rxlist.com/cgi/generic/minocycline.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/min1270.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Minocycline Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Boothe, Petisi, U.S. Pat. 3,148,212 (1964)
Average Molecular Weight 457.4764
Monoisotopic Molecular Weight 457.1849
State Solid
Melting Point Not Available
Experimental Water Solubility 52 mg/mL Source: PhysProp
Predicted Water Solubility 3.31e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 0.5 Source: PhysProp
Predicted LogP 0.30 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.14 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID 1P87 Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES CN(C)[C@H]1[C@@H]2C[C@@H]3CC4=C(C=CC(O)=C4C(O)=C3C(=O)[C@]2(O)C(=O)\C(C1=O)=C(/N)O)N(C)C
Canonical SMILES CN(C)C1C2CC3CC4=C(C=CC(O)=C4C(O)=C3C(=O)C2(O)C(=O)C(C1=O)=C(N)O)N(C)C
Drug Category
  • Anti-Bacterial Agents
  • Tetracyclines
ATC Codes
AHFS Codes
  • 08:12.24
Indication For the treatment of infections caused by susceptible strains of microorganisms, such as Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox and tick fevers caused by Rickettsiae, upper respiratory tract infections caused by Streptococcus pneumoniae and for the treatment of asymptomatic carriers of Neisseria meningitidis.
Pharmacology Minocycline, the most lipid soluble and most active tetracycline antibiotic, is, like doxycycline, a long-acting tetracycline. Minocycline's effects are related to the inhibition of protein synthesis. Although minocycline's broader spectrum of activity, compared to other members of the group, includes activity against Neisseria meningitidis, its use as a prophylaxis is no longer recomended because of side effects (dizziness and vertigo). Current research is examining the possible neuroprotective effects of minocycline against progression of Huntington's Disease, an inherited neurodegenerative disorder. The neuroprotective action of minocycline may include its inhibitory effect on 5-lipoxygenase, an inflammatory enzyme associated with brain aging.
Mechanism of Action Minocycline passes directly through the lipid bilayer or passively diffuses through porin channels in the bacterial membrane. Tetracyclines like minocycline bind to the 30S ribosomal subunit, preventing the binding of tRNA to the mRNA-ribosome complex and interfering with protein synthesis.
Absorption Rapidly absorbed from the gastrointestinal tract and absorption is not significantly impaired by ingestion of food or milk. Oral bioavailability is 100%.
Toxicity Minocycline has been observed to cause a dark discoloration of the thyroid in experimental animals (rats, minipigs, dogs and monkeys). In the rat, chronic treatment with minocycline has resulted in goiter accompanied by elevated radioactive iodine uptake and evidence of thyroid tumor production. Minocycline has also been found to produce thyroid hyperplasia in rats and dogs. LD50=2380 mg/kg (rat, oral), LD50=3600 mg/kg (mouse, oral)
Protein Binding 55% to 76%
Biotransformation Hepatic.
Half Life 11-22 hours
Dosage Forms
Form Route
Capsule Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol The tetracycline increases the anticoagulant effect
Acitretin Increased risk of intracranial hypertension
Aluminium Formation of non-absorbable complexes
Amoxicillin Possible antagonism of action
Ampicillin Possible antagonism of action
Anisindione The tetracycline increases the anticoagulant effect
Attapulgite Formation of non-absorbable complexes
Azlocillin Possible antagonism of action
Aztreonam Possible antagonism of action
Bacampicillin Possible antagonism of action
Bismuth Formation of non-absorbable complexes
Bismuth Subsalicylate Formation of non-absorbable complexes
Calcium Formation of non-absorbable complexes
Carbenicillin Possible antagonism of action
Clavulanate Possible antagonism of action
Cloxacillin Possible antagonism of action
Cyclacillin Possible antagonism of action
Dicloxacillin Possible antagonism of action
Dicumarol The tetracycline increases the anticoagulant effect
Digoxin The tetracycline increases the effect of digoxin in 10% of patients
Ethinyl Estradiol This anti-infectious agent could decrease the effect of the oral contraceptive
Etretinate Increased risk of intracranial hypertension
Flucloxacillin Possible antagonism of action
Hetacillin Possible antagonism of action
Insulin The tetracycline increases the risk of hypoglycemia
Iron Formation of non-absorbable complexes
Isotretinoin This anti-infectious agent could decrease the effect of the oral contraceptive
Magnesium Formation of non-absorbable complexes
Magnesium oxide Formation of non-absorbable complexes
Mestranol This anti-infectious agent could decrease the effect of the oral contraceptive
Methicillin Acyl-Serine Possible antagonism of action
Methoxyflurane The tetracycline increases the renal toxicity of methoxyflurane
Mezlocillin Possible antagonism of action
Nafcillin Possible antagonism of action
Oxacillin Possible antagonism of action
Penicillin G Possible antagonism of action
Penicillin V Possible antagonism of action
Piperacillin Possible antagonism of action
Pivampicillin Possible antagonism of action
Pivmecillinam Possible antagonism of action
Salicylate-magnesium Formation of non-absorbable complexes
Tazobactam Possible antagonism of action
Ticarcillin Possible antagonism of action
Trisalicylate-choline Formation of non-absorbable complexes
Warfarin The tetracycline increases the anticoagulant effect
Zinc Formation of non-absorbable complexes
Food Interactions
  • Calcium and iron needs increased with long term use.
  • Do not take Aluminum or magnesium antacids or supplements while on this medication.
  • Take with food.
Pathways
Name SMPDB Link KEGG Link
Minocycline Pathway SMP00292 Link Image
General References
  1. Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, Bian J, Guo L, Farrell LA, Hersch SM, Hobbs W, Vonsattel JP, Cha JH, Friedlander RM: Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med. 2000 Jul;6(7):797-801. [PubMed Link Image]
  2. Tikka TM, Koistinaho JE: Minocycline provides neuroprotection against N-methyl-D-aspartate neurotoxicity by inhibiting microglia. J Immunol. 2001 Jun 15;166(12):7527-33. [PubMed Link Image]
  3. Song Y, Wei EQ, Zhang WP, Zhang L, Liu JR, Chen Z: Minocycline protects PC12 cells from ischemic-like injury and inhibits 5-lipoxygenase activation. Neuroreport. 2004 Oct 5;15(14):2181-4. [PubMed Link Image]
  4. Nirmalananthan N, Greensmith L: Amyotrophic lateral sclerosis: recent advances and future therapies. Curr Opin Neurol. 2005 Dec;18(6):712-9. [PubMed Link Image]
  5. Gough A, Chapman S, Wagstaff K, Emery P, Elias E: Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome. BMJ. 1996 Jan 20;312(7024):169-72. [PubMed Link Image]
  6. http://en.wikipedia.org/wiki/Minocycline
  7. Drugs.com Link Image
  8. http://www.medsafe.govt.nz/profs/Datasheet/m/Minotabtab.htm
  9. Wikipedia Link Image
  10. RxList Link Image
  11. PDRhealth Link Image
Organisms Affected
  • Enteric bacteria and other eubacteria
Targets
  1. 30S ribosomal protein S4
  2. Matrix metalloproteinase-9
  3. 30S ribosomal protein S9
  4. Vascular endothelial growth factor A
  5. Arachidonate 5-lipoxygenase
  6. Caspase-1
  7. 16S rRNA
  8. Cytochrome c
  9. Interleukin-1 beta
  10. Caspase-3
Drug Target 1 [top]
Target 1 ID 22
Target 1 Name 30S ribosomal protein S4
Target 1 Synonyms Not Available
Target 1 Gene Name rpsD
Target 1 Protein Sequence >30S ribosomal protein S4 
ARYLGPKLKLSRREGTDLFLKSGVRAIDTKCKIEQAPGQHGARKPRLSDYGVQLREKQKV
RRIYGVLERQFRNYYKEAARLKGNTGENLLALLEGRLDNVVYRMGFGATRAEARQLVSHK
AIMVNGRVVNIASYQVSPNDVVSIREKAKKQSRVKAALELAEQREKPTWLEVDAGKMEGT
FKRKPERSDLSADINEHLIVELYSK
Target 1 Number of Residues 208
Target 1 Molecular Weight 23338
Target 1 Theoretical pI 10.66
Target 1 GO Classification
Function
binding
nucleic acid binding
RNA binding
structural molecule activity
structural constituent of ribosome
Process
physiological process
metabolism
macromolecule metabolism
macromolecule biosynthesis
protein biosynthesis
Component
cell
intracellular
protein complex
ribonucleoprotein complex
ribosome
small ribosomal subunit
Target 1 General Function Translation, ribosomal structure and biogenesis
Target 1 Specific Function Also functions as a rho-dependent antiterminator of rRNA transcription, increasing the synthesis of rRNA under conditions of excess protein, allowing a more rapid return to homeostasis. Binds directly to RNA polymerase
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Essential
Target 1 GenBank ID Protein 42798 Link Image
Target 1 UniProtKB/Swiss-Prot ID P0A7V8 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name RS4_ECOLI Link Image
Target 1 PDB ID 1P87 Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Cytoplasmic
Target 1 Gene Sequence >621 bp 
ATGGCAAGATATTTGGGTCCTAAGCTCAAGCTGAGCCGTCGTGAGGGCACCGACTTATTC
CTTAAGTCTGGCGTTCGCGCGATCGATACCAAGTGTAAAATTGAACAAGCTCCTGGCCAG
CACGGTGCGCGTAAACCGCGTCTGTCTGACTATGGTGTGCAGTTGCGTGAAAAGCAAAAA
GTTCGCCGTATCTATGGTGTGCTGGAGCGTCAGTTCCGTAACTACTACAAAGAAGCAGCA
CGTCTGAAAGGCAACACCGGTGAAAACCTGTTGGCTCTGCTGGAAGGTCGTCTGGACAAC
GTTGTATACCGTATGGGCTTCGGTGCCACTCGTGCAGAAGCACGTCAGCTGGTTAGCCAT
AAAGCAATTATGGTAAACGGTCGTGTTGTTAACATCGCTTCTTATCAGGTTAGTCCGAAT
GACGTTGTAAGCATTCGTGAGAAAGCGAAGAAGCAGTCTCGCGTGAAAGCCGCTCTGGAG
CTGGCTGAGCAGCGTGAAAAGCCAACCTGGCTGGAAGTTGATGCTGGCAAGATGGAAGGT
ACGTTTAAGCGTAAGCCGGAGCGTTCTGATCTGTCTGCGGACATTAACGAACACCTGATC
GTCGAGCTTTACTCCAAGTAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID Not Available
Target 1 HGNC ID Not Available
Target 1 Chromosome Location Not Available
Target 1 Locus Not Available
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Arnold RJ, Reilly JP: Observation of Escherichia coli ribosomal proteins and their posttranslational modifications by mass spectrometry. Anal Biochem. 1999 Apr 10;269(1):105-12. [PubMed Link Image]
  2. Schiltz E, Reinbolt J: Determination of the complete amino-acid sequence of protein S4 from Escherichia coli ribosomes. Eur J Biochem. 1975 Aug 15;56(2):467-81. [PubMed Link Image]
  3. Dahlgren A, Ryden-Aulin M: A novel mutation in ribosomal protein S4 that affects the function of a mutated RF1. Biochimie. 2000 Aug;82(8):683-91. [PubMed Link Image]
  4. Torres M, Condon C, Balada JM, Squires C, Squires CL: Ribosomal protein S4 is a transcription factor with properties remarkably similar to NusA, a protein involved in both non-ribosomal and ribosomal RNA antitermination. EMBO J. 2001 Jul 16;20(14):3811-20. [PubMed Link Image]
  5. Tung CS, Joseph S, Sanbonmatsu KY: All-atom homology model of the Escherichia coli 30S ribosomal subunit. Nat Struct Biol. 2002 Oct;9(10):750-5. [PubMed Link Image]
  6. Gao H, Sengupta J, Valle M, Korostelev A, Eswar N, Stagg SM, Van Roey P, Agrawal RK, Harvey SC, Sali A, Chapman MS, Frank J: Study of the structural dynamics of the E coli 70S ribosome using real-space refinement. Cell. 2003 Jun 13;113(6):789-801. [PubMed Link Image]
  7. Nowotny V, Nierhaus KH: Assembly of the 30S subunit from Escherichia coli ribosomes occurs via two assembly domains which are initiated by S4 and S7. Biochemistry. 1988 Sep 6;27(18):7051-5. [PubMed Link Image]
  8. Allen PN, Noller HF: Mutations in ribosomal proteins S4 and S12 influence the higher order structure of 16 S ribosomal RNA. J Mol Biol. 1989 Aug 5;208(3):457-68. [PubMed Link Image]
  9. Bedwell D, Davis G, Gosink M, Post L, Nomura M, Kestler H, Zengel JM, Lindahl L: Nucleotide sequence of the alpha ribosomal protein operon of Escherichia coli. Nucleic Acids Res. 1985 Jun 11;13(11):3891-903. [PubMed Link Image]
  10. Thomas MS, Bedwell DM, Nomura M: Regulation of alpha operon gene expression in Escherichia coli. A novel form of translational coupling. J Mol Biol. 1987 Jul 20;196(2):333-45. [PubMed Link Image]
  11. 387752 Post LE, Nomura M: Nucleotide sequence of the intercistronic region preceding the gene for RNA polymerase subunit alpha in Escherichia coli. J Biol Chem. 1979 Nov 10;254(21):10604-6.
  12. 4587210 Reinbolt J, Schiltz E: The primary structure of ribosomal protein S4 from Escherichia coli. FEBS Lett. 1973 Nov 1;36(3):250-2.
  13. 7556101 Urlaub H, Kruft V, Bischof O, Muller EC, Wittmann-Liebold B: Protein-rRNA binding features and their structural and functional implications in ribosomes as determined by cross-linking studies. EMBO J. 1995 Sep 15;14(18):4578-88.
  14. 7559430 Baker AM, Draper DE: Messenger RNA recognition by fragments of ribosomal protein S4. J Biol Chem. 1995 Sep 29;270(39):22939-45.
  15. 9278503 Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-74.
  16. 9716382 Choi KM, Atkins JF, Gesteland RF, Brimacombe R: Flexibility of the nascent polypeptide chain within the ribosome--contacts from the peptide N-terminus to a specific region of the 30S subunit. Eur J Biochem. 1998 Jul 15;255(2):409-13.
Target 1 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 65
Target 2 Name Matrix metalloproteinase-9
Target 2 Synonyms
  1. 92 kDa gelatinase
  2. 92 kDa type IV collagenase
  3. EC 3.4.24.35
  4. GELB
  5. Gelatinase B
  6. MMP-9
  7. Matrix metalloproteinase-9 precursor
Target 2 Gene Name MMP9
Target 2 Protein Sequence >Matrix metalloproteinase-9 precursor 
MSLWQPLVLVLLVLGCCFAAPRQRQSTLVLFPGDLRTNLTDRQLAEEYLYRYGYTRVAEM
RGESKSLGPALLLLQKQLSLPETGELDSATLKAMRTPRCGVPDLGRFQTFEGDLKWHHHN
ITYWIQNYSEDLPRAVIDDAFARAFALWSAVTPLTFTRVYSRDADIVIQFGVAEHGDGYP
FDGKDGLLAHAFPPGPGIQGDAHFDDDELWSLGKGVVVPTRFGNADGAACHFPFIFEGRS
YSACTTDGRSDGLPWCSTTANYDTDDRFGFCPSERLYTRDGNADGKPCQFPFIFQGQSYS
ACTTDGRSDGYRWCATTANYDRDKLFGFCPTRADSTVMGGNSAGELCVFPFTFLGKEYST
CTSEGRGDGRLWCATTSNFDSDKKWGFCPDQGYSLFLVAAHEFGHALGLDHSSVPEALMY
PMYRFTEGPPLHKDDVNGIRHLYGPRPEPEPRPPTTTTPQPTAPPTVCPTGPPTVHPSER
PTAGPTGPPSAGPTGPPTAGPSTATTVPLSPVDDACNVNIFDAIAEIGNQLYLFKDGKYW
RFSEGRGSRPQGPFLIADKWPALPRKLDSVFEEPLSKKLFFFSGRQVWVYTGASVLGPRR
LDKLGLGADVAQVTGALRSGRGKMLLFSGRRLWRFDVKAQMVDPRSASEVDRMFPGVPLD
THDVFQYREKAYFCQDRFYWRVSSRSELNQVDQVGYVTYDILQCPED
Target 2 Number of Residues 718
Target 2 Molecular Weight 78428
Target 2 Theoretical pI 5.92
Target 2 GO Classification
Function
binding
ion binding
cation binding
transition metal ion binding
zinc ion binding
metallopeptidase activity
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
metalloendopeptidase activity
Process
carbohydrate metabolism
cellular carbohydrate metabolism
peptidoglycan metabolism
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
Component
extracellular matrix
extracellular matrix (sensu Metazoa)
Target 2 General Function Involved in proteolysis and tissue remodeling
Target 2 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
Target 2 Pathways Not Available
Target 2 Reactions
  • Cleavage of gelatin types I and V and collagen types IV and V COFACTOR Zinc; Metal; Calcium
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-19
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 177205 Link Image
Target 2 UniProtKB/Swiss-Prot ID P14780 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name MMP9_HUMAN Link Image
Target 2 PDB ID 1L6J Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Cytoplasmic
Target 2 Gene Sequence >2124 bp 
ATGAGCCTCTGGCAGCCCCTGGTCCTGGTGCTCCTGGTGCTGGGCTGCTGCTTTGCTGCC
CCCAGACAGCGCCAGTCCACCCTTGTGCTCTTCCCTGGAGACCTGAGAACCAATCTCACC
GACAGGCAGCTGGCAGAGGAATACCTGTACCGCTATGGTTACACTCGGGTGGCAGAGATG
CGTGGAGAGTCGAAATCTCTGGGGCCTGCGCTGCTGCTTCTCCAGAAGCAACTGTCCCTG
CCCGAGACCGGTGAGCTGGATAGCGCCACGCTGAAGGCCATGCGAACCCCACGGTGCGGG
GTCCCAGACCTGGGCAGATTCCAAACCTTTGAGGGCGACCTCAAGTGGCACCACCACAAC
ATCACCTATTGGATCCAAAACTACTCGGAAGACTTGCCGCGGGCGGTGATTGACGACGCC
TTTGCCCGCGCCTTCGCACTGTGGAGCGCGGTGACGCCGCTCACCTTCACTCGCGTGTAC
AGCCGGGACGCAGACATCGTCATCCAGTTTGGTGTCGCGGAGCACGGAGACGGGTATCCC
TTCGACGGGAAGGACGGGCTCCTGGCACACGCCTTTCCTCCTGGCCCCGGCATTCAGGGA
GACGCCCATTTCGACGATGACGAGTTGTGGTCCCTGGGCAAGGGCGTCGTGGTTCCAACT
CGGTTTGGAAACGCAGATGGCGCGGCCTGCCACTTCCCCTTCATCTTCGAGGGCCGCTCC
TACTCTGCCTGCACCACCGACGGTCGCTCCGACGGCTTGCCCTGGTGCAGTACCACGGCC
AACTACGACACCGACGACCGGTTTGGCTTCTGCCCCAGCGAGAGACTCTACACCCGGGAC
GGCAATGCTGATGGGAAACCCTGCCAGTTTCCATTCATCTTCCAAGGCCAATCCTACTCC
GCCTGCACCACGGACGGTCGCTCCGACGGCTACCGCTGGTGCGCCACCACCGCCAACTAC
GACCGGGACAAGCTCTTCGGCTTCTGCCCGACCCGAGCTGACTCGACGGTGATGGGGGGC
AACTCGGCGGGGGAGCTGTGCGTCTTCCCCTTCACTTTCCTGGGTAAGGAGTACTCGACC
TGTACCAGCGAGGGCCGCGGAGATGGGCGCCTCTGGTGCGCTACCACCTCGAACTTTGAC
AGCGACAAGAAGTGGGGCTTCTGCCCGGACCAAGGATACAGTTTGTTCCTCGTGGCGGCG
CATGAGTTCGGCCACGCGCTGGGCTTAGATCATTCCTCAGTGCCGGAGGCGCTCATGTAC
CCTATGTACCGCTTCACTGAGGGGCCCCCCTTGCATAAGGACGACGTGAATGGCATCCGG
CACCTCTATGGTCCTCGCCCTGAACCTGAGCCACGGCCTCCAACCACCACCACACCGCAG
CCCACGGCTCCCCCGACGGTCTGCCCCACCGGACCCCCCACTGTCCACCCCTCAGAGCGC
CCCACAGCTGGCCCCACAGGTCCCCCCTCAGCTGGCCCCACAGGTCCCCCCACTGCTGGC
CCTTCTACGGCCACTACTGTGCCTTTGAGTCCGGTGGACGATGCCTGCAACGTGAACATC
TTCGACGCCATCGCGGAGATTGGGAACCAGCTGTATTTGTTCAAGGATGGGAAGTACTGG
CGATTCTCTGAGGGCAGGGGGAGCCGGCCGCAGGGCCCCTTCCTTATCGCCGACAAGTGG
CCCGCGCTGCCCCGCAAGCTGGACTCGGTCTTTGAGGAGCCGCTCTCCAAGAAGCTTTTC
TTCTTCTCTGGGCGCCAGGTGTGGGTGTACACAGGCGCGTCGGTGCTGGGCCCGAGGCGT
CTGGACAAGCTGGGCCTGGGAGCCGACGTGGCCCAGGTGACCGGGGCCCTCCGGAGTGGC
AGGGGGAAGATGCTGCTGTTCAGCGGGCGGCGCCTCTGGAGGTTCGACGTGAAGGCGCAG
ATGGTGGATCCCCGGAGCGCCAGCGAGGTGGACCGGATGTTCCCCGGGGTGCCTTTGGAC
ACGCACGACGTCTTCCAGTACCGAGAGAAAGCCTATTTCTGCCAGGACCGCTTCTACTGG
CGCGTGAGTTCCCGGAGTGAGTTGAACCAGGTGGACCAAGTGGGCTACGTGACCTATGAC
ATCCTGCAGTGCCCTGAGGACTAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID MMP9 Link Image
Target 2 GenAtlas ID MMP9 Link Image
Target 2 HGNC ID HGNC:7176 Link Image
Target 2 Chromosome Location 20
Target 2 Locus 20q11.2-q13.1
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Zhang B, Henney A, Eriksson P, Hamsten A, Watkins H, Ye S: Genetic variation at the matrix metalloproteinase-9 locus on chromosome 20q12.2-13.1. Hum Genet. 1999 Nov;105(5):418-23. [PubMed Link Image]
  2. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [PubMed Link Image]
  3. Takino T, Koshikawa N, Miyamori H, Tanaka M, Sasaki T, Okada Y, Seiki M, Sato H: Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by matrix metalloproteinases. Oncogene. 2003 Jul 24;22(30):4617-26. [PubMed Link Image]
  4. Ogata Y, Enghild JJ, Nagase H: Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem. 1992 Feb 25;267(6):3581-4. [PubMed Link Image]
  5. Masure S, Proost P, Van Damme J, Opdenakker G: Purification and identification of 91-kDa neutrophil gelatinase. Release by the activating peptide interleukin-8. Eur J Biochem. 1991 Jun 1;198(2):391-8. [PubMed Link Image]
  6. Van Ranst M, Norga K, Masure S, Proost P, Vandekerckhove F, Auwerx J, Van Damme J, Opdenakker G: The cytokine-protease connection: identification of a 96-kD THP-1 gelatinase and regulation by interleukin-1 and cytokine inducers. Cytokine. 1991 May;3(3):231-9. [PubMed Link Image]
  7. Huhtala P, Tuuttila A, Chow LT, Lohi J, Keski-Oja J, Tryggvason K: Complete structure of the human gene for 92-kDa type IV collagenase. Divergent regulation of expression for the 92- and 72-kilodalton enzyme genes in HT-1080 cells. J Biol Chem. 1991 Sep 5;266(25):16485-90. [PubMed Link Image]
  8. Opdenakker G, Masure S, Grillet B, Van Damme J: Cytokine-mediated regulation of human leukocyte gelatinases and role in arthritis. Lymphokine Cytokine Res. 1991 Aug;10(4):317-24. [PubMed Link Image]
  9. Wilhelm SM, Collier IE, Marmer BL, Eisen AZ, Grant GA, Goldberg GI: SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. J Biol Chem. 1989 Oct 15;264(29):17213-21. [PubMed Link Image]
  10. Sang QX, Birkedal-Hansen H, Van Wart HE: Proteolytic and non-proteolytic activation of human neutrophil progelatinase B. Biochim Biophys Acta. 1995 Sep 6;1251(2):99-108. [PubMed Link Image]
  11. 8426746 Sato H, Seiki M: Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. Oncogene. 1993 Feb;8(2):395-405.
Target 2 Drug References
  1. Brundula V, Rewcastle NB, Metz LM, Bernard CC, Yong VW: Targeting leukocyte MMPs and transmigration: minocycline as a potential therapy for multiple sclerosis. Brain. 2002 Jun;125(Pt 6):1297-308. [PubMed Link Image]
  2. Sutton TA, Kelly KJ, Mang HE, Plotkin Z, Sandoval RM, Dagher PC: Minocycline reduces renal microvascular leakage in a rat model of ischemic renal injury. Am J Physiol Renal Physiol. 2005 Jan;288(1):F91-7. Epub 2004 Sep 7. [PubMed Link Image]
  3. Koistinaho M, Malm TM, Kettunen MI, Goldsteins G, Starckx S, Kauppinen RA, Opdenakker G, Koistinaho J: Minocycline protects against permanent cerebral ischemia in wild type but not in matrix metalloprotease-9-deficient mice. J Cereb Blood Flow Metab. 2005 Apr;25(4):460-7. [PubMed Link Image]
  4. Lee CZ, Yao JS, Huang Y, Zhai W, Liu W, Guglielmo BJ, Lin E, Yang GY, Young WL: Dose-response effect of tetracyclines on cerebral matrix metalloproteinase-9 after vascular endothelial growth factor hyperstimulation. J Cereb Blood Flow Metab. 2006 Sep;26(9):1157-64. Epub 2006 Jan 4. [PubMed Link Image]
  5. Machado LS, Kozak A, Ergul A, Hess DC, Borlongan CV, Fagan SC: Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke. BMC Neurosci. 2006 Jul 17;7:56. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 140
Target 3 Name 30S ribosomal protein S9
Target 3 Synonyms Not Available
Target 3 Gene Name rpsI
Target 3 Protein Sequence >30S ribosomal protein S9 
AENQYYGTGRRKSSAARVFIKPGNGKIVINQRSLEQYFGRETARMVVRQPLELVDMVEKL
DLYITVKGGGISGQAGAIRHGITRALMEYDESLRSELRKAGFVTRDARQVERKKVGLRKA
RRRPQFSKR
Target 3 Number of Residues 131
Target 3 Molecular Weight 14725
Target 3 Theoretical pI 11.52
Target 3 GO Classification
Function
structural molecule activity
structural constituent of ribosome
Process
physiological process
metabolism
macromolecule metabolism
macromolecule biosynthesis
protein biosynthesis
Component
protein complex
ribonucleoprotein complex
ribosome
cell
intracellular
Target 3 General Function Translation, ribosomal structure and biogenesis
Target 3 Specific Function The C-terminal tail plays a role in the affinity of the 30S P site for different tRNAs. Mutations that decrease this affinity are suppressed in the 70S ribosome
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Essential
Target 3 GenBank ID Protein 535073 Link Image
Target 3 UniProtKB/Swiss-Prot ID P0A7X3 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name RS9_ECOLI Link Image
Target 3 PDB ID 1P87 Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location Not Available
Target 3 Gene Sequence >393 bp 
ATGGCTGAAAATCAATACTACGGCACTGGTCGCCGCAAAAGTTCCGCAGCTCGCGTTTTC
ATCAAACCGGGCAACGGTAAAATCGTAATCAACCAACGTTCTCTGGAACAGTACTTCGGT
CGTGAAACTGCCCGCATGGTAGTTCGTCAGCCGCTGGAACTGGTCGACATGGTTGAGAAA
CTGGACCTGTACATCACCGTTAAAGGTGGTGGTATCTCTGGTCAGGCTGGTGCGATCCGT
CACGGTATCACCCGCGCTCTGATGGAATACGACGAGTCCCTGCGTTCTGAACTGCGTAAA
GCTGGCTTCGTTACTCGTGACGCTCGTCAGGTTGAACGTAAGAAAGTCGGTCTGCGTAAA
GCACGTCGTCGTCCGCAGTTCTCCAAACGTTAA
Target 3 GenBank Gene ID
Target 3 GeneCard ID Not Available
Target 3 GenAtlas ID Not Available
Target 3 HGNC ID Not Available
Target 3 Chromosome Location Not Available
Target 3 Locus Not Available
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Arnold RJ, Reilly JP: Observation of Escherichia coli ribosomal proteins and their posttranslational modifications by mass spectrometry. Anal Biochem. 1999 Apr 10;269(1):105-12. [PubMed Link Image]
  2. Chen R, Wittmann-Liebold B: The primary structure of protein S9 from the 30S subunit of Escherichia coli ribosomes. FEBS Lett. 1975 Mar 15;52(1):139-40. [PubMed Link Image]
  3. Tung CS, Joseph S, Sanbonmatsu KY: All-atom homology model of the Escherichia coli 30S ribosomal subunit. Nat Struct Biol. 2002 Oct;9(10):750-5. [PubMed Link Image]
  4. Gao H, Sengupta J, Valle M, Korostelev A, Eswar N, Stagg SM, Van Roey P, Agrawal RK, Harvey SC, Sali A, Chapman MS, Frank J: Study of the structural dynamics of the E coli 70S ribosome using real-space refinement. Cell. 2003 Jun 13;113(6):789-801. [PubMed Link Image]
  5. Isono S, Thamm S, Kitakawa M, Isono K: Cloning and nucleotide sequencing of the genes for ribosomal proteins S9 (rpsI) and L13 (rplM) of Escherichia coli. Mol Gen Genet. 1985;198(2):279-82. [PubMed Link Image]
  6. Marsh RC, Parmeggiani A: Requirement of proteins S5 and S9 from 30S subunits for the ribosome-dependent GTPase activity of elongation factor G. Proc Natl Acad Sci U S A. 1973 Jan;70(1):151-5. [PubMed Link Image]
  7. Urlaub H, Kruft V, Bischof O, Muller EC, Wittmann-Liebold B: Protein-rRNA binding features and their structural and functional implications in ribosomes as determined by cross-linking studies. EMBO J. 1995 Sep 15;14(18):4578-88. [PubMed Link Image]
  8. Osswald M, Doring T, Brimacombe R: The ribosomal neighbourhood of the central fold of tRNA: cross-links from position 47 of tRNA located at the A, P or E site. Nucleic Acids Res. 1995 Nov 25;23(22):4635-41. [PubMed Link Image]
  9. Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-74. [PubMed Link Image]
Target 3 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 183
Target 4 Name Vascular endothelial growth factor A
Target 4 Synonyms
  1. VEGF-A
  2. VPF
  3. Vascular endothelial growth factor A precursor
  4. Vascular permeability factor
Target 4 Gene Name VEGF
Target 4 Protein Sequence >Vascular endothelial growth factor A precursor 
MNFLLSWVHWSLALLLYLHHAKWSQAAPMAEGGGQNHHEVVKFMDVYQRSYCHPIETLVD
IFQEYPDEIEYIFKPSCVPLMRCGGCCNDEGLECVPTEESNITMQIMRIKPHQGQHIGEM
SFLQHNKCECRPKKDRARQEKKSVRGKGKGQKRKRKKSRYKSWSVYVGARCCLMPWSLPG
PHPCGPCSERRKHLFVQDPQTCKCSCKNTDSRCKARQLELNERTCRCDKPRR
Target 4 Number of Residues 235
Target 4 Molecular Weight 27043
Target 4 Theoretical pI 9.08
Target 4 GO Classification
Function
signal transducer activity
receptor binding
growth factor activity
Process
Not Available
Component
cell
membrane
Target 4 General Function Involved in growth factor activity
Target 4 Specific Function Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis, and induces permeabilization of blood vessels. Binds to the VEGFR1/Flt-1 and VEGFR2/Kdr receptors, heparan sulfate and heparin. Neuropilin-1 binds isoforms VEGF-165 and VEGF-145
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • 1-26
Target 4 Transmembrane Regions
  • None
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 181971 Link Image
Target 4 UniProtKB/Swiss-Prot ID P15692 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name VEGFA_HUMAN Link Image
Target 4 PDB ID 1TZI Link Image
Target 4 PDB File Show
Target 4 3D Structure
Target 4 Cellular Location
  • Secreted protein. VEGF121 is acidic and freely secreted. VEGF165 is more basic, has heparin-binding
Target 4 Gene Sequence >699 bp 
ATGAACTTTCTGCTGTCTTGGGTGCATTGGAGCCTTGCCTTGCTGCTCTACCTCCACCAT
GCCAAGTGGTCCCAGGCTGCACCCATGGCAGAAGGAGGAGGGCAGAATCATCACGAAGTG
GTGAAGTTCATGGATGTCTATCAGCGCAGCTACTGCCATCCAATCGAGACCCTGGTGGAC
ATCTTCCAGGAGTACCCTGATGAGATCGAGTACATCTTCAAGCCATCCTGTGTGCCCCTG
ATGCGATGCGGGGGCTGCTGCAATGACGAGGGCCTGGAGTGTGTGCCCACTGAGGAGTCC
AACATCACCATGCAGATTATGCGGATCAAACCTCACCAAGGCCAGCACATAGGAGAGATG
AGCTTCCTACAGCACAACAAATGTGAATGCAGACCAAAGAAAGATAGAGCAAGACAAGAA
AAAAAATCAGTTCGAGGAAAGGGAAAGGGGCAAAAACGAAAGCGCAAGAAATCCCGGTAT
AAGTCCTGGAGCGTGTACGTTGGTGCCCGCTGCTGTCTAATGCCCTGGAGCCTCCCTGGC
CCCCATCCCTGTGGGCCTTGCTCAGAGCGGAGAAAGCATTTGTTTGTACAAGATCCGCAG
ACGTGTAAATGTTCCTGCAAAAACACAGACTCGCGTTGCAAGGCGAGGCAGCTTGAGTTA
AACGAACGTACTTGCAGATGTGACAAGCCGAGGCGGTGA
Target 4 GenBank Gene ID
Target 4 GeneCard ID VEGF Link Image
Target 4 GenAtlas ID VEGF Link Image
Target 4 HGNC ID HGNC:12680 Link Image
Target 4 Chromosome Location 6
Target 4 Locus 6p12
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Jingjing L, Xue Y, Agarwal N, Roque RS: Human Muller cells express VEGF183, a novel spliced variant of vascular endothelial growth factor. Invest Ophthalmol Vis Sci. 1999 Mar;40(3):752-9. [PubMed Link Image]
  2. Whittle C, Gillespie K, Harrison R, Mathieson PW, Harper SJ: Heterogeneous vascular endothelial growth factor (VEGF) isoform mRNA and receptor mRNA expression in human glomeruli, and the identification of VEGF148 mRNA, a novel truncated splice variant. Clin Sci (Lond). 1999 Sep;97(3):303-12. [PubMed Link Image]
  3. Murphy JF, Fitzgerald DJ: Vascular endothelial growth factor induces cyclooxygenase-dependent proliferation of endothelial cells via the VEGF-2 receptor. FASEB J. 2001 Jul;15(9):1667-9. [PubMed Link Image]
  4. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [PubMed Link Image]
  5. Weindel K, Marme D, Weich HA: AIDS-associated Kaposi's sarcoma cells in culture express vascular endothelial growth factor. Biochem Biophys Res Commun. 1992 Mar 31;183(3):1167-74. [PubMed Link Image]
  6. Tischer E, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA: The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem. 1991 Jun 25;266(18):11947-54. [PubMed Link Image]
  7. Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW: The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol. 1991 Dec;5(12):1806-14. [PubMed Link Image]
  8. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N: Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989 Dec 8;246(4935):1306-9. [PubMed Link Image]
  9. Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT: Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science. 1989 Dec 8;246(4935):1309-12. [PubMed Link Image]
  10. Connolly DT, Olander JV, Heuvelman D, Nelson R, Monsell R, Siegel N, Haymore BL, Leimgruber R, Feder J: Human vascular permeability factor. Isolation from U937 cells. J Biol Chem. 1989 Nov 25;264(33):20017-24. [PubMed Link Image]
  11. 7678805 Fiebich BL, Jager B, Schollmann C, Weindel K, Wilting J, Kochs G, Marme D, Hug H, Weich HA: Synthesis and assembly of functionally active human vascular endothelial growth factor homodimers in insect cells. Eur J Biochem. 1993 Jan 15;211(1-2):19-26.
  12. 9054410 Poltorak Z, Cohen T, Sivan R, Kandelis Y, Spira G, Vlodavsky I, Keshet E, Neufeld G: VEGF145, a secreted vascular endothelial growth factor isoform that binds to extracellular matrix. J Biol Chem. 1997 Mar 14;272(11):7151-8.
  13. 9207067 Muller YA, Li B, Christinger HW, Wells JA, Cunningham BC, de Vos AM: Vascular endothelial growth factor: crystal structure and functional mapping of the kinase domain receptor binding site. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7192-7.
  14. 9336848 Fairbrother WJ, Champe MA, Christinger HW, Keyt BA, Starovasnik MA: 1H, 13C, and 15N backbone assignment and secondary structure of the receptor-binding domain of vascular endothelial growth factor. Protein Sci. 1997 Oct;6(10):2250-60.
  15. 9351807 Muller YA, Christinger HW, Keyt BA, de Vos AM: The crystal structure of vascular endothelial growth factor (VEGF) refined to 1.93 A resolution: multiple copy flexibility and receptor binding. Structure. 1997 Oct 15;5(10):1325-38.
  16. 9450968 Claffey KP, Shih SC, Mullen A, Dziennis S, Cusick JL, Abrams KR, Lee SW, Detmar M: Identification of a human VPF/VEGF 3' untranslated region mediating hypoxia-induced mRNA stability. Mol Biol Cell. 1998 Feb;9(2):469-81.
  17. 9634701 Fairbrother WJ, Champe MA, Christinger HW, Keyt BA, Starovasnik MA: Solution structure of the heparin-binding domain of vascular endothelial growth factor. Structure. 1998 May 15;6(5):637-48.
  18. 9878851 Lei J, Jiang A, Pei D: Identification and characterization of a new splicing variant of vascular endothelial growth factor: VEGF183. Biochim Biophys Acta. 1998 Dec 22;1443(3):400-6.
  19. 9922142 Wiesmann C, Christinger HW, Cochran AG, Cunningham BC, Fairbrother WJ, Keenan CJ, Meng G, de Vos AM: Crystal structure of the complex between VEGF and a receptor-blocking peptide. Biochemistry. 1998 Dec 22;37(51):17765-72.
Target 4 Drug References
  1. Sasamura H, Takahashi A, Miyao N, Yanase M, Masumori N, Kitamura H, Itoh N, Tsukamoto T: Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma. Br J Cancer. 2002 Mar 4;86(5):768-73. [PubMed Link Image]
  2. Yao JS, Chen Y, Zhai W, Xu K, Young WL, Yang GY: Minocycline exerts multiple inhibitory effects on vascular endothelial growth factor-induced smooth muscle cell migration: the role of ERK1/2, PI3K, and matrix metalloproteinases. Circ Res. 2004 Aug 20;95(4):364-71. Epub 2004 Jul 15. [PubMed Link Image]
  3. Rocchetti R, Talevi S, Margiotta C, Calza R, Corallini A, Possati L: Antiangiogenic drugs for chemotherapy of bladder tumours. Chemotherapy. 2005 Oct;51(6):291-9. Epub 2005 Oct 13. [PubMed Link Image]
Drug Target 5 [top]
Target 5 ID 275
Target 5 Name Arachidonate 5-lipoxygenase
Target 5 Synonyms
  1. 5-LO
  2. 5-lipoxygenase
  3. EC 1.13.11.34
Target 5 Gene Name ALOX5
Target 5 Protein Sequence >Arachidonate 5-lipoxygenase 
PSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEE
LGEIQLVRIEKRKYWLNDDWYLKYITLKTPHGDYIEFPCYRWITGDVEVVLRDGRAKLAR
DDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVLN
YSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNGC
NPVLIRRCTELPEKLPVTTEMVECSLERQLSLEQEVQQGNIFIVDFELLDGIDANKTDPC
TLQFLAAPICLLYKNLANKIVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDFH
VHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAHVRFTIAINTKAREQLICECGL
FDKANATGGGGHVQMVQRAMKDLTYASLCFPEAIKARGMESKEDIPYYFYRDDGLLVWEA
IRTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSREQLSEYLT
VVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCWH
LGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMARFRKNLEAIVSVIAERNKKKQLPYY
YLSPDRIPNSVAI
Target 5 Number of Residues 684
Target 5 Molecular Weight 77853
Target 5 Theoretical pI 5.54
Target 5 GO Classification
Function
catalytic activity
oxidoreductase activity
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
lipoxygenase activity
binding
ion binding
cation binding
transition metal ion binding
iron ion binding
Process
organic acid metabolism
carboxylic acid metabolism
fatty acid metabolism
icosanoid metabolism
leukotriene metabolism
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport
Component
Not Available
Target 5 General Function Involved in oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
Target 5 Specific Function Not Available
Target 5 Pathways
Name SMPDB Link KEGG Link
Prostaglandin and leukotriene metabolism map00590 Link Image
Target 5 Reactions
  • arachidonate + O2 = (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyicosa-6,8,11,14-tetraenoate
Target 5 Pfam Domain Function
Target 5 Signals
  • None
Target 5 Transmembrane Regions
  • None
Target 5 Essentiality Non-Essential
Target 5 GenBank ID Protein 187193 Link Image
Target 5 UniProtKB/Swiss-Prot ID P09917 Link Image
Target 5 UniProtKB/Swiss-Prot Entry Name LOX5_HUMAN Link Image
Target 5 PDB ID Not Available
Target 5 Cellular Location
  • Cytoplasm
Target 5 Gene Sequence >2025 bp 
ATGCCCTCCTACACGGTCACCGTGGCCACTGGCAGCCAGTGGTTCGCCGGCACTGACGAC
TACATCTACCTCAGCCTCGTGGGCTCGGCGGGCTGCAGCGAGAAGCACCTGCTGGACAAG
CCCTTCTACAACGACTTCGAGCGTGGCGCGGTGGATTCATACGACGTGACTGTGGACGAG
GAACTGGGCGAGATCCAGCTGGTCAGAATCGAGAAGCGCAAGTACTGGCTGAATGACGAC
TGGTACCTGAAGTACATCACGCTGAAGACGCCCCACGGGGACTACATCGAGTTCCCCTGC
TACCGCTGGATCACCGGCGATGTCGAGGTTGTCCTGAGGGATGGACGCGCAAAGTTGGCC
CGAGATGACCAAATTCACATTCTCAAGCAACACCGACGTAAAGAACTGGAAACACGGCAA
AAACAATATCGATGGATGGAGTGGAACCCTGGCTTCCCCTTGAGCATCGATGCCAAATGC
CACAAGGATTTACCCCGTGATATCCAGTTTGATAGTGAAAAAGGAGTGGACTTTGTTCTG
AATTACTCCAAAGCGATGGAGAACCTGTTCATCAACCGCTTCATGCACATGTTCCAGTCT
TCTTGGAATGACTTCGCCGACTTTGAGAAAATCTTTGTCAAGATCAGCAACACTATTTCT
GAGCGGGTCATGAATCACTGGCAGGAAGACCTGATGTTTGGCTACCAGTTCCTGAATGGC
TGCAACCCTGTGTTGATCCGGCGCTGCACAGAGCTGCCCGAGAAGCTCCCGGTGACCACG
GAGATGGTAGAGTGCAGCCTGGAGCGGCAGCTCAGCTTGGAGCAGGAGGTCCAGCAAGGG
AACATTTTCATCGTGGACTTTGAGCTGCTGGATGGCATCGATGCCAACAAAACAGACCCC
TGCACACTCCAGTTCCTGGCCGCTCCCATCTGCTTGCTGTATAAGAACCTGGCCAACAAG
ATTGTCCCCATTGCCATCCAGCTCAACCAAATCCCGGGAGATGAGAACCCTATTTTCCTC
CCTTCGGATGCAAAATACGACTGGCTTTTGGCCAAAATCTGGGTGCGTTCCAGTGACTTC
CACGTCCACCAGACCATCACCCACCTTCTGCGAACACATCTGGTGTCTGAGGTTTTTGGC
ATTGCAATGTACCGCCAGCTGCCTGCTGTGCACCCCATTTTCAAGCTGCTGGTGGCACAC
GTGAGATTCACCATTGCAATCAACACCAAGGCCCGTGAGCAGCTCATCTGCGAGTGTGGC
CTCTTTGACAAGGCCAACGCCACAGGGGGCGGTGGGCACGTGCAGATGGTGCAGAGGGCC
ATGAAGGACCTGACCTATGCCTCCCTGTGCTTTCCCGAGGCCATCAAGGCCCGGGGCATG
GAGAGCAAAGAAGACATCCCCTACTACTTCTACCGGGACGACGGGCTCCTGGTGTGGGAA
GCCATCAGGACGTTCACGGCCGAGGTGGTAGACATCTACTACGAGGGCGACCAGGTGGTG
GAGGAGGACCCGGAGCTGCAGGACTTCGTGAACGATGTCTACGTGTACGGCATGCGGGGC
CGCAAGTCCTCAGGCTTCCCCAAGTCGGTCAAGAGCCGGGAGCAGCTGTCGGAGTACCTG
ACCGTGGTGATCTTCACCGCCTCCGCCCAGCACGCCGCGGTCAACTTCGGCCAGTACGAC
TGGTGCTCCTGGATCCCCAATGCGCCCCCAACCATGCGAGCCCCGCCACCGACTGCCAAG
GGCGTGGTGACCATTGAGCAGATCGTGGACACGCTGCCCGACCGCGGCCGCTCCTGCTGG
CATCTGGGTGCAGTGTGGGCGCTGAGCCAGTTCCAGGAAAACGAGCTGTTCCTGGGCATG
TACCCAGAAGAGCATTTTATCGAGAAGCCTGTGAAGGAAGCCATGGCCCGATTCCGCAAG
AACCTCGAGGCCATTGTCAGCGTGATTGCTGAGCGCAACAAGAAGAAGCAGCTGCCATAT
TACTACTTGTCCCCAGACCGGATTCCGAACAGTGTGGCCATCTGA
Target 5 GenBank Gene ID
Target 5 GeneCard ID ALOX5 Link Image
Target 5 GenAtlas ID ALOX5 Link Image
Target 5 HGNC ID HGNC:435 Link Image
Target 5 Chromosome Location 10
Target 5 Locus 10q11.2
Target 5 SNPs SNPJam Report Link Image
Target 5 General References
  1. Werz O, Szellas D, Steinhilber D, Radmark O: Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2). J Biol Chem. 2002 Apr 26;277(17):14793-800. Epub 2002 Feb 13. [PubMed Link Image]
  2. Ishii S, Noguchi M, Miyano M, Matsumoto T, Noma M: Mutagenesis studies on the amino acid residues involved in the iron-binding and the activity of human 5-lipoxygenase. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1482-90. [PubMed Link Image]
  3. Nguyen T, Falgueyret JP, Abramovitz M, Riendeau D: Evaluation of the role of conserved His and Met residues among lipoxygenases by site-directed mutagenesis of recombinant human 5-lipoxygenase. J Biol Chem. 1991 Nov 15;266(32):22057-62. [PubMed Link Image]
  4. Hoshiko S, Radmark O, Samuelsson B: Characterization of the human 5-lipoxygenase gene promoter. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9073-7. [PubMed Link Image]
  5. Matsumoto T, Funk CD, Radmark O, Hoog JO, Jornvall H, Samuelsson B: Molecular cloning and amino acid sequence of human 5-lipoxygenase. Adv Prostaglandin Thromboxane Leukot Res. 1989;19:466-9. [PubMed Link Image]
  6. Funk CD, Hoshiko S, Matsumoto T, Rdmark O, Samuelsson B: Characterization of the human 5-lipoxygenase gene. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2587-91. [PubMed Link Image]
  7. Matsumoto T, Funk CD, Radmark O, Hoog JO, Jornvall H, Samuelsson B: Molecular cloning and amino acid sequence of human 5-lipoxygenase. Proc Natl Acad Sci U S A. 1988 Jan;85(1):26-30. [PubMed Link Image]
  8. Dixon RA, Jones RE, Diehl RE, Bennett CD, Kargman S, Rouzer CA: Cloning of the cDNA for human 5-lipoxygenase. Proc Natl Acad Sci U S A. 1988 Jan;85(2):416-20. [PubMed Link Image]
Target 5 Drug References
  1. Song Y, Wei EQ, Zhang WP, Zhang L, Liu JR, Chen Z: Minocycline protects PC12 cells from ischemic-like injury and inhibits 5-lipoxygenase activation. Neuroreport. 2004 Oct 5;15(14):2181-4. [PubMed Link Image]
  2. Song Y, Wei EQ, Zhang WP, Ge QF, Liu JR, Wang ML, Huang XJ, Hu X, Chen Z: Minocycline protects PC12 cells against NMDA-induced injury via inhibiting 5-lipoxygenase activation. Brain Res. 2006 Apr 26;1085(1):57-67. Epub 2006 Mar 30. [PubMed Link Image]
  3. Chu LS, Fang SH, Zhou Y, Yu GL, Wang ML, Zhang WP, Wei EQ: Minocycline inhibits 5-lipoxygenase activation and brain inflammation after focal cerebral ischemia in rats. Acta Pharmacol Sin. 2007 Jun;28(6):763-72. [PubMed Link Image]
Drug Target 6 [top]
Target 6 ID 494
Target 6 Name Caspase-1
Target 6 Synonyms
  1. CASP-1
  2. Caspase-1 precursor
  3. EC 3.4.22.36
  4. ICE
  5. IL-1 beta-converting enzyme
  6. IL-1BC
  7. Interleukin- 1 beta-converting enzyme
  8. Interleukin-1 beta convertase
  9. p45
Target 6 Gene Name CASP1
Target 6 Protein Sequence >Caspase-1 precursor 
MADKVLKEKRKLFIRSMGEGTINGLLDELLQTRVLNKEEMEKVKRENATVMDKTRALIDS
VIPKGAQACQICITYICEEDSYLAGTLGLSADQTSGNYLNMQDSQGVLSSFPAPQAVQDN
PAMPTSSGSEGNVKLCSLEEAQRIWKQKSAEIYPIMDKSSRTRLALIICNEEFDSIPRRT
GAEVDITGMTMLLQNLGYSVDVKKNLTASDMTTELEAFAHRPEHKTSDSTFLVFMSHGIR
EGICGKKHSEQVPDILQLNAIFNMLNTKNCPSLKDKPKVIIIQACRGDSPGVVWFKDSVG
VSGNLSLPTTEEFEDDAIKKAHIEKDFIAFCSSTPDNVSWRHPTMGSVFIGRLIEHMQEY
ACSCDVEEIFRKVRFSFEQPDGRAQMPTTERVTLTRCFYLFPGH
Target 6 Number of Residues 410
Target 6 Molecular Weight 45159
Target 6 Theoretical pI 5.71
Target 6 GO Classification
Function
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
cysteine-type endopeptidase activity
caspase activity
binding
protein binding
Process
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
regulation of biological process
regulation of physiological process
regulation of cellular physiological process
regulation of programmed cell death
regulation of apoptosis
Component
cell
intracellular
Target 6 General Function Involved in signal transduction activity
Target 6 Specific Function Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Specifically inhibited by the cowpox virus Crma protein
Target 6 Pathways Not Available
Target 6 Reactions
  • Strict requirement for an Asp residue at position P1 and has a preferred cleavage sequence of Tyr-Val-Ala-Asp!
Target 6 Pfam Domain Function
Target 6 Signals
  • None
Target 6 Transmembrane Regions
  • None
Target 6 Essentiality Non-Essential
Target 6 GenBank ID Protein 33793 Link Image
Target 6 UniProtKB/Swiss-Prot ID P29466 Link Image
Target 6 UniProtKB/Swiss-Prot Entry Name CASP1_HUMAN Link Image
Target 6 PDB ID 1IBC Link Image
Target 6 PDB File Show
Target 6 3D Structure
Target 6 Cellular Location
  • Cytoplasm
Target 6 Gene Sequence >1215 bp 
ATGGCCGACAAGGTCCTGAAGGAGAAGAGAAAGCTGTTTATCCGTTCCATGGGTGAAGGT
ACAATAAATGGCTTACTGGATGAATTATTACAGACAAGGGTGCTGAACAAGGAAGAGATG
GAGAAAGTAAAACGTGAAAATGCTACAGTTATGGATAAGACCCGAGCTTTGATTGACTCC
GTTATTCCGAAAGGGGCACAGGCATGCCAAATTTGCATCACATACATTTGTGAAGAAGAC
AGTTACCTGGCAGGGACGCTGGGACTCTCAGCAGATCAAACATCTGGAAATTACCTTAAT
ATGCAAGACTCTCAAGGAGTACTTTCTTCCTTTCCAGCTCCTCAGGCAGTGCAGGACAAC
CCAGCTATGCCCACATCCTCAGGCTCAGAAGGGAATGTCAAGCTTTGCTCCCTAGAAGAA
GCTCAAAGGATATGGAAACAAAAGTCGGCAGAGATTTATCCAATAATGGACAAGTCAAGC
CGCACACGTCTTGCTCTCATTATCTGCAATGAAGAATTTGACAGTATTCCTAGAAGAACT
GGAGCTGAGGTTGACATCACAGGCATGACAATGCTGCTACAAAATCTGGGGTACAGCGTA
GATGTGAAAAAAAATCTCACTGCTTCGGACATGACTACAGAGCTGGAGGCATTTGCACAC
CGCCCAGAGCACAAGACCTCTGACAGCACGTTCCTGGTGTTCATGTCTCATGGTATTCGG
GAAGGCATTTGTGGGAAGAAACACTCTGAGCAAGTCCCAGATATACTACAACTCAATGCA
ATCTTTAACATGTTGAATACCAAGAACTGCCCAAGTTTGAAGGACAAACCGAAGGTGATC
ATCATCCAGGCCTGCCGTGGTGACAGCCCTGGTGTGGTGTGGTTTAAAGATTCAGTAGGA
GTTTCTGGAAACCTATCTTTACCAACTACAGAAGAGTTTGAGGATGATGCTATTAAGAAA
GCCCACATAGAGAAGGATTTTATCGCTTTCTGCTCTTCCACACCAGATAATGTTTCTTGG
AGACATCCCACAATGGGCTCTGTTTTTATTGGAAGACTCATTGAACATATGCAAGAATAT
GCCTGTTCCTGTGATGTGGAGGAAATTTTCCGCAAGGTTCGATTTTCATTTGAGCAGCCA
GATGGTAGAGCGCAGATGCCCACCACTGAAAGAGTGACTTTGACAAGATGTTTCTACCTC
TTCCCAGGACATTAA
Target 6 GenBank Gene ID
Target 6 GeneCard ID CASP1 Link Image
Target 6 GenAtlas ID CASP1 Link Image
Target 6 HGNC ID HGNC:1499 Link Image
Target 6 Chromosome Location 11
Target 6 Locus 11q23
Target 6 SNPs SNPJam Report Link Image
Target 6 General References
  1. Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K, Greenstreet TA, March CJ, Kronheim SR, Druck T, Cannizzaro LA, et al.: Molecular cloning of the interleukin-1 beta converting enzyme. Science. 1992 Apr 3;256(5053):97-100. [PubMed Link Image]
  2. Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR, Aunins J, et al.: A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature. 1992 Apr 30;356(6372):768-74. [PubMed Link Image]
  3. Alnemri ES, Fernandes-Alnemri T, Litwack G: Cloning and expression of four novel isoforms of human interleukin-1 beta converting enzyme with different apoptotic activities. J Biol Chem. 1995 Mar 3;270(9):4312-7. [PubMed Link Image]
  4. Walker NP, Talanian RV, Brady KD, Dang LC, Bump NJ, Ferenz CR, Franklin S, Ghayur T, Hackett MC, Hammill LD, et al.: Crystal structure of the cysteine protease interleukin-1 beta-converting enzyme: a (p20/p10)2 homodimer. Cell. 1994 Jul 29;78(2):343-52. [PubMed Link Image]
  5. Rano TA, Timkey T, Peterson EP, Rotonda J, Nicholson DW, Becker JW, Chapman KT, Thornberry NA: A combinatorial approach for determining protease specificities: application to interleukin-1beta converting enzyme (ICE). Chem Biol. 1997 Feb;4(2):149-55. [PubMed Link Image]
  6. Okamoto Y, Anan H, Nakai E, Morihira K, Yonetoku Y, Kurihara H, Sakashita H, Terai Y, Takeuchi M, Shibanuma T, Isomura Y: Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: synthesis, structure activity relationships and crystallographic study of the ICE-inhibitor complex. Chem Pharm Bull (Tokyo). 1999 Jan;47(1):11-21. [PubMed Link Image]
Target 6 Drug References
  1. Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, Bian J, Guo L, Farrell LA, Hersch SM, Hobbs W, Vonsattel JP, Cha JH, Friedlander RM: Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med. 2000 Jul;6(7):797-801. [PubMed Link Image]
  2. Sanchez Mejia RO, Ona VO, Li M, Friedlander RM: Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction. Neurosurgery. 2001 Jun;48(6):1393-9; discussion 1399-401. [PubMed Link Image]
  3. Vincent JA, Mohr S: Inhibition of caspase-1/interleukin-1beta signaling prevents degeneration of retinal capillaries in diabetes and galactosemia. Diabetes. 2007 Jan;56(1):224-30. [PubMed Link Image]
Drug Target 7 [top]
Target 7 ID 883
Target 7 Name 16S rRNA
Target 7 Synonyms
  1. 16S ribosomal ribonucleic acid
Target 7 Gene Name Not Available
Target 7 Protein Sequence Not Available
Target 7 Number of Residues 0
Target 7 Molecular Weight Not Available
Target 7 Theoretical pI Not Available
Target 7 GO Classification
Function
transferase activity
translation
RNA binding
Process
rRNA processing
RNA processing and modification
Component
cell
Target 7 General Function Translation, ribosomal structure and biogenesis
Target 7 Specific Function In prokaryotes, the 16S rRNA is essential for recognizing the 5' end of mRNA and hence positioning it correctly on the ribosome. The 16S rRNA has a characteristic secondary structure in which half of the nucleotides are base-paired. The 16S rRNA sequence has been highly conserved and is often used for evolutionary and species comparative analysis.
Target 7 Pathways
Name SMPDB Link KEGG Link
Ribosome map03010 Link Image
Target 7 Reactions
  • rRNA + mRNA + Amino Acids = Polypeptide
Target 7 Pfam Domain Function Not Available
Target 7 Signals
  • None
Target 7 Transmembrane Regions
  • None
Target 7 Essentiality Essential
Target 7 GenBank ID Protein Not Available
Target 7 UniProtKB/Swiss-Prot ID Not Available
Target 7 UniProtKB/Swiss-Prot Entry Name Not Available
Target 7 PDB ID 1EMI Link Image
Target 7 PDB File Show
Target 7 3D Structure
Target 7 Cellular Location
  • Cytoplasmic
Target 7 Gene Sequence >16S rRNA sequence 
AAATTGAAGAGTTTGATCATGGCTCAGATTGAACGCTGGCGGCAGGCCTAACACATGCAA
GTCGAACGGTAACAGGAAACAGCTTGCTGTTTCGCTGACGAGTGGCGGACGGGTGAGTAA
TGTCTGGGAAACTGCCTGATGGAGGGGGATAACTACTGGAAACGGTAGCTAATACCGCAT
AACGTCGCAAGACCAAAGAGGGGGACCCTCGGGCCTCTTGCCATCGGATGTGCCCAGATG
GGATTAGCTTGTTGGTGGGGTAACGGCTCACCAAGGCGACGATCCCTAGCTGGTCTGAGA
GGATGACCAGCCACACTGGAACTGAGACACGGTCCAGACTCCTACGGGAGGCAGCAGTGG
GGAATATTGCACAATGGGCGCAAGCCTGATGCAGCCATGCCGCGTGTATGAAGAAGGCCT
TCGGGTTGTAAAGTACTTTCAGCGGGGAGGAAGGGAGTAAAGTTAATACCTTTGCTCATT
GACGTTACCCGCAGAAGAAGCACCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAG
GGTGCAAGCGTTAATCGGAATTACTGGGCGTAAAGCGCACGCAGGCGGTTTGTTAAGTCA
GATGTGAAATCCCCGGGCTCAACCTGGGAACTGCATCTGATACTGGCAAGCTTGAGTCTC
GTAGAGGGGGGTAGAATTCCAGGTGTAGCGGTGAAATGCGTAGAGATCTGGAGGAATACC
GGTGGCGAAGGCGGCCCCCTGGACGAAGACTGACGCTCAGGTGCGAAAGCGTGGGGAGCA
AACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGTCGACTTGGAGGTTGTGCC
CTTGAGGCGTGGCTTCCGGAGCTAACGCGTTAAGTCGACCGCCTGGGGAGTACGGCCGCA
AGGTTAAAACTCAAATGAATTGACGGGGGCCCGCACAAGCGGTGGAGCATGTGGTTTAAT
TCGATGCAACGCGAAGAACCTTACCTGGTCTTGACATCCACGGAAGTTTTCAGAGATGAG
AATGTGCCTTCGGGAACCGTGAGACAGGTGCTGCATGGCTGTCGTCAGCTCGTGTTGTGA
AATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCCTTTGTTGCCAGCGGTCCGGC
CGGGAACTCAAAGGAGACTGCCAGTGATAAACTGGAGGAAGGTGGGGATGACGTCAAGTC
ATCATGGCCCTTACGACCAGGGCTACACACGTGCTACAATGGCGCATACAAAGAGAAGCG
ACCTCGCGAGAGCAAGCGGACCTCATAAAGTGCGTCGTAGTCCGGATTGGAGTCTGCAAC
TCGACTCCATGAAGTCGGAATCGCTAGTAATCGTGGATCAGAATGCCACGGTGAATACGT
TCCCGGGCCTTGTACACACCGCCCGTCACACCATGGGAGTGGGTTGCAAAAGAAGTAGGT
AGCTTAACCTTCGGGAGGGCGCTTACCACTTTGTGATTCATGACTGGGGTGAAGTCGTAA
CAAGGTAACCGTAGGGGAACCTGCGGTTGGATCACCTCCTTA
Target 7 GenBank Gene ID
Target 7 GeneCard ID Not Available
Target 7 GenAtlas ID Not Available
Target 7 HGNC ID Not Available
Target 7 Chromosome Location Not Available
Target 7 Locus Not Available
Target 7 SNPs Not Available
Target 7 General References
  1. Gu XR, Gustafsson C, Ku J, Yu M, Santi DV: Identification of the 16S rRNA m5C967 methyltransferase from Escherichia coli. Biochemistry. 1999 Mar 30;38(13):4053-7. [PubMed Link Image]
  2. Martin JF, Barreiro C, Gonzalez-Lavado E, Barriuso M: Ribosomal RNA and ribosomal proteins in corynebacteria. J Biotechnol. 2003 Sep 4;104(1-3):41-53. [PubMed Link Image]
  3. Srivastava AK, Schlessinger D: Structure and organization of ribosomal DNA. Biochimie. 1991 Jun;73(6):631-8. [PubMed Link Image]
  4. Gutell RR, Larsen N, Woese CR: Lessons from an evolving rRNA: 16S and 23S rRNA structures from a comparative perspective. Microbiol Rev. 1994 Mar;58(1):10-26. [PubMed Link Image]
Target 7 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 8 [top]
Target 8 ID 1507
Target 8 Name Cytochrome c
Target 8 Synonyms Not Available
Target 8 Gene Name CYCS
Target 8 Protein Sequence >Cytochrome c 
MGDVEKGKKIFIMKCSQCHTVEKGGKHKTGPNLHGLFGRKTGQAPGYSYTAANKNKGIIW
GEDTLMEYLENPKKYIPGTKMIFVGIKKKEERADLIAYLKKATNE
Target 8 Number of Residues 106
Target 8 Molecular Weight 11749
Target 8 Theoretical pI 10.16
Target 8 GO Classification
Function
binding
tetrapyrrole binding
heme binding
transporter activity
electron transporter activity
Process
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport
Component
Not Available
Target 8 General Function Energy production and conversion
Target 8 Specific Function Plays a role in apoptosis. Suppression of the anti- apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases
Target 8 Pathways Not Available
Target 8 Reactions Not Available
Target 8 Pfam Domain Function
Target 8 Signals
  • None
Target 8 Transmembrane Regions
  • None
Target 8 Essentiality Non-Essential
Target 8 GenBank ID Protein 181242 Link Image
Target 8 UniProtKB/Swiss-Prot ID P99999 Link Image
Target 8 UniProtKB/Swiss-Prot Entry Name CYC_HUMAN Link Image
Target 8 PDB ID 1J3S Link Image
Target 8 PDB File Show
Target 8 3D Structure
Target 8 Cellular Location
  • Mitochondrion
  • mitochondrial matrix
Target 8 Gene Sequence >318 bp 
ATGGGTGATGTTGAGAAAGGCAAGAAGATTTTTATTATGAAGTGTTCCCAGTGCCACACC
GTTGAAAAGGGAGGCAAGCACAAGACTGGGCCAAATCTCCATGGTCTCTTTGGGCGGAAG
ACAGGTCAGGCCCCTGGATACTCTTACACAGCCGCCAATAAGAACAAAGGCATCATCTGG
GGAGAGGATACACTGATGGAGTATTTGGAGAATCCCAAGAAGTACATCCCTGGAACAAAA
ATGATCTTTGTCGGCATTAAGAAGAAGGAAGAAAGGGCAGACTTAATAGCTTATCTCAAA
AAAGCTACTAATGAGTAA
Target 8 GenBank Gene ID
Target 8 GeneCard ID CYCS Link Image
Target 8 GenAtlas ID CYCS Link Image
Target 8 HGNC ID HGNC:19986 Link Image
Target 8 Chromosome Location 7
Target 8 Locus 7p15.2
Target 8 SNPs SNPJam Report Link Image
Target 8 General References
  1. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [PubMed Link Image]
  2. Evans MJ, Scarpulla RC: The human somatic cytochrome c gene: two classes of processed pseudogenes demarcate a period of rapid molecular evolution. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9625-9. [PubMed Link Image]
  3. Skulachev VP: Cytochrome c in the apoptotic and antioxidant cascades. FEBS Lett. 1998 Feb 27;423(3):275-80. [PubMed Link Image]
Target 8 Drug References
  1. Zhu S, Stavrovskaya IG, Drozda M, Kim BY, Ona V, Li M, Sarang S, Liu AS, Hartley DM, Wu DC, Gullans S, Ferrante RJ, Przedborski S, Kristal BS, Friedlander RM: Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature. 2002 May 2;417(6884):74-8. [PubMed Link Image]
  2. Matsuki S, Iuchi Y, Ikeda Y, Sasagawa I, Tomita Y, Fujii J: Suppression of cytochrome c release and apoptosis in testes with heat stress by minocycline. Biochem Biophys Res Commun. 2003 Dec 19;312(3):843-9. [PubMed Link Image]
  3. Chu HC, Lin YL, Sytwu HK, Lin SH, Liao CL, Chao YC: Effects of minocycline on Fas-mediated fulminant hepatitis in mice. Br J Pharmacol. 2005 Jan;144(2):275-82. [PubMed Link Image]
  4. Heo K, Cho YJ, Cho KJ, Kim HW, Kim HJ, Shin HY, Lee BI, Kim GW: Minocycline inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after treatment with kainic acid in mice. Neurosci Lett. 2006 May 8;398(3):195-200. Epub 2006 Feb 15. [PubMed Link Image]
  5. Mansson R, Hansson MJ, Morota S, Uchino H, Ekdahl CT, Elmer E: Re-evaluation of mitochondrial permeability transition as a primary neuroprotective target of minocycline. Neurobiol Dis. 2007 Jan;25(1):198-205. Epub 2006 Oct 24. [PubMed Link Image]
Drug Target 9 [top]
Target 9 ID 1654
Target 9 Name Interleukin-1 beta
Target 9 Synonyms
  1. Catabolin
  2. IL-1 beta
  3. Interleukin-1 beta precursor
Target 9 Gene Name IL1B
Target 9 Protein Sequence >Interleukin-1 beta precursor 
MAEVPELASEMMAYYSGNEDDLFFEADGPKQMKCSFQDLDLCPLDGGIQLRISDHHYSKG
FRQAASVVVAMDKLRKMLVPCPQTFQENDLSTFFPFIFEEEPIFFDTWDNEAYVHDAPVR
SLNCTLRDSQQKSLVMSGPYELKALHLQGQDMEQQVVFSMSFVQGEESNDKIPVALGLKE
KNLYLSCVLKDDKPTLQLESVDPKNYPKKKMEKRFVFNKIEINNKLEFESAQFPNWYIST
SQAENMPVFLGGTKGGQDITDFTMQFVSS
Target 9 Number of Residues 273
Target 9 Molecular Weight 30748
Target 9 Theoretical pI 4.45
Target 9 GO Classification
Function
cytokine activity
interleukin-1 receptor binding
signal transducer activity
receptor binding
growth factor activity
Process
response to stimulus
response to biotic stimulus
defense response
immune response
inflammatory response
Component
extracellular region
Target 9 General Function Involved in growth factor activity
Target 9 Specific Function Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells
Target 9 Pathways Not Available
Target 9 Reactions Not Available
Target 9 Pfam Domain Function
Target 9 Signals
  • None
Target 9 Transmembrane Regions
  • None
Target 9 Essentiality Non-Essential
Target 9 GenBank ID Protein 307043 Link Image
Target 9 UniProtKB/Swiss-Prot ID P01584 Link Image
Target 9 UniProtKB/Swiss-Prot Entry Name IL1B_HUMAN Link Image
Target 9 PDB ID 9ILB Link Image
Target 9 PDB File Show
Target 9 3D Structure
Target 9 Cellular Location
  • Secreted protein. Note=The lack of a specific hydrophobic segment in the precursor sequence suggests
Target 9 Gene Sequence >810 bp 
ATGGCAGAAGTACCTAAGCTCGCCAGTGAAATGATGGCTTATTACAGTGGCAATGAGGAT
GACTTGTTCTTTGAAGCTGATGGCCCTAAACAGATGAAGTGCTCCTTCCAGGACCTGGAC
CTCTGCCCTCTGGATGGCGGCATCCAGCTACGAATCTCCGACCACCACTACAGCAAGGGC
TTCAGGCAGGCCGCGTCAGTTGTTGTGGCCATGGACAAGCTGAGGAAGATGCTGGTTCCC
TGCCCACAGACCTTCCAGGAGAATGACCTGAGCACCTTCTTTCCCTTCATCTTTGAAGAA
GAACCTATCTTCTTCGACACATGGGATAACGAGGCTTATGTGCACGATGCACCTGTACGA
TCACTGAACTGCACGCTCCGGGACTCACAGCAAAAAAGCTTGGTGATGTCTGGTCCATAT
GAACTGAAAGCTCTCCACCTCCAGGGACAGGATATGGAGCAACAAGTGGTGTTCTCCATG
TCCTTTGTACAAGGAGAAGAAAGTAATGACAAAATACCTGTGGCCTTGGGCCTCAAGGAA
AAGAATCTGTACCTGTCCTGCGTGTTGAAAGATGATAAGCCCACTCTACAGCTGGAGAGT
GTAGATCCCAAAAATTACCCAAAGAAGAAGATGGAAAAGCGATTTGTCTTCAACAAGATA
GAAATCAATAACAAGCTGGAATTTGAGTCTGCCCAGTTCCCCAACTGGTACATCAGCACC
TCTCAAGCAGAAAACATGCCCGTCTTCCTGGGAGGGACCAAAGGCGGCCAGGATATAACT
GACTTCACCATGCAATTTGTGTCTTCCTAA
Target 9 GenBank Gene ID
Target 9 GeneCard ID IL1B Link Image
Target 9 GenAtlas ID IL1B Link Image
Target 9 HGNC ID HGNC:5992 Link Image
Target 9 Chromosome Location 2
Target 9 Locus 2q14
Target 9 SNPs SNPJam Report Link Image
Target 9 General References
  1. Nicklin MJ, Barton JL, Nguyen M, FitzGerald MG, Duff GW, Kornman K: A sequence-based map of the nine genes of the human interleukin-1 cluster. Genomics. 2002 May;79(5):718-25. [PubMed Link Image]
  2. Nanduri VB, Hulmes JD, Pan YC, Kilian PL, Stern AS: The role of arginine residues in interleukin 1 receptor binding. Biochim Biophys Acta. 1991 Dec 11;1118(1):25-35. [PubMed Link Image]
  3. Mizutani H, Schechter N, Lazarus G, Black RA, Kupper TS: Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase. J Exp Med. 1991 Oct 1;174(4):821-5. [PubMed Link Image]
  4. Clore GM, Wingfield PT, Gronenborn AM: High-resolution three-dimensional structure of interleukin 1 beta in solution by three- and four-dimensional nuclear magnetic resonance spectroscopy. Biochemistry. 1991 Mar 5;30(9):2315-23. [PubMed Link Image]
  5. Driscoll PC, Gronenborn AM, Wingfield PT, Clore GM: Determination of the secondary structure and molecular topology of interleukin-1 beta by use of two- and three-dimensional heteronuclear 15N-1H NMR spectroscopy. Biochemistry. 1990 May 15;29(19):4668-82. [PubMed Link Image]
  6. Finzel BC, Clancy LL, Holland DR, Muchmore SW, Watenpaugh KD, Einspahr HM: Crystal structure of recombinant human interleukin-1 beta at 2.0 A resolution. J Mol Biol. 1989 Oct 20;209(4):779-91. [PubMed Link Image]
  7. Priestle JP, Schar HP, Grutter MG: Crystallographic refinement of interleukin 1 beta at 2.0 A resolution. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9667-71. [PubMed Link Image]
  8. Kotenko SV, Bulenkov MT, Veiko VP, Epishin SM, Lomakin IB: [Cloning of the cDNA coding for human prointerleukin-1 alpha and prointerleukin-1 beta] Dokl Akad Nauk SSSR. 1989;309(4):1005-8. [PubMed Link Image]
  9. Bensi G, Raugei G, Palla E, Carinci V, Tornese Buonamassa D, Melli M: Human interleukin-1 beta gene. Gene. 1987;52(1):95-101. [PubMed Link Image]
  10. March CJ, Mosley B, Larsen A, Cerretti DP, Braedt G, Price V, Gillis S, Henney CS, Kronheim SR, Grabstein K, et al.: Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985 Jun 20-26;315(6021):641-7. [PubMed Link Image]
  11. 3259176 Priestle JP, Schar HP, Grutter MG: Crystal structure of the cytokine interleukin-1 beta. EMBO J. 1988 Feb;7(2):339-43.
  12. 3281727 Zsebo KM, Wypych J, Yuschenkoff VN, Lu H, Hunt P, Dukes PP, Langley KE: Effects of hematopoietin-1 and interleukin 1 activities on early hematopoietic cells of the bone marrow. Blood. 1988 Apr;71(4):962-8.
  13. 3490654 Clark BD, Collins KL, Gandy MS, Webb AC, Auron PE: Genomic sequence for human prointerleukin 1 beta: possible evolution from a reverse transcribed prointerleukin 1 alpha gene. Nucleic Acids Res. 1986 Oct 24;14(20):7897-914.
  14. 3493774 Nishida T, Nishino N, Takano M, Kawai K, Bando K, Masui Y, Nakai S, Hirai Y: cDNA cloning of IL-1 alpha and IL-1 beta from mRNA of U937 cell line. Biochem Biophys Res Commun. 1987 Feb 27;143(1):345-52.
  15. 6083565 Auron PE, Webb AC, Rosenwasser LJ, Mucci SF, Rich A, Wolff SM, Dinarello CA: Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7907-11.
  16. 9062193 Vigers GP, Anderson LJ, Caffes P, Brandhuber BJ: Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1beta. Nature. 1997 Mar 13;386(6621):190-4.
Target 9 Drug References
  1. Sadowski T, Steinmeyer J: Minocycline inhibits the production of inducible nitric oxide synthase in articular chondrocytes. J Rheumatol. 2001 Feb;28(2):336-40. [PubMed Link Image]
  2. Oringer RJ, Al-Shammari KF, Aldredge WA, Iacono VJ, Eber RM, Wang HL, Berwald B, Nejat R, Giannobile WV: Effect of locally delivered minocycline microspheres on markers of bone resorption. J Periodontol. 2002 Aug;73(8):835-42. [PubMed Link Image]
  3. Amin AR, Attur MG, Thakker GD, Patel PD, Vyas PR, Patel RN, Patel IR, Abramson SB: A novel mechanism of action of tetracyclines: effects on nitric oxide synthases. Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14014-9. [PubMed Link Image]
  4. Steinmeyer J, Daufeldt S, Taiwo YO: Pharmacological effect of tetracyclines on proteoglycanases from interleukin-1-treated articular cartilage. Biochem Pharmacol. 1998 Jan 1;55(1):93-100. [PubMed Link Image]
Drug Target 10 [top]
Target 10 ID 2077
Target 10 Name Caspase-3
Target 10 Synonyms
  1. Apopain
  2. CASP-3
  3. CPP-32
  4. Caspase-3 precursor
  5. Cysteine protease CPP32
  6. EC 3.4.22.56
  7. SCA-1
  8. SREBP cleavage activity 1
  9. Yama protein
Target 10 Gene Name CASP3
Target 10 Protein Sequence >Caspase-3 precursor 
MENTENSVDSKSIKNLEPKIIHGSESMDSGISLDNSYKMDYPEMGLCIIINNKNFHKSTG
MTSRSGTDVDAANLRETFRNLKYEVRNKNDLTREEIVELMRDVSKEDHSKRSSFVCVLLS
HGEEGIIFGTNGPVDLKKITNFFRGDRCRSLTGKPKLFIIQACRGTELDCGIETDSGVDD
DMACHKIPVEADFLYAYSTAPGYYSWRNSKDGSWFIQSLCAMLKQYADKLEFMHILTRVN
RKVATEFESFSFDATFHAKKQIPCIVSMLTKELYFYH
Target 10 Number of Residues 281
Target 10 Molecular Weight 31608
Target 10 Theoretical pI 6.51
Target 10 GO Classification
Function
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
cysteine-type endopeptidase activity
caspase activity
Process
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
Component
Not Available
Target 10 General Function Involved in caspase activity
Target 10 Specific Function Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop- helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin
Target 10 Pathways Not Available
Target 10 Reactions
  • Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp! with a hydrophobic amino-acid residue at P2 and a hydrophilic amino-acid residue at P3, although Val or Ala are also accepted at this position
Target 10 Pfam Domain Function
Target 10 Signals
  • None
Target 10 Transmembrane Regions
  • None
Target 10 Essentiality Non-Essential
Target 10 GenBank ID Protein 561666 Link Image
Target 10 UniProtKB/Swiss-Prot ID P42574 Link Image
Target 10 UniProtKB/Swiss-Prot Entry Name CASP3_HUMAN Link Image
Target 10 PDB ID 1CP3 Link Image
Target 10 PDB File Show
Target 10 3D Structure
Target 10 Cellular Location
  • Cytoplasm
Target 10 Gene Sequence >834 bp 
ATGGAGAACACTGAAAACTCAGTGGATTCAAAATCCATTAAAAATTTGGAACCAAAGATC
ATACATGGAAGCGAATCAATGGACTCTGGAATATCCCTGGACAACAGTTATAAAATGGAT
TATCCTGAGATGGGTTTATGTATAATAATTAATAATAAGAATTTTCATAAAAGCACTGGA
ATGACATCTCGGTCTGGTACAGATGTCGATGCAGCAAACCTCAGGGAAACATTCAGAAAC
TTGAAATATGAAGTCAGGAATAAAAATGATCTTACACGTGAAGAAATTGTGGAATTGATG
CGTGATGTTTCTAAAGAAGATCACAGCAAAAGGAGCAGTTTTGTTTGTGTGCTTCTGAGC
CATGGTGAAGAAGGAATAATTTTTGGAACAAATGGACCTGTTGACCTGAAAAAAATAACA
AACTTTTTCAGAGGGGATCGTTGTAGAAGTCTAACTGGAAAACCCAAACTTTTCATTATT
CAGGCCTGCCGTGGTACAGAACTGGACTGTGGCATTGAGACAGACAGTGGTGTTGATGAT
GACATGGCGTGTCATAAAATACCAGTGGATGCCGACTTCTTGTATGCATACTCCACAGCA
CCTGGTTATTATTCTTGGCGAAATTCAAAGGATGGCTCCTGGTTCATCCAGTCGCTTTGT
GCCATGCTGAAACAGTATGCCGACAAGCTTGAATTTATGCACATTCTTACCCGGGTTAAC
CGAAAGGTGGCAACAGAATTTGAGTCCTTTTCCTTTGACGCTACTTTTCATGCAAAGAAA
CAGATTCCATGTATTGTTTCCATGCTCACAAAAGAACTCTATTTTTATCACTAA
Target 10 GenBank Gene ID
Target 10 GeneCard ID CASP3 Link Image
Target 10 GenAtlas ID CASP3 Link Image
Target 10 HGNC ID HGNC:1504 Link Image
Target 10 Chromosome Location 4
Target 10 Locus 4q34
Target 10 SNPs SNPJam Report Link Image
Target 10 General References
  1. Lee D, Long SA, Adams JL, Chan G, Vaidya KS, Francis TA, Kikly K, Winkler JD, Sung CM, Debouck C, Richardson S, Levy MA, DeWolf WE Jr, Keller PM, Tomaszek T, Head MS, Ryan MD, Haltiwanger RC, Liang PH, Janson CA, McDevitt PJ, Johanson K, Concha NO, Chan W, Abdel-Meguid SS, Badger AM, Lark MW, Nadeau DP, Suva LJ, Gowen M, Nuttall ME: Potent and selective nonpeptide inhibitors of caspases 3 and 7 inhibit apoptosis and maintain cell functionality. J Biol Chem. 2000 May 26;275(21):16007-14. [PubMed Link Image]
  2. Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, et al.: Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 1995 Jul 6;376(6535):37-43. [PubMed Link Image]
  3. Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM: Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell. 1995 Jun 2;81(5):801-9. [PubMed Link Image]
  4. Fernandes-Alnemri T, Litwack G, Alnemri ES: CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. J Biol Chem. 1994 Dec 9;269(49):30761-4. [PubMed Link Image]
  5. Rotonda J, Nicholson DW, Fazil KM, Gallant M, Gareau Y, Labelle M, Peterson EP, Rasper DM, Ruel R, Vaillancourt JP, Thornberry NA, Becker JW: The three-dimensional structure of apopain/CPP32, a key mediator of apoptosis. Nat Struct Biol. 1996 Jul;3(7):619-25. [PubMed Link Image]
  6. Goldberg YP, Nicholson DW, Rasper DM, Kalchman MA, Koide HB, Graham RK, Bromm M, Kazemi-Esfarjani P, Thornberry NA, Vaillancourt JP, Hayden MR: Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat Genet. 1996 Aug;13(4):442-9. [PubMed Link Image]
  7. Fernandes-Alnemri T, Armstrong RC, Krebs J, Srinivasula SM, Wang L, Bullrich F, Fritz LC, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES: In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7464-9. [PubMed Link Image]
  8. Mittl PR, Di Marco S, Krebs JF, Bai X, Karanewsky DS, Priestle JP, Tomaselli KJ, Grutter MG: Structure of recombinant human CPP32 in complex with the tetrapeptide acetyl-Asp-Val-Ala-Asp fluoromethyl ketone. J Biol Chem. 1997 Mar 7;272(10):6539-47. [PubMed Link Image]
Target 10 Drug References
  1. Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, Bian J, Guo L, Farrell LA, Hersch SM, Hobbs W, Vonsattel JP, Cha JH, Friedlander RM: Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med. 2000 Jul;6(7):797-801. [PubMed Link Image]
  2. Arvin KL, Han BH, Du Y, Lin SZ, Paul SM, Holtzman DM: Minocycline markedly protects the neonatal brain against hypoxic-ischemic injury. Ann Neurol. 2002 Jul;52(1):54-61. [PubMed Link Image]
  3. Dommergues MA, Plaisant F, Verney C, Gressens P: Early microglial activation following neonatal excitotoxic brain damage in mice: a potential target for neuroprotection. Neuroscience. 2003;121(3):619-28. [PubMed Link Image]
  4. Lee SM, Yune TY, Kim SJ, Park DW, Lee YK, Kim YC, Oh YJ, Markelonis GJ, Oh TH: Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J Neurotrauma. 2003 Oct;20(10):1017-27. [PubMed Link Image]
  5. Baptiste DC, Hartwick AT, Jollimore CA, Baldridge WH, Seigel GM, Kelly ME: An investigation of the neuroprotective effects of tetracycline derivatives in experimental models of retinal cell death. Mol Pharmacol. 2004 Nov;66(5):1113-22. Epub 2004 Aug 10. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.