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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:47:50
Primary Accession Number DB00615
Secondary Accession Number
  • APRD00094
Name Rifabutin
Drug Type
  • Approved
  • Small Molecule
Description A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients. [PubChem]
Synonyms
  1. Ansatipin
  2. Ansatipine
  3. Antibiotic LM 427
  4. RBT
  5. Rifabutina [Spanish]
  6. Rifabutine [French]
  7. Rifabutinum [Latin]
Brand Names
  1. Alfacid
  2. Ansamycin
  3. Mycobutin
Brand Mixtures Not Available
Chemical IUPAC Name (9S,12E,14S,15R,16S,17R,18R,19R,20S,21S,22E,24Z)-6,16,18,20-Tetrahydroxy-1'-isobutyl-14-methoxy-7,9,15,17,19,21,25-hepta-methyl-spiro[9,4-(epoxypentadeca[1,11,13]trienimino)-2H-furo-[2',3':7,8]-naphth[1,2-d]imidazol-2,4'-piperidin]-5,10,26-(3H,9H)-trione 16-acetate
Chemical Formula C46H62N4O11
Chemical Structure Structure
CAS Registry Number 72559-06-9
InChI Identifier InChI=1/C46H62N4O11/c1-22(2)21-50-18-16-46(17-19-50)48-34-31-32-39(54)28(8)42-33(31)43(56)45(10,61-42)59-20-15-30(58-11)25(5)41(60-29(9)51)27(7)38(53)26(6)37(52)23(3)13-12-14-24(4)44(57)47-36(40(32)55)35(34)49-46/h12-15,20,22-23,25-27,30,37-38,41,49,52-54H,16-19,21H2,1-11H3,(H,47,57)/b13-12-,20-15-,24-14-/t23-,25-,26+,27+,30-,37-,38+,41-,45+/m1/s1/f/h47H
InChI Key ATEBXHFBFRCZMA-LDVAWSIDDL
KEGG Drug D00424 Link Image
KEGG Compound C07235 Link Image
PubChem Compound 6323490 Link Image
PubChem Substance 189788 Link Image
ChEBI ID 8857 Link Image
PharmGKB ID PA451249 Link Image
HET ID RBT Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02063786 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/rifabutin.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Rifabutin Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 847.0047
Monoisotopic Molecular Weight 846.4415
State Solid
Melting Point Not Available
Experimental Water Solubility Minimally soluble (0.19 mg/mL) Source: PhysProp
Predicted Water Solubility 1.70e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 4.1 Source: PhysProp
Predicted LogP 4.25 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.70 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 Not Available
Isomeric SMILES CO[C@@H]1\C=C/O[C@@]2(C)OC3=C(C2=O)C2=C(C(=O)C(NC(=O)\C(C)=C/C=C\[C@@H](C)[C@@H](O)[C@H](C)[C@H](O)[C@H](C)[C@H](OC(C)=O)[C@@H]1C)=C1N[C@]4(CCN(CC4)CC(C)C)N=C21)C(O)=C3C
Canonical SMILES COC1C=COC2(C)OC3=C(C2=O)C2=C(C(=O)C(NC(=O)C(C)=CC=CC(C)C(O)C(C)C(O)C(C)C(OC(C)=O)C1C)=C1NC4(CCN(CC4)CC(C)C)N=C21)C(O)=C3C
Drug Category
  • Anti-Bacterial Agents
  • Antibiotics, Antitubercular
ATC Codes
AHFS Codes
  • 08:16.04
Indication For the prevention of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection.
Pharmacology Rifabutin is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifabutin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency.
Mechanism of Action Rifabutin acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.
Absorption Rifabutin is readily absorbed from the gastrointestinal tract, with an absolute bioavailability averaging 20%.
Toxicity LD50 = 4.8 g/kg (mouse, male)
Protein Binding 85%
Biotransformation Hepatic. Of the five metabolites that have been identified, 25-O-desacetyl and 31-hydroxy are the most predominant. The former metabolite has an activity equal to the parent drug and contributes up to 10% to the total antimicrobial activity.
Half Life 45 (± 17) 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 rifamycin decreases the anticoagulant effect
Amitriptyline The rifamycin decreases the effect of tricyclics
Amoxapine The rifamycin decreases the effect of tricyclics
Amprenavir Amprenavir increases the effect and toxicity of rifabutin
Anisindione The rifamycin decreases the anticoagulant effect
Atazanavir Atazanavir increases levels/toxicity of rifabutin
Atorvastatin The rifamycin decreases the effect of the statin drug
Atovaquone Rifabutin decreases the effect of atovaquone
Bupropion Rifampin reduces bupropion levels
Buspirone Rifabutin decreases the effect of buspirone
Cerivastatin The rifamycin decreases the effect of the statin drug
Clarithromycin The rifamycin decreases the effect of the macrolide
Clomipramine The rifamycin decreases the effect of tricyclics
Clozapine Rifabutin decreases the effect of clozapine
Cyclosporine The rifamycin decreases the effect of cyclosporine
Dapsone Decreased levels of dapsone
Delavirdine Rifabutin decreases the effect of delavirdine
Desipramine The rifamycin decreases the effect of tricyclics
Dicumarol The rifamycin decreases the anticoagulant effect
Doxepin The rifamycin decreases the effect of tricyclics
Doxycycline The rifamycin decreases the effect of doxycycline
Erlotinib Decreased levels/effect of erlotinib
Erythromycin The rifamycin decreases the effect of the macrolide
Ethinyl Estradiol This product may cause a slight decrease of the contraceptive effect
Fluconazole Fluconazole increases levels/toxicity of rifabutin
Fluvastatin The rifamycin decreases the effect of the statin drug
Fosamprenavir Amprenavir increases the effect and toxicity of rifabutin
Haloperidol The rifamycin decreases the effect of haloperidol
Imipramine The rifamycin decreases the effect of tricyclics
Indinavir Rifabutin decreases the effect of indinavir
Itraconazole Rifabutin decreases the effect of itraconazole
Josamycin The rifamycin decreases the effect of the macrolide
Lovastatin The rifamycin decreases the effect of the statin drug
Mestranol This product may cause a slight decrease of the contraceptive effect
Methadone The rifamycin decreases the effect of methadone
Norethindrone This product may cause a slight decrease of the contraceptive effect
Nortriptyline The rifamycin decreases the effect of tricyclics
Posaconazole Modification of drug levels for both agents
Propafenone Rifampin decreases the effect of propafenone
Protriptyline The rifamycin decreases the effect of tricyclics
Ritonavir Rifabutin decreases the effect of ritonavir
Saquinavir Rifabutin decreases the effect of saquinavir
Simvastatin The rifamycin decreases the effect of the statin drug
Sirolimus The rifamycin decreases the effect of sirolimus
Sunitinib Possible decrease in sunitinib levels
Tacrolimus The rifamycin decreases the effect of tacrolimus
Tamoxifen The rifamycin decreases the effect of anti-estrogen
Toremifene The rifamycin decreases the effect of anti-estrogen
Trimipramine The rifamycin decreases the effect of tricyclics
Voriconazole Rifabutin decreases the effect of voriconazole
Warfarin The rifamycin decreases the anticoagulant effect
Zidovudine The rifamycin decreases levels of zidovudine
Food Interactions
  • High-fat meals slow the rate of absorption.
  • Take with food to reduce irritation.
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Enteric bacteria and other eubacteria
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
Targets
  1. DNA-directed RNA polymerase alpha chain
  2. Heat shock protein HSP 90-alpha
  3. Endoplasmin
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Drug Target 1 [top]
Target 1 ID 512
Target 1 Name DNA-directed RNA polymerase alpha chain
Target 1 Synonyms
  1. EC 2.7.7.6
  2. RNA polymerase alpha subunit
  3. RNAP alpha subunit
  4. Transcriptase alpha chain
Target 1 Gene Name rpoA
Target 1 Protein Sequence >DNA-directed RNA polymerase alpha chain 
MQGSVTEFLKPRLVDIEQVSSTHAKVTLEPLERGFGHTLGNALRRILLSSMPGCAVTEVE
IDGVLHEYSTKEGVQEDILEILLNLKGLAVRVQGKDEVILTLNKSGIGPVTAADITHDGD
VEIVKPQHVICHLTDENASISMRIKVQRGRGYVPASTRIHSEEDERPIGRLLVDACYSPV
ERIAYNVEAARVEQRTDLDKLVIEMETNGTIDPEEAIRRAATILAEQLEAFVDLRDVRQP
EVKEEKPEFDPILLRPVDDLELTVRSANCLKAEAIHYIGDLVQRTEVELLKTPNLGKKSL
TEIKDVLASRGLSLGMRLENWPPASIADE
Target 1 Number of Residues 334
Target 1 Molecular Weight 36512
Target 1 Theoretical pI 4.70
Target 1 GO Classification
Function
protein binding
protein dimerization activity
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
nucleotidyltransferase activity
DNA-directed RNA polymerase activity
binding
nucleic acid binding
DNA binding
Process
transcription, DNA-dependent
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
transcription
Component
Not Available
Target 1 General Function Transcription
Target 1 Specific Function DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. This subunit plays an important role in subunit assembly since its dimerization is the first step in the sequential assembly of subunits to form the holoenzyme
Target 1 Pathways
Name SMPDB Link KEGG Link
Purine metabolism SMP00050 Link Image map00230 Link Image
Pyrimidine metabolism SMP00046 Link Image map00240 Link Image
RNA polymerase map03020 Link Image
Target 1 Reactions
  • nucleoside triphosphate + RNAn = diphosphate + RNAn+1
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Essential
Target 1 GenBank ID Protein 147715 Link Image
Target 1 UniProtKB/Swiss-Prot ID P0A7Z4 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name RPOA_ECOLI Link Image
Target 1 PDB ID 1BDF Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Cytoplasmic
Target 1 Gene Sequence >990 bp 
ATGCAGGGTTCTGTGACAGAGTTTCTAAAACCGCGCCTGGTTGATATCGAGCAAGTGAGT
TCGACGCACGCCAAGGTGACCCTTGAGCCTTTAGAGCGTGGCTTTGGCCATACTCTGGGT
AACGCACTGCGCCGTATTCTGCTCTCATCGATGCCGGGTTGCGCGGTGACCGAGGTTGAG
ATTGATGGTGTACTACATGAGTACAGCACCAAAGAAGGCGTTCAGGAAGATATCCTGGAA
ATCCTGCTCAACCTGAAAGGGCTGGCGGTGAGAGTTCAGGGCAAAGATGAAGTTATTCTT
ACCTTGAATAAATCTGGCATTGGCCCTGTGACTGCAGCCGATATCACCCACGACGGTGAT
GTCGAAATCGTCAAGCCGCAGCACGTGATCTGCCACCTGACCGATGAGAACGCGTCTATT
AGCATGCGTATCAAAGTTCAGCGCGGTCGTGGTTATGTGCCGGCTTCTACCCGAATTCAT
TCGGAAGAAGATGAGCGCCCAATCGGCCGTCTGCTGGTCGACGCATGCTACAGCCCTGTG
GAGCGTATTGCCTACAATGTTGAAGCAGCGCGTGTAGAACAGCGTACCGACCTGGACAAG
CTGGTCATCGAAATGGAAACCAACGGCACAATCGATCCTGAAGAGGCGATTCGTCGTGCG
GCAACCATTCTGGCTGAACAACTGGAAGCTTTCGTTGACTTACGTGATGTACGTCAGCCT
GAAGTGAAAGAAGAGAAACCAGAGTTCGATCCGATCCTGCTGCGCCCTGTTGACGATCTG
GAATTGACTGTCCGCTCTGCTAACTGCCTTAAAGCAGAAGCTATCCACTATATCGGTGAT
CTGGTACAGCGTACCGAGGTTGAGCTCCTTAAAACGCCTAACCTTGGTAAAAAATCTCTT
ACTGAGATTAAAGACGTGCTGGCTTCCCGTGGACTGTCTCTGGGCATGCGCCTGGAAAAC
TGGCCACCGGCAAGCATCGCTGACGAGTAA
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. Igarashi K, Fujita N, Ishihama A: Sequence analysis of two temperature-sensitive mutations in the alpha subunit gene (rpoA) of Escherichia coli RNA polymerase. Nucleic Acids Res. 1990 Oct 25;18(20):5945-8. [PubMed Link Image]
  2. 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]
  3. Ovchinnikov YA, Lipkin VM, Modyanov NN, Chertov OY, Smirnov YV: Primary structure of alpha-subunit of DNA-dependent RNA polymerase from Escherichia coli. FEBS Lett. 1977 Apr 1;76(1):108-11. [PubMed Link Image]
  4. 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. [PubMed Link Image]
  5. Schnier J, Isono S, Cumberlidge AG, Isono K: Unstable mutations caused by regional tandem multiplications in the gene for ribosomal protein S4 show thermosensitivity in Escherichia coli. Mol Gen Genet. 1985;199(2):265-70. [PubMed Link Image]
  6. Meek DW, Hayward RS: Nucleotide sequence of the rpoA-rplQ DNA of Escherichia coli: a second regulatory binding site for protein S4? Nucleic Acids Res. 1984 Jul 25;12(14):5813-21. [PubMed Link Image]
  7. Jeon YH, Negishi T, Shirakawa M, Yamazaki T, Fujita N, Ishihama A, Kyogoku Y: Solution structure of the activator contact domain of the RNA polymerase alpha subunit. Science. 1995 Dec 1;270(5241):1495-7. [PubMed Link Image]
  8. 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]
  9. Link AJ, Robison K, Church GM: Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12. Electrophoresis. 1997 Aug;18(8):1259-313. [PubMed Link Image]
  10. Zhang G, Darst SA: Structure of the Escherichia coli RNA polymerase alpha subunit amino-terminal domain. Science. 1998 Jul 10;281(5374):262-6. [PubMed Link Image]
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 1939
Target 2 Name Heat shock protein HSP 90-alpha
Target 2 Synonyms
  1. HSP 86
  2. Renal carcinoma antigen NY- REN-38
Target 2 Gene Name HSP90AA1
Target 2 Protein Sequence >Heat shock protein HSP 90-alpha 
MPEETQTQDQPMEEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNSSDALDKIR
YESLTDPSKLDSGKELHINLIPNKQDRTLTIVDTGIGMTKADLINNLGTIAKSGTKAFME
ALQAGADISMIGQFGVGFYSAYLVAEKVTVITKHNDDEQYAWESSAGGSFTVRTDTGEPM
GRGTKVILHLKEDQTEYLEERRIKEIVKKHSQFIGYPITLFVEKERDKEVSDDEAEEKED
KEEEKEKEEKESEDKPEIEDVGSDEEEEKKDGDKKKKKKIKEKYIDQEELNKTKPIWTRN
PDDITNEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFRALLFVPRRAPFDLFENRKKKNN
IKLYVRRVFIMDNCEELIPEYLNFIRGVVDSEDLPLNISREMLQQSKILKVIRKNLVKKC
LELFTELAEDKENYKKFYEQFSKNIKLGIHEDSQNRKKLSELLRYYTSASGDEMVSLKDY
CTRMKENQKHIYYITGETKDQVANSAFVERLRKHGLEVIYMIEPIDEYCVQQLKEFEGKT
LVSVTKEGLELPEDEEEKKKQEEKKTKFENLCKIMKDILEKKVEKVVVSNRLVTSPCCIV
TSTYGWTANMERIMKAQALRDNSTMGYMAAKKHLEINPDHSIIETLRQKAEADKNDKSVK
DLVILLYETALLSSGFSLEDPQTHANRIYRMIKLGLGIDEDDPTADDTSAAVTEEMPPLE
GDDDTSRMEEVD
Target 2 Number of Residues 744
Target 2 Molecular Weight 84661
Target 2 Theoretical pI 4.66
Target 2 GO Classification
Function
protein binding
unfolded protein binding
binding
nucleotide binding
purine nucleotide binding
adenyl nucleotide binding
ATP binding
Process
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
protein folding
Component
Not Available
Target 2 General Function Posttranslational modification, protein turnover, chaperones
Target 2 Specific Function Molecular chaperone. Has ATPase activity
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 32488 Link Image
Target 2 UniProtKB/Swiss-Prot ID P07900 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name HS90A_HUMAN Link Image
Target 2 PDB ID 1UYL Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Cytoplasm. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to
Target 2 Gene Sequence >2199 bp 
ATGCCTGAGGAAACCCAGACCCAAGACCAACCGATGGAGGAGGAGGAGGTTGAGACGTTC
GCCTTTCAGGCAGAAATTGCCCAGTTGATGTCATTGATCATCAATACTTTCTACTCGAAC
AAAGAGATCTTTCTGAGAGAGCTCATTTCAAATTCATCAGATGCATTGGACAAAATCCGG
TATGAAACTTTGACAGATCCCAGTAAATTAGACTCTGGGAAAGAGCTGCATATTAACCTT
ATACCGAACAAACAAGATCGAACTCTCACTATTGTGGATACTGGAATTGGAATGACCAAG
GCTGACTTGATCAATAACCTTGGTACTATCGCCAAGTCTGGGACCAAAGCGTTCATGGAA
GCTTTGCAGGCTGGTGCAGATATCTCTATGATTGGCCAGTTCGGTGTTGGTTTTTATTCT
GCTTATTTGGTTGCTGAGAAAGTAACTGTGATCACCAAACATAACGATGATGAGCAGTAC
GCTTGGGAGTCCTCAGCAGGGGGATCATTCACAGTGAGGACAGACACAGGTGAACCTATG
GGTCGTGGAACAAAAGTTATCCTACACCTGAAAGAAGACCAAACTGAGTACTTGGAGGAA
CGAAGAATAAAGGAGATTGTGAAGAAACATTCTCAGTTTATTGGATATCCCATTACTCTT
TTTGTGGAGAAGGAACGTGATAAAGAAGTAAGCGATGATGAGGCTGAAGAAAAGGAAGAC
AAAGAAGAAGAAAAAGAAAAAGAAGAGAAAGAGTCGGAAGACAAACCTGAAATTGAAGAT
GTTGGTTCTGATGAGGAAGAAGAAAAGAAGGATGGTGACAAGAAGAAGAAGAAGAAGATT
AAGGAAAAGTACATCGATCAAGAAGAGCTCAACAAAACAAAGCCCATCTGGACCAGAAAT
CCCGACGATATTACTAATGAGGAGTACGGAGAATTCTATAAGAGCTTGACCAATGACTGG
GAAGATCACTTGGCAGTGAAGCATTTTTCAGTTGAAGGACAGTTGGAATTCAGAGCCCTT
CTATTTGTCCCACGACGTGCTCCTTTTGATCTGTTTGAAAACAGAAAGAAAAAGAACAAT
ATCAAATTGTATGTACGCAGAGTTTTCATCATGGATAACTGTGAGGAGCTAATCCCTGAA
TATCTGAACTTCATTAGAGGGGTGGTAGACTCGGAGGATCTCCCTCTAAACATATCCCGT
GAGATGTTGCAACAAAGCAAAATTTTGAAAGTTATCAGGAAGAATTTGGTCAAAAAATGC
TTAGAACTCTTTACTGAACTGGCGGAAGATAAAGAGAACTACAAGAAATTCTATGAGCAG
TTCTCTAAAAACATAAAGCTTGGAATACACGAAGACTCTCAAAATCGGAAGAAGCTTTCA
GAGCTGTTAAGGTACTACACATCTGCCTCTGGTGATGAGATGGTTTCTCTCAAGGACTAC
TGCACCAGAATGAAGGAGAACCAGAAACATATCTATTATATCACAGGTGAGACCAAGGAC
CAGGTAGCTAACTCAGCCTTTGTGGAACGTCTTCGGAAACATGGCTTAGAAGTGATCTAT
ATGATTGAGCCCATTGATGAGTACTGTGTCCAACAGCTGAAGGAATTTGAGGGGAAGACT
TTAGTGTCAGTCACCAAAGAAGGCCTGGAACTTCCAGAGGATGAAGAAGAGAAAAAGAAG
CAGGAAGAGAAAAAAACAAAGTTTGAGAACCTCTGCAAAATCATGAAAGACATATTGGAG
AAAAAAGTTGAAAAGGTGGTTGTGTCAAACCGATTGGTGACATCTCCATGCTGTATTGTC
ACAAGCACATATGGCTGGACAGCAAACATGGAGAGAATCATGAAAGCTCAAGCCCTAAGA
GACAACTCAACAATGGGTTACATGGCAGCAAAGAAACACCTGGAGATAAACCCTGACCAT
TCCATTATTGAGACCTTAAGGCAAAAGGCAGAGGCTGATAAGAACGACAAGTCTGTGAAG
GATCTGGTCATCTTGCTTTATGAAACTGCGCTCCTGTCTTCTGGCTTCAGTCTGGAAGAT
CCCCAGACACATGCTAACAGGATCTACAGGATGATCAAACTTGGTCTGGGTATTGATGAA
GATGACCCTACTGCTGATGATACCAGTGCTGCTGTAACTGAAGAAATGCCACCCCTTGAA
GGAGATGACGACACATCACGCATGGAAGAAGTAGACTAA
Target 2 GenBank Gene ID
Target 2 GeneCard ID HSP90AA1 Link Image
Target 2 GenAtlas ID HSP90AA1 Link Image
Target 2 HGNC ID HGNC:5253 Link Image
Target 2 Chromosome Location 14
Target 2 Locus 14q32.33
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, Gure AO, Jager D, Jager E, Knuth A, Chen YT, Old LJ: Antigens recognized by autologous antibody in patients with renal-cell carcinoma. Int J Cancer. 1999 Nov 12;83(4):456-64. [PubMed Link Image]
  2. Lotz GP, Lin H, Harst A, Obermann WM: Aha1 binds to the middle domain of Hsp90, contributes to client protein activation, and stimulates the ATPase activity of the molecular chaperone. J Biol Chem. 2003 May 9;278(19):17228-35. Epub 2003 Feb 24. [PubMed Link Image]
  3. Yamazaki M, Tashiro H, Yokoyama K, Soeda E: Molecular cloning of cDNA encoding a human heat-shock protein whose expression is induced by adenovirus type 12 E1A in HeLa cells. Agric Biol Chem. 1990 Dec;54(12):3163-70. [PubMed Link Image]
  4. Hoffmann T, Hovemann B: Heat-shock proteins, Hsp84 and Hsp86, of mice and men: two related genes encode formerly identified tumour-specific transplantation antigens. Gene. 1988 Dec 30;74(2):491-501. [PubMed Link Image]
  5. Lees-Miller SP, Anderson CW: Two human 90-kDa heat shock proteins are phosphorylated in vivo at conserved serines that are phosphorylated in vitro by casein kinase II. J Biol Chem. 1989 Feb 15;264(5):2431-7. [PubMed Link Image]
  6. Lees-Miller SP, Anderson CW: The human double-stranded DNA-activated protein kinase phosphorylates the 90-kDa heat-shock protein, hsp90 alpha at two NH2-terminal threonine residues. J Biol Chem. 1989 Oct 15;264(29):17275-80. [PubMed Link Image]
  7. Hickey E, Brandon SE, Smale G, Lloyd D, Weber LA: Sequence and regulation of a gene encoding a human 89-kilodalton heat shock protein. Mol Cell Biol. 1989 Jun;9(6):2615-26. [PubMed Link Image]
  8. Walter T, Drabent B, Krebs H, Tomalak M, Heiss S, Benecke BJ: Cloning and analysis of a human 86-kDa heat-shock-protein-encoding gene. Gene. 1989 Nov 15;83(1):105-15. [PubMed Link Image]
  9. Yamazaki M, Akaogi K, Miwa T, Imai T, Soeda E, Yokoyama K: Nucleotide sequence of a full-length cDNA for 90 kDa heat-shock protein from human peripheral blood lymphocytes. Nucleic Acids Res. 1989 Sep 12;17(17):7108. [PubMed Link Image]
  10. Nemoto T, Ohara-Nemoto Y, Ota M, Takagi T, Yokoyama K: Mechanism of dimer formation of the 90-kDa heat-shock protein. Eur J Biochem. 1995 Oct 1;233(1):1-8. [PubMed Link Image]
  11. 9108479 Stebbins CE, Russo AA, Schneider C, Rosen N, Hartl FU, Pavletich NP: Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell. 1997 Apr 18;89(2):239-50.
  12. 9660753 Young JC, Obermann WM, Hartl FU: Specific binding of tetratricopeptide repeat proteins to the C-terminal 12-kDa domain of hsp90. J Biol Chem. 1998 Jul 17;273(29):18007-10.
  13. 9817749 Obermann WM, Sondermann H, Russo AA, Pavletich NP, Hartl FU: In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis. J Cell Biol. 1998 Nov 16;143(4):901-10.
Target 2 Drug References
  1. Schnaider T, Somogyi J, Csermely P, Szamel M: The Hsp90-specific inhibitor geldanamycin selectively disrupts kinase-mediated signaling events of T-lymphocyte activation. Cell Stress Chaperones. 2000 Jan;5(1):52-61. [PubMed Link Image]
  2. Neckers L, Schulte TW, Mimnaugh E: Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity. Invest New Drugs. 1999;17(4):361-73. [PubMed Link Image]
  3. Srethapakdi M, Liu F, Tavorath R, Rosen N: Inhibition of Hsp90 function by ansamycins causes retinoblastoma gene product-dependent G1 arrest. Cancer Res. 2000 Jul 15;60(14):3940-6. [PubMed Link Image]
  4. Munster PN, Srethapakdi M, Moasser MM, Rosen N: Inhibition of heat shock protein 90 function by ansamycins causes the morphological and functional differentiation of breast cancer cells. Cancer Res. 2001 Apr 1;61(7):2945-52. [PubMed Link Image]
  5. Yang J, Yang JM, Iannone M, Shih WJ, Lin Y, Hait WN: Disruption of the EF-2 kinase/Hsp90 protein complex: a possible mechanism to inhibit glioblastoma by geldanamycin. Cancer Res. 2001 May 15;61(10):4010-6. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 2091
Target 3 Name Endoplasmin
Target 3 Synonyms
  1. 94 kDa glucose-regulated protein
  2. Endoplasmin precursor
  3. GRP94
  4. Heat shock protein 90 kDa beta member 1
  5. Tumor rejection antigen 1
  6. gp96 homolog
Target 3 Gene Name HSP90B1
Target 3 Protein Sequence >Endoplasmin precursor 
MRALWVLGLCCVLLTFGSVRADDEVDVDGTVEEDLGKSREGSRTDDEVVQREEEAIQLDG
LNASQIRELREKSEKFAFQAEVNRMMKLIINSLYKNKEIFLRELISNASDALDKIRLISL
TDENALSGNEELTVKIKCDKEKNLLHVTDTGVGMTREELVKNLGTIAKSGTSEFLNKMTE
AQEDGQSTSELIGQFGVGFYSAFLVADKVIVTSKHNNDTQHIWESDSNEFSVIADPRGNT
LGRGTTITLVLKEEASDYLELDTIKNLVKKYSQFINFPIYVWSSKTETVEEPMEEEEAAK
EEKEESDDEAAVEEEEEEKKPKTKKVEKTVWDWELMNDIKPIWQRPSKEVEEDEYKAFYK
SFSKESDDPMAYIHFTAEGEVTFKSILFVPTSAPRGLFDEYGSKKSDYIKLYVRRVFITD
DFHDMMPKYLNFVKGVVDSDDLPLNVSRETLQQHKLLKVIRKKLVRKTLDMIKKIADDKY
NDTFWKEFGTNIKLGVIEDHSNRTRLAKLLRFQSSHHPTDITSLDQYVERMKEKQDKIYF
MAGSSRKEAESSPFVERLLKKGYEVIYLTEPVDEYCIQALPEFDGKRFQNVAKEGVKFDE
SEKTKESREAVEKEFEPLLNWMKDKALKDKIEKAVVSQRLTESPCALVASQYGWSGNMER
IMKAQAYQTGKDISTNYYASQKKTFEINPRHPLIRDMLRRIKEDEDDKTVLDLAVVLFET
ATLRSGYLLPDTKAYGDRIERMLRLSLNIDPDAKVEEEPEEEPEETAEDTTEDTEQDEDE
EMDVGTDEEEETAKESTAEKDEL
Target 3 Number of Residues 816
Target 3 Molecular Weight 92470
Target 3 Theoretical pI 4.48
Target 3 GO Classification
Function
protein binding
unfolded protein binding
binding
nucleotide binding
purine nucleotide binding
adenyl nucleotide binding
ATP binding
Process
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
protein folding
Component
Not Available
Target 3 General Function Posttranslational modification, protein turnover, chaperones
Target 3 Specific Function Molecular chaperone that functions in the processing and transport of secreted proteins
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • 1-21
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 553797 Link Image
Target 3 UniProtKB/Swiss-Prot ID P14625 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name ENPL_HUMAN Link Image
Target 3 PDB ID 1QYE Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location
  • Endoplasmic reticulum
  • endoplasmic reticulum lumen. Melanosome. Note=Identified by mass spectrometry
Target 3 Gene Sequence >2412 bp 
ATGAGGGCCCTGTGGGTGCTGGGCCTCTGCTGCGTCCTGCTGACCTTCGGGTCGGTCAGA
GCTGACGATGAAGTTGATGTGGATGGTACAGTAGAAGAGGATCTGGGTAAAAGTAGAGAA
GGATCAAGGACGGATGATGAAGTAGTACAGAGAGAGGAAGAAGCTATTCAGTTGGATGGA
TTAAATGCATCACAAATAAGAGAACTTAGAGAGAAGTCGGAAAAGTTTGCCTTCCAAGCC
GAAGTTAACAGAATGATGAAACTTATCATCAATTCATTGTATAAAAATAAAGAGATTTTC
CTGAGAGAACTGATTTCAAATGCTTCTGATGCTTTAGATAAGATAAGGCTAATATCACTG
ACTGATGAAAATGCTCTTTCTGGAAATGAGGAACTAACAGTCAAAATTAAGTGTGATAAG
GAGAAGAACCTGCTGCATGTCACAGACACCGGTGTAGGAATGACCAGAGAAGAGTTGGTT
AAAAACCTTGGTACCATAGCCAAATCTGGGACAAGCGAGTTTTTAAACAAAATGACTGAA
GCACAGGAAGATGGCCAGTCAACTTCTGAATTGATTGGCCAGTTTGGTGTCGGTTTCTAT
TCCGCCTTCCTTGTAGCAGATAAGGTTATTGTCACTTCAAAACACAACAACGATACCCAG
CACATCTGGGAGTCTGACTCCAATGAATTTTCTGTAATTGCTGACCCAAGAGGAAACACT
CTAGGACGGGGAACGACAATTACCCTTGTCTTAAAAGAAGAAGCATCTGATTACCTTGAA
TTGGATACAATTAAAAATCTCGTCAAAAAATATTCACAGTTCATAAACTTTCCTATTTAT
GTATGGAGCAGCAAGACTGAAACTGTTGAGGAGCCCATGGAGGAAGAAGAAGCAGCCAAA
GAAGAGAAAGAAGAATCTGATGATGAAGCTGCAGTAGAGGAAGAAGAAGAAGAAAAGAAA
CCAAAGACTAAAAAAGTTGAAAAAACTGTCTGGGACTGGGAACTTATGAATGATATCAAA
CCAATATGGCAGAGACCATCAAAAGAAGTAGAAGAAGATGAATACAAAGCTTTCTACAAA
TCATTTTCAAAGGAAAGTGATGACCCCATGGCTTATATTCACTTTACTGCTGAAGGGGAA
GTTACCTTCAAATCAATTTTATTTGTACCCACATCTGCTCCACGTGGTCTGTTTGACGAA
TATGGATCTAAAAAGAGCGATTACATTAAGCTCTATGTGCGCCGTGTATTCATCACAGAC
GACTTCCATGATATGATGCCTAAATACCTCAATTTTGTCAAGGGTGTGGTGGACTCAGAT
GATCTCCCCTTGAATGTTTCCCGCGAGACTCTTCAGCAACATAAACTGCTTAAGGTGATT
AGGAAGAAGCTTGTTCGTAAAACGCTGGACATGATCAAGAAGATTGCTGATGATAAATAC
AATGATACTTTTTGGAAAGAATTTGGTACCAACATCAAGCTTGGTGTGATTGAAGACCAC
TCGAATCGAACACGTCTTGCTAAACTTCTTAGGTTCCAGTCTTCTCATCATCCAACTGAC
ATTACTAGCCTAGACCAGTATGTGGAAAGAATGAAGGAAAAACAAGACAAAATCTACTTC
ATGGCTGGGTCCAGCAGAAAAGAGGCTGAATCTTCTCCATTTGTTGAGCGACTTCTGAAA
AAGGGCTATGAAGTTATTTACCTCACAGAACCTGTGGATGAATACTGTATTCAGGCCCTT
CCCGAATTTGATGGGAAGAGGTTCCAGAATGTTGCCAAGGAAGGAGTGAAGTTCGATGAA
AGTGAGAAAACTAAGGAGAGTCGTGAAGCAGTTGAGAAAGAATTTGAGCCTCTGCTGAAT
TGGATGAAAGATAAAGCCCTTAAGGACAAGATTGAAAAGGCTGTGGTGTCTCAGCGCCTG
ACAGAATCTCCGTGTGCTTTGGTGGCCAGCCAGTACGGATGGTCTGGCAACATGGAGAGA
ATCATGAAAGCACAAGCGTACCAAACGGGCAAGGACATCTCTACAAATTACTATGCGAGT
CAGAAGAAAACATTTGAAATTAATCCCAGACACCCGCTGATCAGAGACATGCTTCGACGA
ATTAAGGAAGATGAAGATGATAAAACAGTTTTGGATCTTGCTGTGGTTTTGTTTGAAACA
GCAACGCTTCGGTCAGGGTATCTTTTACCAGACACTAAAGCATATGGAGATAGAATAGAA
AGAATGCTTCGCCTCAGTTTGAACATTGACCCTGATGCAAAGGTGGAAGAAGAGCCCGAA
GAAGAACCTGAAGAGACAGCAGAAGACACAACAGAAGACACAGAGCAAGACGAAGATGAA
GAAATGGATGTGGGAACAGATGAAGAAGAAGAAACAGCAAAGGAATCTACAGCTGAAAAA
GATGAATTGTAA
Target 3 GenBank Gene ID
Target 3 GeneCard ID HSP90B1 Link Image
Target 3 GenAtlas ID HSP90B1 Link Image
Target 3 HGNC ID HGNC:12028 Link Image
Target 3 Chromosome Location 12
Target 3 Locus 12q24.2-q24.3
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed Link Image]
  2. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. [PubMed Link Image]
  3. Maki RG, Old LJ, Srivastava PK: Human homologue of murine tumor rejection antigen gp96: 5'-regulatory and coding regions and relationship to stress-induced proteins. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5658-62. [PubMed Link Image]
  4. Chang SC, Erwin AE, Lee AS: Glucose-regulated protein (GRP94 and GRP78) genes share common regulatory domains and are coordinately regulated by common trans-acting factors. Mol Cell Biol. 1989 May;9(5):2153-62. [PubMed Link Image]
Target 3 Drug References
  1. Barzilay E, Ben-Califa N, Supino-Rosin L, Kashman Y, Hirschberg K, Elazar Z, Neumann D: Geldanamycin-associated inhibition of intracellular trafficking is attributed to a co-purified activity. J Biol Chem. 2004 Feb 20;279(8):6847-52. Epub 2003 Dec 1. [PubMed Link Image]
  2. Chavany C, Mimnaugh E, Miller P, Bitton R, Nguyen P, Trepel J, Whitesell L, Schnur R, Moyer J, Neckers L: p185erbB2 binds to GRP94 in vivo. Dissociation of the p185erbB2/GRP94 heterocomplex by benzoquinone ansamycins precedes depletion of p185erbB2. J Biol Chem. 1996 Mar 1;271(9):4974-7. [PubMed Link Image]
  3. Lawson B, Brewer JW, Hendershot LM: Geldanamycin, an hsp90/GRP94-binding drug, induces increased transcription of endoplasmic reticulum (ER) chaperones via the ER stress pathway. J Cell Physiol. 1998 Feb;174(2):170-8. [PubMed Link Image]

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