Drugbank Logo

Showing drug card for Fludarabine (DB01073)

Legend: drug field target field enzyme field

for drugs
Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:47
Primary Accession Number DB01073
Secondary Accession Number
  • APRD00594
Name Fludarabine
Drug Type
  • Approved
  • Small Molecule
Description Fludarabine (marketed as fludarabine phosphate under the trade name Fludara) is a chemotherapy drug used in the treatment of hematological malignancies. [Wikipedia]
Synonyms
  1. FAMP
  2. Fludarabine 5'-monophosphate
  3. Fludarabine monophosphate
  4. Fludarabine phosphate
Brand Names
  1. Fludara
  2. Fludura
Brand Mixtures Not Available
Chemical IUPAC Name [(2R,3S,4S,5R)-5-(6-amino-2-fluoropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
Chemical Formula C10H13FN5O7P
Chemical Structure Structure
CAS Registry Number 75607-67-9
InChI Identifier InChI=1/C10H13FN5O7P/c11-10-14-7(12)4-8(15-10)16(2-13-4)9-6(18)5(17)3(23-9)1-22-24(19,20)21/h2-3,5-6,9,17-18H,1H2,(H2,12,14,15)(H2,19,20,21)/t3-,5-,6+,9-/m1/s1/f/h19-20H,12H2
InChI Key GIUYCYHIANZCFB-DOXDFKSTDC
KEGG Drug D01907 Link Image
KEGG Compound Not Available
PubChem Compound 30751 Link Image
PubChem Substance 7848969 Link Image
ChEBI ID Not Available
PharmGKB ID PA449655 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02246226 Link Image
RxList Link http://www.rxlist.com/cgi/generic/fludarabine.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Fludarabine Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference J. A. Montgomery, U.S. pat. 4,210,745 (1980 to U.S. Dept. Health, Education and Welfare)
Average Molecular Weight 365.2117
Monoisotopic Molecular Weight 365.0537
State Solid
Melting Point 260 oC
Experimental Water Solubility 3.53 mg/ml Source: PhysProp
Predicted Water Solubility 2.96e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -2.8 Source: PhysProp
Predicted LogP -2.50 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.09 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 NC1=C2N=CN([C@@H]3O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]3O)C2=NC(F)=N1
Canonical SMILES NC1=C2N=CN(C3OC(COP(O)(O)=O)C(O)C3O)C2=NC(F)=N1
Drug Category
  • Antimetabolites
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Immunosuppressive Agents
ATC Codes
AHFS Codes
  • 10:00.00
Indication For the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating-agent containing regimen
Pharmacology Fludarabine is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia. It acts at DNA polymerase alpha, ribonucleotide reductase and DNA primase, results in the inhibition of DNA synthesis, and destroys the cancer cells.
Mechanism of Action Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.
Absorption Bioavailability is 55% following oral administration.
Toxicity Not Available
Protein Binding 19-29%
Biotransformation Not Available
Half Life 20 hours
Dosage Forms
Form Route
Powder, for solution Intravenous
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Dipyridamole Dipyridamole decreases the effect of fludarabine
Pentostatin Unacceptable pulmonary toxicity
Food Interactions
  • Food slightly increases product bioavailability.
  • Take without regard to meals.
Pathways Not Available
General References
  1. Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, Hines J, Threatte GA, Larson RA, Cheson BD, Schiffer CA: Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000 Dec 14;343(24):1750-7. [PubMed Link Image]
  2. Tournilhac O, Cazin B, Lepretre S, Divine M, Maloum K, Delmer A, Grosbois B, Feugier P, Maloisel F, Villard F, Villemagne B, Bastit D, Belhadj K, Azar N, Michallet M, Manhes G, Travade P: Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood. 2004 Jan 1;103(1):363-5. Epub 2003 Sep 11. [PubMed Link Image]
  3. Gonzalez H, Leblond V, Azar N, Sutton L, Gabarre J, Binet JL, Vernant JP, Dighiero G: Severe autoimmune hemolytic anemia in eight patients treated with fludarabine. Hematol Cell Ther. 1998 Jun;40(3):113-8. [PubMed Link Image]
  4. Drugs.com Link Image
  5. Wikipedia Link Image
  6. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Deoxycytidine kinase
Targets
  1. Apoptosis regulator Bcl-2
  2. Ribonucleoside-diphosphate reductase large subunit
  3. DNA polymerase alpha catalytic subunit
  4. Signal transducer and activator of transcription 1-alpha/beta
  5. Adenosine deaminase
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Deoxycytidine kinase
Enzyme 1 Gene Name DCK
Enzyme 1 SwissProt ID P27707 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P27707|DCK_HUMAN Deoxycytidine kinase (EC 2.7.1.74) (dCK) - Homo sapiens (Human) 
MATPPKRSCPSFSASSEGTRIKKISIEGNIAAGKSTFVNILKQLCEDWEVVPEPVARWCN
VQSTQDEFEELTMSQKNGGNVLQMMYEKPERWSFTFQTYACLSRIRAQLASLNGKLKDAE
KPVLFFERSVYSDRYIFASNLYESECMNETEWTIYQDWHDWMNNQFGQSLELDGIIYLQA
TPETCLHRIYLRGRNEEQGIPLEYLEKLHYKHESWLLHRTLKTNFDYLQEVPILTLDVNE
DFKDKYESLVEKVKEFLSTL
Drug Target 1 [top]
Target 1 ID 273
Target 1 Name Apoptosis regulator Bcl-2
Target 1 Synonyms Not Available
Target 1 Gene Name BCL2
Target 1 Protein Sequence >Apoptosis regulator Bcl-2 
MAHAGRTGYDNREIVMKYIHYKLSQRGYEWDAGDVGAAPPGAAPAPGIFSSQPGHTPHPA
ASRDPVARTSPLQTPAAPGAAAGPALSPVPPVVHLTLRQAGDDFSRRYRRDFAEMSSQLH
LTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVESVNREMSPLVDNIALWMTEY
LNRHLHTWIQDNGGWDAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK
Target 1 Number of Residues 242
Target 1 Molecular Weight 26266
Target 1 Theoretical pI 7.32
Target 1 GO Classification
Function
Not Available
Process
regulation of biological process
regulation of physiological process
regulation of cellular physiological process
regulation of programmed cell death
regulation of apoptosis
Component
cell
membrane
Target 1 General Function Involved in BH3 domain binding
Target 1 Specific Function Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1)
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 212-233
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 179367 Link Image
Target 1 UniProtKB/Swiss-Prot ID P10415 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name BCL2_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Mitochondrion
  • mitochondrial outer membrane
  • nuclear membrane
  • single-pass membrane protein. Nucleus
Target 1 Gene Sequence >720 bp 
ATGGCGCACGCTGGGAGAACGGGGTACGACAACCGGGAGATAGTGATGAAGTACATCCAT
TATAAGCTGTCGCAGAGGGGCTACGAGTGGGATGCGGGAGATGTGGGCGCCGCGCCCCCG
GGGGCCGCCCCCGCACCGGGCATCTTCTCCTCCCAGCCCGGGCACACGCCCCATCCAGCC
GCATCCCGCGACCCGGTCGCCAGGACCTCGCCGCTGCAGACCCCGGCTGCCCCCGGCGCC
GCCGCGGGGCCTGCGCTCAGCCCGGTGCCACCTGTGGTCCACCTGGCCCTCCGCCAAGCC
GGCGACGACTTCTCCCGCCGCTACCGCGGCGACTTCGCCGAGATGTCCAGCCAGCTGCAC
CTGACGCCCTTCACCGCGCGGGGACGCTTTGCCACGGTGGTGGAGGAGCTCTTCAGGGAC
GGGGTGAACTGGGGGAGGATTGTGGCCTTCTTTGAGTTCGGTGGGGTCATGTGTGTGGAG
AGCGTCAACCGGGAGATGTCGCCCCTGGTGGACAACATCGCCCTGTGGATGACTGAGTAC
CTGAACCGGCACCTGCACACCTGGATCCAGGATAACGGAGGCTGGGATGCCTTTGTGGAA
CTGTACGGCCCCAGCATGCGGCCTCTGTTTGATTTCTCCTGGCTGTCTCTGAAGACTCTG
CTCAGTTTGGCCCTGGTGGGAGCTTGCATCACCCTGGGTGCCTATCTGAGCCACAAGTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID BCL2 Link Image
Target 1 GenAtlas ID BCL2 Link Image
Target 1 HGNC ID HGNC:990 Link Image
Target 1 Chromosome Location 18
Target 1 Locus 18q21.33|18q21.3
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Yamamoto K, Ichijo H, Korsmeyer SJ: BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol. 1999 Dec;19(12):8469-78. [PubMed Link Image]
  2. Ruvolo PP, Deng X, May WS: Phosphorylation of Bcl2 and regulation of apoptosis. Leukemia. 2001 Apr;15(4):515-22. [PubMed Link Image]
  3. Yu J, Zhang L, Hwang PM, Kinzler KW, Vogelstein B: PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell. 2001 Mar;7(3):673-82. [PubMed Link Image]
  4. Qin W, Hu J, Guo M, Xu J, Li J, Yao G, Zhou X, Jiang H, Zhang P, Shen L, Wan D, Gu J: BNIPL-2, a novel homologue of BNIP-2, interacts with Bcl-2 and Cdc42GAP in apoptosis. Biochem Biophys Res Commun. 2003 Aug 22;308(2):379-85. [PubMed Link Image]
  5. Tanaka S, Louie DC, Kant JA, Reed JC: Frequent incidence of somatic mutations in translocated BCL2 oncogenes of non-Hodgkin's lymphomas. Blood. 1992 Jan 1;79(1):229-37. [PubMed Link Image]
  6. Eguchi Y, Ewert DL, Tsujimoto Y: Isolation and characterization of the chicken bcl-2 gene: expression in a variety of tissues including lymphoid and neuronal organs in adult and embryo. Nucleic Acids Res. 1992 Aug 25;20(16):4187-92. [PubMed Link Image]
  7. Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ: Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990 Nov 22;348(6299):334-6. [PubMed Link Image]
  8. Seto M, Jaeger U, Hockett RD, Graninger W, Bennett S, Goldman P, Korsmeyer SJ: Alternative promoters and exons, somatic mutation and deregulation of the Bcl-2-Ig fusion gene in lymphoma. EMBO J. 1988 Jan;7(1):123-31. [PubMed Link Image]
  9. Cleary ML, Smith SD, Sklar J: Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 1986 Oct 10;47(1):19-28. [PubMed Link Image]
  10. Hua C, Zorn S, Jensen JP, Coupland RW, Ko HS, Wright JJ, Bakhshi A: Consequences of the t(14;18) chromosomal translocation in follicular lymphoma: deregulated expression of a chimeric and mutated BCL-2 gene. Oncogene Res. 1988 Feb;2(3):263-75. [PubMed Link Image]
  11. 3523487 Tsujimoto Y, Croce CM: Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5214-8.
  12. 8183370 Yin XM, Oltvai ZN, Korsmeyer SJ: BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature. 1994 May 26;369(6478):321-3.
  13. 8668206 Naumovski L, Cleary ML: The p53-binding protein 53BP2 also interacts with Bc12 and impedes cell cycle progression at G2/M. Mol Cell Biol. 1996 Jul;16(7):3884-92.
  14. 9395403 Cheng EH, Kirsch DG, Clem RJ, Ravi R, Kastan MB, Bedi A, Ueno K, Hardwick JM: Conversion of Bcl-2 to a Bax-like death effector by caspases. Science. 1997 Dec 12;278(5345):1966-8.
Target 1 Drug References
  1. Ahmed N, Sammons J, Hassan HT: Bcl-2 protein in human myeloid leukaemia cells and its down-regulation during chemotherapy-induced apoptosis. Oncol Rep. 1999 Mar-Apr;6(2):403-7. [PubMed Link Image]
  2. Vrana JA, Wang Z, Rao AS, Tang L, Chen JH, Kramer LB, Grant S: Induction of apoptosis and differentiation by fludarabine in human leukemia cells (U937): interactions with the macrocyclic lactone bryostatin 1. Leukemia. 1999 Jul;13(7):1046-55. [PubMed Link Image]
  3. Ahmed N, Laverick L, Sammons J, Baumforth KR, Hassan HT: Effect of all-trans retinoic acid on chemotherapy induced apoptosis and down-regulation of Bcl-2 in human myeloid leukaemia CD34 positive cells. Leuk Res. 1999 Aug;23(8):741-9. [PubMed Link Image]
  4. Kitada S, Zapata JM, Andreeff M, Reed JC: Bryostatin and CD40-ligand enhance apoptosis resistance and induce expression of cell survival genes in B-cell chronic lymphocytic leukaemia. Br J Haematol. 1999 Sep;106(4):995-1004. [PubMed Link Image]
  5. Pepper C, Thomas A, Hoy T, Fegan C, Bentley P: Flavopiridol circumvents Bcl-2 family mediated inhibition of apoptosis and drug resistance in B-cell chronic lymphocytic leukaemia. Br J Haematol. 2001 Jul;114(1):70-7. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 360
Target 2 Name Ribonucleoside-diphosphate reductase large subunit
Target 2 Synonyms
  1. EC 1.17.4.1
  2. Ribonucleoside-diphosphate reductase M1 subunit
  3. Ribonucleotide reductase large chain
Target 2 Gene Name RRM1
Target 2 Protein Sequence >Ribonucleoside-diphosphate reductase large subunit 
MHVIKRDGRQERVMFDKITSRIQKLCYGLNMDFVDPAQITMKVIQGLYSGVTTVELDTLA
AETAATLTTKHPDYAILAARIAVSNLHKETKKVFSDVMEDLYNYINPHNGKHSPMVAKST
LDIVLANKDRLNSAIIYDRDFSYNYFGFKTLERSYLLKINGKVAERPQHMLMRVSVGIHK
EDIDAAIETYNLLSERWFTHASPTLFNAGTNRPQLSSCFLLSMKDDSIEGIYDTLKQCAL
ISKSAGGIGVAVSCIRATGSYIAGTNGNSNGLVPMLRVYNNTARYVDQGGNKRPGAFAIY
LEPWHLDIFEFLDLKKNTGKEEQRARDLFFALWIPDLFMKRVETNQDWSLMCPNECPGLD
EVWGEEFEKLYASYEKQGRVRKVVKAQQLWYAIIESQTETGTPYMLYKDSCNRKSNQQNL
GTIKCSNLCTEIVEYTSKDEVAVCNLASLALNMYVTSEHTYDFKKLAEVTKVVVRNLNKI
IDINYYPVPEACLSNKRHRPIGIGVQGLADAFILMRYPFESAEAQLLNKQIFETIYYGAL
EASCDLAKEQGPYETYEGSPVSKGILQYDMWNVTPTDLWDWKVLKEKIAKYGIRNSLLIA
PMPTASTAQILGNNESIEPYTSNIYTRRVLSGEFQIVNPHLLKDLTERGLWHEEMKNQII
ACNGSIQSIPEIPDDLKQLYKTVWEISQKTVLKMAAERGAFIDQSQSLNIHIAEPNYGKL
TSMHFYGWKQGLKTGMYYLRTRPAANPIQFTLNKEKLKDKEKVSKEEEEKERNTAAMVCS
LENRDECLMCGS
Target 2 Number of Residues 805
Target 2 Molecular Weight 90071
Target 2 Theoretical pI 7.16
Target 2 GO Classification
Function
catalytic activity
oxidoreductase activity
oxidoreductase activity, acting on CH2 groups
oxidoreductase activity, acting on CH2 groups, disulfide as acceptor
ribonucleoside-diphosphate reductase activity
Process
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
DNA metabolism
DNA replication
Component
protein complex
ribonucleoside-diphosphate reductase complex
Target 2 General Function Nucleotide transport and metabolism
Target 2 Specific Function Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides
Target 2 Pathways
Name SMPDB Link KEGG Link
Purine metabolism SMP00050 Link Image map00230 Link Image
Pyrimidine metabolism SMP00046 Link Image map00240 Link Image
Target 2 Reactions
  • 2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 36065 Link Image
Target 2 UniProtKB/Swiss-Prot ID P23921 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name RIR1_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Cytoplasm
Target 2 Gene Sequence >2379 bp 
ATGCATGTGATCAAGCGAGATGGCCGCCAAGAACGAGTCATGTTTGACAAAATTACATCT
CGAATCCAGAAGCTTTGTTATGGACTCAATATGGATTTTGTTGATCCTGCTCAGATCACC
ATGAAAGTAATCCAAGGCTTGTACAGTGGGGTCACCACAGTGGAACTAGATACTTTGGCT
GCTGAAACAGCTGCAACCTTGACTACTAAGCACCCTGACTATGCTATCCTGGCAGCCAGG
ATCGCTGTCTCTAACTTGCACAAAGAAACAAAGAAAGTGTTCAGTGATGTGATGGAAGAC
CTCTATAACTACATAAATCCACATAATGGCAAACACTCTCCCATGGTGGCCAAGTCAACA
TTGGATATTGTTCTGGCCAATAAAGATCGCCTGAATTCTGCTATTATCTATGACCGAGAT
TTCTCTTACAATTACTTCGGCTTTAAGACGCTAGAGCGGTCTTATTTGTTGAAGATCAAT
GGAAAAGTGGCTGAAAGACCACAACATATGTTGATGAGAGTATCTGTTGGGATCCACAAA
GAAGACATTGATGCAGCAATTGAAACATATAATCTTCTTTCTGAGAGGTGGTTTACTCAT
GCTTCGCCCACTCTCTTCAATGCTGGTACCAACCGCCCACAACTTTCTAGCTGTTTTCTT
CTGAGTATGAAAGATGACAGCATTGAAGGCATTTATGACACTCTAAAGCAATGTGCATTG
ATTTCTAAGTCTGCTGGAGGAATTGGTGTTGCTGTGAGTTGTATTCGGGCTACTGGCAGC
TACATTGCTGGGACTAATGGCAATTCCAATGGCCTTGTACCGATGCTGAGAGTATATAAC
AACACAGCTCGATATGTGGATCAAGGTGGGAACAAGCGTCCTGGGGCATTTGCTATTTAC
CTGGAGCCTTGGCATTTAGACATCTTTGAATTCCTTGATTTAAAGAAGAACACAGGAAAG
GAAGAGCAGCGTGCCAGAGATCTTTTCTTTGCTCTTTGGATTCCGGATCTCTTCATGAAA
CGAGTGGAGACTAATCAGGACTGGTCTTTGATGTGTCCAAATGAGTGTCCTGGTCTGGAT
GAGGTTTGGGGAGAGGAATTTGAGAAACTATATGCAAGTTATGAGAAACAAGGTCGTGTC
CGCAAAGTTGTAAAAGCTCAGCAGCTTTGGTATGCCATCATTGAGTCTCAGACGGAAACA
GGCACCCCGTATATGCTCTACAAAGATTCCTGTAATCGAAAGAGCAACCAGCAGAACCTG
GGAACCATCAAATGCAGCAACCTGTGCACAGAAATAGTGGAGTACACCAGCAAAGATGAG
GTTGCTGTTTGTAATTTGGCTTCCCTGGCCCTGAATATGTATGTCACATCAGAACACACA
TACGACTTTAAGAAGTTGGCTGAAGTCACTAAAGTCGTTGTCCGAAACTTGAATAAAATT
ATTGATATAAACTACTATCCTGTACCAGAGGCATGCCTATCAAATAAACGCCATCGCCCC
ATTGGAATTGGGGTACAAGGTCTGGCAGATGCTTTTATCCTGATGAGATACCCTTTTGAG
AGTGCAGAAGCCCAGTTACTGAATAAGCAGATCTTTGAAACTATTTATTATGGTGCTCTG
GAAGCCAGCTGTGACCTTGCCAAGGAGCAGGGCCCATACGAAACCTATGAGGGCTCTCCA
GTTAGCAAAGGAATTCTTCAGTATGATATGTGGAATGTTACTCCTACAGACCTATGGGAC
TGGAAGGTTCTCAAGGAGAAGATTGCAAAGTATGGTATAAGAAACAGTTTACTTATTGCC
CCGATGCCTACAGCTTCCACTGCTCAGATCCTGGGGAATAATGAGTCCATTGAACCTTAC
ACCAGCAACATCTATACTCGCAGAGTCTTGTCAGGAGAATTTCAGATTGTAAATCCTCAC
TTATTGAAAGATCTTACCGAGCGGGGCCTATGGCATGAAGAGATGAAAAACCAGATTATT
GCATGCAATGGCTCTATTCAGAGCATACCAGAAATTCCTGATGACCTGAAGCAACTTTAT
AAAACTGTGTGGGAAATCTCTCAGAAAACTGTTCTCAAGATGGCAGCTGAGAGAGGTGCT
TTCATTGATCAAAGCCAATCTTTGAACATCCACATTGCTGAGCCTAACTATGGCAAACTC
ACTAGTATGCACTTCTACGGCTGGAAGCAGGGTTTGAAGACTGGGATGTATTATTTAAGG
ACGAGACCAGCAGCTAATCCAATCCAGTTCACTCTAAATAAGGAGAAGCTAAAAGATAAA
GAAAAGGTATCAAAAGAGGAAGAAGAGAAGGAGAGGAACACAGCAGCCATGGTGTGCTCT
TTGGAGAATAGAGATGAATGTCTGATGTGTGGATCCTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID RRM1 Link Image
Target 2 GenAtlas ID RRM1 Link Image
Target 2 HGNC ID HGNC:10451 Link Image
Target 2 Chromosome Location 11
Target 2 Locus 11p15.5
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Pavloff N, Rivard D, Masson S, Shen SH, Mes-Masson AM: Sequence analysis of the large and small subunits of human ribonucleotide reductase. DNA Seq. 1992;2(4):227-34. [PubMed Link Image]
  2. Parker NJ, Begley CG, Fox RM: Human M1 subunit of ribonucleotide reductase: cDNA sequence and expression in stimulated lymphocytes. Nucleic Acids Res. 1991 Jul 11;19(13):3741. [PubMed Link Image]
  3. Bepler G, O'briant KC, Kim YC, Schreiber G, Pitterle DM: A 1.4-Mb high-resolution physical map and contig of chromosome segment 11p15.5 and genes in the LOH11A metastasis suppressor region. Genomics. 1999 Jan 15;55(2):164-75. [PubMed Link Image]
Target 2 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 3 [top]
Target 3 ID 603
Target 3 Name DNA polymerase alpha catalytic subunit
Target 3 Synonyms
  1. EC 2.7.7.7
Target 3 Gene Name POLA1
Target 3 Protein Sequence >DNA polymerase alpha catalytic subunit 
MAPVHGDDSLSDSGSFVSSRARREKKSKKGRQEALERLKKAKAGEKYKYEVEDFTGVYEE
VDEEQYSKLVQARQDDDWIVDDDGIGYVEDGREIFDDDLEDDALDADEKGKDGKARNKDK
RNVKKLAVTKPNNIKSMFIACAGKKTADKAVDLSKDGLLGDILQDLNTETPQITPPPVMI
LKKKRSIGASPNPFSVHTATAVPSGKIASPVSRKEPPLTPVPLKRAEFAGDDVQVESTEE
EQESGAMEFEDGDFDEPMEVEEVDLEPMAAKAWDKESEPAEEVKQEADSGKGTVSYLGSF
LPDVSCWDIDQEGDSSFSVQEVQVDSSHLPLVKGADEEQVFHFYWLDAYEDQYNQPGVVF
LFGKVWIESAETHVSCCVMVKNIERTLYFLPREMKIDLNTGKETGTPISMKDVYEEFDEK
IATKYKIMKFKSKPVEKNYAFEIPDVPEKSEYLEVKYSAEMPQLPQDLKGETFSHVFGTN
TSSLELFLMNRKIKGPCWLEVKSPQLLNQPVSWCKVEAMALKPDLVNVIKDVSPPPLVVM
AFSMKTMQNAKNHQNEIIAMAALVHHSFALDKAAPKPPFQSHFCVVSKPKDCIFPYAFKE
VIEKKNVKVEVAATERTLLGFFLAKVHKIDPDIIVGHNIYGFELEVLLQRINVCKAPHWS
KIGRLKRSNMPKLGGRSGFGERNATCGRMICDVEISAKELIRCKSYHLSELVQQILKTER
VVIPMENIQNMYSESSQLLYLLEHTWKDAKFILQIMCELNVLPLALQITNIAGNIMSRTL
MGGRSERNEFLLLHAFYENNYIVPDKQIFRKPQQKLGDEDEEIDGDTNKYKKGRKKAAYA
GGLVLDPKVGFYDKFILLLDFNSLYPSIIQEFNICFTTVQRVASEAQKVTEDGEQEQIPE
LPDPSLEMGILPREIRKLVERRKQVKQLMKQQDLNPDLILQYDIRQKALKLTANSMYGCL
GFSYSRFYAKPLAALVTYKGREILMHTKEMVQKMNLEVIYGDTDSIMINTNSTNLEEVFK
LGNKVKSEVNKLYKLLEIDIDGVFKSLLLLKKKKYAALVVEPTSDGNYVTKQELKGLDIV
RRDWCDLAKDTGNFVIGQILSDQSRDTIVENIQKRLIEIGENVLNGSVPVSQFEINKALT
KDPQDYPDKKSLPHVHVALWINSQGGRKVKAGDTVSYVICQDGSNLTASQRAYAPEQLQK
QDNLTIDTQYYLAQQIHPVVARICEPIDGIDAVLIATWLGLDPTQFRVHHYHKDEENDAL
LGGPAQLTDEEKYRDCERFKCPCPTCGTENIYDNVFDGSGTDMEPSLYRCSNIDCKASPL
TFTVQLSNKLIMDIRRFIKKYYDGWLICEEPTCRNRTRHLPLQFSRTGPLCPACMKATLQ
PEYSDKSLYTQLCFYRYIFDAECALEKLTTDHEKDKLKKQFFTPKVLQDYRKLKNTAEQF
LSRSGYSEVNLSKLFAGCAVKS
Target 3 Number of Residues 1486
Target 3 Molecular Weight 165914
Target 3 Theoretical pI 5.59
Target 3 GO Classification
Function
hydrolase activity
hydrolase activity, acting on ester bonds
nuclease activity
exonuclease activity
3'-5' exonuclease activity
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
nucleotidyltransferase activity
DNA-directed DNA polymerase activity
nucleic acid binding
DNA binding
binding
nucleotide binding
Process
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
DNA metabolism
DNA replication
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus
Target 3 General Function Replication, recombination and repair
Target 3 Specific Function Polymerase alpha in a complex with DNA primase is a replicative polymerase
Target 3 Pathways
Name SMPDB Link KEGG Link
DNA polymerase map03030 Link Image
Purine metabolism SMP00050 Link Image map00230 Link Image
Pyrimidine metabolism SMP00046 Link Image map00240 Link Image
Target 3 Reactions
  • deoxynucleoside triphosphate + DNAn = diphosphate + DNAn+1
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 35568 Link Image
Target 3 UniProtKB/Swiss-Prot ID P09884 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name DPOLA_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Nucleus
Target 3 Gene Sequence >4389 bp 
ATGGCACCTGTGCACGGCGACGACTCTCTGTCAGATTCAGGGAGTTTTGTATCTTCTCGA
GCCCGGCGAGAAAAAAAATCAAAGAAGGGGCGCCAAGAAGCCCTAGAAAGACTGAAAAAG
GCTAAAGCTGGTGAGAAGTATAAATATGAAGTCGAGGACTTCACAGGTGTTTATGAAGAA
GTTGATGAAGAACAGTATTCGAAGCTGGTTCAGGCACGCCAGGATGATGACTGGATTGTG
GATGATGATGGTATTGGCTATGTGGAAGATGGCCGAGAGATTTTTGATGATGACCTTGAA
GATGATGCCCTTGATGCTGATGAGAAAGGAAAAGATGGTAAAGCACGCAATAAAGACAAG
AGGAATGTAAAGAAGCTCGCAGTGACAAAACCGAACAACATTAAGTCAATGTTCATTGCT
TGTGCTGGAAAGAAAACTGCAGATAAAGCTGTAGACTTGTCCAAGGATGGTCTGCTAGGT
GACATTCTACAGGATCTTAACACTGAGACACCTCAAATAACTCCACCACCTGTAATGATA
CTGAAGAAGAAAAGATCCATTGGAGCTTCACCGAATCCTTTCTCTGTGCACACCGCCACG
GCAGTTCCTTCAGGAAAAATTGCTTCCCCTGTCTCCAGAAAGGAGCCTCCATTAACTCCT
GTTCCTCTTAAACGTGCTGAATTTGCTGGCGATGATGTACAGGTCGAGAGTACAGAAGAA
GAGCAGGAGTCAGGGGCAATGGAGTTTGAAGATGGTGACTTTGATGAGCCCATGGAAGTT
GAAGAGGTGGACCTGGAGCCTATGGCTGCCAAGGCTTGGGACAAAGAGAGTGAGCCAGCA
GAGGAAGTGAAACAAGAGGCGGATTCTGGGAAAGGGACCGTGTCCTACTTAGGAAGTTTT
CTCCCGGATGTCTCTTGTTGGGACATTGATCAAGAAGGTGATAGCAGTTTCTCAGTGCAA
GAAGTTCAAGTGGATTCCAGTCACCTCCCATTGGTAAAAGGGGCAGATGAGGAACAAGTA
TTCCACTTTTATTGGTTGGATGCTTATGAGGATCAGTACAACCAACCAGGTGTGGTATTT
CTGTTTGGGAAAGTTTGGATTGAATCAGCCGAGACCCATGTGAGCTGTTGTGTCATGGTG
AAAAATATCGAGCGAACGCTTTACTTCCTTCCCCGTGAAATGAAAATTGATCTAAATACG
GGGAAAGAAACAGGAACTCCAATTTCAATGAAGGATGTTTATGAGGAATTTGATGAGAAA
ATAGCAACAAAATATAAAATTATGAAGTTCAAGTCTAAGCCAGTGGAAAAGAACTATGCT
TTTGAGATACCTGATGTTCCAGAAAAATCTGAGTACTTGGAAGTTAAATACTCGGCTGAA
ATGCCACAGCTTCCTCAAGATTTGAAAGGAGAAACTTTTTCTCATGTATTTGGGACCAAC
ACATCTAGCCTGGAACTGTTCTTGATGAACAGAAAGATCAAAGGACCTTGTTGGCTTGAA
GTAAAAAAGTCCACAGCTCTTAATCAGCCAGTCAGTTGGTGTAAAGTTGAGGCAATGGCT
TTGAAACCAGACCTGGTGAATGTAATTAAGGATGTCAGTCCACCACCGCTTGTCGTGATG
GCTTTCAGCATGAAGACAATGCAGAATGCAAAGAACCATCAAAATGAGATTATTGCTATG
GCAGCTTTGGTCCATCACAGTTTTGCATTGGATAAAGCAGCCCCAAAGCCTCCCTTTCAG
TCACACTTCTGTGTTGTGTCTAAACCAAAGGACTGTATTTTTCCATATGCTTTCAAAGAA
GTCATTGAGAAAAAGAATGTGAAGGTTGAGGTTGCTGCAACAGAAAGAACACTGCTAGGT
TTTTTCCTTGCAAAAGTTCACAAAATTGATCCTGATATCATTGTGGGTCATAATATTTAT
GGGTTTGAACTGGAAGTACTACTGCAGAGAATTAATGTGTGCAAAGCTCCTCACTGGTCC
AAGATAGGTCGACTGAAGCGATCCAACATGCCAAAGCTTGGGGGCCGGAGTGGATTTGGT
GAAAGAAATGCTACCTGTGGTCGAATGATCTGTGATGTGGAAATTTCAGCAAAGGAATTG
ATTCGTTGTAAAAGCTACCATCTGTCTGAACTTGTTCAGCAGATTCTAAAAACTGAAAGG
GTTGTAATCCCAATGGAAAATATACAAAATATGTACAGTGAATCTTCTCAACTGTTATAC
CTGTTGGAACACACCTGGAAAGATGCCAAGTTCATTTTGCAGATCATGTGTGAGCTAAAT
GTTCTTCCATTAGCATTGCAGATCACTAACATCGCTGGGAACATTATGTCCAGGACGCTG
ATGGGTGGACGATCCGAGCGTAACGAGTTCTTGTTGCTTCATGCATTTTACGAAAACAAC
TATATTGTGCCTGACAAGCAGATTTTCAGAAAGCCTCAGCAAAAACTGGGAGATGAAGAT
GAAGAAATTGATGGAGATACCAATAAATACAAGAAAGGACGTAAGAAAGGAGCTTATGCT
GGAGGCTTGGTTTTGGACCCCAAAGTTGGTTTTTATGATAAGTTCATTTTGCTTCTGGAC
TTCAACAGTCTATATCCTTCCATCATTCAGGAATTTAACATTTGTTTTACAACAGTACAA
AGAGTTGCTTCAGAGGCACAGAAAGTTACAGAGGATGGAGAACAAGAACAGATCCCTGAG
TTGCCAGATCCAAGCTTAGAAATGGGCATTTTGCCCAGAGAGATCCGGAAACTGGTAGAA
CGGAGAAAACAAGTCAAACAGCTAATGAAACAGCAAGACTTAAATCCAGACCTTATTCTT
CAGTATGACATTCGACAGAAGGCTTTGAAGCTCACAGCGAACAGTATGTATGGTTGCCTG
GGATTTTCCTATAGCAGATTTTACGCCAAACCACTGGCTGCCTTGGTGACATACAAAGGA
AGGGAGATTTTGATGCATACGAAAGAGATGGTACAAAAGATGAATCTTGAAGTTATTTAT
GGAGATACAGATTCAATTATGATAAACACCAATAGCACCAATCTGGAAGAAGTATTTAAG
TTGGGAAACAAGGTAAAAAGTGAAGTGAATAAGTTGTACAAACTGCTTGAAATAGACATT
GATGGGGTTTTCAAGTCTCTGCTACTGCTGAAAAAAAAGAAGTACGCTGCTCTGGTTGTT
GAGCCAACGTCGGATGGGAATTATGTCACCAAACAGGAGCTCAAAGGATTAGATATAGTT
AGAAGAGATTGGTGTGATCTTGCTAAAGACACTGGAAACTTTGTGATTGGCCAGATTCTT
TCTGATCAAAGCCGGGACACTATAGTGGAAAACATTCAGAAGAGGCTGATAGAAATTGGA
GAAAATGTGCTAAATGGCAGTGTCCCAGTGAGCCAGTTTGAAATTAACAAGGCATTGACA
AAGGATCCCCAGGATTACCCTGATAAAAAAAGCCTACCTCATGTACATGTTGCCCTCTGG
ATAAATTCTCAAGGAGGCAGAAAGGTGAAAGCTGGAGATACTGTGTCATATGTCATCTGT
CAGGATGGATCAAACCTCACTGCAAGTCAGAGGGCCTATGCGCCTGAGCAGCTGCAGAAA
CAGGATAATCTAACCATTGACACCCAGTACTACCTGGCCCAGCAGATCCACCCAGTCGTG
GCTCGGATCTGTGAACCAATAGACGGAATTGATGCTGTCCTCATTGCAACGTGGTTGGGA
CTTGACCCCACCCAATTTAGAGTTCATCATTATCATAAAGATGAAGAGAATGATGCTCTA
CTTGGTGGCCCAGCACAGCTCACTGATGAAGAGAAATACAGGGACTGTGAAAGATTCAAA
TGTCCATGCCCTACATGTGGAACTGAGAATATTTATGATAATGTCTTTGATGGTTCGGGA
ACAGATATGGAGCCCAGCTTGTATCGTTGCAGTAACATCGATTGTAAGGCTTCACCTCTG
ACCTTTACAGTACAACTGAGCAACAAATTGATCATGGACATTAGACGTTTCATTAAAAAG
TACTATGATGGCTGGTTGATATGTGAAGAGCCAACCTGTCGCAATCGAACTCGTCACCTT
CCCCTTCAATTCTCCCGAACTGGGCCTCTTTGCCCAGCCTGCATGAAAGCTACACTTCAA
CCAGAGTATTCTGACAAGTCCCTGTACACCCAGCTGTGCTTTTACCGGTACATTTTTGAT
GCGGAGTGTGCACTGGAGAAACTTACTACCGATCATGAGAAAGATAAATTGAAGAAGCAA
TTTTTTACCCCCAAAGTTCTGCAGGACTACAGAAAACTCAAGAACACAGCAGAGCAATTC
TTGTCCCGAAGTGGCTACTCCGAAGTGAATCTGAGCAAACTCTTCGCTGGTTGTGCCGTG
AAATCCTAA
Target 3 GenBank Gene ID
Target 3 GeneCard ID POLA1 Link Image
Target 3 GenAtlas ID POLA1 Link Image
Target 3 HGNC ID HGNC:9173 Link Image
Target 3 Chromosome Location Not Available
Target 3 Locus Not Available
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Evanics F, Maurmann L, Yang WW, Bose RN: Nuclear magnetic resonance structures of the zinc finger domain of human DNA polymerase-alpha. Biochim Biophys Acta. 2003 Sep 23;1651(1-2):163-71. [PubMed Link Image]
  2. Pearson BE, Nasheuer HP, Wang TS: Human DNA polymerase alpha gene: sequences controlling expression in cycling and serum-stimulated cells. Mol Cell Biol. 1991 Apr;11(4):2081-95. [PubMed Link Image]
  3. Hsi KL, Copeland WC, Wang TS: Human DNA polymerase alpha catalytic polypeptide binds ConA and RCA and contains a specific labile site in the N-terminus. Nucleic Acids Res. 1990 Nov 11;18(21):6231-7. [PubMed Link Image]
  4. Wong SW, Wahl AF, Yuan PM, Arai N, Pearson BE, Arai K, Korn D, Hunkapiller MW, Wang TS: Human DNA polymerase alpha gene expression is cell proliferation dependent and its primary structure is similar to both prokaryotic and eukaryotic replicative DNA polymerases. EMBO J. 1988 Jan;7(1):37-47. [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 984
Target 4 Name Signal transducer and activator of transcription 1-alpha/beta
Target 4 Synonyms
  1. Transcription factor ISGF-3 components p91/p84
Target 4 Gene Name STAT1
Target 4 Protein Sequence >Signal transducer and activator of transcription 1-alpha/beta 
MSQWYELQQLDSKFLEQVHQLYDDSFPMEIRQYLAQWLEKQDWEHAANDVSFATIRFHDL
LSQLDDQYSRFSLENNFLLQHNIRKSKRNLQDNFQEDPIQMSMIIYSCLKEERKILENAQ
RFNQAQSGNIQSTVMLDKQKELDSKVRNVKDKVMCIEHEIKSLEDLQDEYDFKCKTLQNR
EHETNGVAKSDQKQEQLLLKKMYLMLDNKRKEVVHKIIELLNVTELTQNALINDELVEWK
RRQQSACIGGPPNACLDQLQNWFTIVAESLQQVRQQLKKLEELEQKYTYEHDPITKNKQV
LWDRTFSLFQQLIQSSFVVERQPCMPTHPQRPLVLKTGVQFTVKLRLLVKLQELNYNLKV
KVLFDKDVNERNTVKGFRKFNILGTHTKVMNMEESTNGSLAAEFRHLQLKEQKNAGTRTN
EGPLIVTEELHSLSFETQLCQPGLVIDLETTSLPVVVISNVSQLPSGWASILWYNMLVAE
PRNLSFFLTPPCARWAQLSEVLSWQFSSVTKRGLNVDQLNMLGEKLLGPNASPDGLIPWT
RFCKENINDKNFPFWLWIESILELIKKHLLPLWNDGCIMGFISKERERALLKDQQPGTFL
LRFSESSREGAITFTWVERSQNGGEPDFHAVEPYTKKELSAVTFPDIIRNYKVMAAENIP
ENPLKYLYPNIDKDHAFGKYYSRPKEAPEPMELDGPKGTGYIKTELISVSEVHPSRLQTT
DNLLPMSPEEFDEVSRIVGSVEFDSMMNTV
Target 4 Number of Residues 762
Target 4 Molecular Weight 87336
Target 4 Theoretical pI 5.92
Target 4 GO Classification
Function
signal transducer activity
nucleic acid binding
DNA binding
transcription factor activity
binding
ion binding
cation binding
calcium ion binding
Process
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent
cellular process
cell communication
signal transduction
intracellular signaling cascade
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus
Target 4 General Function Involved in calcium ion binding
Target 4 Specific Function Signal transducer and activator of transcription that mediates signaling by interferons (IFNs). Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state. In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated. It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • None
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 2281071 Link Image
Target 4 UniProtKB/Swiss-Prot ID P42224 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name STAT1_HUMAN Link Image
Target 4 PDB ID 1YVL Link Image
Target 4 PDB File Show
Target 4 3D Structure
Target 4 Cellular Location
  • Cytoplasm. Nucleus. Note=Translocated into the nucleus upon activation by IFN-alpha/beta
Target 4 Gene Sequence >2253 bp 
ATGTCTCAGTGGTACGAACTTCAGCAGCTTGACTCAAAATTCCTGGAGCAGGTTCACCAG
CTTTATGATGACAGTTTTCCCATGGAAATCAGACAGTACCTGGCACAGTGGTTAGAAAAG
CAAGACTGGGAGCACGCTGCCAATGATGTTTCATTTGCCACCATCCGTTTTCATGACCTC
CTGTCACAGCTGGATGATCAATATAGTCGCTTTTCTTTGGAGAATAACTTCTTGCTACAG
CATAACATAAGGAAAAGCAAGCGTAATCTTCAGGATAATTTTCAGGAAGACCCAATCCAG
ATGTCTATGATCATTTACAGCTGTCTGAAGGAAGAAAGGAAAATTCTGGAAAACGCCCAG
AGATTTAATCAGGCTCAGTCGGGGAATATTCAGAGCACAGTGATGTTAGACAAACAGAAA
GAGCTTGACAGTAAAGTCAGAAATGTGAAGGACAAGGTTATGTGTATAGAGCATGAAATC
AAGAGCCTGGAAGATTTACAAGATGAATATGACTTCAAATGCAAAACCTTGCAGAACAGA
GAACACGAGACCAATGGTGTGGCAAAGAGTGATCAGAAACAAGAACAGCTGTTACTCAAG
AAGATGTATTTAATGCTTGACAATAAGAGAAAGGAAGTAGTTCACAAAATAATAGAGTTG
CTGAATGTCACTGAACTTACCCAGAATGCCCTGATTAATGATGAACTAGTGGAGTGGAAG
CGGAGACAGCAGAGCGCCTGTATTGGGGGGCCGCCCAATGCTTGCTTGGATCAGCTGCAG
AACTGGTTCACTATAGTTGCGGAGAGTCTGCAGCAAGTTCGGCAGCAGCTTAAAAAGTTG
GAGGAATTGGAACAGAAATACACCTACGAACATGACCCTATCACAAAAAACAAACAAGTG
TTATGGGACCGCACCTTCAGTCTTTTCCAGCAGCTCATTCAGAGCTCGTTTGTGGTGGAA
AGACAGCCCTGCATGCCAACGCACCCTCAGAGGCCGCTGGTCTTGAAGACAGGGGTCCAG
TTCACTGTGAAGTTGAGACTGTTGGTGAAATTGCAAGAGCTGAATTATAATTTGAAAGTC
AAAGTCTTATTTGATAAAGATGTGAATGAGAGAAATACAGTAAAAGGATTTAGGAAGTTC
AACATTTTGGGCACGCACACAAAAGTGATGAACATGGAGGAGTCCACCAATGGCAGTCTG
GCGGCTGAATTTCGGCACCTGCAATTGAAAGAACAGAAAAATGCTGGCACCAGAACGAAT
GAGGGTCCTCTCATCGTTACTGAAGAGCTTCACTCCCTTAGTTTTGAAACCCAATTGTGC
CAGCCTGGTTTGGTAATTGACCTCGAGACGACCTCTCTGCCCGTTGTGGTGATCTCCAAC
GTCAGCCAGCTCCCGAGCGGTTGGGCCTCCATCCTTTGGTACAACATGCTGGTGGCGGAA
CCCAGGAATCTGTCCTTCTTCCTGACTCCACCATGTGCACGATGGGCTCAGCTTTCAGAA
GTGCTGAGTTGGCAGTTTTCTTCTGTCACCAAAAGAGGTCTCAATGTGGACCAGCTGAAC
ATGTTGGGAGAGAAGCTTCTTGGTCCTAACGCCAGCCCCGATGGTCTCATTCCGTGGACG
AGGTTTTGTAAGGAAAATATAAATGATAAAAATTTTCCCTTCTGGCTTTGGATTGAAAGC
ATCCTAGAACTCATTAAAAAACACCTGCTCCCTCTCTGGAATGATGGGTGCATCATGGGC
TTCATCAGCAAGGAGCGAGAGCGTGCCCTGTTGAAGGACCAGCAGCCGGGGACCTTCCTG
CTGCGGTTCAGTGAGAGCTCCCGGGAAGGGGCCATCACATTCACATGGGTGGAGCGGTCC
CAGAACGGAGGCGAACCTGACTTCCATGCGGTTGAACCCTACACGAAGAAAGAACTTTCT
GCTGTTACTTTCCCTGACATCATTCGCAATTACAAAGTCATGGCTGCTGAGAATATTCCT
GAGAATCCCCTGAAGTATCTGTATCCAAATATTGACAAAGACCATGCCTTTGGAAAGTAT
TACTCCAGGCCAAAGGAAGCACCAGAGCCAATGGAACTTGATGGCCCTAAAGGAACTGGA
TATATCAAGACTGAGTTGATTTCTGTGTCTGAAGTTCACCCTTCTAGACTTCAGACCACA
GACAACCTGCTCCCCATGTCTCCTGAGGAGTTTGACGAGGTGTCTCGGATAGTGGGCTCT
GTAGAATTCGACAGTATGATGAACACAGTATAG
Target 4 GenBank Gene ID
Target 4 GeneCard ID STAT1 Link Image
Target 4 GenAtlas ID STAT1 Link Image
Target 4 HGNC ID HGNC:11362 Link Image
Target 4 Chromosome Location 2
Target 4 Locus 2q32.2
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Cebulla CM, Miller DM, Sedmak DD: Viral inhibition of interferon signal transduction. Intervirology. 1999;42(5-6):325-30. [PubMed Link Image]
  2. Takeuchi K, Komatsu T, Yokoo J, Kato A, Shioda T, Nagai Y, Gotoh B: Sendai virus C protein physically associates with Stat1. Genes Cells. 2001 Jun;6(6):545-57. [PubMed Link Image]
  3. Schindler C, Fu XY, Improta T, Aebersold R, Darnell JE Jr: Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7836-9. [PubMed Link Image]
  4. Wen Z, Zhong Z, Darnell JE Jr: Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell. 1995 Jul 28;82(2):241-50. [PubMed Link Image]
  5. Quelle FW, Thierfelder W, Witthuhn BA, Tang B, Cohen S, Ihle JN: Phosphorylation and activation of the DNA binding activity of purified Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor receptor. J Biol Chem. 1995 Sep 1;270(35):20775-80. [PubMed Link Image]
  6. Yan R, Qureshi S, Zhong Z, Wen Z, Darnell JE Jr: The genomic structure of the STAT genes: multiple exons in coincident sites in Stat1 and Stat2. Nucleic Acids Res. 1995 Feb 11;23(3):459-63. [PubMed Link Image]
  7. Chen X, Vinkemeier U, Zhao Y, Jeruzalmi D, Darnell JE Jr, Kuriyan J: Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. Cell. 1998 May 29;93(5):827-39. [PubMed Link Image]
Target 4 Drug References
  1. Frank DA, Mahajan S, Ritz J: Fludarabine-induced immunosuppression is associated with inhibition of STAT1 signaling. Nat Med. 1999 Apr;5(4):444-7. [PubMed Link Image]
  2. Fagard R, Mouas H, Dusanter-Fourt I, Devillers C, Bissieres P, Martin A, Lenoir G, VanTan H, Feuillard J, Raphael M: Resistance to fludarabine-induced apoptosis in Epstein-Barr virus infected B cells. Oncogene. 2002 Jul 4;21(29):4473-80. [PubMed Link Image]
  3. Friedberg JW, Dong DA, Li S, Kim H, Stephans K, Noonan K, Neuberg D, Gribben JG, Fisher DC, Freedman AS, Takvorian T, Jurgens R, Battle TE, Frank DA: Oral fludarabine has significant activity in patients with previously untreated chronic lymphocytic leukemia, and leads to increased STAT1 levels in vivo. Leuk Res. 2004 Feb;28(2):139-47. [PubMed Link Image]
  4. Baran-Marszak F, Feuillard J, Najjar I, Le Clorennec C, Bechet JM, Dusanter-Fourt I, Bornkamm GW, Raphael M, Fagard R: Differential roles of STAT1alpha and STAT1beta in fludarabine-induced cell cycle arrest and apoptosis in human B cells. Blood. 2004 Oct 15;104(8):2475-83. Epub 2004 Jun 24. [PubMed Link Image]
  5. Martinez-Lostao L, Briones J, Forne I, Martinez-Gallo M, Ferrer B, Sierra J, Rodriguez-Sanchez JL, Juarez C: Role of the STAT1 pathway in apoptosis induced by fludarabine and JAK kinase inhibitors in B-cell chronic lymphocytic leukemia. Leuk Lymphoma. 2005 Mar;46(3):435-42. [PubMed Link Image]
Drug Target 5 [top]
Target 5 ID 3957
Target 5 Name Adenosine deaminase
Target 5 Synonyms
  1. Adenosine aminohydrolase
  2. EC 3.5.4.4
Target 5 Gene Name ADA
Target 5 Protein Sequence >Adenosine deaminase 
MAQTPAFDKPKVELHVHLDGSIKPETILYYGRRRGIALPANTAEGLLNVIGMDKPLTLPD
FLAKFDYYMPAIAGCREAIKRIAYEFVEMKAKEGVVYVEVRYSPHLLANSKVEPIPWNQA
EGDLTPDEVVALVGQGLQEGERDFGVKARSILCCMRHQPNWSPKVVELCKKYQQQTVVAI
DLAGDETIPGSSLLPGHVQAYQEAVKSGIHRTVHAGEVGSAEVVKEAVDILKTERLGHGY
HTLEDQALYNRLRQENMHFEICPWSSYLTGAWKPDTEHAVIRLKNDQANYSLNTDDPLIF
KSTLDTDYQMTKRDMGFTEEEFKRLNINAAKSSFLPEDEKRELLDLLYKAYGMPPSASAG
QNL
Target 5 Number of Residues 369
Target 5 Molecular Weight 40765
Target 5 Theoretical pI 5.80
Target 5 GO Classification
Function
hydrolase activity
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines
adenosine deaminase activity
catalytic activity
deaminase activity
Process
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
nucleotide metabolism
purine nucleotide metabolism
purine nucleotide biosynthesis
purine nucleoside monophosphate biosynthesis
purine ribonucleoside monophosphate biosynthesis
Component
Not Available
Target 5 General Function Replication, recombination and repair
Target 5 Specific Function Adenosine + H(2)O = inosine + NH(3)
Target 5 Pathways
Name SMPDB Link KEGG Link
Purine metabolism SMP00050 Link Image map00230 Link Image
Target 5 Reactions
  • adenosine + H2O = inosine + NH3
Target 5 Pfam Domain Function
Target 5 Signals
  • None
Target 5 Transmembrane Regions
  • None
Target 5 Essentiality Non-Essential
Target 5 GenBank ID Protein 28380 Link Image
Target 5 UniProtKB/Swiss-Prot ID P00813 Link Image
Target 5 UniProtKB/Swiss-Prot Entry Name ADA_HUMAN Link Image
Target 5 PDB ID Not Available
Target 5 Cellular Location
  • Cytoplasmic
Target 5 Gene Sequence >1092 bp 
ATGGCCCAGACGCCCGCCTTCGACAAGCCCAAAGTAGAACTGCATGTCCACCTAGACGGA
TCCATCAAGCCTGAAACCATCTTATACTATGGCAGGAGGAGAGGGATCGCCCTCCCAGCT
AACACAGCAGAGGGGCTGCTGAACGTCATTGGCATGGACAAGCCGCTCACCCTTCCAGAC
TTCCTGGCCAAGTTTGACTACTACATGCCTGCTATCGCGGGCTGCCGGGAGGCTATCAAA
AGGATCGCCTATGAGTTTGTAGAGATGAAGGCCAAAGAGGGCGTGGTGTATGTGGAGGTG
CGGTACAGTCCGCACCTGCTGGCCAACTCCAAAGTGGAGCCAATCCCCTGGAACCAGGCT
GAAGGGGACCTCACCCCAGACGAGGTGGTGGCCCTAGTGGGCCAGGGCCTGCAGGAGGGG
GAGCGAGACTTCGGGGTCAAGGCCCGGTCCATCCTGTGCTGCATGCGCCACCAGCCCAAC
TGGTCCCCCAAGGTGGTGGAGCTGTGTAAGAAGTACCAGCAGCAGACCGTGGTGGCCATT
GACCTGGCTGGAGATGAGACCATCCCAGGAAGCAGCCTCTTGCCTGGACATGTCCAGGCC
TACCAGGAGGCTGTGAAGAGCGGCATTCACCGTACTGTCCACGCCGGGGAGGTGGGCTCG
GCCGAAGTAGTAAAAGAGGCTGTGGACATACTCAAGACAGAGCGGCTGGGACACGGCTAC
CACACCCTGGAAGACCAGGCCCTTTATAACAGGCTGCGGCAGGAAAACATGCACTTCGAG
ATCTGCCCCTGGTCCAGCTACCTCACTGGTGCCTGGAAGCCGGACACGGAGCATGCAGTC
ATTCGGCTCAAAAATGACCAGGCTAACTACTCGCTCAACACAGATGACCCGCTCATCTTC
AAGTCCACCCTGGACACTGATTACCAGATGACCAAACGGGACATGGGCTTTACTGAAGAG
GAGTTTAAAAGGCTGAACATCAATGCGGCCAAATCTAGTTTCCTCCCAGAAGATGAAAAG
AGGGAGCTTCTCGACCTGCTCTATAAAGCCTATGGGATGCCACCTTCAGCCTCTGCAGGG
CAGAACCTCTGA
Target 5 GenBank Gene ID
Target 5 GeneCard ID ADA Link Image
Target 5 GenAtlas ID ADA Link Image
Target 5 HGNC ID HGNC:186 Link Image
Target 5 Chromosome Location 20
Target 5 Locus 20q12-q13.11
Target 5 SNPs SNPJam Report Link Image
Target 5 General References
  1. 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]
  2. Wiginton DA, Kaplan DJ, States JC, Akeson AL, Perme CM, Bilyk IJ, Vaughn AJ, Lattier DL, Hutton JJ: Complete sequence and structure of the gene for human adenosine deaminase. Biochemistry. 1986 Dec 16;25(25):8234-44. [PubMed Link Image]
  3. Valerio D, Duyvesteyn MG, Dekker BM, Weeda G, Berkvens TM, van der Voorn L, van Ormondt H, van der Eb AJ: Adenosine deaminase: characterization and expression of a gene with a remarkable promoter. EMBO J. 1985 Feb;4(2):437-43. [PubMed Link Image]
  4. Daddona PE, Shewach DS, Kelley WN, Argos P, Markham AF, Orkin SH: Human adenosine deaminase. cDNA and complete primary amino acid sequence. J Biol Chem. 1984 Oct 10;259(19):12101-6. [PubMed Link Image]
  5. Wiginton DA, Adrian GS, Hutton JJ: Sequence of human adenosine deaminase cDNA including the coding region and a small intron. Nucleic Acids Res. 1984 Mar 12;12(5):2439-46. [PubMed Link Image]
  6. Orkin SH, Daddona PE, Shewach DS, Markham AF, Bruns GA, Goff SC, Kelley WN: Molecular cloning of human adenosine deaminase gene sequences. J Biol Chem. 1983 Nov 10;258(21):12753-6. [PubMed Link Image]
  7. Hirschhorn R, Yang DR, Israni A: An Asp8Asn substitution results in the adenosine deaminase (ADA) genetic polymorphism (ADA 2 allozyme): occurrence on different chromosomal backgrounds and apparent intragenic crossover. Ann Hum Genet. 1994 Jan;58(Pt 1):1-9. [PubMed Link Image]
Target 5 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [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.