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Showing drug card for Saquinavir (DB01232)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:05:53
Primary Accession Number DB01232
Secondary Accession Number
  • APRD00623
Name Saquinavir
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases. [PubChem]
Synonyms
  1. SQV
  2. Saquinavir Mesylate
  3. saquinavir
Brand Names
  1. Fortovase
  2. Invirase
  3. ROC
Brand Mixtures Not Available
Chemical IUPAC Name (2S)-N-[(2S,3R)-4-[(3S)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinoline-2-carbonylamino)butanediamide
Chemical Formula C38H50N6O5
Chemical Structure Structure
CAS Registry Number 127779-20-8
InChI Identifier InChI=1/C38H50N6O5/c1-38(2,3)43-37(49)32-20-26-14-7-8-15-27(26)22-44(32)23-33(45)30(19-24-11-5-4-6-12-24)41-36(48)31(21-34(39)46)42-35(47)29-18-17-25-13-9-10-16-28(25)40-29/h4-6,9-13,16-18,26-27,30-33,45H,7-8,14-15,19-23H2,1-3H3,(H2,39,46)(H,41,48)(H,42,47)(H,43,49)/t26?,27?,30-,31-,32-,33+/m0/s1/f/h41-43H,39H2
InChI Key QWAXKHKRTORLEM-QNARNJJIDJ
KEGG Drug D00429 Link Image
KEGG Compound Not Available
PubChem Compound 60787 Link Image
PubChem Substance 197032 Link Image
ChEBI ID Not Available
PharmGKB ID PA451305 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02239083 Link Image
RxList Link http://www.rxlist.com/cgi/generic/saquin.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Saquinavir Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Parkes, Kevin E. B. et al., J. Org. Chem. 59(13) 3656-3664(1994)
Average Molecular Weight 670.8408
Monoisotopic Molecular Weight 670.3843
State Solid
Melting Point 349.84 oC
Experimental Water Solubility Insoluble Source: PhysProp
Predicted Water Solubility 2.47e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3.8 Source: PhysProp
Predicted LogP 4.04 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -5.43 Calculated using ALOGPS
Experimental Caco2 Permeability -6.26 [ADME Research, USCD]
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 1ODW Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES CC(C)(C)NC(=O)[C@@H]1C[C@H]2CCCC[C@@H]2CN1C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(N)=O)NC(=O)C1=NC2=CC=CC=C2C=C1
Canonical SMILES CC(C)(C)NC(=O)C1CC2CCCCC2CN1CC(O)C(CC1=CC=CC=C1)NC(=O)C(CC(N)=O)NC(=O)C1=NC2=CC=CC=C2C=C1
Drug Category
  • Anti-HIV Agents
  • HIV Protease Inhibitors
ATC Codes
AHFS Codes
  • 08:18.08.08
Indication For the treatment of HIV-1 with advanced immunodeficiency together with antiretroviral nucleoside analogues.
Pharmacology Saquinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Saquinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.
Mechanism of Action Saquinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Absorption Absolute bioavailability averages 4%
Toxicity Probably experience pain in the throat
Protein Binding 98%
Biotransformation Hepatic
Half Life Not Available
Dosage Forms
Form Route
Capsule Oral
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions
  • Take after a full meal.
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Human Immunodeficiency Virus
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A5 (CYP3A5)
  2. Cytochrome P450 3A4 (CYP3A4)
Targets
  1. Serum albumin
  2. HIV-1 protease
  3. Tumor necrosis factor
  4. Multidrug resistance-associated protein 1
  5. Multidrug resistance protein 1
  6. ATP-binding cassette sub-family G member 2
  7. Canalicular multispecific organic anion transporter 1
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A5 (CYP3A5)
Enzyme 1 Gene Name CYP3A5
Enzyme 1 SwissProt ID P20815 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P20815|CP3A5_HUMAN Cytochrome P450 3A5
MDLIPNLAVETWLLLAVSLVLLYLYGTRTHGLFKRLGIPGPTPLPLLGNVLSYRQGLWKF
DTECYKKYGKMWGTYEGQLPVLAITDPDVIRTVLVKECYSVFTNRRSLGPVGFMKSAISL
AEDEEWKRIRSLLSPTFTSGKLKEMFPIIAQYGDVLVRNLRREAEKGKPVTLKDIFGAYS
MDVITGTSFGVNIDSLNNPQDPFVESTKKFLKFGFLDPLFLSIILFPFLTPVFEALNVSL
FPKDTINFLSKSVNRMKKSRLNDKQKHRLDFLQLMIDSQNSKETESHKALSDLELAAQSI
IFIFAGYETTSSVLSFTLYELATHPDVQQKLQKEIDAVLPNKAPPTYDAVVQMEYLDMVV
NETLRLFPVAIRLERTCKKDVEINGVFIPKGSMVVIPTYALHHDPKYWTEPEEFRPERFS
KKKDSIDPYIYTPFGTGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLDTQG
LLQPEKPIVLKVDSRDGTLSGE
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 2 Gene Name CYP3A4
Enzyme 2 SwissProt ID P08684 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 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 587
Target 1 Name Serum albumin
Target 1 Synonyms
  1. Serum albumin precursor
Target 1 Gene Name ALB
Target 1 Protein Sequence >Serum albumin precursor
MKWVTFISLLFLFSSAYSRGVFRRDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPF
EDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEP
ERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLF
FAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAV
ARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLK
ECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYAR
RHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFE
QLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVV
LNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTL
SEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLV
AASQAALGL
Target 1 Number of Residues 619
Target 1 Molecular Weight 69367
Target 1 Theoretical pI 6.21
Target 1 GO Classification
Function
transporter activity
carrier activity
Process
physiological process
cellular physiological process
transport
Component
extracellular region
extracellular space
Target 1 General Function Involved in antioxidant activity
Target 1 Specific Function Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-18
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 28590 Link Image
Target 1 UniProtKB/Swiss-Prot ID P02768 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ALBU_HUMAN Link Image
Target 1 PDB ID 1HA2 Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Secreted protein
Target 1 Gene Sequence >1830 bp
ATGAAGTGGGTAACCTTTATTTCCCTTCTTTTTCTCTTTAGCTCGGCTTATTCCAGGGGT
GTGTTTCGTCGAGATGCACACAAGAGTGAGGTTGCTCATCGGTTTAAAGATTTGGGAGAA
GAAAATTTCAAAGCCTTGGTGTTGATTGCCTTTGCTCAGTATCTTCAGCAGTGTCCATTT
GAAGATCATGTAAAATTAGTGAATGAAGTAACTGAATTTGCAAAAACATGTGTTGCTGAT
GAGTCAGCTGAAAATTGTGACAAATCACTTCATACCCTTTTTGGAGACAAATTATGCACA
GTTGCAACTCTTCGTGAAACCTATGGTGAAATGGCTGACTGCTGTGCAAAACAAGAACCT
GGGAGAAATGAATGCTTCTTGCAACACAAAGATGACAACCCAAACCTCCCCCGATTGGTG
AGACCAGAGGTTGATGTGATGTGCACTGCTTTTCATGACAATGAAGAGACATTTTTGAAA
AAATACTTATATGAAATTGCCAGAAGACATCCTTACTTTTATGCCCCGGAACTCCTTTTC
TTTGCTAAAAGGTATAAAGCTGCTTTTACAGAATGTTGCCAAGCTGCTGATAAAGCTGCC
TGCCTGTTGCCAAAGCTCGATGAACTTCGGGATGAAGGGAAGGCTTCGTCTGCCAAACAG
AGACTCAAGTGTGCCAGTCTCCAAAAATTTGGAGAAAGAGCTTTCAAAGCATGGGCAGTA
GCTCGCCTGAGCCAGAGATTTCCCAAAGCTGAGTTTGCAGAAGTTTCCAAGTTAGTGACA
GATCTTACCAAAGTCCACACGGAATGCTGCCATGGAGATCTGCTTGAATGTGCTGATGAC
AGGGCGGACCTTGCCAAGTATATCTGTGAAAATCAAGATTCGATCTCCAGTAAACTGAAG
GAATGCTGTGAAAAACCTCTGTTGGAAAAATCCCACTGCATTGCCGAAGTGGAAAATGAT
GAGATGCCTGCTGACTTGCCTTCATTAGCTGCTGATTTTGTTGAAAGTAAGGATGTTTGC
AAAAACTATGCTGAGGCAAAGGATGTCTTCTTGGGCATGTTTTTGTATGAATATGCAAGA
AGGCATCCTGATTACTCTGTCGTGCTGCTGCTGAGACTTGCCAAGACATATGAAACCACT
CTAGAGAAGTGCTGTGCCGCTGCAGATCCTCATGAATGCTATGCCAAAGTGTTCGATGAA
TTTAAACCTCTTGTGGAAGAGCCTCAGAATTTAATCAAACAAAATTGTGAGCTTTTTGAG
CAGCTTGGAGAGTACAAATTCCAGAATGCGCTGTTAGTTCGTTACACCAAGAAAGTACCC
GAAGTGTCAACTCCAACTCTTGTAGAGGTCTCAAGAAACCTAGGAAAAGTGGGCAGCAAA
TGTTGTAAACATCCTGAAGCAAAAAGAATGCCCTGTGCAGAAGACTATCTATCCGTGGTC
CTGAACCAGTTATGTGTGTTGCATGAGAAAACGCCAGTAAGTGACAGAGTCACCAAATGC
TGCACAGAATCCTTGGTGAACAGGCGACCATGCTTTTCAGCTCTGGAAGTCGATGAAACA
TACGTTCCCAAAGAGTTTAATGCTGAAACATTCACCTTCCATGCAGATATATGCACACTT
TCTGAGAAGGAGAGACAAATCAAGAAACAAACTGCACTTGTTGAGCTCGTGAAACACAAG
CCCAAGGCAACAAAAGAGCAACTGAAAGCTGTTATGGATGATTTCGCTGCTTTTGTAGAG
AAGTGCTGCAAGGCTGACGATAAGGAGACCTGCTTTGCCGAGGAGGGTAAAAAACTTGTT
GCTGCAAGTCAAGCTGCCTTAGGCTTATAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID ALB Link Image
Target 1 GenAtlas ID ALB Link Image
Target 1 HGNC ID HGNC:399 Link Image
Target 1 Chromosome Location 4
Target 1 Locus 4q11-q13
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Sugio S, Kashima A, Mochizuki S, Noda M, Kobayashi K: Crystal structure of human serum albumin at 2.5 A resolution. Protein Eng. 1999 Jun;12(6):439-46. [PubMed Link Image]
  2. Bhattacharya AA, Curry S, Franks NP: Binding of the general anesthetics propofol and halothane to human serum albumin. High resolution crystal structures. J Biol Chem. 2000 Dec 8;275(49):38731-8. [PubMed Link Image]
  3. Minchiotti L, Campagnoli M, Rossi A, Cosulich ME, Monti M, Pucci P, Kragh-Hansen U, Granel B, Disdier P, Weiller PJ, Galliano M: A nucleotide insertion and frameshift cause albumin Kenitra, an extended and O-glycosylated mutant of human serum albumin with two additional disulfide bridges. Eur J Biochem. 2001 Jan;268(2):344-52. [PubMed Link Image]
  4. Yu Y, Zhang C, Zhou G, Wu S, Qu X, Wei H, Xing G, Dong C, Zhai Y, Wan J, Ouyang S, Li L, Zhang S, Zhou K, Zhang Y, Wu C, He F: Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs. Genome Res. 2001 Aug;11(8):1392-403. [PubMed Link Image]
  5. Spahr CS, Davis MT, McGinley MD, Robinson JH, Bures EJ, Beierle J, Mort J, Courchesne PL, Chen K, Wahl RC, Yu W, Luethy R, Patterson SD: Towards defining the urinary proteome using liquid chromatography-tandem mass spectrometry. I. Profiling an unfractionated tryptic digest. Proteomics. 2001 Jan;1(1):93-107. [PubMed Link Image]
  6. Petitpas I, Grune T, Bhattacharya AA, Curry S: Crystal structures of human serum albumin complexed with monounsaturated and polyunsaturated fatty acids. J Mol Biol. 2001 Dec 14;314(5):955-60. [PubMed Link Image]
  7. Meloun B, Moravek L, Kostka V: Complete amino acid sequence of human serum albumin. FEBS Lett. 1975 Oct 15;58(1):134-7. [PubMed Link Image]
  8. 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]
  9. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [PubMed Link Image]
  10. Minchiotti L, Galliano M, Stoppini M, Ferri G, Crespeau H, Rochu D, Porta F: Two alloalbumins with identical electrophoretic mobility are produced by differently charged amino acid substitutions. Biochim Biophys Acta. 1992 Mar 12;1119(3):232-8. [PubMed Link Image]
  11. 1518850 Carlson J, Sakamoto Y, Laurell CB, Madison J, Watkins S, Putnam FW: Alloalbuminemia in Sweden: structural study and phenotypic distribution of nine albumin variants. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8225-9.
  12. 1630489 He XM, Carter DC: Atomic structure and chemistry of human serum albumin. Nature. 1992 Jul 16;358(6383):209-15.
  13. 1859851 Peach RJ, Brennan SO: Structural characterization of a glycoprotein variant of human serum albumin: albumin Casebrook (494 Asp----Asn). Biochim Biophys Acta. 1991 Jul 26;1097(1):49-54.
  14. 1946412 Madison J, Arai K, Sakamoto Y, Feld RD, Kyle RA, Watkins S, Davis E, Matsuda Y, Amaki I, Putnam FW: Genetic variants of serum albumin in Americans and Japanese. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9853-7.
  15. 2068071 Watkins S, Madison J, Davis E, Sakamoto Y, Galliano M, Minchiotti L, Putnam FW: A donor splice mutation and a single-base deletion produce two carboxyl-terminal variants of human serum albumin. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):5959-63.
  16. 2104980 Brennan SO, Myles T, Peach RJ, Donaldson D, George PM: Albumin Redhill (-1 Arg, 320 Ala----Thr): a glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site. Proc Natl Acad Sci U S A. 1990 Jan;87(1):26-30.
  17. 2247440 Galliano M, Minchiotti L, Porta F, Rossi A, Ferri G, Madison J, Watkins S, Putnam FW: Mutations in genetic variants of human serum albumin found in Italy. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8721-5.
  18. 2374930 Carter DC, He XM: Structure of human serum albumin. Science. 1990 Jul 20;249(4966):302-3.
  19. 2404284 Arai K, Madison J, Shimizu A, Putnam FW: Point substitutions in albumin genetic variants from Asia. Proc Natl Acad Sci U S A. 1990 Jan;87(1):497-501.
  20. 2419329 Urano Y, Watanabe K, Sakai M, Tamaoki T: The human albumin gene. Characterization of the 5' and 3' flanking regions and the polymorphic gene transcripts. J Biol Chem. 1986 Mar 5;261(7):3244-51.
  21. 2437111 Carraway RE, Mitra SP, Cochrane DE: Structure of a biologically active neurotensin-related peptide obtained from pepsin-treated albumin(s). J Biol Chem. 1987 May 5;262(13):5968-73.
  22. 2727704 Carter DC, He XM, Munson SH, Twigg PD, Gernert KM, Broom MB, Miller TY: Three-dimensional structure of human serum albumin. Science. 1989 Jun 9;244(4909):1195-8.
  23. 2762316 Arai K, Madison J, Huss K, Ishioka N, Satoh C, Fujita M, Neel JV, Sakurabayashi I, Putnam FW: Point substitutions in Japanese alloalbumins. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6092-6.
  24. 2911589 Arai K, Ishioka N, Huss K, Madison J, Putnam FW: Identical structural changes in inherited albumin variants from different populations. Proc Natl Acad Sci U S A. 1989 Jan;86(2):434-8.
  25. 3009475 Minghetti PP, Ruffner DE, Kuang WJ, Dennison OE, Hawkins JW, Beattie WG, Dugaiczyk A: Molecular structure of the human albumin gene is revealed by nucleotide sequence within q11-22 of chromosome 4. J Biol Chem. 1986 May 25;261(15):6747-57.
  26. 3087352 Mogard MH, Kobayashi R, Chen CF, Lee TD, Reeve JR Jr, Shively JE, Walsh JH: The amino acid sequence of kinetensin, a novel peptide isolated from pepsin-treated human plasma: homology with human serum albumin, neurotensin and angiotensin. Biochem Biophys Res Commun. 1986 May 14;136(3):983-8.
  27. 3474609 Takahashi N, Takahashi Y, Blumberg BS, Putnam FW: Amino acid substitutions in genetic variants of human serum albumin and in sequences inferred from molecular cloning. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4413-7.
  28. 3479777 Takahashi N, Takahashi Y, Isobe T, Putnam FW, Fujita M, Satoh C, Neel JV: Amino acid substitutions in inherited albumin variants from Amerindian and Japanese populations. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8001-5.
  29. 3828358 Brennan SO, Herbert P: Albumin Canterbury (313 Lys----Asn). A point mutation in the second domain of serum albumin. Biochim Biophys Acta. 1987 Apr 8;912(2):191-7.
  30. 6171778 Lawn RM, Adelman J, Bock SC, Franke AE, Houck CM, Najarian RC, Seeburg PH, Wion KL: The sequence of human serum albumin cDNA and its expression in E. coli. Nucleic Acids Res. 1981 Nov 25;9(22):6103-114.
  31. 6275391 Dugaiczyk A, Law SW, Dennison OE: Nucleotide sequence and the encoded amino acids of human serum albumin mRNA. Proc Natl Acad Sci U S A. 1982 Jan;79(1):71-5.
  32. 656055 Jacobsen C: Lysine residue 240 of human serum albumin is involved in high-affinity binding of bilirubin. Biochem J. 1978 May 1;171(2):453-9.
  33. 7852505 Rushbrook JI, Becker E, Schussler GC, Divino CM: Identification of a human serum albumin species associated with familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab. 1995 Feb;80(2):461-7.
  34. 7895732 Corbett JM, Wheeler CH, Baker CS, Yacoub MH, Dunn MJ: The human myocardial two-dimensional gel protein database: update 1994. Electrophoresis. 1994 Nov;15(11):1459-65.
  35. 7902134 Galliano M, Minchiotti L, Iadarola P, Stoppini M, Giagnoni P, Watkins S, Madison J, Putnam FW: Protein and DNA sequence analysis of a 'private' genetic variant: albumin Ortonovo (Glu-505-->Lys). Biochim Biophys Acta. 1993 Nov 25;1225(1):27-32.
  36. 8022807 Madison J, Galliano M, Watkins S, Minchiotti L, Porta F, Rossi A, Putnam FW: Genetic variants of human serum albumin in Italy: point mutants and a carboxyl-terminal variant. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6476-80.
  37. 8048949 Sunthornthepvarakul T, Angkeow P, Weiss RE, Hayashi Y, Refetoff S: An identical missense mutation in the albumin gene results in familial dysalbuminemic hyperthyroxinemia in 8 unrelated families. Biochem Biophys Res Commun. 1994 Jul 29;202(2):781-7.
  38. 8347685 Brennan SO, Fellowes AP: Albumin Hawkes Bay; a low level variant caused by loss of a sulphydryl group at position 177. Biochim Biophys Acta. 1993 Aug 4;1182(1):46-50.
  39. 8513793 Minchiotti L, Galliano M, Zapponi MC, Tenni R: The structural characterization and bilirubin-binding properties of albumin Herborn, a [Lys240-->Glu] albumin mutant. Eur J Biochem. 1993 Jun 1;214(2):437-44.
  40. 9329347 Wada N, Chiba H, Shimizu C, Kijima H, Kubo M, Koike T: A novel missense mutation in codon 218 of the albumin gene in a distinct phenotype of familial dysalbuminemic hyperthyroxinemia in a Japanese kindred. J Clin Endocrinol Metab. 1997 Oct;82(10):3246-50.
  41. 955075 Walker JE: Lysine residue 199 of human serum albumin is modified by acetylsalicyclic acid. FEBS Lett. 1976 Jul 15;66(2):173-5.
  42. 9589637 Sunthornthepvarakul T, Likitmaskul S, Ngowngarmratana S, Angsusingha K, Kitvitayasak S, Scherberg NH, Refetoff S: Familial dysalbuminemic hypertriiodothyroninemia: a new, dominantly inherited albumin defect. J Clin Endocrinol Metab. 1998 May;83(5):1448-54.
  43. 9731778 Curry S, Mandelkow H, Brick P, Franks N: Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites. Nat Struct Biol. 1998 Sep;5(9):827-35.
Target 1 Drug References
  1. Holladay JW, Dewey MJ, Michniak BB, Wiltshire H, Halberg DL, Weigl P, Liang Z, Halifax K, Lindup WE, Back DJ: Elevated alpha-1-acid glycoprotein reduces the volume of distribution and systemic clearance of saquinavir. Drug Metab Dispos. 2001 Mar;29(3):299-303. [PubMed Link Image]
  2. Forestier F, de Renty P, Peytavin G, Dohin E, Farinotti R, Mandelbrot L: Maternal-fetal transfer of saquinavir studied in the ex vivo placental perfusion model. Am J Obstet Gynecol. 2001 Jul;185(1):178-81. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 731
Target 2 Name HIV-1 protease
Target 2 Synonyms
  1. Fragment
Target 2 Gene Name HIV-1 protease
Target 2 Protein Sequence >HIV-1 protease
PQVTLWQRPIVTIKIGGQLKEALLDTGADDTVLEEMSLPGKWKPKMIGGIGGFIKVRQYD
QVSIEICGHKAIGTVLIGPTPVNIIGRNLLTQLGCTLNF
Target 2 Number of Residues 100
Target 2 Molecular Weight 10725
Target 2 Theoretical pI 8.77
Target 2 GO Classification
Function
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
aspartic-type endopeptidase activity
Process
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
Component
Not Available
Target 2 General Function Involved in aspartic-type endopeptidase activity
Target 2 Specific Function Not Available
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 4377614 Link Image
Target 2 UniProtKB/Swiss-Prot ID O90777 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name O90777_9PLVG Link Image
Target 2 PDB ID 1ODW Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Cytoplasmic
Target 2 Gene Sequence >297 bp
CCTCAGGTCACTCTTTGGCAACGACCCATAGTCACAATAAAGATAGGGGGGCAACTAAAG
GAAGCTCTATTAGATACAGGAGCAGATGATACAGTATTAGAAGAAATGAGTTTGCCAGGA
AAATGGAAACCAAAAATGATAGGGGGAATTGGAGGTTTTATCAAAGTAAGACAGTATGAT
CAGGTATCCATAGAAATCTGCGGACATAAAGCTATAGGTACAGTATTAATAGGACCTACA
CCTGTCAACATAATTGGAAGGAATCTGTTGACTCAGCTTGGCTGCACTTTAAATTTT
Target 2 GenBank Gene ID
Target 2 GeneCard ID Not Available
Target 2 GenAtlas ID Not Available
Target 2 HGNC ID Not Available
Target 2 Chromosome Location Not Available
Target 2 Locus Not Available
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Servais J, Lambert C, Fontaine E, Plesseria JM, Robert I, Arendt V, Staub T, Schneider F, Hemmer R, Burtonboy G, Schmit JC: Comparison of DNA sequencing and a line probe assay for detection of human immunodeficiency virus type 1 drug resistance mutations in patients failing highly active antiretroviral therapy. J Clin Microbiol. 2001 Feb;39(2):454-9. [PubMed Link Image]
  2. Servais J, Lambert C, Fontaine E, Plesseria JM, Robert I, Arendt V, Staub T, Schneider F, Hemmer R, Burtonboy G, Schmit JC: Variant human immunodeficiency virus type 1 proteases and response to combination therapy including a protease inhibitor. Antimicrob Agents Chemother. 2001 Mar;45(3):893-900. [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]
  3. Dandache S, Sevigny G, Yelle J, Stranix BR, Parkin N, Schapiro JM, Wainberg MA, Wu JJ: In Vitro Antiviral Activity and Cross-Resistance Profile of PL-100, a Next Generation Protease Inhibitor of Human Immunodeficiency Virus Type 1. Antimicrob Agents Chemother. 2007 Jul 16;. [PubMed Link Image]
  4. Wittayanarakul K, Hannongbua S, Feig M: Accurate prediction of protonation state as a prerequisite for reliable MM-PB(GB)SA binding free energy calculations of HIV-1 protease inhibitors. J Comput Chem. 2007 Sep 11;. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 777
Target 3 Name Tumor necrosis factor
Target 3 Synonyms
  1. Cachectin
  2. TNF-a
  3. TNF-alpha
  4. Tumor necrosis factor ligand superfamily member 2
  5. Tumor necrosis factor precursor
Target 3 Gene Name TNF
Target 3 Protein Sequence >Tumor necrosis factor precursor
MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR
EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR
DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE
TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL
Target 3 Number of Residues 236
Target 3 Molecular Weight 25645
Target 3 Theoretical pI 6.92
Target 3 GO Classification
Function
signal transducer activity
receptor binding
cytokine activity
tumor necrosis factor receptor binding
Process
response to stimulus
response to biotic stimulus
defense response
immune response
Component
cell
membrane
Target 3 General Function Involved in tumor necrosis factor receptor binding
Target 3 Specific Function Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin 1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 36-56
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 339741 Link Image
Target 3 UniProtKB/Swiss-Prot ID P01375 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name TNFA_HUMAN Link Image
Target 3 PDB ID 1A8M Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location
  • Cell membrane
  • single-pass type II membrane protein. Processed form:Secreted protein. Also exists as
Target 3 Gene Sequence >702 bp
ATGAGCACTGAAAGCATGATCCGGGACGTGGAGCTGGCCGAGGAGGCGCTCCCCAAGAAG
ACAGGGGGGCCCCAGGGCTCCAGGCGGTGCTTGTTCCTCAGCCTCTTCTCCTTCCTGATC
GTGGCAGGCGCCACCACGCTCTTCTGCCTGCTGCACTTTGGAGTGATCGGCCCCCAGAGG
GAAGAGTTCCCCAGGGACCTCTCTCTAATCAGCCCTCTGGCCCAGGCAGTCAGATCATCT
TCTCGAACCCCGAGTGACAAGCCTGTAGCCCATGTTGTAGCAAACCCTCAAGCTGAGGGG
CAGCTCCAGTGGCTGAACCGCCGGGCCAATGCCCTCCTGGCCAATGGCGTGGAGCTGAGA
GATAACCAGCTGGTGGTGCCATCAGAGGGCCTGTACCTCATCTACTCCCAGGTCCTCTTC
AAGGGCCAAGGCTGCCCCTCCACCCATGTGCTCCTCACCCACACCATCAGCCGCATCGCC
GTCTCCTACCAGACCAAGGTCAACCTCCTCTCTGCCATCAAGAGCCCCTGCCAGAGGGAG
ACCCCAGAGGGGGCTGAGGCCAAGCCCTGGTATGAGCCCATCTATCTGGGAGGGGTCTTC
CAGCTGGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCGGCCCGACTATCTCGACTTT
GCCGAGTCTGGGCAGGTCTACTTTGGGATCATTGCCCTGTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID TNF Link Image
Target 3 GenAtlas ID TNF Link Image
Target 3 HGNC ID HGNC:11892 Link Image
Target 3 Chromosome Location 6
Target 3 Locus 6p21.3
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Neville MJ, Campbell RD: A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC. J Immunol. 1999 Apr 15;162(8):4745-54. [PubMed Link Image]
  2. Watts AD, Hunt NH, Wanigasekara Y, Bloomfield G, Wallach D, Roufogalis BD, Chaudhri G: A casein kinase I motif present in the cytoplasmic domain of members of the tumour necrosis factor ligand family is implicated in 'reverse signalling'. EMBO J. 1999 Apr 15;18(8):2119-26. [PubMed Link Image]
  3. Stevenson FT, Bursten SL, Locksley RM, Lovett DH: Myristyl acylation of the tumor necrosis factor alpha precursor on specific lysine residues. J Exp Med. 1992 Oct 1;176(4):1053-62. [PubMed Link Image]
  4. Jones EY, Stuart DI, Walker NP: The structure of tumour necrosis factor--implications for biological function. J Cell Sci Suppl. 1990;13:11-8. [PubMed Link Image]
  5. Van Ostade X, Tavernier J, Prange T, Fiers W: Localization of the active site of human tumour necrosis factor (hTNF) by mutational analysis. EMBO J. 1991 Apr;10(4):827-36. [PubMed Link Image]
  6. Eck MJ, Sprang SR: The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding. J Biol Chem. 1989 Oct 15;264(29):17595-605. [PubMed Link Image]
  7. Jones EY, Stuart DI, Walker NP: Structure of tumour necrosis factor. Nature. 1989 Mar 16;338(6212):225-8. [PubMed Link Image]
  8. Nedwin GE, Naylor SL, Sakaguchi AY, Smith D, Jarrett-Nedwin J, Pennica D, Goeddel DV, Gray PW: Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization. Nucleic Acids Res. 1985 Sep 11;13(17):6361-73. [PubMed Link Image]
  9. Nedospasov SA, Shakhov AN, Turetskaya RL, Mett VA, Azizov MM, Georgiev GP, Korobko VG, Dobrynin VN, Filippov SA, Bystrov NS, et al.: Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome. Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:611-24. [PubMed Link Image]
  10. Wang AM, Creasey AA, Ladner MB, Lin LS, Strickler J, Van Arsdell JN, Yamamoto R, Mark DF: Molecular cloning of the complementary DNA for human tumor necrosis factor. Science. 1985 Apr 12;228(4696):149-54. [PubMed Link Image]
  11. 3883195 Shirai T, Yamaguchi H, Ito H, Todd CW, Wallace RB: Cloning and expression in Escherichia coli of the gene for human tumour necrosis factor. Nature. 1985 Feb 28-Mar 6;313(6005):803-6.
  12. 3932069 Marmenout A, Fransen L, Tavernier J, Van der Heyden J, Tizard R, Kawashima E, Shaw A, Johnson MJ, Semon D, Muller R, et al.: Molecular cloning and expression of human tumor necrosis factor and comparison with mouse tumor necrosis factor. Eur J Biochem. 1985 Nov 4;152(3):515-22.
  13. 6392892 Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV: Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20-1985 Jan 2;312(5996):724-9.
  14. 8499947 Iris FJ, Bougueleret L, Prieur S, Caterina D, Primas G, Perrot V, Jurka J, Rodriguez-Tome P, Claverie JM, Dausset J, et al.: Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment. Nat Genet. 1993 Feb;3(2):137-45.
  15. 8597870 Pocsik E, Duda E, Wallach D: Phosphorylation of the 26 kDa TNF precursor in monocytic cells and in transfected HeLa cells. J Inflamm. 1995;45(3):152-60.
  16. 9034191 Moss ML, Jin SL, Milla ME, Bickett DM, Burkhart W, Carter HL, Chen WJ, Clay WC, Didsbury JR, Hassler D, Hoffman CR, Kost TA, Lambert MH, Leesnitzer MA, McCauley P, McGeehan G, Mitchell J, Moyer M, Pahel G, Rocque W, Overton LK, Schoenen F, Seaton T, Su JL, Becherer JD, et al.: Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature. 1997 Feb 20;385(6618):733-6.
  17. 9442056 Cha SS, Kim JS, Cho HS, Shin NK, Jeong W, Shin HC, Kim YJ, Hahn JH, Oh BH: High resolution crystal structure of a human tumor necrosis factor-alpha mutant with low systemic toxicity. J Biol Chem. 1998 Jan 23;273(4):2153-60.
  18. 9488135 Reed C, Fu ZQ, Wu J, Xue YN, Harrison RW, Chen MJ, Weber IT: Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2. Protein Eng. 1997 Oct;10(10):1101-7.
Target 3 Drug References
  1. Muto NF, Martinand-Mari C, Adelson ME, Suhadolnik RJ: Inhibition of replication of reactivated human immunodeficiency virus type 1 (HIV-1) in latently infected U1 cells transduced with an HIV-1 long terminal repeat-driven PKR cDNA construct. J Virol. 1999 Nov;73(11):9021-8. [PubMed Link Image]
  2. Wolf T, Findhammer S, Nolte B, Helm EB, Brodt HR: Inhibition of TNF-alpha mediated cell death by HIV-1 specific protease inhibitors. Eur J Med Res. 2003 Jan 28;8(1):17-24. [PubMed Link Image]
  3. Equils O, Shapiro A, Madak Z, Liu C, Lu D: Human immunodeficiency virus type 1 protease inhibitors block toll-like receptor 2 (TLR2)- and TLR4-Induced NF-kappaB activation. Antimicrob Agents Chemother. 2004 Oct;48(10):3905-11. [PubMed Link Image]
  4. Jones SP, Janneh O, Back DJ, Pirmohamed M: Altered adipokine response in murine 3T3-F442A adipocytes treated with protease inhibitors and nucleoside reverse transcriptase inhibitors. Antivir Ther. 2005;10(2):207-13. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 862
Target 4 Name Multidrug resistance-associated protein 1
Target 4 Synonyms
  1. ATP-binding cassette sub- family C member 1
  2. LTC4 transporter
  3. Leukotriene C(4
Target 4 Gene Name ABCC1
Target 4 Protein Sequence >Multidrug resistance-associated protein 1
MALRGFCSADGSDPLWDWNVTWNTSNPDFTKCFQNTVLVWVPCFYLWACFPFYFLYLSRH
DRGYIQMTPLNKTKTALGFLLWIVCWADLFYSFWERSRGIFLAPVFLVSPTLLGITTLLA
TFLIQLERRKGVQSSGIMLTFWLVALVCALAILRSKIMTALKEDAQVDLFRDITFYVYFS
LLLIQLVLSCFSDRSPLFSETIHDPNPCPESSASFLSRITFWWITGLIVRGYRQPLEGSD
LWSLNKEDTSEQVVPVLVKNWKKECAKTRKQPVKVVYSSKDPAQPKESSKVDANEEVEAL
IVKSPQKEWNPSLFKVLYKTFGPYFLMSFFFKAIHDLMMFSGPQILKLLIKFVNDTKAPD
WQGYFYTVLLFVTACLQTLVLHQYFHICFVSGMRIKTAVIGAVYRKALVITNSARKSSTV
GEIVNLMSVDAQRFMDLATYINMIWSAPLQVILALYLLWLNLGPSVLAGVAVMVLMVPVN
AVMAMKTKTYQVAHMKSKDNRIKLMNEILNGIKVLKLYAWELAFKDKVLAIRQEELKVLK
KSAYLSAVGTFTWVCTPFLVALCTFAVYVTIDENNILDAQTAFVSLALFNILRFPLNILP
MVISSIVQASVSLKRLRIFLSHEELEPDSIERRPVKDGGGTNSITVRNATFTWARSDPPT
LNGITFSIPEGALVAVVGQVGCGKSSLLSALLAEMDKVEGHVAIKGSVAYVPQQAWIQND
SLRENILFGCQLEEPYYRSVIQACALLPDLEILPSGDRTEIGEKGVNLSGGQKQRVSLAR
AVYSNADIYLFDDPLSAVDAHVGKHIFENVIGPKGMLKNKTRILVTHSMSYLPQVDVIIV
MSGGKISEMGSYQELLARDGAFAEFLRTYASTEQEQDAEENGVTGVSGPGKEAKQMENGM
LVTDSAGKQLQRQLSSSSSYSGDISRHHNSTAELQKAEAKKEETWKLMEADKAQTGQVKL
SVYWDYMKAIGLFISFLSIFLFMCNHVSALASNYWLSLWTDDPIVNGTQEHTKVRLSVYG
ALGISQGIAVFGYSMAVSIGGILASRCLHVDLLHSILRSPMSFFERTPSGNLVNRFSKEL
DTVDSMIPEVIKMFMGSLFNVIGACIVILLATPIAAIIIPPLGLIYFFVQRFYVASSRQL
KRLESVSRSPVYSHFNETLLGVSVIRAFEEQERFIHQSDLKVDENQKAYYPSIVANRWLA
VRLECVGNCIVLFAALFAVISRHSLSAGLVGLSVSYSLQVTTYLNWLVRMSSEMETNIVA
VERLKEYSETEKEAPWQIQETAPPSSWPQVGRVEFRNYCLRYREDLDFVLRHINVTINGG
EKVGIVGRTGAGKSSLTLGLFRINESAEGEIIIDGINIAKIGLHDLRFKITIIPQDPVLF
SGSLRMNLDPFSQYSDEEVWTSLELAHLKDFVSALPDKLDHECAEGGENLSVGQRQLVCL
ARALLRKTKILVLDEATAAVDLETDDLIQSTIRTQFEDCTVLTIAHRLNTIMDYTRVIVL
DKGEIQEYGAPSDLLQQRGLFYSMAKDAGLV
Target 4 Number of Residues 1556
Target 4 Molecular Weight 171563
Target 4 Theoretical pI 7.11
Target 4 GO Classification
Function
transporter activity
ATPase activity
hydrolase activity, acting on acid anhydrides, catalyzing transmembrane movement of substances
ATPase activity, coupled to transmembrane movement of substances
purine nucleotide binding
adenyl nucleotide binding
ATP binding
catalytic activity
hydrolase activity
hydrolase activity, acting on acid anhydrides
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
pyrophosphatase activity
nucleoside-triphosphatase activity
binding
nucleotide binding
Process
physiological process
cellular physiological process
transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 4 General Function Drug defense mechanisms
Target 4 Specific Function May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Confers resistance to anticancer drugs. Transports LTC4. May protect milk against xenobiotics
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • 34-54
  • 75-95
  • 101-121
  • 134-154
  • 173-193
  • 317-337
  • 364-384
  • 441-461
  • 465-485
  • 548-568
  • 591-611
  • 968-988
  • 1026-1046
  • 1090-1110
  • 1112-1132
  • 1204-1224
  • 1227-1247
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 1835659 Link Image
Target 4 UniProtKB/Swiss-Prot ID P33527 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name MRP1_HUMAN Link Image
Target 4 PDB ID Not Available
Target 4 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 4 Gene Sequence >4596 bp
ATGGCGCTCCGGGGCTTCTGCAGCGCCGATGGCTCCGACCCGCTCTGGGACTGGAATGTC
ACGTGGAATACCAGCAACCCCGACTTCACCAAGTGCTTTCAGAACACGGTCCTCGTGTGG
GTGCCTTGTTTTTACCTCTGGGCCTGTTTCCCCTTCTACTTCCTCTATCTCTCCCGACAT
GACCGAGGCTACATTCAGATGACACCTCTCAACAAAACCAAAACTGCCTTGGGATTTTTG
CTGTGGATCGTCTGCTGGGCAGACCTCTTCTACTCTTTCTGGGAAAGAAGTCGGGGCATA
TTCCTGGCCCCAGTGTTTCTGGTCAGCCCAACTCTCTTGGGCATCACCACGCTGCTTGCT
ACCTTTTTAATTCAGCTGGAGAGGAGGAAGGGAGTTCAGTCTTCAGGGATCATGCTCACT
TTCTGGCTGGTAGCCCTAGTGTGTGCCCTAGCCATCCTGAGATCCAAAATTATGACAGCC
TTAAAAGAGGATGCCCAGGTGGACCTGTTTCGTGACATCACTTTCTACGTCTACTTTTCC
CTCTTACTCATTCAGCTCGTCTTGTCCTGTTTCTCAGATCGCTCACCCCTGTTCTCGGAA
ACCATCCACGACCCTAATCCCTGCCCAGAGTCCAGCGCTTCCTTCCTGTCGAGGATCACC
TTCTGGTGGATCACAGGGTTGATTGTCCGGGGCTACCGCCAGCCCCTGGAGGGCAGTGAC
CTCTGGTCCTTAAACAAGGAGGACACGTCGGAACAAGTCGTGCCTGTTTTGGTAAAGAAC
TGGAAGAAGGAATGCGCCAAGACTAGGAAGCAGCCGGTGAAGGTTGTGTACTCCTCCAAG
GATCCTGCCCAGCCGAAAGAGAGTTCCAAGGTGGATGCGAATGAGGAGGTGGAGGCTTTG
ATCGTCAAGTCCCCACAGAAGGAGTGGAACCCCTCTCTGTTTAAGGTGTTATACAAGACC
TTTGGGCCCTACTTCCTCATGAGCTTCTTCTTCAAGGCCATCCACGACCTGATGATGTTT
TCCGGGCCGCAGATCTTAAAGTTGCTCATCAAGTTCGTGAATGACACGAAGGCCCCAGAC
TGGCAGGGCTACTTCTACACCGTGCTGCTGTTTGTCACTGCCTGCCTGCAGACCCTCGTG
CTGCACCAGTACTTCCACATCTGCTTCGTCAGTGGCATGAGGATCAAGACCGCTGTCATT
GGGGCTGTCTATCGGAAGGCCCTGGTGATCACCAATTCAGCCAGAAAATCCTCCACGGTC
GGGGAGATTGTCAACCTCATGTCTGTGGACGCTCAGAGGTTCATGGACTTGGCCACGTAC
ATTAACATGATCTGGTCAGCCCCCCTGCAAGTCATCCTTGCTCTCTACCTCCTGTGGCTG
AATCTGGGCCCTTCCGTCCTGGCTGGAGTGGCGGTGATGGTCCTCATGGTGCCCGTCAAT
GCTGTGATGGCGATGAAGACCAAGACGTATCAGGTGGCCCACATGAAGAGCAAAGACAAT
CGGATCAAGCTGATGAACGAAATTCTCAATGGGATCAAAGTGCTAAAGCTTTATGCCTGG
GAGCTGGCATTCAAGGACAAGGTGCTGGCCATCAGGCAGGAGGAGCTGAAGGTGCTGAAG
AAGTCTGCCTACCTGTCAGCCGTGGGCACCTTCACCTGGGTCTGCACGCCCTTTCTGGTG
GCCTTGTGCACATTTGCCGTCTACGTGACCATTGACGAGAACAACATCCTGGATGCCCAG
ACAGCCTTCGTGTCTTTGGCCTTGTTCAACATCCTCCGGTTTCCCCTGAACATTCTCCCC
ATGGTCATCAGCAGCATCGTGCAGGCGAGTGTCTCCCTCAAACGCCTGAGGATCTTTCTC
TCCCATGAGGAGCTGGAACCTGACAGCATCGAGCGACGGCCTGTCAAAGACGGCGGGGGC
ACGAACAGCATCACCGTGAGGAATGCCACATTCACCTGGGCCAGGAGCGACCCTCCCACA
CTGAATGGCATCACCTTCTCCATCCCCGAAGGTGCTTTGGTGGCCGTGGTGGGCCAGGTG
GGCTGCGGAAAGTCGTCCCTGCTCTCAGCCCTCTTGGCTGAGATGGACAAAGTGGAGGGG
CACGTGGCTATCAAGGGCTCCGTGGCCTATGTGCCACAGCAGGCCTGGATTCAGAATGAT
TCTCTCCGAGAAAACATCCTTTTTGGATGTCAGCTGGAGGAACCATATTACAGGTCCGTG
ATACAGGCCTGTGCCCTCCTCCCAGACCTGGAAATCCTGCCCAGTGGGGATCGGACAGAG
ATTGGCGAGAAGGGCGTGAACCTGTCTGGGGGCCAGAAGCAGCGCGTGAGCCTGGCCCGG
GCCGTGTACTCCAACGCTGACATTTACCTCTTCGATGATCCCCTCTCAGCAGTGGATGCC
CATGTGGGAAAACACATCTTTGAAAATGTGATTGGCCCCAAGGGGATGCTGAAGAACAAG
ACGCGGATCTTGGTCACGCACAGCATGAGCTACTTGCCGCAGGTGGACGTCATCATCGTC
ATGAGTGGCGGCAAGATCTCTGAGATGGGCTCCTACCAGGAGCTGCTGGCTCGAGACGGC
GCCTTCGCTGAGTTCCTGCGTACCTATGCCAGCACAGAGCAGGAGCAGGATGCAGAGGAG
AACGGGGTCACGGGCGTCAGCGGTCCAGGGAAGGAAGCAAAGCAAATGGAGAATGGCATG
CTGGTGACGGACAGTGCAGGGAAGCAACTGCAGAGACAGCTCAGCAGCTCCTCCTCCTAT
AGTGGGGACATCAGCAGGCACCACAACAGCACCGCAGAACTGCAGAAAGCTGAGGCCAAG
AAGGAGGAGACCTGGAAGCTGATGGAGGCTGACAAGGCGCAGACAGGGCAGGTCAAGCTT
TCCGTGTACTGGGACTACATGAAGGCCATCGGACTCTTCATCTCCTTCCTCAGCATCTTC
CTTTTCATGTGTAACCATGTGTCCGCGCTGGCTTCCAACTATTGGCTCAGCCTCTGGACT
GATGACCCCATCGTCAACGGGACTCAGGAGCACACGAAAGTCCGGCTGAGCGTCTATGGA
GCCCTGGGCATTTCACAAGGGATCGCCGTGTTTGGCTACTCCATGGCCGTGTCCATCGGG
GGGATCTTGGCTTCCCGCTGTCTGCACGTGGACCTGCTGCACAGCATCCTGCGGTCACCC
ATGAGCTTCTTTGAGCGGACCCCCAGTGGGAACCTGGTGAACCGCTTCTCCAAGGAGCTG
GACACAGTGGACTCCATGATCCCGGAGGTCATCAAGATGTTCATGGGCTCCCTGTTCAAC
GTCATTGGTGCCTGCATCGTTATCCTGCTGGCCACGCCCATCGCCGCCATCATCATCCCG
CCCCTTGGCCTCATCTACTTCTTCGTCCAGAGGTTCTACGTGGCTTCCTCCCGGCAGCTG
AAGCGCCTCGAGTCGGTCAGCCGCTCCCCGGTCTATTCCCATTTCAACGAGACCTTGCTG
GGGGTCAGCGTCATTCGAGCCTTCGAGGAGCAGGAGCGCTTCATCCACCAGAGTGACCTG
AAGGTGGACGAGAACCAGAAGGCCTATTACCCCAGCATCGTGGCCAACAGGTGGCTGGCC
GTGCGGCTGGAGTGTGTGGGCAACTGCATCGTTCTGTTTGCTGCCCTGTTTGCGGTGATC
TCCAGGCACAGCCTCAGTGCTGGCTTGGTGGGCCTCTCAGTGTCTTACTCATTGCAGGTC
ACCACGTACTTGAACTGGCTGGTTCGGATGTCATCTGAAATGGAAACCAACATCGTGGCC
GTGGAGAGGCTCAAGGAGTATTCAGAGACTGAGAAGGAGGCGCCCTGGCAAATCCAGGAG
ACAGCTCCGCCCAGCAGCTGGCCCCAGGTGGGCCGAGTGGAATTCCGGAACTACTGCCTG
CGCTACCGAGAGGACCTGGACTTCGTTCTCAGGCACATCAATGTCACGATCAATGGGGGA
GAAAAGGTCGGCATCGTGGGGCGGACGGGAGCTGGGAAGTCGTCCCTGACCCTGGGCTTA
TTTCGGATCAACGAGTCTGCCGAAGGAGAGATCATCATCGATGGCATCAACATCGCCAAG
ATCGGCCTGCACGACCTCCGCTTCAAGATCACCATCATCCCCCAGGACCCTGTTTTGTTT
TCGGGTTCCCTCCGAATGAACCTGGACCCATTCAGCCAGTACTCGGATGAAGAAGTCTGG
ACGTCCCTGGAGCTGGCCCACCTGAAGGACTTCGTGTCAGCCCTTCCTGACAAGCTAGAC
CATGAATGTGCAGAAGGCGGGGAGAACCTCAGTGTCGGGCAGCGCCAGCTTGTGTGCCTA
GCCCGGGCCCTGCTGAGGAAGACGAAGATCCTTGTGTTGGATGAGGCCACGGCAGCCGTG
GACCTGGAAACGGACGACCTCATCCAGTCCACCATCCGGACACAGTTCGAGGACTGCACC
GTCCTCACCATCGCCCACCGGCTCAACACCATCATGGACTACACAAGGGTGATCGTCTTG
GACAAAGGAGAAATCCAGGAGTACGGCGCCCCATCGGACCTCCTGCAGCAGAGAGGTCTT
TTCTACAGCATGGCCAAAGACGCCGGCTTGGTGTGA
Target 4 GenBank Gene ID
Target 4 GeneCard ID ABCC1 Link Image
Target 4 GenAtlas ID ABCC1 Link Image
Target 4 HGNC ID HGNC:51 Link Image
Target 4 Chromosome Location 16
Target 4 Locus 16p13.1
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD: Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q. Genomics. 1999 Sep 15;60(3):295-308. [PubMed Link Image]
  2. Ringpfeil F, Lebwohl MG, Christiano AM, Uitto J: Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6001-6. [PubMed Link Image]
  3. Le Saux O, Urban Z, Tschuch C, Csiszar K, Bacchelli B, Quaglino D, Pasquali-Ronchetti I, Pope FM, Richards A, Terry S, Bercovitch L, de Paepe A, Boyd CD: Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet. 2000 Jun;25(2):223-7. [PubMed Link Image]
  4. Robbiani DF, Finch RA, Jager D, Muller WA, Sartorelli AC, Randolph GJ: The leukotriene C(4) transporter MRP1 regulates CCL19 (MIP-3beta, ELC)-dependent mobilization of dendritic cells to lymph nodes. Cell. 2000 Nov 22;103(5):757-68. [PubMed Link Image]
  5. Perdu J, Germain DP: Identification of novel polymorphisms in the pM5 and MRP1 (ABCC1) genes at locus 16p13.1 and exclusion of both genes as responsible for pseudoxanthoma elasticum. Hum Mutat. 2001;17(1):74-5. [PubMed Link Image]
  6. Ito S, Ieiri I, Tanabe M, Suzuki A, Higuchi S, Otsubo K: Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects. Pharmacogenetics. 2001 Mar;11(2):175-84. [PubMed Link Image]
  7. Ito K, Olsen SL, Qiu W, Deeley RG, Cole SP: Mutation of a single conserved tryptophan in multidrug resistance protein 1 (MRP1/ABCC1) results in loss of drug resistance and selective loss of organic anion transport. J Biol Chem. 2001 May 11;276(19):15616-24. Epub 2001 Feb 21. [PubMed Link Image]
  8. Cui L, Hou YX, Riordan JR, Chang XB: Mutations of the Walker B motif in the first nucleotide binding domain of multidrug resistance protein MRP1 prevent conformational maturation. Arch Biochem Biophys. 2001 Aug 1;392(1):153-61. [PubMed Link Image]
  9. Conrad S, Kauffmann HM, Ito K, Deeley RG, Cole SP, Schrenk D: Identification of human multidrug resistance protein 1 (MRP1) mutations and characterization of a G671V substitution. J Hum Genet. 2001;46(11):656-63. [PubMed Link Image]
  10. Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley RG: Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 1992 Dec 4;258(5088):1650-4. [PubMed Link Image]
  11. 8098549 Cole SP, Deeley RG: Multidrug resistance-associated protein: sequence correction. Science. 1993 May 14;260(5110):879.
  12. 8649356 Stride BD, Valdimarsson G, Gerlach JH, Wilson GM, Cole SP, Deeley RG: Structure and expression of the messenger RNA encoding the murine multidrug resistance protein, an ATP-binding cassette transporter. Mol Pharmacol. 1996 Jun;49(6):962-71.
  13. 9295302 Hipfner DR, Almquist KC, Leslie EM, Gerlach JH, Grant CE, Deeley RG, Cole SP: Membrane topology of the multidrug resistance protein (MRP). A study of glycosylation-site mutants reveals an extracytosolic NH2 terminus. J Biol Chem. 1997 Sep 19;272(38):23623-30.
  14. 9334225 Kast C, Gros P: Topology mapping of the amino-terminal half of multidrug resistance-associated protein by epitope insertion and immunofluorescence. J Biol Chem. 1997 Oct 17;272(42):26479-87.
  15. 9344662 Grant CE, Kurz EU, Cole SP, Deeley RG: Analysis of the intron-exon organization of the human multidrug-resistance protein gene (MRP) and alternative splicing of its mRNA. Genomics. 1997 Oct 15;45(2):368-78.
  16. 9485377 Kast C, Gros P: Epitope insertion favors a six transmembrane domain model for the carboxy-terminal portion of the multidrug resistance-associated protein. Biochemistry. 1998 Feb 24;37(8):2305-13.
Target 4 Drug References
  1. Meaden ER, Hoggard PG, Newton P, Tjia JF, Aldam D, Cornforth D, Lloyd J, Williams I, Back DJ, Khoo SH: P-glycoprotein and MRP1 expression and reduced ritonavir and saquinavir accumulation in HIV-infected individuals. J Antimicrob Chemother. 2002 Oct;50(4):583-8. [PubMed Link Image]
  2. Williams GC, Liu A, Knipp G, Sinko PJ: Direct evidence that saquinavir is transported by multidrug resistance-associated protein (MRP1) and canalicular multispecific organic anion transporter (MRP2). Antimicrob Agents Chemother. 2002 Nov;46(11):3456-62. [PubMed Link Image]
  3. Dallas S, Ronaldson PT, Bendayan M, Bendayan R: Multidrug resistance protein 1-mediated transport of saquinavir by microglia. Neuroreport. 2004 May 19;15(7):1183-6. [PubMed Link Image]
  4. Janneh O, Owen A, Chandler B, Hartkoorn RC, Hart CA, Bray PG, Ward SA, Back DJ, Khoo SH: Modulation of the intracellular accumulation of saquinavir in peripheral blood mononuclear cells by inhibitors of MRP1, MRP2, P-gp and BCRP. AIDS. 2005 Dec 2;19(18):2097-102. [PubMed Link Image]
  5. Srinivas RV, Middlemas D, Flynn P, Fridland A: Human immunodeficiency virus protease inhibitors serve as substrates for multidrug transporter proteins MDR1 and MRP1 but retain antiviral efficacy in cell lines expressing these transporters. Antimicrob Agents Chemother. 1998 Dec;42(12):3157-62. [PubMed Link Image]
Drug Target 5 [top]
Target 5 ID 1588
Target 5 Name Multidrug resistance protein 1
Target 5 Synonyms
  1. ATP-binding cassette sub-family B member 1
  2. CD243 antigen
  3. EC 3.6.3.44
  4. P-glycoprotein 1
Target 5 Gene Name ABCB1
Target 5 Protein Sequence >Multidrug resistance protein 1
MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLYMVVGTLAAII
HGAGLPLMMLVFGEMTDIFANAGNLEDLMSNITNRSDINDTGFFMNLEEDMTRYAYYYSG
IGAGVLVAAYIQVSFWCLAAGRQIHKIRKQFFHAIMRQEIGWFDVHDVGELNTRLTDDVS
KINEGIGDKIGMFFQSMATFFTGFIVGFTRGWKLTLVILAISPVLGLSAAVWAKILSSFT
DKELLAYAKAGAVAEEVLAAIRTVIAFGGQKKELERYNKNLEEAKRIGIKKAITANISIG
AAFLLIYASYALAFWYGTTLVLSGEYSIGQVLTVFFSVLIGAFSVGQASPSIEAFANARG
AAYEIFKIIDNKPSIDSYSKSGHKPDNIKGNLEFRNVHFSYPSRKEVKILKGLNLKVQSG
QTVALVGNSGCGKSTTVQLMQRLYDPTEGMVSVDGQDIRTINVRFLREIIGVVSQEPVLF
ATTIAENIRYGRENVTMDEIEKAVKEANAYDFIMKLPHKFDTLVGERGAQLSGGQKQRIA
IARALVRNPKILLLDEATSALDTESEAVVQVALDKARKGRTTIVIAHRLSTVRNADVIAG
FDDGVIVEKGNHDELMKEKGIYFKLVTMQTAGNEVELENAADESKSEIDALEMSSNDSRS
SLIRKRSTRRSVRGSQAQDRKLSTKEALDESIPPVSFWRIMKLNLTEWPYFVVGVFCAII
NGGLQPAFAIIFSKIIGVFTRIDDPETKRQNSNLFSLLFLALGIISFITFFLQGFTFGKA
GEILTKRLRYMVFRSMLRQDVSWFDDPKNTTGALTTRLANDAAQVKGAIGSRLAVITQNI
ANLGTGIIISFIYGWQLTLLLLAIVPIIAIAGVVEMKMLSGQALKDKKELEGAGKIATEA
IENFRTVVSLTQEQKFEHMYAQSLQVPYRNSLRKAHIFGITFSFTQAMMYFSYAGCFRFG
AYLVAHKLMSFEDVLLVFSAVVFGAMAVGQVSSFAPDYAKAKISAAHIIMIIEKTPLIDS
YSTEGLMPNTLEGNVTFGEVVFNYPTRPDIPVLQGLSLEVKKGQTLALVGSSGCGKSTVV
QLLERFYDPLAGKVLLDGKEIKRLNVQWLRAHLGIVSQEPILFDCSIAENIAYGDNSRVV
SQEEIVRAAKEANIHAFIESLPNKYSTKVGDKGTQLSGGQKQRIAIARALVRQPHILLLD
EATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQL
LAQKGIYFSMVSVQAGTKRQ
Target 5 Number of Residues 1301
Target 5 Molecular Weight 141464
Target 5 Theoretical pI 9.44
Target 5 GO Classification
Function
ATPase activity
hydrolase activity, acting on acid anhydrides, catalyzing transmembrane movement of substances
ATPase activity, coupled to transmembrane movement of substances
purine nucleotide binding
adenyl nucleotide binding
ATP binding
catalytic activity
hydrolase activity
hydrolase activity, acting on acid anhydrides
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
pyrophosphatase activity
nucleoside-triphosphatase activity
binding
nucleotide binding
Process
physiological process
cellular physiological process
transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 5 General Function Defense mechanisms and drug export
Target 5 Specific Function Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Target 5 Pathways Not Available
Target 5 Reactions
  • ATP + H2O + xenobioticin = ADP + phosphate + xenobioticout
Target 5 Pfam Domain Function
Target 5 Signals
  • None
Target 5 Transmembrane Regions
  • 52-72
  • 120-140
  • 189-209
  • 216-236
  • 297-317
  • 326-346
  • 711-731
  • 757-777
  • 833-853
  • 854-874
  • 937-957
  • 974-994
Target 5 Essentiality Non-Essential
Target 5 GenBank ID Protein 307180 Link Image
Target 5 UniProtKB/Swiss-Prot ID P08183 Link Image
Target 5 UniProtKB/Swiss-Prot Entry Name MDR1_HUMAN Link Image
Target 5 PDB ID Not Available
Target 5 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 5 Gene Sequence >3843 bp
ATGGATCTTGAAGGGGACCGCAATGGAGGAGCAAAGAAGAAGAACTTTTTTAAACTGAAC
AATAAAAGTGAAAAAGATAAGAAGGAAAAGAAACCAACTGTCAGTGTATTTTCAATGTTT
CGCTATTCAAATTGGCTTGACAAGTTGTATATGGTGGTGGGAACTTTGGCTGCCATCATC
CATGGGGCTGGACTTCCTCTCATGATGCTGGTGTTTGGAGAAATGACAGATATCTTTGCA
AATGCAGGAAATTTAGAAGATCTGATGTCAAACATCACTAATAGAAGTGATATCAATGAT
ACAGGGTTCTTCATGAATCTGGAGGAAGACATGACCAGGTATGCCTATTATTACAGTGGA
ATTGGTGCTGGGGTGCTGGTTGCTGCTTACATTCAGGTTTCATTTTGGTGCCTGGCAGCT
GGAAGACAAATACACAAAATTAGAAAACAGTTTTTTCATGCTATAATGCGACAGGAGATA
GGCTGGTTTGATGTGCACGATGTTGGGGAGCTTAACACCCGACTTACAGATGATGTCTCT
AAGATTAATGAAGTTATTGGTGACAAAATTGGAATGTTCTTTCAGTCAATGGCAACATTT
TTCACTGGGTTTATAGTAGGATTTACACGTGGTTGGAAGCTAACCCTTGTGATTTTGGCC
ATCAGTCCTGTTCTTGGACTGTCAGCTGCTGTCTGGGCAAAGATACTATCTTCATTTACT
GATAAAGAACTCTTAGCGTATGCAAAAGCTGGAGCAGTAGCTGAAGAGGTCTTGGCAGCA
ATTAGAACTGTGATTGCATTTGGAGGACAAAAGAAAGAACTTGAAAGGTACAACAAAAAT
TTAGAAGAAGCTAAAAGAATTGGGATAAAGAAAGCTATTACAGCCAATATTTCTATAGGT
GCTGCTTTCCTGCTGATCTATGCATCTTATGCTCTGGCCTTCTGGTATGGGACCACCTTG
GTCCTCTCAGGGGAATATTCTATTGGACAAGTACTCACTGTATTCTTTTCTGTATTAATT
GGGGCTTTTAGTGTTGGACAGGCATCTCCAAGCATTGAAGCATTTGCAAATGCAAGAGGA
GCAGCTTATGAAATCTTCAAGATAATTGATAATAAGCCAAGTATTGACAGCTATTCGAAG
AGTGGGCACAAACCAGATAATATTAAGGGAAATTTGGAATTCAGAAATGTTCACTTCAGT
TACCCATCTCGAAAAGAAGTTAAGATCTTGAAGGGCCTGAACCTGAAGGTGCAGAGTGGG
CAGACGGTGGCCCTGGTTGGAAACAGTGGCTGTGGGAAGAGCACAACAGTCCAGCTGATG
CAGAGGCTCTATGACCCCACAGAGGGGATGGTCAGTGTTGATGGACAGGATATTAGGACC
ATAAATGTAAGGTTTCTACGGGAAATCATTGGTGTGGTGAGTCAGGAACCTGTATTGTTT
GCCACCACGATAGCTGAAAACATTCGCTATGGCCGTGAAAATGTCACCATGGATGAGATT
GAGAAAGCTGTCAAGGAAGCCAATGCCTATGACTTTATCATGAAACTGCCTCATAAATTT
GACACCCTGGTTGGAGAGAGAGGGGCCCAGTTGAGTGGTGGGCAGAAGCAGAGGATCGCC
ATTGCACGTGCCCTGGTTCGCAACCCCAAGATCCTCCTGCTGGATGAGGCCACGTCAGCC
TTGGACACAGAAAGCGAAGCAGTGGTTCAGGTGGCTCTGGATAAGGCCAGAAAAGGTCGG
ACCACCATTGTGATAGCTCATCGTTTGTCTACAGTTCGTAATGCTGACGTCATCGCTGGT
TTCGATGATGGAGTCATTGTGGAGAAAGGAAATCATGATGAACTCATGAAAGAGAAAGGC
ATTTACTTCAAACTTGTCACAATGCAGACAGCAGGAAATGAAGTTGAATTAGAAAATGCA
GCTGATGAATCCAAAAGTGAAATTGATGCCTTGGAAATGTCTTCAAATGATTCAAGATCC
AGTCTAATAAGAAAAAGATCAACTCGTAGGAGTGTCCGTGGATCACAAGCCCAAGACAGA
AAGCTTAGTACCAAAGAGGCTCTGGATGAAAGTATACCTCCAGTTTCCTTTTGGAGGATT
ATGAAGCTAAATTTAACTGAATGGCCTTATTTTGTTGTTGGTGTATTTTGTGCCATTATA
AATGGAGGCCTGCAACCAGCATTTGCAATAATATTTTCAAAGATTATAGGGGTTTTTACA
AGAATTGATGATCCTGAAACAAAACGACAGAATAGTAACTTGTTTTCACTATTGTTTCTA
GCCCTTGGAATTATTTCTTTTATTACATTTTTCCTTCAGGGTTTCACATTTGGCAAAGCT
GGAGAGATCCTCACCAAGCGGCTCCGATACATGGTTTTCCGATCCATGCTCAGACAGGAT
GTGAGTTGGTTTGATGACCCTAAAAACACCACTGGAGCATTGACTACCAGGCTCGCCAAT
GATGCTGCTCAAGTTAAAGGGGCTATAGGTTCCAGGCTTGCTGTAATTACCCAGAATATA
GCAAATCTTGGGACAGGAATAATTATATCCTTCATCTATGGTTGGCAACTAACACTGTTA
CTCTTAGCAATTGTACCCATCATTGCAATAGCAGGAGTTGTTGAAATGAAAATGTTGTCT
GGACAAGCACTGAAAGATAAGAAAGAACTAGAAGGTGCTGGGAAGATCGCTACTGAAGCA
ATAGAAAACTTCCGAACCGTTGTTTCTTTGACTCAGGAGCAGAAGTTTGAACATATGTAT
GCTCAGAGTTTGCAGGTACCATACAGAAACTCTTTGAGGAAAGCACACATCTTTGGAATT
ACATTTTCCTTCACCCAGGCAATGATGTATTTTTCCTATGCTGGATGTTTCCGGTTTGGA
GCCTACTTGGTGGCACATAAACTCATGAGCTTTGAGGATGTTCTGTTAGTATTTTCAGCT
GTTGTCTTTGGTGCCATGGCCGTGGGGCAAGTCAGTTCATTTGCTCCTGACTATGCCAAA
GCCAAAATATCAGCAGCCCACATCATCATGATCATTGAAAAAACCCCTTTGATTGACAGC
TACAGCACGGAAGGCCTAATGCCGAACACATTGGAAGGAAATGTCACATTTGGTGAAGTT
GTATTCAACTATCCCACCCGACCGGACATCCCAGTGCTTCAGGGACTGAGCCTGGAGGTG
AAGAAGGGCCAGACGCTGGCTCTGGTGGGCAGCAGTGGCTGTGGGAAGAGCACAGTGGTC
CAGCTCCTGGAGCGGTTCTACGACCCCTTGGCAGGGAAAGTGCTGCTTGATGGCAAAGAA
ATAAAGCGACTGAATGTTCAGTGGCTCCGAGCACACCTGGGCATCGTGTCCCAGGAGCCC
ATCCTGTTTGACTGCAGCATTGCTGAGAACATTGCCTATGGAGACAACAGCCGGGTGGTG
TCACAGGAAGAGATCGTGAGGGCAGCAAAGGAGGCCAACATACATGCCTTCATCGAGTCA
CTGCCTAATAAATATAGCACTAAAGTAGGAGACAAAGGAACTCAGCTCTCTGGTGGCCAG
AAACAACGCATTGCCATAGCTCGTGCCCTTGTTAGACAGCCTCATATTTTGCTTTTGGAT
GAAGCCACGTCAGCTCTGGATACAGAAAGTGAAAAGGTTGTCCAAGAAGCCCTGGACAAA
GCCAGAGAAGGCCGCACCTGCATTGTGATTGCTCACCGCCTGTCCACCATCCAGAATGCA
GACTTAATAGTGGTGTTTCAGAATGGCAGAGTCAAGGAGCATGGCACGCATCAGCAGCTG
CTGGCACAGAAAGGCATCTATTTTTCAATGGTCAGTGTCCAGGCTGGAACAAAGCGCCAG
TGA
Target 5 GenBank Gene ID
Target 5 GeneCard ID ABCB1 Link Image
Target 5 GenAtlas ID ABCB1 Link Image
Target 5 HGNC ID HGNC:40 Link Image
Target 5 Chromosome Location 7
Target 5 Locus 7q21.1
Target 5 SNPs SNPJam Report Link Image
Target 5 General References
  1. Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmoller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M, Brinkmann U: Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3473-8. [PubMed Link Image]
  2. Decleves X, Chevillard S, Charpentier C, Vielh P, Laplanche JL: A new polymorphism (N21D) in the exon 2 of the human MDR1 gene encoding the P-glycoprotein. Hum Mutat. 2000 May;15(5):486. [PubMed Link Image]
  3. Cascorbi I, Gerloff T, Johne A, Meisel C, Hoffmeyer S, Schwab M, Schaeffeler E, Eichelbaum M, Brinkmann U, Roots I: Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther. 2001 Mar;69(3):169-74. [PubMed Link Image]
  4. Kerb R, Hoffmeyer S, Brinkmann U: ABC drug transporters: hereditary polymorphisms and pharmacological impact in MDR1, MRP1 and MRP2. Pharmacogenomics. 2001 Feb;2(1):51-64. [PubMed Link Image]
  5. Saito S, Iida A, Sekine A, Miura Y, Ogawa C, Kawauchi S, Higuchi S, Nakamura Y: Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population. J Hum Genet. 2002;47(1):38-50. [PubMed Link Image]
  6. 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]
  7. Chen CJ, Clark D, Ueda K, Pastan I, Gottesman MM, Roninson IB: Genomic organization of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins. J Biol Chem. 1990 Jan 5;265(1):506-14. [PubMed Link Image]
  8. Gekeler V, Weger S, Probst H: mdr1/P-glycoprotein gene segments analyzed from various human leukemic cell lines exhibiting different multidrug resistance profiles. Biochem Biophys Res Commun. 1990 Jun 15;169(2):796-802. [PubMed Link Image]
  9. Kioka N, Tsubota J, Kakehi Y, Komano T, Gottesman MM, Pastan I, Ueda K: P-glycoprotein gene (MDR1) cDNA from human adrenal: normal P-glycoprotein carries Gly185 with an altered pattern of multidrug resistance. Biochem Biophys Res Commun. 1989 Jul 14;162(1):224-31. [PubMed Link Image]
  10. Chen CJ, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, Roninson IB: Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell. 1986 Nov 7;47(3):381-9. [PubMed Link Image]
  11. 2897240 Choi KH, Chen CJ, Kriegler M, Roninson IB: An altered pattern of cross-resistance in multidrug-resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene. Cell. 1988 May 20;53(4):519-29.
  12. 9038218 Chen G, Duran GE, Steger KA, Lacayo NJ, Jaffrezou JP, Dumontet C, Sikic BI: Multidrug-resistant human sarcoma cells with a mutant P-glycoprotein, altered phenotype, and resistance to cyclosporins. J Biol Chem. 1997 Feb 28;272(9):5974-82.
  13. 9473242 Mickley LA, Lee JS, Weng Z, Zhan Z, Alvarez M, Wilson W, Bates SE, Fojo T: Genetic polymorphism in MDR-1: a tool for examining allelic expression in normal cells, unselected and drug-selected cell lines, and human tumors. Blood. 1998 Mar 1;91(5):1749-56.
Target 5 Drug References
  1. Gutmann H, Fricker G, Drewe J, Toeroek M, Miller DS: Interactions of HIV protease inhibitors with ATP-dependent drug export proteins. Mol Pharmacol. 1999 Aug;56(2):383-9. [PubMed Link Image]
  2. Profit L, Eagling VA, Back DJ: Modulation of P-glycoprotein function in human lymphocytes and Caco-2 cell monolayers by HIV-1 protease inhibitors. AIDS. 1999 Sep 10;13(13):1623-7. [PubMed Link Image]
  3. Smit JW, Huisman MT, van Tellingen O, Wiltshire HR, Schinkel AH: Absence or pharmacological blocking of placental P-glycoprotein profoundly increases fetal drug exposure. J Clin Invest. 1999 Nov;104(10):1441-7. [PubMed Link Image]
  4. Eagling VA, Profit L, Back DJ: Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components. Br J Clin Pharmacol. 1999 Oct;48(4):543-52. [PubMed Link Image]
  5. Washington CB, Wiltshire HR, Man M, Moy T, Harris SR, Worth E, Weigl P, Liang Z, Hall D, Marriott L, Blaschke TF: The disposition of saquinavir in normal and P-glycoprotein deficient mice, rats, and in cultured cells. Drug Metab Dispos. 2000 Sep;28(9):1058-62. [PubMed Link Image]
Drug Target 6 [top]
Target 6 ID 1732
Target 6 Name ATP-binding cassette sub-family G member 2
Target 6 Synonyms
  1. Breast cancer resistance protein
  2. CD338 antigen
  3. CDw338
  4. Mitoxantrone resistance-associated protein
  5. Placenta-specific ATP- binding cassette transporter
Target 6 Gene Name ABCG2
Target 6 Protein Sequence >ATP-binding cassette sub-family G member 2
MSSSNVEVFIPVSQGNTNGFPATASNDLKAFTEGAVLSFHNICYRVKLKSGFLPCRKPVE
KEILSNINGIMKPGLNAILGPTGGGKSSLLDVLAARKDPSGLSGDVLINGAPRPANFKCN
SGYVVQDDVVMGTLTVRENLQFSAALRLATTMTNHEKNERINRVIQELGLDKVADSKVGT
QFIRGVSGGERKRTSIGMELITDPSILFLDEPTTGLDSSTANAVLLLLKRMSKQGRTIIF
SIHQPRYSIFKLFDSLTLLASGRLMFHGPAQEALGYFESAGYHCEAYNNPADFFLDIING
DSTAVALNREEDFKATEIIEPSKQDKPLIEKLAEIYVNSSFYKETKAELHQLSGGEKKKK
ITVFKEISYTTSFCHQLRWVSKRSFKNLLGNPQASIAQIIVTVVLGLVIGAIYFGLKNDS
TGIQNRAGVLFFLTTNQCFSSVSAVELFVVEKKLFIHEYISGYYRVSSYFLGKLLSDLLP
MRMLPSIIFTCIVYFMLGLKPKADAFFVMMFTLMMVAYSASSMALAIAAGQSVVSVATLL
MTICFVFMMIFSGLLVNLTTIASWLSWLQYFSIPRYGFTALQHNEFLGQNFCPGLNATGN
NPCNYATCTGEEYLVKQGIDLSPWGLWKNHVALACMIVIFLTIAYLKLLFLKKYS
Target 6 Number of Residues 665
Target 6 Molecular Weight 72315
Target 6 Theoretical pI 8.90
Target 6 GO Classification
Function
ATPase activity
purine nucleotide binding
adenyl nucleotide binding
ATP binding
catalytic activity
hydrolase activity
hydrolase activity, acting on acid anhydrides
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
pyrophosphatase activity
nucleoside-triphosphatase activity
binding
nucleotide binding
Process
Not Available
Component
Not Available
Target 6 General Function Defense mechanisms and xenobiotic export
Target 6 Specific Function Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123
Target 6 Pathways Not Available
Target 6 Reactions Not Available
Target 6 Pfam Domain Function
Target 6 Signals
  • None
Target 6 Transmembrane Regions
  • 396-416
  • 429-449
  • 478-498
  • 507-527
  • 536-556
  • 631-651
Target 6 Essentiality Non-Essential
Target 6 GenBank ID Protein 4185796 Link Image
Target 6 UniProtKB/Swiss-Prot ID Q9UNQ0 Link Image
Target 6 UniProtKB/Swiss-Prot Entry Name ABCG2_HUMAN Link Image
Target 6 PDB ID Not Available
Target 6 Cellular Location
  • Cell membrane
  • multi-pass membrane protein
Target 6 Gene Sequence >1968 bp
ATGTCTTCCAGTAATGTCGAAGTTTTTATCCCAGTGTCACAAGGAAACACCAATGGCTTC
CCCGCGACAGTTTCCAATGACCTGAAGGCATTTACTGAAGGAGCTGTGTTAAGTTTTCAT
AACATCTGCTATCGAGTAAAACTGAAGAGTGGCTTTCTACCTTGTCGAAAACCAGTTGAG
AAAGAAATATTATCGAATATCAATGGGATCATGAAACCTGGTCTCAACGCCATCCTGGGA
CCCACAGGTGGAGGCAAATCTTCGTTATTAGATGTCTTAGCTGCAAGGAAAGATCCAAGT
GGATTATCTGGAGATGTTCTGATAAATGGAGCACCGCGACCTGCCAATTTCAAATGTAAT
TCAGGTTACGTGGTACAAGATGATGTTGTGATGGGCACTCTGACGGTGAGAGAAAACTTA
CAGTTCTCAGCAGCTCTTCGGCTTGCAACAACTATGACGAATCATGAAAAAAACGAACGG
ATTAACAGGGTCATTGAAGAGTTAGGTCTGGATAAAGTGGCAGACTCCAAGGTTGGAACT
CAGTTTATCCGTGGTGTGTCTGGAGGAGAAAGAAAAAGGACTAGTATAGGAATGGAGCTT
ATCACTGATCCTTCCATCTTGTCCTTGGATGAGCCTACAACTGGCTTAGACTCAAGCACA
GCAAATGCTGTCCTTTTGCTCCTGAAAAGGATGTCTAAGCAGGGACGAACAATCATCTTC
TCCATTCATCAGCCTCGATATTCCATCTTCAAGTTGTTTGATAGCCTCACCTTATTGGCC
TCAGGAAGACTTATGTTCCACGGGCCTGCTCAGGAGGCCTTGGGATACTTTGAATCAGCT
GGTTATCACTGTGAGGCCTATAATAACCCTGCAGACTTCTTCTTGGACATCATTAATGGA
GATTCCACTGCTGTGGCATTAAACAGAGAAGAAGACTTTAAAGCCACAGAGATCATAGAG
CCTTCCAAGCAGGATAAGCCACTCATAGAAAAATTAGCGGAGATTTATGTCAACTCCTCC
TTCTACAAAGAGACAAAAGCTGAATTACATCAACTTTCCGGGGGTGAGAAGAAGAAGAAG
ATCACAGTCTTCAAGGAGATCAGCTACACCACCTCCTTCTGTCATCAACTCAGATGGGTT
TCCAAGCGTTCATTCAAAAACTTGCTGGGTAATCCCCAGGCCTCTATAGCTCAGATCATT
GTCACAGTCGTACTGGGACTGGTTATAGGTGCCATTTACTTTGGGCTAAAAAATGATTCT
ACTGGAATCCAGAACAGAGCTGGGGTTCTCTTCTTCCTGACGACCAACCAGTGTTTCAGC
AGTGTTTCAGCCGTGGAACTCTTTGTGGTAGAGAAGAAGCTCTTCATACATGAATACATC
AGCGGATACTACAGAGTGTCATCTTATTTCCTTGGAAAACTGTTATCTGATTTATTACCC
ATGAGGATGTTACCAAGTATTATATTTACCTGTATAGTGTACTTCATGTTAGGATTGAAG
CCAAAGGCAGATGCCTTCTTCGTTATGATGTTTACCCTTATGATGGTGGCTTATTCAGCC
AGTTCCATGGCACTGGCCATAGCAGCAGGTCAGAGTGTGGTTTCTGTAGCAACACTTCTC
ATGACCATCTGTTTTGTGTTTATGATGATTTTTTCAGGTCTGTTGGTCAATCTCACAACC
ATTGCATCTTGGCTGTCATGGCTTCAGTACTTCAGCATTCCACGATATGGATTTACGGCT
TTGCAGCATAATGAATTTTTGGGACAAAACTTCTGCCCAGGACTCAATGCAACAGGAAAC
AATCCTTGTAACTATGCAACATGTACTGGCGAAGAATATTTGGTAAAGCAGGGCATCGAT
CTCTCACCCTGGGGCTTGTGGAAGAATCACGTGGCCTTGGCTTGTATGATTGTTATTTTC
CTCACAATTGCCTACCTGAAATTGTTATTTCTTAAAAAATATTCTTAA
Target 6 GenBank Gene ID
Target 6 GeneCard ID ABCG2 Link Image
Target 6 GenAtlas ID ABCG2 Link Image
Target 6 HGNC ID HGNC:74 Link Image
Target 6 Chromosome Location 4
Target 6 Locus 4q22
Target 6 SNPs SNPJam Report Link Image
Target 6 General References
  1. Komatani H, Kotani H, Hara Y, Nakagawa R, Matsumoto M, Arakawa H, Nishimura S: Identification of breast cancer resistant protein/mitoxantrone resistance/placenta-specific, ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole structure. Cancer Res. 2001 Apr 1;61(7):2827-32. [PubMed Link Image]
  2. Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP: The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med. 2001 Sep;7(9):1028-34. [PubMed Link Image]
  3. Schmitz G, Langmann T, Heimerl S: Role of ABCG1 and other ABCG family members in lipid metabolism. J Lipid Res. 2001 Oct;42(10):1513-20. [PubMed Link Image]
  4. Iida A, Saito S, Sekine A, Mishima C, Kitamura Y, Kondo K, Harigae S, Osawa S, Nakamura Y: Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8, ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8. J Hum Genet. 2002;47(6):285-310. [PubMed Link Image]
  5. Zhang W, Mojsilovic-Petrovic J, Andrade MF, Zhang H, Ball M, Stanimirovic DB: The expression and functional characterization of ABCG2 in brain endothelial cells and vessels. FASEB J. 2003 Nov;17(14):2085-7. Epub 2003 Sep 4. [PubMed Link Image]
  6. Allikmets R, Schriml LM, Hutchinson A, Romano-Spica V, Dean M: A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res. 1998 Dec 1;58(23):5337-9. [PubMed Link Image]
  7. Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, Ross DD: A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15665-70. [PubMed Link Image]
Target 6 Drug References
  1. Gupta A, Zhang Y, Unadkat JD, Mao Q: HIV protease inhibitors are inhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther. 2004 Jul;310(1):334-41. Epub 2004 Mar 8. [PubMed Link Image]
  2. Janneh O, Owen A, Chandler B, Hartkoorn RC, Hart CA, Bray PG, Ward SA, Back DJ, Khoo SH: Modulation of the intracellular accumulation of saquinavir in peripheral blood mononuclear cells by inhibitors of MRP1, MRP2, P-gp and BCRP. AIDS. 2005 Dec 2;19(18):2097-102. [PubMed Link Image]
Drug Target 7 [top]
Target 7 ID 1735
Target 7 Name Canalicular multispecific organic anion transporter 1
Target 7 Synonyms
  1. ATP-binding cassette sub-family C member 2
  2. Canalicular multidrug resistance protein
  3. Multidrug resistance-associated protein 2
Target 7 Gene Name ABCC2
Target 7 Protein Sequence >Canalicular multispecific organic anion transporter 1
MLEKFCNSTFWNSSFLDSPEADLPLCFEQTVLVWIPLGFLWLLAPWQLLHVYKSRTKRSS
TTKLYLAKQVFVGFLLILAAIELALVLTEDSGQATVPAVRYTNPSLYLGTWLLVLLIQYS
RQWCVQKNSWFLSLFWILSILCGTFQFQTLIRTLLQGDNSNLAYSCLFFISYGFQILILI
FSAFSENNESSNNPSSIASFLSSITYSWYDSIILKGYKRPLTLEDVWEVDEEMKTKTLVS
KFETHMKRELQKARRALQRRQEKSSQQNSGARLPGLNKNQSQSQDALVLEDVEKKKKKSG
TKKDVPKSWLMKALFKTFYMVLLKSFLLKLVNDIFTFVSPQLLKLLISFASDRDTYLWIG
YLCAILLFTAALIQSFCLQCYFQLCFKLGVKVRTAIMASVYKKALTLSNLARKEYTVGET
VNLMSVDAQKLMDVTNFMHMLWSSVLQIVLSIFFLWRELGPSVLAGVGVMVLVIPINAIL
STKSKTIQVKNMKNKDKRLKIMNEILSGIKILKYFAWEPSFRDQVQNLRKKELKNLLAFS
QLQCVVIFVFQLTPVLVSVVTFSVYVLVDSNNILDAQKAFTSITLFNILRFPLSMLPMMI
SSMLQASVSTERLEKYLGGDDLDTSAIRHDCNFDKAMQFSEASFTWEHDSEATVRDVNLD
IMAGQLVAVIGPVGSGKSSLISAMLGEMENVHGHITIKGTTAYVPQQSWIQNGTIKDNIL
FGTEFNEKRYQQVLEACALLPDLEMLPGGDLAEIGEKGINLSGGQKQRISLARATYQNLD
IYLLDDPLSAVDAHVGKHIFNKVLGPNGLLKGKTRLLVTHSMHFLPQVDEIVVLGNGTIV
EKGSYSALLAKKGEFAKNLKTFLRHTGPEEEATVHDGSEEEDDDYGLISSVEEIPEDAAS
ITMRRENSFRRTLSRSSRSNGRHLKSLRNSLKTRNVNSLKEDEELVKGQKLIKKEFIETG
KVKFSIYLEYLQAIGLFSIFFIILAFVMNSVAFIGSNLWLSAWTSDSKIFNSTDYPASQR
DMRVGVYGALGLAQGIFVFIAHFWSAFGFVHASNILHKQLLNNILRAPMRFFDTTPTGRI
VNRFAGDISTVDDTLPQSLRSWITCFLGIISTLVMICMATPVFTIIVIPLGIIYVSVQMF
YVSTSRQLRRLDSVTRSPIYSHFSETVSGLPVIRAFEHQQRFLKHNEVRIDTNQKCVFSW
ITSNRWLAIRLELVGNLTVFFSALMMVIYRDTLSGDTVGFVLSNALNITQTLNWLVRMTS
EIETNIVAVERITEYTKVENEAPWVTDKRPPPDWPSKGKIQFNNYQVRYRPELDLVLRGI
TCDIGSMEKIGVVGRTGAGKSSLTNCLFRILEAAGGQIIIDGVDIASIGLHDLREKLTII
PQDPILFSGSLRMNLDPFNNYSDEEIWKALELAHLKSFVASLQLGLSHEVTEAGGNLSIG
QRQLLCLGRALLRKSKILVLDEATAAVDLETDNLIQTTIQNEFAHCTVITIAHRLHTIMD
SDKVMVLDNGKIIECGSPEELLQIPGPFYFMAKEAGIENVNSTKF
Target 7 Number of Residues 1570
Target 7 Molecular Weight 174194
Target 7 Theoretical pI 8.46
Target 7 GO Classification
Function
transporter activity
ATPase activity
hydrolase activity, acting on acid anhydrides, catalyzing transmembrane movement of substances
ATPase activity, coupled to transmembrane movement of substances
purine nucleotide binding
adenyl nucleotide binding
ATP binding
catalytic activity
hydrolase activity
hydrolase activity, acting on acid anhydrides
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
pyrophosphatase activity
nucleoside-triphosphatase activity
binding
nucleotide binding
Process
physiological process
cellular physiological process
transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 7 General Function Defense mechanisms and drug export
Target 7 Specific Function Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter
Target 7 Pathways Not Available
Target 7 Reactions Not Available
Target 7 Pfam Domain Function
Target 7 Signals
  • None
Target 7 Transmembrane Regions
  • 28-48
  • 69-89
  • 94-114
  • 127-147
  • 166-186
  • 314-334
  • 361-381
  • 438-458
  • 462-482
  • 545-565
  • 588-608
  • 972-992
  • 1034-1054
  • 1098-1118
  • 1120-1140
  • 1212-1232
  • 1235-1255
Target 7 Essentiality Non-Essential
Target 7 GenBank ID Protein 1764162 Link Image
Target 7 UniProtKB/Swiss-Prot ID Q92887 Link Image
Target 7 UniProtKB/Swiss-Prot Entry Name MRP2_HUMAN Link Image
Target 7 PDB ID Not Available
Target 7 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 7 Gene Sequence >4638 bp
ATGCTGGAGAAGTTCTGCAACTCTACTTTTTGGAATTCCTCATTCCTGGACAGTCCGGAG
GCAGACCTGCCACTTTGTTTTGAGCAAACTGTTCTGGTGTGGATTCCCTTGGGCTTCCTA
TGGCTCCTGGCCCCCTGGCAGCTTCTCCACGTGTATAAATCCAGGACCAAGAGATCCTCT
ACCACCAAACTCTATCTTGCTAAGCAGGTATTCGTTGGTTTTCTTCTTATTCTAGCAGCC
ATAGAGCTGGCCCTTGTACTCACAGAAGACTCTGGACAAGCCACAGTCCCTGCTGTTCGA
TATACCAATCCAAGCCTCTACCTAGGCACATGGCTCCTGGTTTTGCTGATCCAATACAGC
AGACAATGGTGTGTACAGAAAAACTCCTGGTTCCTGTCCCTATTCTGGATTCTCTCGATA
CTCTGTGGCACTTTCCAATTTCAGACTCTGATCCGGACACTCTTACAGGGTGACAATTCT
AATCTAGCCTACTCCTGCCTGTTCTTCATCTCCTACGGATTCCAGATCCTGATCCTGATC
TTTTCAGCATTTTCAGAAAATAATGAGTCATCAAATAATCCATCATCCATAGCTTCATTC
CTGAGTAGCATTACCTACAGCTGGTATGACAGCATCATTCTGAAAGGCTACAAGCGTCCT
CTGACACTCGAGGATGTCTGGGAAGTTGATGAAGAGATGAAAACCAAGACATTAGTGAGC
AAGTTTGAAACGCACATGAAGAGAGAGCTGCAGAAAGCCAGGCGGGCACTCCAGAGACGG
CAGGAGAAGAGCTCCCAGCAGAACTCTGGAGCCAGGCTGCCTGGCTTGAACAAGAATCAG
AGTCAAAGCCAAGATGCCCTTGTCCTGGAAGATGTTGAAAAGAAAAAAAAGAAGTCTGGG
ACCAAAAAAGATGTTCCAAAATCCTGGTTGATGAAGGCTCTGTTCAAAACTTTCTACATG
GTGCTCCTGAAATCATTCCTACTGAAGCTAGTGAATGACATCTTCACGTTTGTGAGTCCT
CAGCTGCTGAAATTGCTGATCTCCTTTGCAAGTGACCGTGACACATATTTGTGGATTGGA
TATCTCTGTGCAATCCTCTTATTCACTGCGGCTCTCATTCAGTCTTTCTGCCTTCAGTGT
TATTTCCAACTGTGCTTCAAGCTGGGTGTAAAAGTACGGACAGCTATCATGGCTTCTGTA
TATAAGAAGGCATTGACCCTATCCAACTTGGCCAGGAAGGAGTACACCGTTGGAGAAACA
GTGAACCTGATGTCTGTGGATGCCCAGAAGCTCATGGATGTGACCAACTTCATGCACATG
CTGTGGTCAAGTGTTCTACAGATTGTCTTATCTATCTTCTTCCTATGGAGAGAGTTGGGA
CCCTCAGTCTTAGCAGGTGTTGGGGTGATGGTGCTTGTAATCCCAATTAATGCGATACTG
TCCACCAAGAGTAAGACCATTCAGGTCAAAAATATGAAGAATAAAGACAAACGTTTAAAG
ATCATGAATGAGATTCTTAGTGGAATCAAGATCCTGAAATATTTTGCCTGGGAACCTTCA
TTCAGAGACCAAGTACAAAACCTCCGGAAGAAAGAGCTCAAGAACCTGCTGGCCTTTAGT
CAACTACAGTGTGTAGTAATATTCGTCTTCCAGTTAACTCCAGTCCTGGTATCTGTGGTC
ACATTTTCTGTTTATGTCCTGGTGGATAGCAACAATATTTTGGATGCACAAAAGGCCTTC
ACCTCCATTACCCTCTTCAATATCCTGCGCTTTCCCCTGAGCATGCTTCCCATGATGATC
TCCTCCATGCTCCAGGCCAGTGTTTCCACAGAGCGGCTAGAGAAGTACTTGGGAGGGGAT
GACTTGGACACATCTGCCATTCGACATGACTGCAATTTTGACAAAGCCATGCAGTTTTCT
GAGGCCTCCTTTACCTGGGAACATGATTCGGAAGCCACAGTCCGAGATGTGAACCTGGAC
ATTATGGCAGGCCAACTTGTGGCTGTGATAGGCCCTGTCGGCTCTGGGAAATCCTCCTTG
ATATCAGCCATGCTGGGAGAAATGGAAAATGTCCACGGGCACATCACCATCAAGGGCACC
ACTGCCTATGTCCCACAGCAGTCCTGGATTCAGAATGGCACCATAAAGGACAACATCCTT
TTTGGAACAGAGTTTAATGAAAAGAGGTACCAGCAAGTACTGGAGGCCTGTGCTCTCCTC
CCAGACTTGGAAATGCTGCCTGGAGGAGATTTGGCTGAGATTGGAGAGAAGGGTATAAAT
CTTAGTGGGGGTCAGAAGCAGCGGATCAGCCTGGCCAGAGCTACCTACCAAAATTTAGAC
ATCTATCTTCTAGATGACCCCCTGTCTGCAGTGGATGCTCATGTAGGAAAACATATTTTT
AATAAGGTCTTGGGCCCCAATGGCCTGTTGAAAGGCAAGACTCGACTCTTGGTTACACAT
AGCATGCACTTTCTTCCTCAAGTGGATGAGATTGTAGTTCTGGGGAATGGAACAATTGTA
GAGAAAGGATCCTACAGTGCTCTCCTGGCCAAAAAAGGAGAGTTTGCTAAGAATCTGAAG
ACATTTCTAAGACATACAGGCCCTGAAGAGGAAGCCACAGTCCATGATGGCAGTGAAGAA
GAAGACGATGACTATGGGCTGATATCCAGTGTGGAAGAGATCCCCGAAGATGCAGCCTCC
ATAACCATGAGAAGAGAGAACAGCTTTCGTCGAACACTTAGCCGCAGTTCTAGGTCCAAT
GGCAGGCATCTGAAGTCCCTGAGAAACTCCTTGAAAACTCGGAATGTGAATAGCCTGAAG
GAAGACGAAGAACTAGTGAAAGGACAAAAACTAATTAAGAAGGAATTCATAGAAACTGGA
AAGGTGAAGTTCTCCATCTACCTGGAGTACCTACAAGCAATAGGATTGTTTTCGATATTC
TTCATCATCCTTGCGTTTGTGATGAATTCTGTGGCTTTTATTGGATCCAACCTCTGGCTC
AGTGCTTGGACCAGTGACTCTAAAATCTTCAATAGCACCGACTATCCAGCATCTCAGAGG
GACATGAGAGTTGGAGTCTACGGAGCTCTGGGATTAGCCCAAGGTATATTTGTGTTCATA
GCACATTTCTGGAGTGCCTTTGGTTTCGTCCATGCATCAAATATCTTGCACAAGCAACTG
CTGAACAATATCCTTCGAGCACCTATGAGATTTTTTGACACAACACCCACAGGCCGGATT
GTGAACAGGTTTGCCGGCGATATTTCCACAGTGGATGACACCCTGCCTCAGTCCTTGCGC
AGCTGGATTACATGCTTCCTGGGGATAATCAGCACCCTTGTCATGATCTGCATGGCCACT
CCTGTCTTCACCATCATCGTCATTCCTCTTGGCATTATTTATGTATCTGTTCAGATGTTT
TATGTGTCTACCTCCCGCCAGCTGAGGCGTCTGGACTCTGTCACCAGGTCCCCAATCTAC
TCTCACTTCAGCGAGACCGTATCAGGTTTGCCAGTTATCCGTGCCTTTGAGCACCAGCAG
CGATTTCTGAAACACAATGAGGTGAGGATTGACACCAACCAGAAATGTGTCTTTTCCTGG
ATCACCTCCAACAGGTGGCTTGCAATTCGCCTGGAGCTGGTTGGGAACCTGACTGTCTTC
TTTTCAGCCTTGATGATGGTTATTTATAGAGATACCCTAAGTGGGGACACTGTTGGCTTT
GTTCTGTCCAATGCACTCAATATCACACAAACCCTGAACTGGCTGGTGAGGATGACATCA
GAAATAGAGACCAACATTGTGGCTGTTGAGCGAATAACTGAGTACACAAAAGTGGAAAAT
GAGGCACCCTGGGTGACTGATAAGAGGCCTCCGCCAGATTGGCCCAGCAAAGGCAAGATC
CAGTTTAACAACTACCAAGTGCGGTACCGACCTGAGCTGGATCTGGTCCTCAGAGGGATC
ACTTGTGACATCGGTAGCATGGAGAAGATTGGTGTGGTGGGCAGGACAGGAGCTGGAAAG
TCATCCCTCACAAACTGCCTCTTCAGAATCTTAGAGGCTGCCGGTGGTCAGATTATCATT
GATGGAGTAGATATTGCTTCCATTGGGCTCCACGACCTCCGAGAGAAGCTGACCATCATC
CCCCAGGACCCCATCCTGTTCTCTGGAAGCCTGAGGATGAATCTCGACCCTTTCAACAAC
TACTCAGATGAGGAGATTTGGAAGGCCTTGGAGCTGGCTCACCTCAAGTCTTTTGTGGCC
AGCCTGCAACTTGGGTTATCCCACGAAGTGACAGAGGCTGGTGGCAACCTGAGCATAGGC
CAGAGGCAGCTGCTGTGCCTGGGCAGGGCTCTGCTTCGGAAATCCAAGATCCTGGTCCTG
GATGAGGCCACTGCTGCGGTGGATCTAGAGACAGACAACCTCATTCAGACGACCATCCAA
AACGAGTTCGCCCACTGCACAGTGATCACCATCGCCCACAGGCTGCACACCATCATGGAC
AGTGACAAGGTAATGGTCCTAGACAACGGGAAGATTATAGAGTGCGGCAGCCCTGAAGAA
CTGCTACAAATCCCTGGACCCTTTTACTTTATGGCTAAGGAAGCTGGCATTGAGAATGTG
AACAGCACAAAATTCTAG
Target 7 GenBank Gene ID
Target 7 GeneCard ID ABCC2 Link Image
Target 7 GenAtlas ID ABCC2 Link Image
Target 7 HGNC ID HGNC:53 Link Image
Target 7 Chromosome Location 10
Target 7 Locus 10q24
Target 7 SNPs SNPJam Report Link Image
Target 7 General References
  1. Toh S, Wada M, Uchiumi T, Inokuchi A, Makino Y, Horie Y, Adachi Y, Sakisaka S, Kuwano M: Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome. Am J Hum Genet. 1999 Mar;64(3):739-46. [PubMed Link Image]
  2. Tsujii H, Konig J, Rost D, Stockel B, Leuschner U, Keppler D: Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome. Gastroenterology. 1999 Sep;117(3):653-60. [PubMed Link Image]
  3. Keppler D, Konig J: Hepatic secretion of conjugated drugs and endogenous substances. Semin Liver Dis. 2000;20(3):265-72. [PubMed Link Image]
  4. Keitel V, Kartenbeck J, Nies AT, Spring H, Brom M, Keppler D: Impaired protein maturation of the conjugate export pump multidrug resistance protein 2 as a consequence of a deletion mutation in Dubin-Johnson syndrome. Hepatology. 2000 Dec;32(6):1317-28. [PubMed Link Image]
  5. Ito S, Ieiri I, Tanabe M, Suzuki A, Higuchi S, Otsubo K: Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects. Pharmacogenetics. 2001 Mar;11(2):175-84. [PubMed Link Image]
  6. Mor-Cohen R, Zivelin A, Rosenberg N, Shani M, Muallem S, Seligsohn U: Identification and functional analysis of two novel mutations in the multidrug resistance protein 2 gene in Israeli patients with Dubin-Johnson syndrome. J Biol Chem. 2001 Oct 5;276(40):36923-30. Epub 2001 Jul 26. [PubMed Link Image]
  7. Ito K, Oleschuk CJ, Westlake C, Vasa MZ, Deeley RG, Cole SP: Mutation of Trp1254 in the multispecific organic anion transporter, multidrug resistance protein 2 (MRP2) (ABCC2), alters substrate specificity and results in loss of methotrexate transport activity. J Biol Chem. 2001 Oct 12;276(41):38108-14. Epub 2001 Aug 10. [PubMed Link Image]
  8. Buchler M, Konig J, Brom M, Kartenbeck J, Spring H, Horie T, Keppler D: cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats. J Biol Chem. 1996 Jun 21;271(25):15091-8. [PubMed Link Image]
  9. Taniguchi K, Wada M, Kohno K, Nakamura T, Kawabe T, Kawakami M, Kagotani K, Okumura K, Akiyama S, Kuwano M: A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. Cancer Res. 1996 Sep 15;56(18):4124-9. [PubMed Link Image]
  10. Wada M, Toh S, Taniguchi K, Nakamura T, Uchiumi T, Kohno K, Yoshida I, Kimura A, Sakisaka S, Adachi Y, Kuwano M: Mutations in the canilicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome. Hum Mol Genet. 1998 Feb;7(2):203-7. [PubMed Link Image]
Target 7 Drug References
  1. Gutmann H, Fricker G, Drewe J, Toeroek M, Miller DS: Interactions of HIV protease inhibitors with ATP-dependent drug export proteins. Mol Pharmacol. 1999 Aug;56(2):383-9. [PubMed Link Image]
  2. Williams GC, Liu A, Knipp G, Sinko PJ: Direct evidence that saquinavir is transported by multidrug resistance-associated protein (MRP1) and canalicular multispecific organic anion transporter (MRP2). Antimicrob Agents Chemother. 2002 Nov;46(11):3456-62. [PubMed Link Image]
  3. Huisman MT, Smit JW, Crommentuyn KM, Zelcer N, Wiltshire HR, Beijnen JH, Schinkel AH: Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs. AIDS. 2002 Nov 22;16(17):2295-301. [PubMed Link Image]
  4. Zelcer N, Huisman MT, Reid G, Wielinga P, Breedveld P, Kuil A, Knipscheer P, Schellens JH, Schinkel AH, Borst P: Evidence for two interacting ligand binding sites in human multidrug resistance protein 2 (ATP binding cassette C2). J Biol Chem. 2003 Jun 27;278(26):23538-44. Epub 2003 Apr 17. [PubMed Link Image]
  5. Honda Y, Ushigome F, Koyabu N, Morimoto S, Shoyama Y, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux. Br J Pharmacol. 2004 Dec;143(7):856-64. Epub 2004 Oct 25. [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.