Target Information
| Target General Information | Top | |||||
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| Target ID |
T56556
(Former ID: TTDS00528)
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| Target Name |
ATP-binding cassette transporter G2 (ABCG2)
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| Synonyms |
Urate exporter; Placenta-specific ATP-binding cassette transporter; Mitoxantrone resistance-associated protein; MXR; CDw338; CD338; Breast cancer resistance protein; BCRP1; BCRP; ABCP
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| Gene Name |
ABCG2
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Irritable bowel syndrome [ICD-11: DD91] | |||||
| 2 | Rheumatoid arthritis [ICD-11: FA20] | |||||
| Function |
Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. Implicated in the efflux of numerous drugs and xenobiotics: mitoxantrone, the photosensitizer pheophorbide, camptothecin, methotrexate, azidothymidine (AZT), and the anthracyclines daunorubicin and doxorubicin. High-capacity urate exporter functioning in both renal and extrarenal urate excretion.
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| BioChemical Class |
ABC transporter
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| UniProt ID | ||||||
| Sequence |
MSSSNVEVFIPVSQGNTNGFPATASNDLKAFTEGAVLSFHNICYRVKLKSGFLPCRKPVE
KEILSNINGIMKPGLNAILGPTGGGKSSLLDVLAARKDPSGLSGDVLINGAPRPANFKCN SGYVVQDDVVMGTLTVRENLQFSAALRLATTMTNHEKNERINRVIQELGLDKVADSKVGT QFIRGVSGGERKRTSIGMELITDPSILFLDEPTTGLDSSTANAVLLLLKRMSKQGRTIIF SIHQPRYSIFKLFDSLTLLASGRLMFHGPAQEALGYFESAGYHCEAYNNPADFFLDIING DSTAVALNREEDFKATEIIEPSKQDKPLIEKLAEIYVNSSFYKETKAELHQLSGGEKKKK ITVFKEISYTTSFCHQLRWVSKRSFKNLLGNPQASIAQIIVTVVLGLVIGAIYFGLKNDS TGIQNRAGVLFFLTTNQCFSSVSAVELFVVEKKLFIHEYISGYYRVSSYFLGKLLSDLLP MRMLPSIIFTCIVYFMLGLKPKADAFFVMMFTLMMVAYSASSMALAIAAGQSVVSVATLL MTICFVFMMIFSGLLVNLTTIASWLSWLQYFSIPRYGFTALQHNEFLGQNFCPGLNATGN NPCNYATCTGEEYLVKQGIDLSPWGLWKNHVALACMIVIFLTIAYLKLLFLKKYS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A01261 ; BADD_A02149 ; BADD_A03260 ; BADD_A04623 | |||||
| HIT2.0 ID | T97FEF | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Sulfasalazine | Drug Info | Approved | Rheumatoid arthritis | [2], [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | Sulfasalazine | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Adenosine triphosphate | Ligand Info | |||||
| Structure Description | Cryo-EM structure of the ABCG2 E211Q mutant bound to ATP and Magnesium | PDB:6HBU | ||||
| Method | Electron microscopy | Resolution | 3.09 Å | Mutation | Yes | [4] |
| PDB Sequence |
GAVLSFHNIC
43 YRVKLPVEKE62 ILSNINGIMK72 PGLNAILGPT82 GGGKSSLLDV92 LAARKDPSGL 102 SGDVLINGAP112 RPANFKCNSG122 YVVQDDVVMG132 TLTVRENLQF142 SAALRLATTM 152 TNHEKNERIN162 RVIQELGLDK172 VADSKVGTQF182 IRGVSGGERK192 RTSIGMELIT 202 DPSILFLDQP212 TTGLDSSTAN222 AVLLLLKRMS232 KQGRTIIFSI242 HQPRYSIFKL 252 FDSLTLLASG262 RLMFHGPAQE272 ALGYFESAGY282 HCEAYNNPAD292 FFLDIINGDS 302 TAVALNREKP327 LIEKLAEIYV337 NSSFYKETKA347 ELHQLSISYT370 TSFCHQLRWV 380 SKRSFKNLLG390 NPQASIAQII400 VTVVLGLVIG410 AIYFGLKNDS420 TGIQNRAGVL 430 FFLTTNQCFS440 SVSAVELFVV450 EKKLFIHEYI460 SGYYRVSSYF470 LGKLLSDLLP 480 MRMLPSIIFT490 CIVYFMLGLK500 PKADAFFVMM510 FTLMMVAYSA520 SSMALAIAAG 530 QSVVSVATLL540 MTICFVFMMI550 FSGLLVNLTT560 IASWLSWLQY570 FSIPRYGFTA 580 LQHNEFLGQN590 FCPGLNATGN600 NPCNYATCTG610 EEYLVKQGID620 LSPWGLWKNH 630 VALACMIVIF640 LTIAYLKLLF650 LKKY
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Topotecan | Ligand Info | |||||
| Structure Description | Structure of topotecan-bound ABCG2 | PDB:7NEZ | ||||
| Method | Electron microscopy | Resolution | 3.39 Å | Mutation | No | [5] |
| PDB Sequence |
AVLSFHNICY
44 RVKEILSNIN68 GIMKPGLNAI78 LGPTGGGKSS88 LLDVLAARKD98 PSGLSGDVLI 108 NGAPRPANFK118 CNSGYVVQDD128 VVMGTLTVRE138 NLQFSAALRL148 ATTMTNHEKN 158 ERINRVIQEL168 GLDKVADSKV178 GTQFIRGVSG188 GERKRTSIGM198 ELITDPSILF 208 LDEPTTGLDS218 STANAVLLLL228 KRMSKQGRTI238 IFSIHQPRYS248 IFKLFDSLTL 258 LASGRLMFHG268 PAQEALGYFE278 SAGYHCEAYN288 NPADFFLDII298 NGDLIEKLAE 334 IYVNSSFYKE344 TKAELHQLSG354 SFCHQLRWVS381 KRSFKNLLGN391 PQASIAQIIV 401 TVVLGLVIGA411 IYFGLKNDST421 GIQNRAGVLF431 FLTTNQCFSS441 VSAVELFVVE 451 KKLFIHEYIS461 GYYRVSSYFL471 GKLLSDLLPM481 RMLPSIIFTC491 IVYFMLGLKP 501 KADAFFVMMF511 TLMMVAYSAS521 SMALAIAAGQ531 SVVSVATLLM541 TICFVFMMIF 551 SGLLVNLTTI561 ASWLSWLQYF571 SIPRYGFTAL581 QHNEFLGQNF591 CPGLNATGNN 601 PCNYATCTGE611 EYLVKQGIDL621 SPWGLWKNHV631 ALACMIVIFL641 TIAYLKLLFL 651 KKY
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| ABC transporters | hsa02010 | Affiliated Target |
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| Class: Environmental Information Processing => Membrane transport | Pathway Hierarchy | ||
| Bile secretion | hsa04976 | Affiliated Target |
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| Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
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| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Drug Resistance Mutation (DRM) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | The anti-inflammatory mechanism of sulfasalazine is related to adenosine release at inflamed sites. J Immunol. 1996 Mar 1;156(5):1937-41. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4840). | |||||
| REF 3 | Emerging drugs for rheumatoid arthritis. Expert Opin Emerg Drugs. 2008 Mar;13(1):175-96. | |||||
| REF 4 | Cryo-EM structures of a human ABCG2 mutant trapped in ATP-bound and substrate-bound states. Nature. 2018 Nov;563(7731):426-430. | |||||
| REF 5 | Structural Basis of Drug Recognition by the Multidrug Transporter ABCG2. J Mol Biol. 2021 Jun 25;433(13):166980. | |||||
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