Target Information
| Target General Information | Top | |||||
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| Target ID |
T81386
(Former ID: TTDI02000)
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| Target Name |
Positive transcription elongation factor b (P-TEFb)
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| Synonyms |
P-TEFb
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| Gene Name |
CDK9-CCNT1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Malignant haematopoietic neoplasm [ICD-11: 2B33] | |||||
| 2 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| Function |
The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC- box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.
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| BioChemical Class |
S-phase kinase-associated protein
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| UniProt ID | ||||||
| Sequence |
MEGERKNNNKRWYFTREQLENSPSRRFGVDPDKELSYRQQAANLLQDMGQRLNVSQLTIN
TAIVYMHRFYMIQSFTQFPGNSVAPAALFLAAKVEEQPKKLEHVIKVAHTCLHPQESLPD TRSEAYLQQVQDLVILESIILQTLGFELTIDHPHTHVVKCTQLVRASKDLAQTSYFMATN SLHLTTFSLQYTPPVVACVCIHLACKWSNWEIPVSTDGKHWWEYVDATVTLELLDELTHE FLQILEKTPNRLKRIWNWRACEAAKKTKADDRGTDEKTSEQTILNMISQSSSDTTIAGLM SMSTSTTSAVPSLPVSEESSSNLTSVEMLPGKRWLSSQPSFKLEPTQGHRTSENLALTGV DHSLPQDGSNAFISQKQNSKSVPSAKVSLKEYRAKHAEELAAQKRQLENMEANVKSQYAY AAQNLLSHHDSHSSVILKMPIEGSENPERPFLEKADKTALKMRIPVAGGDKAASSKPEEI KMRIKVHAAADKHNSVEDSVTKSREHKEKHKTHPSNHHHHHNHHSHKHSHSQLPVGTGNK RPGDPKHSSQTSNLAHKTYSLSSSFSSSSSTRKRGPSEETGGAVFDHPAKIAKSTKSSSL NFSFPSLPTMGQMPGHSSDTSGLSFSQPSCKTRVPHSKLDKGPTGANGHNTTQTIDYQDT VNMLHSLLSAQGVQPTQPTAFEFVRPYSDYLNPRSGGISSRSGNTDKPRPPPLPSEPPPP LPPLPKMAKQYDSVECPFCDEVSKYEKLAKIGQGTFGEVFKARHRKTGQKVALKKVLMEN EKEGFPITALREIKILQLLKHENVVNLIEICRTKASPYNRCKGSIYLVFDFCEHDLAGLL SNVLVKFTLSEIKRVMQMLLNGLYYIHRNKILHRDMKAANVLITRDGVLKLADFGLARAF SLAKNSQPNRYTNRVVTLWYRPPELLLGERDYGPPIDLWGAGCIMAEMWTRSPIMQGNTE QHQLALISQLCGSITPEVWPNVDNYELYEKLELVKGQKRKVKDRLKAYVRDPYALDLIDK LLVLDPAQRIDSDDALNHDFFWSDPMPSDLKGMLSTHLTSMFEYLAPPRRKGSQITQQST NQSRNPATTNQTEFERVF Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | BAY1143572 | Drug Info | Phase 1 | Solid tumour/cancer | [2] | |
| 2 | BAY1251152 | Drug Info | Phase 1 | Haematological malignancy | [3] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | BAY1143572 | Drug Info | [1] | |||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | BAY1251152 | Drug Info | [3] | |||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Phosphonothreonine | Ligand Info | |||||
| Structure Description | crystal structure of P-TEFb complex with AFF4 and Tat | PDB:4OGR | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [4] |
| PDB Sequence |
NNNKRWYFTR
16 EQLENSPSRR26 FGVDPDKELS36 YRQQAANLLQ46 DMGQRLNVSQ56 LTINTAIVYM 66 HRFYMIQSFT76 QFPGNSVAPA86 ALFLAAKVEE96 QPKKLEHVIK106 VAHTCLHPQE 116 SLPDTRSEAY126 LQQVQDLVIL136 ESIILQTLGF146 ELTIDHPHTH156 VVKCTQLVRA 166 SKDLAQTSYF176 MATNSLHLTT186 FSLQYTPPVV196 ACVCIHLACK206 WSNWEIPVST 216 DGKHWWEYVD226 ATVTLELLDE236 LTHEFLQILE246 KTPNRLKRIW256 NWRAC |
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
| 1 | HIF-1 signaling pathway | |||||
| 2 | Ubiquitin mediated proteolysis | |||||
| 3 | Pathways in cancer | |||||
| 4 | Renal cell carcinoma | |||||
| References | Top | |||||
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| REF 1 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 2 | ClinicalTrials.gov (NCT02345382) Phase I Dose Escalation of BAY1143572 in Subjects With Acute Leukemia. U.S. National Institutes of Health. | |||||
| REF 3 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 4 | AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoter. Elife. 2014 Apr 24;3:e02375. | |||||
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