Source:
Generated By: https://synbiohub.org/public/igem/igem2sbol/1
Created by: Raik Gruenberg
Date created: 2010-01-26 12:00:00
Date modified: 2015-08-31 04:08:36
FRB(T2098L)
| Types | DnaRegion |
| Roles | polypeptide_domain Protein_Domain |
| Sequences | BBa_J18926_sequence (Version 1) |
Description
Modified FKBP12-rapamycin-binding domain (FRB) of human mTOR Kinase (=mammalian Target of Rapamycin, also called FRAP = FKBP12-rapamycin associated protein). In presence of the immunosupressant drug rapamycin, FRB forms a high-affinity complex with FKBP12. There is no detectable FKBP12 - FRB interaction in absence of rapamycin.Modification for a non-toxic dimerizer
Rapamycin arrests growth and proliferation of many cell types (reviewed in Jacinto and Hall, 2003) by inhibiting protein translation. The mutation T2089L (mTor numbering) makes FRB binding to a non-toxic Rapamycin analogue (rapalogue) AP21967 as well as the original Rapamycin. The FRB - FKBP12 heterodimerization can then be triggered by both Rapamycin and the non-toxic rapalogue. This variant of FRB and the synthetic dimerizer AP21967 are the basis of the Argent(tm) heterodimerization kit from Ariad Pharmaceuticals Inc.
Note: Two additional mutations would convert FRB into FRB* which is used for conditional (drug-reversible) degradation of fusion proteins. These two additional mutations are not implemented in this part.
Protein Parameters:
* Number of amino acids: 93
* Molecular weight: 11285.9
* Theoretical pI: 6.47
Notes
- aa translation from human mTOR,
- mutation T2089L (verified against pC4-RHE from Ariad)
- GeneArt codon optimization for E. coli
- gene synthesis
Source
human mTOR (aa sequence)gene synthesis