Protein domains/Degradation

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Degradation tags are short peptide sequences that mark a protein for degradation by the cell's protein recycling machinery. In doing so, the degradation tag effectively decreases the protein half-life or the typical length of time that a protein, once translated, will exist in the cell. (Formally, the half-life is the interval time it takes for the level of the protein to decay to half its initial value.) In practice, adding a degradation tag will also tend to decrease the concentration of the protein in the cell.

Many of the degradation tags available via the Registry are "ssRA tags" which function in E. coli. In the natural system, ssRA tagging occurs when a ribosome gets stuck on a broken ("truncated") mRNA. Without a normal termination codon, the ribosome cannot detach from the defective mRNA. A special type of RNA known as ssRA ("small stable RNA A") or tmRNA ("transfer-messenger RNA") rescues the ribosome by adding an eleven codon degradation tag followed by a stop codon. This allows the ribosome to break free and continue functioning. The tagged, incomplete protein then gets degraded by the proteases ClpXP or ClpAP.

Although the originally identified ssRA/tmRNA tag had the sequence AANDENYALAA Keiler, additional designed degradation tags that vary in the final three amino acids (AAV, ASV, LVA, LAA) have since been found that result in different protein half-lives Andersen.


More...
NameDescriptionChassisHalflifeAA sequenceLength
BBa_I11012AAV degradation tag   33
BBa_K105013cin8 - cell cycle specific degradation tag in yeast   228
BBa_K105014cln2 PEST destabilization domain for rapid protein turnover   537
BBa_K105015hsl1 - cell cycle dependent degradation tag in yeast   618
BBa_K145012N-terminal UmuD-derived degradation tag   87
BBa_K1471001MerB.   639
BBa_K2382001MSMEG_5998   477
BBa_K2382006T7 promoter + Thioredoxin-MSMEG_5998 fusion protein   1108
BBa_K2382009Thioredoxin-MSMEG_5998 fusion protein   882
BBa_K2812001Coding sequence for trunctated Lysostaphin    738
BBa_K2812003Coding sequence for trunctated Lysostaphin regulated by T7-promoter   776
BBa_K2812004Coding sequence for trunctated Lysostaphin fused to His-tagged HlyA   1458
BBa_K2812005Coding sequence for trunctated Lysostaphin with HlyA and His6-tag regulated by T7-promoter   1496
BBa_K2812006Coding sequence for Pyocin S5 with HlyA and His6-tag   2217
BBa_K2812007Coding sequence for Pyocin S5 with HlyA and His6-tag regulated by pBAD-ara promoter   2288
BBa_K2825000PETase-Linker-CBDcipA-Linker-HlyA tag   6943
BBa_K2835003His-tagged laccase from Trametes versicolor   1518
BBa_K2835005His-tagged fungal laccase with start codon (ATG)   1521
BBa_K3425046LAA degradation tag   35
BBa_K3831040SVN TagBacillus subtilis  48
BBa_K3831041SVN TagBacillus subtilis  48
BBa_K3831045SVN TagBacillus subtilis  45
BBa_K525001Fusion protein of SgsE, NADP+ Oxidoreductase, BisdA and BisdB with PT7/lacE. coli  4746
BBa_K525002Fusion protein of SbpA, NADP+ Oxidoreductase, BisdA and BisdB with PT7/lacE. coli  5538
BBa_K525007Fusion protein of S-Layer SgsE with T7/lac and BisdA and BisdBE. coli  3999
BBa_K525008Fusion protein of S-Layer SbpA with T7/lac and BisdA and BisdBE. coli  4791
BBa_K863000bpul (laccase from Bacillus pumilus) with T7 promoter, RBS and HIS tag   1587
BBa_K863001bpul laccase from Bacillus pumilus   1533
BBa_K863005ecol laccase from E. coli with T7 promoter, RBS and His-tag   1605
BBa_K863006ecol laccase from E. coli   1551
BBa_K863010tthl laccase from Thermus thermophilus with T7 promoter, RBS and His-tag    1443
BBa_K863011tthl laccase from Thermus thermophilus    1389
BBa_K863012tthl laccase from T. thermophilus with constitutive promoter J23100, RBS and His-tag   1471
BBa_K863015xccl laccase from Xanthomonas campestris with T7 promoter, RBS and His-tag   1863
BBa_K863020bhal laccase from Bacillus halodurans with T7 promoter, RBS and His-tag   1557
BBa_K863021bhal laccase from Bacillus halodurans    1503
BBa_M0050AANDENYALAA. (Very fast) SsrA degradation tag.    33
BBa_M0051AANDENYNYADAS. (Fast) SsrA degradation tag.   39
BBa_M0052AANDENYADAS (moderately fast) SsrA degradation tag.   33


References

<biblio>

  1. Jentsch pmid=8584931
  2. Keiler pmid=8584937
  3. Triccas pmid=12234013
  4. Andersen pmid=9603842
  5. Karzai pmid=10881189
  6. Jabri pmid=12942138

</biblio>