. Author manuscript; available in PMC: 2021 Mar 2.

Published in final edited form as: Nat Struct Mol Biol. 2020 Jun 15;27(7):605–614. doi: 10.1038/s41594-020-0438-0

Table 2.

Genetic fusion strategies of degradation tags for targeted protein degradation.

System	Tag	Tag size (kDa)	Drug	Molecular machinery for degradation	Note	Applications
AID	Auxin-inducible degron	7	Indole-3-acetic acid (IAA)	CRL1^TIR1	• CRISPR-Cas9 knock-In applicable • Exogenous expression of TIR1 is required	^{13,82,106–108}
Destabilizing domain	FKBP12^L106P mutant	12	Shld1	Unidentified quality control pathway	• Continuous treatment of Shld1 ligand is required to keep the POI from degradation	^12,83–85
dTAG	FKBP12^F36V	12	dTAG13	CRL4^CRBN	• CRISPR-Cas9 knock-In applicable • Available in vivo	^{15,86,87,109,110}
IKZF3-peptidic Degron	IKZF3 degron	3	Pomalidomide	CRL4^CRBN	• CRISPR-Cas9 knock-In applicable • Available in vivo	¹⁴
HaloPROTACs	HaloTag	34	HaloPROTAC-3	CRL2^VHL/cIAP	• CRISPR-Cas9 knock-In applicable • Available in vivo	^16,91–93
Hydrophobic	HaloTag	34	HyT13	Unidentified quality control pathway	• Potential cellular perturbation from artificially unfolded protein	^88,89
SMASh	NS3-NS4A	34	Asunaprevir	Unidentified quality control pathway	• No structural modification from tagging • Existing proteins cannot be degraded	^11,111–114