Table 1.

Other perspective for clinical application of iICPs

Protein	Targeted protein	Mechanism of targeting	Preclinical trials	References
A20	MALT1	Deubiquitination	Yes	115 116
CMIP	LCK, FYN	Not determined	No	155
Csk	LCK, FYN	Phosphorylation	No	156 157
CYLD	TAK1	Deubiquitination	No	80
DELTEX1	PLCγ1, PKC, MEKK	Ubiquitination	No	83 158
DGK	DAG	Phosphorylation	Yes	8
DOK family	LCK, PI3K, RAS	Sequestration	Yes	121
DRAK2	Not determined	Phosphorylation	No	87
DUSP2	ERK	Dephosphorylation	Yes	108
Fam49B	RAC1	Sequestration	No	159
GAB2/3	PI3K-AKT	Sequestration	No	160
GRAIL	TCRβ, CD3ζ	Ubiquitination	Yes	112
GRAP	ERK	Sequestration	No	161
LAX/ALX	NFAT	Sequestration	No	162
LRCH1	LAT	Sequestration	Yes	122
MDM2	NFAT	Ubiquitination	Yes	109
NEDD4 Family	PLCγ1, PKC	Ubiquitination	No	163
NRDP1	ZAP-70	Ubiquitination	Yes	110
NTAL	GRB2	Sequestration	No	164
PAG	CSK	Sequestration	No	85
Peli1	c-REL, TSC1	Ubiquitination	Yes	113
PTEN	PI3K	Dephosphorylation	No	165
PTPN2	LCK, FYN	Dephosphorylation	Yes	86 97
PTPN22	FYN, LYN	Dephosphorylation	Yes	105–107
RASA2	RAS	Hydrolysis	Yes	118
RASA3	RAP1	Hydrolysis	No	166
SHIP-1	PI3K	Dephosphorylation	No	167 168
SHP-1	LCK, ZAP-70, PI3K	Dephosphorylation	Yes	98–100
SIT	ZAP-70, LAT, PLCγ1, AKT	Dephosphorylation	No	169
SOCS family	LCK, PI3K	Ubiquitination	No	170 171
TIPE2	IKK, MEKK	Phosphorylation	No	172
TRAF6	PI3K	Not determined	Yes	125
TULA family	ZAP-70	Dephosphorylation	No	173 174

iICP, intracellular immune checkpoint.