| Name | References | Type of E3 ligase | Function |
| Cbl-b | [40–45] | RING type | Ubiquitinates PLC-γ1 and PKC-θ downstream of TCR signalling. Also binds to and ubiquitinates P85 subunit of PI3K to inhibit CD28-mediated triggering of PI3K. Critical role in T-cell anergy. | Itch | [46–50] | HECT type | Important role in Th cell differentiation. Binds to a number of substrates including Notch, c-Flip, Smad2, p63, and p73. Ubiquitinates Bcl-10, JunB, Cbl-b, and PKC-θ and targets them for degradation. Binds to and is regulated by the E3 ligase Ndfip1. | Nedd4 | [51] | HECT type | Binds to and ubiquitinates a number of targets that targets them for degradation including JunB, Cbl-b, c-Cbl, Notch, PTEN, PLC-γ1, and Bcl-10. | Ndfip1 | [52–54] | HECT type | Associates with Nedd4 and is a negative regulator of Itch. Other targets include p63, p73, and c-Flip. | Grail | [55–57] | RING type | Selectively inhibits RhoGTPase activity but does not affect the Ras/MAPK kinase pathway. Inhibits IL-2 production and T-cell proliferation. | Traf6 | [26, 58] | RING type | Binds to and ubiquitinates NEMO targeting it for degradation. Leads to upregulation of NF-κB signalling in response to TCR signaling. | Roquin | [59–61] | RING type | Binds to RNA-protein complexes and targets themfor degradation. Important role in posttranscriptional regulation of target gene expression. Targets include ICOS, CXCR5, PDCD1, CCL5, Il21, and CD100. |
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