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UBA domain found in E3 ubiquitin-protein ligase Cbl-b and similar proteins Cbl-b, also called casitas B-lineage lymphoma proto-oncogene b, RING finger protein 56, SH3-binding protein Cbl-b, or signal transduction protein Cbl-b, has been identified as a regulator of antigen-specific, T cell-intrinsic, peripheral immune tolerance (a state also called clonal anergy). It may inhibit activation of the p85 subunit of phosphoinositide 3-kinase (PI3K), protein kinase C-theta (PKC-theta), and phospholipase C-gamma1 (PLC-gamma1) and negatively regulates T-cell receptor-induced transcription factor nuclear factor-kappaB (NF-kappaB) activation. In addition, Cbl-b may target multiple signaling molecules involved in transforming growth factor (TGF)-beta-mediated transactivation pathways. Cbl-b contains a proline rich domain, a nuclear localization signal, a C3HC4 zinc finger and a ubiquitin-associated (UBA) domain.
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