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Subunit: Interacts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. May interact with CBL. Interacts with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two copies of the other protein. Interacts with poly-ubiquitinated proteins. Dimerization is required for the binding of poly-ubiquitin, but not for the binding of mono-ubiquitin. Interacts with EGFR (phosphorylated) Miscellaneous: This protein has one functional calcium-binding site (By similarity) Sequence caution: Sequence=BAE45748.1; Type=Erroneous termination; Positions=904; Note=Translated as Arg; Sequence=CAH56175.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact; Selected PDB 3D structures from [IMAGE] and Proteopedia [IMAGE] for CBLB (see all 11): 2AK5 (3D) [IMAGE] 2BZ8 (3D) [IMAGE] 2DO6 (3D) [IMAGE] 2J6F (3D) [IMAGE] 2JNH (3D) [IMAGE] 2LDR (3D) [IMAGE]
Tissue specificity: Expressed in placenta, heart, lung, kidney, spleen, ovary and testis, as well as fetal brain and liver and hematopoietic cell lines, but not in adult brain, liver, pancreas, salivary gland, or skeletal muscle. Present in lymphocytes (at protein level) [IM
Function: UniProtKB/Swiss-Prot Summary: CBLB_HUMAN, Q13191 Function: E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3
Similarity: Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain Contains 1 RING-type zinc finger Contains 1 UBA domain [IMAGE]
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