Summary

Name CBL
Full Name E3 ubiquitin-protein ligase CBL
Synonyms Casitas B-lineage lymphoma proto-oncogene, Proto-oncogene c-Cbl, RING finger protein 55, Signal transduction protein CBL | CBL2, RNF55
Primary ID P22681
Links - -
Type protein
Relations 50
Pathways Acute Myeloid Leukemia, FLT3 in AML, KIT in AML, Glioblastoma Multiforme
Function Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome (PubMed:17094949). Ubiquitinates SPRY2 (PubMed:17094949, PubMed:17974561). Ubiquitinates EGFR (PubMed:17974561). Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The 'Tyr-731' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBLB, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity).

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates quantity img/direct_inhibition.png phosphorylation CBL 0.328
Publications: 4 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation CBL 0.395
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CBL 0.508
Publications: 3 Organism: Mus Musculus
+ up-regulates activity img/direct-activation.png phosphorylation CBL 0.805
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding CBL 0.589
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination PI3K 0.596
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3 in AML, KIT in AML
+ down-regulates img/direct_inhibition.png ubiquitination PIK3R1 0.683
Publications: 1 Organism: Homo Sapiens
Pathways:Glioblastoma Multiforme
+ up-regulates activity img/direct-activation.png phosphorylation CBL 0.362
Publications: 1 Organism: Mus Musculus
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination EGFR 0.883
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, Glioblastoma Multiforme
+ down-regulates img/direct_inhibition.png ubiquitination FRS2 0.559
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding CBL 0.676
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle
+ img/unknown.png phosphorylation CBL 0.654
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/direct-activation.png monoubiquitination MYCBPAP 0.303
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding CBL 0.737
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/indirect_inhibition.png CBL 0.329
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ up-regulates img/direct-activation.png binding CBL 0.632
Publications: 2 Organism: Homo Sapiens, Cricetulus Griseus
Tissue: Ovary
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination MET 0.722
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png relocalization CBL 0.883
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, Glioblastoma Multiforme
+ up-regulates img/direct-activation.png binding CBL 0.377
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination SORBS2 0.526
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png binding EPHA2 0.624
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding CBL 0.68
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CBL 0.377
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding FLT3 0.447
Publications: 1 Organism: Mus Musculus
Pathways:Acute Myeloid Leukemia, FLT3 in AML
+ down-regulates img/direct_inhibition.png ubiquitination INSR 0.508
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png ubiquitination KIT 0.602
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, KIT in AML
+ down-regulates img/direct_inhibition.png binding CBL 0.453
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination PDGFRB 0.614
Publications: 2 Organism: Homo Sapiens, Mus Musculus
+ up-regulates img/direct-activation.png binding CBL 0.572
Publications: 1 Organism: Homo Sapiens
Tissue: Skin
+ down-regulates activity img/direct_inhibition.png ubiquitination SYK 0.809
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination PIK3R2 0.59
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination LRIG1 0.572
Publications: 1 Organism: Homo Sapiens
Tissue: Skin
+ up-regulates img/direct-activation.png relocalization CBL 0.902
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3 in AML, KIT in AML, Glioblastoma Multiforme
+ up-regulates activity img/direct-activation.png ubiquitination CBL 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination ERBB2 0.619
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination ABL1 0.609
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination PDGFRA 0.468
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding CBL 0.379
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination LCK 0.699
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding CBL 0.818
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination CFLAR 0.2
Publications: 1 Organism: Homo Sapiens