| + |
CBL | down-regulates quantity by destabilization 
ubiquitination
|
JAK2 |
0.604 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278538 |
Lys970 |
GMEYLGTkRYIHRDL |
Homo sapiens |
|
| pmid |
sentence |
| 28676638 |
K63 linked poly-ubiquitination on K970 of JAK2 kinase domain is promoted by Cbl. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, KIT in AML |
| + |
PRKCA | down-regulates quantity
phosphorylation
|
CBL |
0.315 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249054 |
Ser619 |
RELTNRHsLPFSLPS |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 11024037 |
However, under normal conditions, PKC activation resulting from CD43 engagement was required to activate the MAPK pathway, suggesting that phosphorylation of Cbl on serine residues by PKC and its association with 14-3-3 molecules may play a role in preventing the Cbl inhibitory effect on the Ras-MAPK pathway. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249055 |
Ser623 |
NRHSLPFsLPSQMEP |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 11024037 |
However, under normal conditions, PKC activation resulting from CD43 engagement was required to activate the MAPK pathway, suggesting that phosphorylation of Cbl on serine residues by PKC and its association with 14-3-3 molecules may play a role in preventing the Cbl inhibitory effect on the Ras-MAPK pathway. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249056 |
Ser639 |
PDVPRLGsTFSLDTS |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 11024037 |
However, under normal conditions, PKC activation resulting from CD43 engagement was required to activate the MAPK pathway, suggesting that phosphorylation of Cbl on serine residues by PKC and its association with 14-3-3 molecules may play a role in preventing the Cbl inhibitory effect on the Ras-MAPK pathway. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249057 |
Ser642 |
PRLGSTFsLDTSMSM |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 11024037 |
However, under normal conditions, PKC activation resulting from CD43 engagement was required to activate the MAPK pathway, suggesting that phosphorylation of Cbl on serine residues by PKC and its association with 14-3-3 molecules may play a role in preventing the Cbl inhibitory effect on the Ras-MAPK pathway. |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| + |
PTPN22 | down-regulates
dephosphorylation
|
CBL |
0.378 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-65405 |
Ser798 |
SDISNASsSFGWLSL |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 10068674 |
The tyrosine phosphatase lyp1 was found to be constitutively associated with the proto-oncogene c-cbl in thymocytes and t cells. Overexpression of lyp1 reduces cbl tyrosine phosphorylation. It is known that cbl is heavily tyrosine phosphorylated after tcr stimulation and can associate with the syk and zap tyrosine kinases, negatively regulating their activities. Tyrosine phosphatases keep cbl in a basally dephosphorylated state. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EGFR | up-regulates activity 
phosphorylation
|
CBL |
0.89 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279998 |
Tyr371 |
TQEQYELyCEMGSTF |
Homo sapiens |
|
| pmid |
sentence |
| 29920512 |
As activated EGFR induces phosphorylation (on tyrosine 371) and activation of Cbl (reaction 19) , which eventually leads to EGFR degradation, EGFR and Cbl are connected via a negative feedback.|As activated EGFR induces phosphorylation (on tyrosine 371) and activation of Cbl (reaction 19) [ xref ], which eventually leads to EGFR degradation, EGFR and Cbl are connected via a negative feedback. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, Glioblastoma Multiforme |
| + |
INSR | up-regulates activity
phosphorylation
|
CBL |
0.543 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251304 |
Tyr371 |
TQEQYELyCEMGSTF |
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 11997497 |
Insulin receptor phosphorylates Cbl on tyrosines 371, 700, and 774 in the presence of APS. This phosphorylation event is required for the recruitment of Crk to the CAP/Cbl complex and for the subsequent activation of GLUT4 translocation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251305 |
Tyr700 |
EGEEDTEyMTPSSRP |
Mus musculus |
|
| pmid |
sentence |
| 11997497 |
Insulin receptor phosphorylates Cbl on tyrosines 371, 700, and 774 in the presence of APS. This phosphorylation event is required for the recruitment of Crk to the CAP/Cbl complex and for the subsequent activation of GLUT4 translocation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251306 |
Tyr774 |
SENEDDGyDVPKPPV |
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 11997497 |
Insulin receptor phosphorylates Cbl on tyrosines 371, 700, and 774 in the presence of APS. This phosphorylation event is required for the recruitment of Crk to the CAP/Cbl complex and for the subsequent activation of GLUT4 translocation. |
|
| Publications: |
3 |
Organism: |
Mus Musculus |
| + |
FYN | up-regulates activity
phosphorylation
|
CBL |
0.818 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-63968 |
Tyr731 |
QQIDSCTyEAMYNIQ |
Homo sapiens |
|
| pmid |
sentence |
| 9890970 |
Fyn associates with cbl and phosphorylates tyrosine 731 in cbl, a binding site for phosphatidylinositol 3-kinasecbl represents a substrate for src-like kinases that are activated in response to the engagement of cell surface receptors, and that src-like kinases are responsible for the phosphorylation of a tyrosine residue in cbl that may regulate activation of phosphatidylinositol 3-kinase |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates quantity by destabilization
ubiquitination
|
PDGFRA |
0.487 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-68024 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10347229 |
Cbl overexpression in nih3t3 cells enhanced the ubiquitination and degradation of the platelet-derived growth factor receptor-alpha (pdgfralpha) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates quantity
ubiquitination
|
SYK |
0.822 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278689 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19081591 |
Thus, c-Cbl specifically downregulates Syk levels in the presence of LMP2A.|c-Cbl promoted LMP2A degradation through ubiquitination, specifically degraded the Syk protein tyrosine kinase in the presence of LMP2A, and inhibited LMP2A induction of the EBV lytic cycle |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Ub:E2 | up-regulates activity
ubiquitination
|
CBL |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271100 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 34199813 |
The ubiquitination process is mediated sequentially by three classes of enzymes consisting of a Ub-activating enzyme E1, a Ub-conjugating enzyme E2, and a Ub ligase E3. Ub is first activated by E1 in an adenosine 5′-triphosphate (ATP)-dependent manner t |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
UBASH3B | down-regulates
binding
|
CBL |
0.433 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-124897 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15159412 |
Sts-1 and sts-2 contain sh3 domains that interacted with cbl, ub-associated domains, which bound directly to mono-ub or to the egfr/ub chimera as well as phosphoglycerate mutase domains that mediated oligomerization of sts-1/2. Ligand-induced recruitment of sts-1/sts-2 into activated egfr complexes led to inhibition of receptor internalization, reduction in the number of egfr-containing endocytic vesicles, and subsequent block of receptor degradation followed by prolonged activation of mitogenic signaling pathways. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRIG1 | up-regulates
binding
|
CBL |
0.605 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-127298 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15282549 |
We report upregulation of lrig1 transcript and protein upon egf stimulation, and physical association of the encoded protein with the four egfr orthologs of mammals. Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Skin |
| + |
CBL | down-regulates
ubiquitination
|
PIK3R2 |
0.62 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-110063 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11526404 |
Cbl-b, a ring-type e3 ubiquitin protein ligase, is implicated in setting the threshold of t lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (pi3k) was identified as a substrate for cbl-b. We have shown that cbl-b negatively regulated p85 in a proteolysis-independent manner. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ERBB4 | up-regulates
binding
|
CBL |
0.556 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-147841 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16829981 |
Erbb4 might not be able to directly recruit cbl, and therefore downregulation of this receptor is slow. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-180895 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18793634 |
Erbb4 might not be able to directly recruit cbl, and therefore downregulation of this receptor is slow. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
PTK6 | down-regulates activity
phosphorylation
|
CBL |
0.507 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279348 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23352614 |
Herein we report that PTK6 phosphorylates and down-regulates E3 ubiquitin ligase c-Cbl. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EGFR | up-regulates
relocalization
|
CBL |
0.89 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-114701 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11823423 |
Consistent with a negative role for c-Cbl, here we report that defective Tyr1045 of EGFR, an inducible c-Cbl docking site, enhances the mitogenic response to EGF |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-147826 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16829981 |
Likewise, cbl is recruited to erbb1 either directly (tyr1045), or indirectly, trough grb2 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, Glioblastoma Multiforme |
| + |
LTK | up-regulates
phosphorylation
|
CBL |
0.36 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-49528 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 9223670 |
Although c-cbl is found to be phosphorylated by ltk and therefore is a second candidate linking ltk with the pi3-kinase pathway along with irs-1, we found that the p85 subunit of pi3 kinase directly binds to tyrosine 753 of ltk, which is located within a yxxm motif, a consensus binding amino acid sequence for the sh2 domain of p85. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates activity
binding
|
FLT3 |
0.427 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255739 |
|
|
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 19276253 |
Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML |
| + |
CBL | down-regulates quantity by destabilization
ubiquitination
|
EGFR |
0.89 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-65642 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20332299 |
Ligand binding to EGFR also leads to rapid internalization and proteosomal/lysosomal degradation of the receptors. This process results in a dramatic downregulation of both total and cell surface receptors. EGF-induced degradation of EGFR is thought to be initiated by phosphorylation of tyrosine 1045 of the receptor followed by binding of Cbl adaptor proteins and ubiquitination of the receptor. Internalized EGFR is transported to early endosomes where receptor-ligand complexes are sorted for either degradation or recycling to the cell surface. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, Glioblastoma Multiforme |
| + |
CBL | down-regulates
ubiquitination
|
INSR |
0.544 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-109688 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11498022 |
Aps couples c-cbl to theinsulinreceptor, resulting in ubiquitination of theinsulinreceptor |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates activity
ubiquitination
|
KIT |
0.632 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260104 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15315962 |
KIT binds to and induces the phosphorylation of Cbl proteins, which in turn act as E3 ligases, mediating the ubiquitination and degradation of KIT and themselves. Tyrosine kinase binding and RING finger domains of Cbl are essential for Cbl-mediated ubiquitination and degradation of KIT. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, KIT in AML |
| + |
CBL | down-regulates quantity by destabilization
polyubiquitination
|
PDGFRB |
0.642 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272553 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10514377 |
Ubiquitination of the PDGF β-receptor (Rβ) by the c-Cbl RING in an SH2-dependent manner. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272549 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 10347229 |
Overexpression of wild type Cbl in NIH3T3 cells led to an enhancement of the ligand-dependent ubiquitination and subsequent degradation of the PDGFRbeta, as observed with PDGFRalpha. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Mus Musculus |
| + |
CBL | down-regulates
ubiquitination
|
SORBS2 |
0.5 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-96325 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12475393 |
Cbl-argbp2 complex mediates ubiquitination and degradation of c-abl |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates quantity by destabilization
ubiquitination
|
NCK1 |
0.658 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278606 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24287595 |
Taken together, these results show that lysine 178 in Nck1 is the acceptor site for ubiquitin transferred by c-Cbl, and that the ubiquitination of Nck1 by c-Cbl is blocked in the presence of synaptopodin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates quantity by destabilization
ubiquitination
|
ERBB2 |
0.584 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-30794 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20332299 |
Ligand binding to EGFR also leads to rapid internalization and proteosomal/lysosomal degradation of the receptors. This process results in a dramatic downregulation of both total and cell surface receptors. EGF-induced degradation of EGFR is thought to be initiated by phosphorylation of tyrosine 1045 of the receptor followed by binding of Cbl adaptor proteins and ubiquitination of the receptor. Internalized EGFR is transported to early endosomes where receptor-ligand complexes are sorted for either degradation or recycling to the cell surface. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates quantity by destabilization
polyubiquitination
|
LCK |
0.722 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272614 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 11904433 |
Coexpression in 293T cells demonstrated that Lck kinase activity and Cbl ubiquitin ligase activity were essential for Lck ubiquitination and negative regulation of Lck-dependent serum response element-luciferase reporter activity. The Lck SH3 domain was pivotal for Cbl-Lck association and Cbl-mediated Lck degradation, with a smaller role for interactions mediated by the Cbl tyrosine kinase-binding domain. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates
ubiquitination
|
FRS2 |
0.592 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-87166 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11997436 |
The experiments presented in this report illustrate that in response to fgf stimulation, cbl is recruited by grb2 binding to the frs2_ multiprotein complex, resulting in ubiquitination of frs2_ and fgfr. grb2 functions as a link between frs2_ and cbl;grb2 is bound to tyrosine-phosphorylated frs2_ by means of its sh2 domain and to a proline-rich region in the c terminus of cbl by means of its sh3 domains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PTPRJ | down-regulates activity 
|
CBL |
0.319 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248839 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19836242 |
Because c-CBL’s activation is achieved via tyrosine phosphorylation, we tested the effect of DEP-1 on modification of a major site of phosphorylation, namely tyro- sine 731. Upon DEP-1 overexpression, c-CBL displayed reduced phosphorylation on this site compared to control cells (Figure 7B). This result offers a mechanism by which DEP-1 affects EGFR trafficking: by dephosphorylating EGFR, and possibly also SRC family kinases involved in phosphoryla- tion of c-CBL [31, 32], DEP-1 reduces activation of c-CBL and its recruitment to the activated EGFR, hence inhibiting subsequent receptor internalization and degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia |
| + |
CBL | down-regulates quantity by destabilization
binding
|
EPHA2 |
0.651 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272590 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12496371 |
In our present study, we demonstrate that ligand-mediated stimulation causes EphA2 to be internalized and degraded. The mechanism of this response involves ligand-mediated autophosphorylation of EphA2, which promotes an association between EphA2 and the c-Cbl adaptor protein. We also show that c-Cbl promotes stimulation-dependent EphA2 degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
VAV1 | up-regulates
binding
|
CBL |
0.705 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-49188 |
|
|
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 9200440 |
Hese data imply that c-cbl is a molecular adapter that regulates the function of vav |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKCQ | up-regulates activity
phosphorylation
|
CBL |
0.347 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-274144 |
|
|
Mus musculus |
T-lymphocyte |
| pmid |
sentence |
| 26284074 |
PKC-θ-mediated phosphorylation of serine and tyrosine residues of c-Cbl prevents its inhibitory effect. Phosphorylation of c-Cbl by PKC-θ inhibits the recruitment of Sh2-containing proteins and subsequent association of cbl E3 ubiquitin ligase with its target proteins |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
CBL | up-regulates activity
monoubiquitination
|
MYCBPAP |
0.292 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272627 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17255943 |
We moreover found that AMAP1 is monoubiquitinated, rather than polyubiquitinated, by virtue of Cbl and provide evidence that the ability of AMAP1 to be monoubiquitinated is important for its involvement in invasion. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SORBS1 | up-regulates
binding
|
CBL |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-82283 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11001060 |
Cbl is recruited to the insulin receptor by interaction with the adapter protein cap, through one of three adjacent sh3 domains in the carboxy terminus of cap |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle |
| + |
CBL | down-regulates quantity by destabilization
ubiquitination
|
SRC |
0.749 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278539 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12907674 |
Cbl-b also targets active Src for degradation in cells, and Nedd4 similarly reverses Cbl mediated Src degradation.|Cbl-b also targets active Src for degradation in cells, and Nedd4 similarly reverses Cbl-mediated Src degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates
ubiquitination
|
LRIG1 |
0.605 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-127289 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15282549 |
We report upregulation of lrig1 transcript and protein upon egf stimulation, and physical association of the encoded protein with the four egfr orthologs of mammals. Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Skin |
| + |
CBL | down-regulates quantity by destabilization
ubiquitination
|
MET |
0.741 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-185680 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19450681 |
Tyrosine y1001, which when phosphorylated upon met activation, is involved in cbl recruitment, allowing receptor ubiquitination and down regulation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates
ubiquitination
|
PIK3R1 |
0.703 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-110060 |
|
|
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 11526404 |
Cbl-b, a ring-type e3 ubiquitin protein ligase, is implicated in setting the threshold of t lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (pi3k) was identified as a substrate for cbl-b. We have shown that cbl-b negatively regulated p85 in a proteolysis-independent manner. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Glioblastoma Multiforme |
| + |
GRB2 | up-regulates
relocalization
|
CBL |
0.907 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-114704 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11823423 |
The underlying mechanism seems to involve recruitment of a grb2 c-cbl complex to grb2-specific docking sites of egfr, and concurrent acceleration of receptor ubiquitylation and desensitization. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, KIT in AML, Glioblastoma Multiforme |
| + |
CRK | up-regulates
binding
|
CBL |
0.829 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-39241 |
|
|
Homo sapiens |
T-lymphocyte, Leukemia Cell |
| pmid |
sentence |
| 8524328 |
These results indicate that crk binds to c-cbl in a tyrosine phosphorylation-dependent manner. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KIT | up-regulates activity
phosphorylation
|
CBL |
0.632 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279199 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15315962 |
The activated KIT in turn induces phosphorylation and activation of Cbl proteins. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, KIT in AML |
| + |
CBL | down-regulates quantity by destabilization
ubiquitination
|
ABL1 |
0.618 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167194 |
|
|
Homo sapiens |
Leukemia Cell |
| pmid |
sentence |
| 20675402 |
We found that while c-cbl e3 ligase induced ubiquitin-dependent degradation of mature and phosphorylated bcr-abl proteins |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SH3GLB1 | up-regulates
binding
|
CBL |
0.42 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-115826 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11894095 |
Cbl rapidly recruits cin85 (cbl-interacting protein of 85k;ref. 6) and endophilins (regulatory components of clathrin-coated vesicles) to form a complex with activated egf receptors, thus controlling receptor internalization. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates quantity
ubiquitination
|
LCK |
0.722 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278804 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18535581 |
One study indicated that loss of CBL expression increases the constitutive level of LCK 80, but other studies have not shown this - .|The ubiquitylation of LCK by CBL (Casitas B-lineage lymphoma) is known to be a negative mechanism that regulates the signalling function of LCK xref . |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates activity
ubiquitination
|
SYK |
0.822 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272620 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 11742985 |
Intact tyrosine kinase-binding and RING finger domains of Cbl were found to be essential for Syk ubiquitylation in 293T cells and for in vitro Syk ubiquitylation. Altogether, our results support an essential role for Cbl ubiquitin ligase activity in the negative regulation of Syk, and establish that ubiquitylation provides a mechanism of Cbl-mediated negative regulation of cytoplasmic targets. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HCK |
phosphorylation
|
CBL |
0.679 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251262 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 10092522 |
Hck is one member of the Src-family PTKs that is able to phosphorylate Cbl. Upon enzymatic activation of Hck either by pharmacological agents or genetic mutation, Cbl becomes tyrosine phosphorylated. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
SH2B2 | up-regulates
binding
|
CBL |
0.66 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-109691 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11498022 |
Aps couples c-cbl to theinsulinreceptor, resulting in ubiquitination of theinsulinreceptor. The aps adapter protein couples theinsulinreceptor to the phosphorylation of c-cbl and facilitates ligand-stimulated ubiquitination of theinsulinreceptor. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-78337 |
|
|
Cricetulus griseus |
Ovary Cell Line |
| pmid |
sentence |
| 10854852 |
APS-mediated recruitment of c-Cbl to the insulin receptor led to rapid ubiquitination of the insulin receptor beta-subunit in CHO. T-APS but not in parental CHO.T cells. These results suggest that the function of APS is to facilitate coupling of the insulin receptor to c-Cbl in order to catalyse the ubiquitination of the receptor and initiation of internalisation or degradation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Cricetulus Griseus |
| Tissue: |
Ovary |
| + |
ABI1 | up-regulates
binding
|
CBL |
0.364 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154162 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17395426 |
Here we uncover a novel interaction between abi-1 and the cbl ubiquitin ligase and show that abi-1 mediates cbl accumulation to the plasma membrane upon stimulation by egf. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates
ubiquitination
|
PI3K |
0.625 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252668 |
|
|
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 11526404 |
Cbl-b, a ring-type e3 ubiquitin protein ligase, is implicated in setting the threshold of t lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (pi3k) was identified as a substrate for cbl-b. We have shown that cbl-b negatively regulated p85 in a proteolysis-independent manner. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, KIT in AML |
| + |
SH3KBP1 | up-regulates
binding
|
CBL |
0.758 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-203139 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24167568 |
The cin85 sh3 domains interact with c-cbl, an e3 ubiquitin ligase, via an unconventional pxxxpr ligand sequence, with the highest affinity displayed by the sh3-b domain. Interaction with cin85 recruits c-cbl to the amap1 complex where its ubiquitination activity is necessary for cancer cells to develop an invasive phenotype and to degrade the matrix. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBL | down-regulates quantity by destabilization
ubiquitination
|
CFLAR |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-186998 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19597496 |
We therefore conclude that c-cbl is a e3 ubiquitin ligase for flips and that the interaction of flips with c-cbl requires phosphorylation of both ser4 and tyr211 of flips.This interaction triggered proteasomal degradation of FLIP(S), which promoted activation of caspase-8 and apoptosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
4.0
CBL
- 
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