Homo sapiens Protein: CBL | |||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||
InnateDB Protein | IDBP-74419.6 | ||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||
Gene Symbol | CBL | ||||||||||||||||||||||||
Protein Name | Cas-Br-M (murine) ecotropic retroviral transforming sequence | ||||||||||||||||||||||||
Synonyms | C-CBL; CBL2; FRA11B; NSLL; RNF55; | ||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||
Ensembl Protein | ENSP00000264033 | ||||||||||||||||||||||||
InnateDB Gene | IDBG-74417 (CBL) | ||||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||||
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. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, 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. {ECO:0000269PubMed:10514377, ECO:0000269PubMed:11896602, ECO:0000269PubMed:14661060, ECO:0000269PubMed:14739300, ECO:0000269PubMed:15190072, ECO:0000269PubMed:17509076, ECO:0000269PubMed:18374639, ECO:0000269PubMed:19689429, ECO:0000269PubMed:21596750}. | ||||||||||||||||||||||||
Subcellular Localization | Cytoplasm. Cell membrane. Note=Colocalizes with FGFR2 in lipid rafts at the cell membrane. | ||||||||||||||||||||||||
Disease Associations | Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL) [MIM:613563]: A syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects. Some have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia. {ECO:0000269PubMed:20619386}. Note=The disease is caused by mutations affecting the gene represented in this entry. | ||||||||||||||||||||||||
Tissue Specificity | |||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 365 experimentally validated interaction(s) in this database.
They are also associated with 52 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||
InterPro |
IPR000449
Ubiquitin-associated domain/translation elongation factor EF-Ts, N-terminal IPR000980 SH2 domain IPR001841 Zinc finger, RING-type IPR003153 Adaptor protein Cbl, N-terminal helical IPR009060 UBA-like IPR014741 Adaptor protein Cbl, EF hand-like IPR014742 Adaptor protein Cbl, SH2-like IPR015940 Ubiquitin-associated/translation elongation factor EF1B, N-terminal, eukaryote IPR018957 Zinc finger, C3HC4 RING-type |
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PFAM |
PF00627
PF00017 PF14633 PF13639 PF14634 PF02262 PF02761 PF02762 PF00097 |
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PRINTS |
PR00401
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PIRSF | |||||||||||||||||||||||||
SMART |
SM00252
SM00184 SM00165 |
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TIGRFAMs | |||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||
SwissProt | P22681 | ||||||||||||||||||||||||
PhosphoSite | PhosphoSite-P22681 | ||||||||||||||||||||||||
TrEMBL | |||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||
Entrez Gene | 867 | ||||||||||||||||||||||||
UniGene | Hs.504096 | ||||||||||||||||||||||||
RefSeq | NP_005179 | ||||||||||||||||||||||||
HUGO | HGNC:1541 | ||||||||||||||||||||||||
OMIM | 165360 | ||||||||||||||||||||||||
CCDS | CCDS8418 | ||||||||||||||||||||||||
HPRD | 01320 | ||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||
EMBL | AP002956 BC132733 BC136463 X57110 | ||||||||||||||||||||||||
GenPept | AAI32734 AAI36464 CAA40393 | ||||||||||||||||||||||||