PROSITE documentation PDOC51506 [for PROSITE entry PS51506]Cbl-type phosphotyrosine-binding (Cbl-PTB) domain profile
Cbl (Casitas B-lineage lymphoma) is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface. The evolutionarily conserved amino-terminal region of Cbl (Cbl-N) binds to phosphorylated tyrosine residues and has cell-transforming activity. The N-terminal Cbl-type phosphotyrosine-binding (Cbl-PTB) domain is composed of three interacting domains: a four-helix bundle (4H), an EF-hand-like calcium-binding domain (see <PDOC00018>), and a divergent SH2-like domain (see <PDOC50001>). The calcium-bound EF-hand wedges between the 4H and SH2 domains, and roughly determines their relative orientation. The three domains together form an integrated phosphoprotein-recognition module. The Cbl-PTB has also been named Cbl N-terminal (Cbl-N) or tyrosine kinase binding (TKB) domain [1,2].
The N-terminal 4H domain contains four long α-helices. The C and D helices in this domain pack against the adjacent EF-hand-like domain, and a highly conserved loop connecting the A and B helices contacts the SH2-like domain. The EF-hand motif is similar to classical EF-hand proteins. The SH2-like domain in Cbl-N retains the general helix-sheet-helix architecture of the SH2 fold, but lacks the secondary β-sheet, comprising β-strands D', E and F, and also a prominent BG loop (see <PDB:2CBL>) [1].
The profile we developed covers the entire Cbl-PTB domain.
Last update:August 2010 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Meng W. Sawasdikosol S. Burakoff S.J. Eck M.J. |
| Title | Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase. | |
| Source | Nature 398:84-90(1999). | |
| PubMed ID | 10078535 | |
| DOI | 10.1038/18050 |
| 2 | Authors | Langenick J. Araki T. Yamada Y. Williams J.G. |
| Title | A Dictyostelium homologue of the metazoan Cbl proteins regulates STAT signalling. | |
| Source | J. Cell. Sci. 121:3524-3530(2008). | |
| PubMed ID | 18840649 | |
| DOI | 10.1242/jcs.036798 |
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