|PROSITE documentation PDOC51506 [for PROSITE entry PS51506]|
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>) .
The profile we developed covers the entire Cbl-PTB domain.Last update:
August 2010 / First entry.
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.|
|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).|