{PDOC51506}
{PS51506; CBL_PTB}
{BEGIN}
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* Cbl-type phosphotyrosine-binding (Cbl-PTB) domain profile *
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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 alpha-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 beta-sheet, comprising beta-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: August 2010 / First entry.

[ 1] Meng W., Sawasdikosol S., Burakoff S.J., Eck M.J.
     "Structure of the amino-terminal domain of Cbl complexed to its
     binding site on ZAP-70 kinase."
     Nature 398:84-90(1999).
     PubMed=10078535; DOI=10.1038/18050
[ 2] Langenick J., Araki T., Yamada Y., Williams J.G.
     "A Dictyostelium homologue of the metazoan Cbl proteins regulates STAT
     signalling."
     J. Cell. Sci. 121:3524-3530(2008).
     PubMed=18840649; DOI=10.1242/jcs.036798

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