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Overview
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Pathways & interactions
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Cross-references
Adaptor protein Cbl, N-terminal domain superfamily (IPR036537)
Short name: Adaptor_Cbl_N_dom_sf
Overlapping entries
- Adaptor protein Cbl, N-terminal helical (IPR003153)
- Adaptor protein Cbl, PTB domain (IPR024159)
Description
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 N-terminal region of Cbl contains a Cbl-type phosphotyrosine-binding (Cbl-PTB) domain, which is composed of three evolutionarily conserved domains: an N-terminal four-helix bundle (4H) domain, an EF hand-like calcium-binding domain, and a divergent SH2-like domain. The calcium-bound EF-hand wedges between the 4H and SH2 domains, and roughly determines their relative orientation. The Cbl-PTB domain has also been named Cbl N-terminal (Cbl-N) or tyrosine kinase binding (TKB) domain [PMID: 10078535, PMID: 18840649].
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 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 [PMID: 10078535].
This entry represents the N-terminal four-helical bundle domain superfamily. This domain can also be found in the N terminus of mammalian MLKL, a pseudokinase essential for TNF-alpha-induced necroptosis [PMID: 28827318]. The four-helical bundle (NB) domain of MLK is involved in oligomerization to facilitate plasma membrane targeting through the low-affinity binding of NB to phosphorylated inositol polar head groups of phosphatidylinositol phosphate (PIP) phospholipids [PMID: 26853145, PMID: 26337687].
GO terms
Biological Process
GO:0007166 cell surface receptor signaling pathway
Molecular Function
GO:0004871 signal transducer activity
Cellular Component
No terms assigned in this category.
Contributing signatures
- SSF47668 (SSF47668)
- G3DSA:1.20.930.20 (G3DSA:1.20.930.20)