Homologous Superfamily

Adaptor protein Cbl, N-terminal domain superfamily (IPR036537)

Short name: Adaptor_Cbl_N_dom_sf

Overlapping entries


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

No terms assigned in this category.

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.