PTB

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain
PTB
SMART accession number:SM00462
Description: PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.
Interpro abstract (IPR006020):

The Shc-like PID specifically binds to the Asn-Pro-Xaa-Tyr(P) motif found in many tyrosine-phosphorylated proteins including growth factor receptors. On the other hand the Dab-like PID domain binds to non-phosphorylated tyrosine residue or even a phenylalanine at the same position [ (PUBMED:7534213) ]. Most of the ligands for Shc-like PID domains are RTK or cytokine, whereas phosphotyrosine independent Dab-like PID domains seems to mediate other types of signaling pathways, like endocytosis/processing or exocytosis. This domain binds both peptides and headgroups of phosphatidylinositides, utilising two distinct binding motifs to mediate spatial organisation and localisation within cells [ (PUBMED:15567406) (PUBMED:7534213) (PUBMED:7527937) (PUBMED:7798194) ].

The 3D structure of PID domain has been solved [ (PUBMED:12737822) ]. It shares a folding pattern, commonly referred to as the PH-domain "superfold". The core "superfold" consists of seven antiparallel beta strands forming two orthogonal beta sheets. This beta sandwich is capped at the C terminus by an alpha helix. It contains a peptide binding pocket (formed by the beta strand 5 and C-terminal alpha helix) and a highly basic phospholipid binding "crown" (largely composed of residues from loop regions near the N terminus). Both Shc and Dab1 have two additional alpha helices, one of which is located at the N terminus and the other between beta 1 and beta 2 strands.

Proteins encoding phosphotyrosine binding (PTB) domains function as adaptors or scaffolds to organise the signaling complexes involved in wide-ranging physiological processes including neural development, immunity, tissue homeostasis and cell growth. Due to structural differences, PTB domains are divided into three groups represented by phosphotyrosine-dependent IRS-like, phosphotyrosine-dependent Shc-like, and phosphotyrosine-independent Dab-like PTBs. The last two PTBs have been named as phosphotyrosine interaction domain (PID or PI domain). PID domain has an average length of about 160 amino acids [ (PUBMED:15567406) ].

GO function:protein binding (GO:0005515)
Family alignment:
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There are 18492 PTB domains in 16250 proteins in SMART's nrdb database.

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