|PROSITE documentation PDOC00907 [for PROSITE entry PS01179]|
Proteins encoding phosphotyrosine binding (PTB) domains function as adaptors or scaffolds to organize 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 (see <PDOC51064>), 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 .
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 . 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, utilizing two distinct binding motifs to mediate spatial organization and localization within cells [1,2,3,4].
The 3D structure of PID domain has been solved (see <PDB:1NTV>) . It shares a folding pattern, commonly referred to as the PH-domain "superfold". The core "superfold" consists of seven antiparallel β strands forming two orthogonal β sheets. This β sandwich is capped at the C terminus by an α helix. It contains a peptide binding pocket (formed by the β strand 5 and C-terminal α 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 α helices, one of which is located at the N terminus and the other between β 1 and β 2 strands.
PID has also been found in the proteins listed below.
The profile we developed covers the entire PID domain.Expert(s) to contact by email:
January 2005 / Text revised.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Uhlik M.T. Temple B. Bencharit S. Kimple A.J. Siderovski D.P. Johnson G.L.|
|Title||Structural and evolutionary division of phosphotyrosine binding (PTB) domains.|
|Source||J. Mol. Biol. 345:1-20(2005).|
|2||Authors||Bork P. Margolis B.|
|Title||A phosphotyrosine interaction domain.|
|3||Authors||Kavanaugh W.M. Williams L.T.|
|Title||An alternative to SH2 domains for binding tyrosine-phosphorylated proteins.|
|4||Authors||Blaikie P. Immanuel D. Wu J. Li N. Yajnik V. Margolis B.|
|Title||A region in Shc distinct from the SH2 domain can bind tyrosine-phosphorylated growth factor receptors.|
|Source||J. Biol. Chem. 269:32031-32034(1994).|
|5||Authors||Stolt P.C. Jeon H. Song H.K. Herz J. Eck M.J. Blacklow S.C.|
|Title||Origins of peptide selectivity and phosphoinositide binding revealed by structures of disabled-1 PTB domain complexes.|