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PROSITE documentation PDOC00907 |
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 [1].
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 [2]. 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>) [5]. 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: Last update:January 2005 / Text revised.
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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). | |
PubMed ID | 15567406 | |
DOI | 10.1016/j.jmb.2004.10.038 |
2 | Authors | Bork P. Margolis B. |
Title | A phosphotyrosine interaction domain. | |
Source | Cell 80:693-694(1995). | |
PubMed ID | 7534213 |
3 | Authors | Kavanaugh W.M. Williams L.T. |
Title | An alternative to SH2 domains for binding tyrosine-phosphorylated proteins. | |
Source | Science 266:1862-1865(1994). | |
PubMed ID | 7527937 |
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). | |
PubMed ID | 7798194 |
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. | |
Source | Structure 11:569-579(2003). | |
PubMed ID | 12737822 |