PTBPhosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain
|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 PI domain has a similar structure to the insulin receptor substrate-1 PTB domain, a 7-stranded beta-sandwich, capped by a C-terminal helix. However, the PI domain contains an additional short N-terminal helix and a large insertion between strands 1 and 2, which forms a helix and 2 long connecting loops. The substrate peptide fits into a surface cleft formed from the C-terminal helix and strand 5 [(PUBMED:8599766)].
|GO function:||protein binding (GO:0005515)|
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- Evolution (species in which this domain is found)
Click on to expand nodes. To display all proteins with a PTB domain in a specific node, click on it.
This tree shows only several representative species. The complete taxonomic breakdown of all proteins with PTB domain is also avaliable.
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Go to specific node: Anopheles gambiae, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes
- Cellular role (predicted cellular role)
Cellular role: signalling, interaction
Binding / catalysis: phosphotyrosine-binding
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Cowburn D
- Peptide recognition by PTB and PDZ domains.
- Curr Opin Struct Biol. 1997; 7: 835-8
- Display abstract
Protein tyrosine binding (PTB) and 'post synaptic density disc-large zo-1' (PDZ) domains bind to short peptidic ligands by augmentation of one of the domain's beta sheets and other recognition mechanisms. The two domain classes have a superficial resemblance to each other, even though no sequential homology exists. The structural bases of the interactions are well understood for the few domains now experimentally determined, and ligand-target pairs can probably be identified in favorable cases by analogy with the known domains. For both PTB and PDZ classes, functional activities are still not fully defined: it is possible that these domain classes, along with pleckstrin homology domains, have multiple roles.
- Fanning AS, Anderson JM
- Protein-protein interactions: PDZ domain networks.
- Curr Biol. 1996; 6: 1385-8
- Display abstract
PDZ domains can dimerize or bind to the carboxyl termini of unrelated proteins. Crystallographic studies demonstrate the structural basis for these interactions, which contribute to the ability of PDZ domains to create networks associated with the plasma membrane.
- Bork P, Margolis B
- A phosphotyrosine interaction domain.
- Cell. 1995; 80: 693-4
- Kavanaugh WM, Turck CW, Williams LT
- PTB domain binding to signaling proteins through a sequence motif containing phosphotyrosine.
- Science. 1995; 268: 1177-9
- Display abstract
Src homology 2 (SH2) domains mediate assembly of signaling complexes by binding specifically to tyrosine-phosphorylated proteins. A phosphotyrosine binding (PTB) domain has been identified which also binds specifically to tyrosine-phosphorylated targets, but is structurally different from SH2 domains. Expression cloning was used to identify targets of PTB domains. PTB domains bound to phosphotyrosine within a sequence motif, asparagine-X1-X2-phosphotyrosine (where X represents any amino acid), that is found in many signaling proteins and is not recognized by SH2 domains. Mutational studies indicated that high affinity binding of PTB domains may require a specific conformation of the motif.
- Trub T et al.
- Specificity of the PTB domain of Shc for beta turn-forming pentapeptide motifs amino-terminal to phosphotyrosine.
- J Biol Chem. 1995; 270: 18205-8
- Display abstract
Shc phosphorylation in cells following growth factor, insulin, cytokine, and lymphocyte receptor activation leads to its association with Grb2 and activation of Ras. In addition to being a cytoplasmic substrate of tyrosine kinases, Shc contains an SH2 domain and a non-SH2 phosphotyrosine binding (PTB) domain. Here we show that the Shc PTB domain, but not the SH2 domain, binds with high affinity (ID50 approximately equal to 1 microM) to phosphopeptides corresponding to the sequence surrounding Tyr250 of the polyoma virus middle T (mT) antigen (LLSNPTpYSVMRSK). Truncation studies show that five residues amino-terminal to tyrosine are required for high affinity binding, whereas all residues carboxyl-terminal to tyrosine can be deleted without loss of affinity. Substitution studies show that tyrosine phosphorylation is required and residues at -5, -3, -2, and -1 positions relative to pTyr are important for this interaction. 1H NMR studies demonstrate that the phosphorylated mT antigen-derived sequence forms a stable beta turn in solution, and correlations between structure and function indicate that the beta turn is important for PTB domain recognition. These results show that PTB domains are functionally distinct from SH2 domains. Whereas SH2 domain binding specificity derives from peptide sequences carboxyl-terminal to phosphotyrosine, the Shc PTB domain gains specificity by interacting with beta turn-forming sequences amino-terminal to phosphotyrosine.
- Zhou MM et al.
- Structure and ligand recognition of the phosphotyrosine binding domain of Shc.
- Nature. 1995; 378: 584-92
- Display abstract
The nuclear magnetic resonance structure of the phosphotyrosine binding (PTB) domain of Shc complexed to a phosphopeptide reveals an alternative means of recognizing tyrosine-phosphorylated proteins. Unlike in SH2 domains, the phosphopeptide forms an antiparallel beta-strand with a beta-sheet of the protein, interacts with a hydrophobic pocket through the (pY-5) residue, and adopts a beta-turn. The PTB domain is structurally similar to pleckstrin homology domains (a beta-sandwich capped by an alpha-helix) and binds to acidic phospholipids, suggesting a possible role in membrane localization.
- vanderGeer P, Pawson T
- The PTB domain: a new protein module implicated in signal transduction.
- Trends Biochem Sci. 1995; 20: 277-80
- Display abstract
Src homology 2 (SH2) domains have been identified in a large number of proteins involved in signal transduction downstream of receptor tyrosine kinases. They allow cytoplasmic signalling proteins to bind specifically to other polypeptides that are phosphorylated on tyrosine in response to growth factor stimulation. A novel phosphotyrosine-binding (PTB) domain has been identified recently in the amino terminus of Shc, an adaptor molecule that appears to be involved in Ras activation PTB domains are longer than SH2 domains, and recognize phosphotyrosine in the context of amino-terminal residues, in contrast to SH2 domains, which recognize them in the context of carboxy-terminal residues.
- Kavanaugh WM, Williams LT
- An alternative to SH2 domains for binding tyrosine-phosphorylated proteins.
- Science. 1994; 266: 1862-5
- Display abstract
Src homology 2 (SH2) domains bind specifically to tyrosine-phosphorylated proteins that participate in signaling by growth factors and oncogenes. A protein domain was identified that bound specifically to the tyrosine-phosphorylated form of its target protein but differs from known SH2 sequences. Phosphotyrosine-binding (PTB) domains were found in two proteins: SHC, a protein implicated in signaling through Ras; and SCK, encoded by a previously uncharacterized gene. The PTB domain of SHC specifically bound to a tyrosine-phosphorylated 145-kilodalton protein. PTB domains are an alternative to SH2 domains for specifically recruiting tyrosine-phosphorylated proteins into signaling complexes and are likely to take part in signaling by many growth factors.
- Metabolism (metabolic pathways involving proteins which contain this domain)
% proteins involved KEGG pathway ID Description 12.90 map04012 ErbB signaling pathway 12.90 map05214 Glioma 12.90 map05220 Chronic myeloid leukemia 12.90 map04510 Focal adhesion 12.90 map04910 Insulin signaling pathway 12.90 map04650 Natural killer cell mediated cytotoxicity 11.61 map04330 Notch signaling pathway 7.10 map04010 MAPK signaling pathway 3.87 map05010 Alzheimer's disease
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PTB domain which could be assigned to a KEGG orthologous group, and not all proteins containing PTB domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of PTB domains in PDB
PDB code Main view Title 1aqc X11 ptb domain-10mer peptide complex 1ddm Solution structure of the numb ptb domain complexed to a nak peptide 1m7e Crystal structure of the phosphotyrosine binding domain(ptb) of mouse disabled 2(dab2):implications for reeling signaling 1n3h Coupling of folding and binding in the ptb domain of the signaling protein shc 1ntv Crystal structure of the disabled-1 (dab1) ptb domain- apoer2 peptide complex 1nu2 Crystal structure of the murine disabled-1 (dab1) ptb domain-apoer2 peptide-pi-4,5p2 ternary complex 1oqn Crystal structure of the phosphotyrosine binding domain (ptb) of mouse disabled 1 (dab1) 1oy2 Coupling of folding and binding in the ptb domain of the signaling protein shc 1p3r Crystal structure of the phosphotyrosin binding domain(ptb) of mouse disabled 1(dab1) 1shc Shc ptb domain complexed with a trka receptor phosphopeptide, nmr, minimized average structure 1wgu Solution structure of the c-terminal phosphotyrosine interaction domain of apbb2 from mouse 1wj1 Solution structure of phosphotyrosine interaction domain of mouse numb protein 1wvh Crystal structure of tensin1 ptb domain 1x11 X11 ptb domain 2cy4 Crystal structure of phosphotyrosine binding (ptb) domain of epidermal growth factor receptor pathway substrate-8 (eps8) related protein 1 from mus musculus (form-1 crystal) 2cy5 Crystal structure of phosphotyrosine binding (ptb) domain of epidermal growth factor receptor pathway substrate-8 (eps8) related protein 1 from mus musculus (form-2 crystal) 2dkq Solution structure of the ptb domain of kiaa1075 protein from human 2dyq Crystal structure of the c-terminal phophotyrosine interaction domain of human apbb3 2ej8 Crystal structure of appl1 ptb domain at 1.8a 2ela Crystal structure of the ptb domain of human appl1 2gjy Nmr solution structure of tensin1 ptb domain 2nmb Dnumb ptb domain complexed with a phosphotyrosine peptide, nmr, ensemble of structures. 2roz Structure of the c-terminal pid domain of fe65l1 complexed with the cytoplasmic tail of app reveals a novel peptide binding mode 2ysz Solution structure of the chimera of the c-terminal pid domain of fe65l and the c-terminal tail peptide of app 2yt0 Solution structure of the chimera of the c-terminal tail peptide of app and the c-terminal pid domain of fe65l 2yt1 Solution structure of the chimera of the c-terminal tail peptide of app and the c-terminal pid domain of fe65l 3d8d Crystal structure of the human fe65-ptb1 domain 3d8e Crystal structure of the human fe65-ptb1 domain (trigonal crystal form) 3d8f Crystal structure of the human fe65-ptb1 domain with bound phosphate (trigonal crystal form) 3dxc Crystal structure of the intracellular domain of human app in complex with fe65-ptb2 3dxd Crystal structure of the intracellular domain of human app (t668e mutant) in complex with fe65-ptb2 3dxe Crystal structure of the intracellular domain of human app (t668a mutant) in complex with fe65-ptb2 3f0w Human numb-like protein, phosphotyrosine interaction domain 3hqc Crystal structure of phosphotyrosine-binding domain from the human tensin-like c1 domain-containing phosphatase (tenc1)
- Links (links to other resources describing this domain)
PFAM PID INTERPRO IPR006020 PROSITE PID