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About PepCyber:P~Pep
 
  • PepCyber :P~Pep is the largest public database of human protein-protein interactions mediated by phosphoprotein binding domains (PPBDs).
  • Current release: v. 1.2 (May 2010), includes 11,269 records of interactions between 387 PPBD proteins and 1,471 substrate proteins, curated from 4,852 published studies.
  • Please direct questions and comments to help@pepcyber.org.
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    References
     
  • Gong, W., Zhou, D., Ren, Y., Wang, Y., Zuo, Z., Shen, Y., Xiao, F., Zhu, Q., Hong, A., Zhou, X., Gao, X and Li, T. (2008) PepCyber:P~PEP: a database of human protein protein interactions mediated by phosphoprotein-binding domains. Nucleic Acids Res , 36 , D679-683. [PubMed] [Full text]
  • Wan, J., Kang, S., Tang, C., Yan, J., Ren, Y., Liu, J., Gao, X., Banerjee, A., Ellis, L.B. and Li, T. (2008) Meta-prediction of phosphorylation sites with weighted voting and restricted grid search parameter selection. Nucleic Acids Res . [PubMed] [Full text]
  •  
    Related databases
     
  • BOND (formerly BIND), by Unleashed Informatics.
  • DIP, developed at the University of California Los Angeles.
  • DOMINO, developed at the University of Rome Tor Vergata, Italy.
  • ELM, by Eukaryotic Linear Motif (ELM) consortium.
  • HPRD , developed at Institute of Bioinformatics, Bangalore, India and Johns Hopkins University.
  • Phospho.ELM, by Eukaryotic Linear Motif (ELM) consortium.
  • Scansite, developed at Massachusetts Institute of Technology.
  • STRING, by European Molecular Biology Laboratory (EMBL) and University of Zürich (UniZH)
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    14-3-3 | BRCT | C2 | FHA | MH2 | PBD | PTB | SH2 | WD40 | WW

    All SH2 PPBD-containing proteins.
    Search interactions involving SH2.

    SH2 Domain

        The Src homology 2 (SH2) domain is a pY binding domain of about 100 amino-acid residues first identified as a region with conserved sequence between the oncoproteins Src and Fps (Sadowski I 1986). Similar sequences have been found in many other intracellular signal-transducing proteins (Russell, Breed et al. 1992)

    Binding Specificity

        SH2 domains can interact with pY-containing target peptides in a sequence-specific manner, and recognize between 3-6 residues C-terminal to the pY in a fashion that differs from one SH2 domain to another, and strictly phosphorylation-dependent manner (Mayer and Baltimore 1993; Pawson and Schlessingert 1993; Songyang, Shoelson et al. 1993; Marengere and Pawson 1994; Pawson 1995). The SH2 domain fold, which is composed of an anti-parallel beta-sheet in center sandwiched between two alpha-helices, provides a positively charged pocket on one side of the beta-sheet for binding of the ligands pY moiety, and an extended surface on the other side for binding to ligand residues C-terminal to the pY.

    Structure

        The structure of SH2 domain belongs to the alpha+beta class, its overall shape making a compact flattened hemisphere. The core structural elements comprise a hydrophobic anti-parallel beta-sheet in center, flanked by 2 short alpha-helices. The loop between strands 2 and 3 provides many of the binding interactions with the phosphate group of its phosphopeptide ligand, and is hence designated the phosphate binding loop, the phosphorylated ligand binds perpendicular to the beta-sheet and typically interacts with the phosphate binding loop and a hydrophobic binding pocket that interacts with a pY+3 side chain. The N- and C-termini of the domain are close adjacent in space and on the opposite face from the phosphopeptide binding surface and it has been presumed that this has facilitated their integration into surface-exposed regions of host proteins (Pawson, Raina et al. 2002).

    Typical Proteins

        SH2 domains are found in a wide variety of proteins, include: phospholipase Cgamma (PLCG1) and the non-receptor protein tyrosine kinases; structural proteins such as tensin (TNS1); a group of small adaptor molecules, i.e CRK and NCK1. Sometimes the SH2 domains are found as repeats in a single protein sequence and will then often bind both mono- and di-phosphorylated substrates.

    Concerned Biological Process

        SH2 domains function as regulatory modules in intracellular signalling cascades and some other pathways, such as kinases, adaptors, phosphatases, and so on.

    References

    Marengere, L. E. and T. Pawson (1994). "Structure and function of SH2 domains." J Cell Sci Suppl 18: 97-104.

    Mayer, B. J. and D. Baltimore (1993). "Signalling through SH2 and SH3 domains." Trends Cell Biol 3(1): 8-13.

    Pawson, T. (1995). "Protein modules and signalling networks." Nature 373(6515): 573-80.

    Pawson, T., M. Raina, et al. (2002). "Interaction domains: from simple binding events to complex cellular behavior." FEBS Lett 513(1): 2-10.

    Pawson, T. and J. Schlessingert (1993). "SH2 and SH3 domains." Curr Biol 3(7): 434-42.

    Russell, R. B., J. Breed, et al. (1992). "Conservation analysis and structure prediction of the SH2 family of phosphotyrosine binding domains." FEBS Lett 304(1): 15-20.

    Sadowski I, S. J., Pawson T. (1986). "A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps." Mol Cell Biol 6(12): 4396-408.

    Songyang, Z., S. E. Shoelson, et al. (1993). "SH2 domains recognize specific phosphopeptide sequences." Cell 72(5): 767-78.

    All SH2 PPBD-containing proteins.
    Search interactions involving SH2.
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