Version 1.2 last updated 22 February, 2008 contains 566 public entries |
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Short description of the SH2base: The Src homology 2 (SH2) domains are about 100 residues in length with an average of 28% pairwise residue identity (Pfam code PF00017). More than 100 different human SH2 domains have been identified or predicted (Pawson et al., 2002). SH2 domains mediate intramolecular recognition and intermolecular protein-protein association almost invariably by binding to phosphorylated tyrosine (pY) residues in specific sequence contexts. They usually appear in multidomain proteins, together with catalytic domains, or other protein binding modules, such as Src homology 3 (SH3), phosphotyrosine binding (PTB) or pleckstrin homology (PH) domains (Figure 1). The genome-wide search for disease-causing mutations in the SH2 domains revealed eight genes: Bruton tyrosine kinase (BTK), SH2 domain-containing protein 1A (SH2D1A), Ras GTPase activating protein (RasGAP), tyrosine protein kinase Zap-70, SHP-2, the p85α subunit of the PIP3 kinase (PI3-K), signal transducer and activator of transcription 1α/β (STAT1) and STAT5B. Mutations in these genes cause nine distinct clinical phenotypes (Table 1). The domain organization of the proteins is given in Figure 1. The mutation types range from large gross deletions of the whole gene to single point mutations. Missense mutations comprise the most common mutational event. Although SH2 domain containing proteins have been shown to have redundant functions in the cellular signaling network, proteins with defective SH2 domains either have a crucial role during cell development process or they regulate multiple signaling cascades. We have collated all pathogenic mutations affecting SH2 domains into locus-specific mutation databases (Table 1). The mutations were mapped on corresponding protein structures and a set of sequence- and structure-based rules were assigned to give a description of each mutation. Other IBT bioinformatics services: Immunodeficiency Resource (IDR) Immunodeficiency Mutation Databases (MUTbase) IDdiagnostics Immunome - Database for genes and proteins of the Human Immune System SH2base - Database for pathogenic SH2 domain mutations |
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SH2base Database for pathogenic SH2 domain mutations |
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