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Short description of the idbase: 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. 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. The genome-wide search for disease-causing variations 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. Variations in these genes cause nine distinct clinical phenotypes. The variation types range from large gross deletions of the whole gene to single point variations. Amino acid substitutions comprise the most common mutational event. Although SH2 domain containing proteins have been shown to have redundant functions in the cellular signaling networks, 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 variations affecting SH2 domains. Our other bioinformatics services: Immunodeficiency Resource (IDR) Immunodeficiency Mutation Databases (MUTbase) IDdiagnostics Immunome - Database for genes and proteins of the Human Immune System |
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SH2base Database for pathogenic SH2 domain variations |
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