ArticleThe EMBO journal2002
A "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain: structural basis and relevance to the XLP syndrome.
Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 86 citations in OpenAlex.
- SLAMF receptors: key regulators of tumor progression and emerging targets for cancer immunotherapy.Molecular cancer · 2025Review
- SH2 Domains: Folding, Binding and Therapeutical Approaches.International journal of molecular sciences · 2022Review
- Exon skipping caused by a complex structural variation in SH2D1A resulted in X-linked lymphoproliferative syndrome type 1.Molecular genetics & genomic medicine · 2022Article
- SAP interacts with CD28 to inhibit PD-1 signaling in T lymphocytes.Clinical immunology (Orlando, Fla.) · 2020Article
- The GTPase-activating protein p120RasGAP has an evolutionarily conserved "FLVR-unique" SH2 domain.The Journal of biological chemistry · 2020Article
- SH2 Domain Binding: Diverse FLVRs of Partnership.Frontiers in endocrinology · 2020Review
- Specificity and regulation of phosphotyrosine signaling through SH2 domains.Journal of structural biology: X · 2020Article
- Surface Loops in a Single SH2 Domain Are Capable of Encoding the Spectrum of Specificity of the SH2 Family.Molecular & cellular proteomics : MCP · 2019Article
- Identification of a novel nonsense mutation in SH2D1A in a patient with X-linked lymphoproliferative syndrome type 1: a case report.BMC medical genetics · 2018Article
- Affinity purification mass spectrometry analysis of PD-1 uncovers SAP as a new checkpoint inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- A polymorphism in a phosphotyrosine signalling motif of CD229 (Ly9, SLAMF3) alters SH2 domain binding and T-cell activation.Immunology · 2015Article
- CBAP promotes thymocyte negative selection by facilitating T-cell receptor proximal signaling.Cell death & disease · 2014Article
- A novel interaction between the SH2 domain of signaling adaptor protein Nck-1 and the upstream regulator of the Rho family GTPase Rac1 engulfment and cell motility 1 (ELMO1) promotes Rac1 activation and cell motility.The Journal of biological chemistry · 2014Article
- Solubility of recombinant Src homology 2 domains expressed in E. coli can be predicted by TANGO.BMC biotechnology · 2014Article
- Differential recognition of syk-binding sites by each of the two phosphotyrosine-binding pockets of the Vav SH2 domain.Biopolymers · 2013Article
- SAP modulates B cell functions in a genetic background-dependent manner.Immunology letters · 2013Article
- Phosphotyrosine recognition domains: the typical, the atypical and the versatile.Cell communication and signaling : CCS · 2012Article
- Towards mimicking short linear peptide motifs: identification of new mixed α,β-peptidomimetic ligands for SLAM-Associated Protein (SAP) by confocal on-bead screening.Journal of chemical biology · 2012Article
- Characterization of Ly108 in the thymus: evidence for distinct properties of a novel form of Ly108.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- The adaptor protein SAP directly associates with CD3ζ chain and regulates T cell receptor signaling.PloS one · 2012Article
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The SH2 domain protein SAP/SH2D1A, encoded by the X-linked lymphoproliferative (XLP) syndrome gene, associates with the hematopoietic cell surface receptor SLAM in a phosphorylation-independent manner. By screening a repertoire of synthetic peptides, the specificity of SAP/SH2D1A has been mapped and a consensus sequence motif for binding identified, T/S-x-x-x-x-V/I, where x represents any amino acid. Remarkably, this motif contains neither a Tyr nor a pTyr residue, a hallmark of conventional SH2 domain-ligand interactions. The structures of the protein, determined by NMR, in complex with two distinct peptides provide direct evidence in support of a "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain in contrast to the "two-pronged" binding for conventional SH2 domains. Differences in the structures of the two complexes suggest considerable flexibility in the SH2 domain, as further confirmed and characterized by hydrogen exchange studies. The structures also explain binding defects observed in disease-causing SAP/SH2D1A mutants and suggest that phosphorylation-independent interactions mediated by SAP/SH2D1A likely play an important role in the pathogenesis of XLP.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.