ArticleThe Journal of biological chemistry2015
Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- CD2AP at the junction of nephropathy and Alzheimer's disease.Molecular neurodegeneration · 2025Review
- SHARK-capture identifies functional motifs in intrinsically disordered protein regions.Protein science : a publication of the Protein Society · 2025Article
- The Alzheimer's Disease Risk Gene CD2AP Functions in Dendritic Spines by Remodeling F-Actin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Genome assemblies forFrontiers in genetics · 2024Article
- Studying the Association of TKS4 and CD2AP Scaffold Proteins and Their Implications in the Partial Epithelial-Mesenchymal Transition (EMT) Process.International journal of molecular sciences · 2023Article
- A Systematic Compilation of Human SH3 Domains: A Versatile Superfamily in Cellular Signaling.Cells · 2023Review
- Crystal Structure of the SH3 Domain of ASAP1 in Complex with the Proline Rich Motif (PRM) of MICAL1 Reveals a Unique SH3/PRM Interaction Mode.International journal of molecular sciences · 2023Article
- Cell-type-specific cis-eQTLs in eight human brain cell types identify novel risk genes for psychiatric and neurological disorders.Nature neuroscience · 2022Article
- DAPLE orchestrates apical actomyosin assembly from junctional polarity complexes.The Journal of cell biology · 2022Article
- Function of SYDE C2-RhoGAP family as signaling hubs for neuronal development deduced by computational analysis.Scientific reports · 2022Article
- Ras and Rab Interactor 3: From Cellular Mechanisms to Human Diseases.Frontiers in cell and developmental biology · 2022Review
- Synaptic tau: A pathological or physiological phenomenon?Acta neuropathologica communications · 2021Review
- Role of Microglia in Regulating Cholesterol and Tau Pathology in Alzheimer's Disease.Cellular and molecular neurobiology · 2021Review
- Nutrient transceptors physically interact with the yeast S6/protein kinase B homolog, Sch9, a TOR kinase target.The Biochemical journal · 2021Article
- Single-cell epigenomic analyses implicate candidate causal variants at inherited risk loci for Alzheimer's and Parkinson's diseases.Nature genetics · 2020Article
- Upregulation of RIN3 induces endosomal dysfunction in Alzheimer's disease.Translational neurodegeneration · 2020Article
- Molecular structure in biomolecular condensates.Current opinion in structural biology · 2020Review
- Article
- CD2-associated protein (CD2AP) overexpression accelerates amyloid precursor protein (APP) transfer from early endosomes to the lysosomal degradation pathway.The Journal of biological chemistry · 2019Article
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
CD2AP is an adaptor protein involved in membrane trafficking, with essential roles in maintaining podocyte function within the kidney glomerulus. CD2AP contains three Src homology 3 (SH3) domains that mediate multiple protein-protein interactions. However, a detailed comparison of the molecular binding preferences of each SH3 remained unexplored, as well as the discovery of novel interactors. Thus, we studied the binding properties of each SH3 domain to the known interactor Casitas B-lineage lymphoma protein (c-CBL), conducted a peptide array screen based on the recognition motif PxPxPR and identified 40 known or novel candidate binding proteins, such as RIN3, a RAB5-activating guanine nucleotide exchange factor. CD2AP SH3 domains 1 and 2 generally bound with similar characteristics and specificities, whereas the SH3-3 domain bound more weakly to most peptide ligands tested yet recognized an unusually extended sequence in ALG-2-interacting protein X (ALIX). RIN3 peptide scanning arrays revealed two CD2AP binding sites, recognized by all three SH3 domains, but SH3-3 appeared non-functional in precipitation experiments. RIN3 recruited CD2AP to RAB5a-positive early endosomes via these interaction sites. Permutation arrays and isothermal titration calorimetry data showed that the preferred binding motif is Px(P/A)xPR. Two high-resolution crystal structures (1.65 and 1.11 Å) of CD2AP SH3-1 and SH3-2 solved in complex with RIN3 epitopes 1 and 2, respectively, indicated that another extended motif is relevant in epitope 2. In conclusion, we have discovered novel interaction candidates for CD2AP and characterized subtle yet significant differences in the recognition preferences of its three SH3 domains for c-CBL, ALIX, and RIN3.
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