Affinage

CD2AP

CD2-associated protein · UniProt Q9Y5K6

Length
639 aa
Mass
71.5 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD2AP is a multi-SH3-domain scaffolding protein that organizes signaling complexes at membrane-cytoskeleton interfaces, functioning in podocyte slit diaphragm integrity, receptor tyrosine kinase endocytosis, vesicle trafficking, cell adhesion, and synaptic proteostasis. At the slit diaphragm, CD2AP bridges nephrin, podocin, and the actin cytoskeleton, gates TGF-β1–induced dendrin nuclear translocation and cathepsin L expression to control podocyte survival, and activates PI3K/AKT antiapoptotic signaling through direct interaction with TβRI (PMID:11733379, PMID:11733557, PMID:21911934, PMID:19679673). CD2AP also caps barbed ends of actin filaments to stabilize adherens junctions, enhances c-Cbl–mediated ubiquitination and endocytic degradation of receptor tyrosine kinases including VEGFR-1 and Ret51, regulates GLUT4 vesicle trafficking and insulin-stimulated glucose uptake, and modulates TCR signal duration in T cells (PMID:24322428, PMID:15001553, PMID:24425877, PMID:26546360, PMID:29734372). In neurons, CD2AP controls synaptic vesicle recycling, synaptic protein turnover via the ubiquitin-proteasome system, and calcium homeostasis, and its neuronal loss activates p38 MAPK leading to tau hyperphosphorylation and cognitive impairment (PMID:31412248, PMID:39696695).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 2001 High

    Establishing that CD2AP is a core slit diaphragm scaffolding protein resolved the question of how nephrin signaling is linked to the podocyte cytoskeleton, revealing that CD2AP binds the nephrin cytoplasmic tail and forms a ternary complex with podocin in lipid rafts.

    Evidence Immunoelectron microscopy, co-IP, and GST pull-down from podocyte cell lines and glomerular extracts

    PMID:11733379 PMID:11733557

    Open questions at the time
    • Stoichiometry of the nephrin–CD2AP–podocin complex unresolved
    • Dynamic regulation of complex assembly not addressed
  2. 2003 Medium

    Defining the antagonistic relationship between CD2AP and CIN85 at the CD2 cytoplasmic tail established that these paralogous adaptors have opposing roles in T cell adhesion and polarization, raising the broader principle that their balance tunes signaling output.

    Evidence Interaction trap cloning, co-localization, and T cell functional assays

    PMID:12618476

    Open questions at the time
    • Mechanism of antagonism between CD2AP and CIN85 not molecularly defined
    • No structural basis for differential target recognition
  3. 2004 High

    Demonstrating that CD2AP bridges c-Cbl to activated VEGFR-1 and promotes its ubiquitination and internalization established CD2AP as a general adaptor for Cbl-dependent receptor tyrosine kinase endocytosis.

    Evidence Co-IP, dominant-negative overexpression, internalization and ubiquitination assays

    PMID:15001553

    Open questions at the time
    • Whether CD2AP recruits Cbl to all RTKs or only specific subsets unclear
    • Structural basis for CD2AP–Cbl–RTK ternary complex unknown
  4. 2005 High

    Live imaging of CD2AP on cortactin/F-actin–positive endosomal structures with rapid FRAP turnover linked CD2AP to actin-dependent endosomal sorting, moving its role beyond static scaffolding.

    Evidence Confocal time-lapse microscopy, FRAP, Rab4 co-localization in podocytes

    PMID:15956777

    Open questions at the time
    • Cargo specificity of CD2AP-dependent endosomal sorting not identified
    • How CD2AP turnover is regulated at endosomes unknown
  5. 2006 High

    Bigenic haploinsufficiency between Cd2ap and Fyn or synaptopodin causing spontaneous proteinuria established a genetic interaction network at the slit diaphragm and demonstrated that partial loss of CD2AP sensitizes to glomerular disease.

    Evidence Bigenic heterozygous mouse models, co-IP, epistasis analysis

    PMID:16628251

    Open questions at the time
    • Molecular mechanism by which reduced CD2AP plus Fyn or synaptopodin triggers FSGS not delineated
    • Human genetic confirmation of digenic inheritance lacking
  6. 2007 High

    Identifying dendrin as a dual-function molecule that binds CD2AP/nephrin at the slit diaphragm but translocates to the nucleus upon injury to drive apoptosis revealed a signaling relay gated by CD2AP.

    Evidence Co-IP, immunofluorescence, nuclear import and apoptosis assays

    PMID:17537921

    Open questions at the time
    • Signal that triggers dendrin release from the CD2AP complex not fully defined
    • Transcriptional targets of nuclear dendrin beyond CatL unclear
  7. 2007 High

    Showing that CIN85 upregulation in CD2AP-null podocytes impairs RTK signaling, and that CIN85 knockdown rescues PI3K/AKT and ERK output, quantified the CD2AP/CIN85 balance as a determinant of podocyte survival signaling.

    Evidence CD2AP−/− podocytes, siRNA rescue of CIN85, growth factor stimulation and signaling assays

    PMID:17213204

    Open questions at the time
    • Mechanism by which CIN85 is upregulated upon CD2AP loss not identified
    • Whether this balance operates in non-podocyte contexts untested
  8. 2008 High

    Drosophila Cindr linking IgCAM adhesion receptors and E-cadherin to actin-capping proteins demonstrated an evolutionarily conserved role for CD2AP in coupling adhesion receptors to barbed-end actin dynamics.

    Evidence Genetic loss-of-function in Drosophila, co-IP, immunofluorescence

    PMID:18362180

    Open questions at the time
    • Whether mammalian CD2AP recruits the same capping protein heterodimer at adherens junctions untested at this point
  9. 2009 High

    Direct binding of CD2AP to TβRI and its requirement for TβRI–p85 interaction activating PI3K/AKT (independently of Smad2/3) uncovered a non-canonical TGF-β survival pathway in podocytes that depends on CD2AP scaffolding.

    Evidence Co-IP, CD2AP-deficient cell lines and genetic mouse models

    PMID:19679673

    Open questions at the time
    • Whether CD2AP discriminates between TβRI and TβRII binding unknown
    • Structural basis for CD2AP–TβRI interaction not determined
  10. 2011 High

    Elucidating a feed-forward loop in which CD2AP loss permits dendrin nuclear translocation, cathepsin L induction, and cathepsin L-mediated proteolysis of CD2AP itself, dynamin, and synaptopodin provided a complete molecular cascade from slit diaphragm disassembly to podocyte death.

    Evidence Knockout mice, nuclear fractionation, in vitro proteolysis, cell biological assays

    PMID:21911934

    Open questions at the time
    • Whether the CatL feedback loop is active in human FSGS not directly shown
    • Kinetics and regulation of CatL-mediated CD2AP cleavage in vivo uncharacterized
  11. 2011 Medium

    NMR structural characterization of all three CD2AP SH3 domains revealed that SH3-A is exceptionally thermostable, providing a structural basis for its role as the primary target-binding domain.

    Evidence NMR spectroscopy and differential scanning calorimetry

    PMID:21519904

    Open questions at the time
    • Functional significance of SH3-A thermostability not experimentally validated in cells
    • No co-crystal structures with full-length physiological targets
  12. 2012 High

    Discovery that CD2AP/SHIP1 inhibits Cbl E3 ligase activity to sustain ITAM signaling in plasmacytoid dendritic cells expanded CD2AP's role from a Cbl co-activator (in RTK degradation) to a context-dependent Cbl inhibitor.

    Evidence IP/mass spectrometry, siRNA knockdown, ubiquitination assays in pDCs

    PMID:22706086

    Open questions at the time
    • Molecular switch determining whether CD2AP promotes or inhibits Cbl activity not identified
  13. 2012 High

    Identification of a septin 7–CD2AP–nephrin complex controlling GLUT4 storage vesicle trafficking and glucose uptake connected the slit diaphragm scaffold to metabolic regulation.

    Evidence Co-IP, siRNA knockdown, subcellular fractionation, glucose uptake assay

    PMID:22809625

    Open questions at the time
    • Whether insulin directly modulates the septin 7–CD2AP interaction unknown
    • In vivo metabolic consequence of podocyte GLUT4 missorting not characterized
  14. 2013 High

    In vitro reconstitution demonstrating that CD2AP directly caps actin filament barbed ends and is required for adherens junction actin stability and adhesive strength established a direct biochemical activity beyond scaffolding.

    Evidence In vitro actin reconstitution, cross-linking, siRNA knockdown, mechanical stress assays

    PMID:24322428

    Open questions at the time
    • Whether capping activity requires dimerization or co-factors in vivo unknown
    • Regulation of capping versus scaffolding modes not addressed
  15. 2013 High

    Biophysical demonstration that CD2AP SH3-A forms distinct dimeric binding modes (type I and type II) with CD2 versus Cbl-b revealed how a single SH3 domain generates signaling diversity through multimeric complex formation.

    Evidence NMR, ITC, and SAXS

    PMID:23663663

    Open questions at the time
    • Whether these multimeric modes occur in intact cellular complexes not shown
    • Allosteric coupling between SH3 domains during multivalent binding unexplored
  16. 2014 High

    Demonstrating that CD2AP SH3 domains selectively enhance Cbl-3/c-mediated ubiquitination of Ret51 (but not Ret9) defined isoform-selective RTK degradation as a CD2AP function.

    Evidence siRNA, Co-IP, ubiquitination assays, domain deletion/mutagenesis

    PMID:24425877

    Open questions at the time
    • Structural basis for Ret51 versus Ret9 discrimination by CD2AP not defined
  17. 2015 High

    Linking CD2AP to GGA2, clathrin recycling, and insulin-stimulated GLUT4 trafficking (with CD2AP−/− podocytes failing to increase glucose uptake) provided the trafficking mechanism underlying the earlier septin 7 observation.

    Evidence Co-IP, live-cell imaging, subcellular fractionation, glucose uptake in CD2AP−/− podocytes

    PMID:26546360

    Open questions at the time
    • Whether CD2AP–GGA2 interaction is relevant in adipocytes or muscle cells unknown
  18. 2015 Medium

    Showing that CD2AP-deficient mice (with kidney rescue) have reduced blood-brain barrier integrity independent of nephrotic syndrome established a CNS-intrinsic role for CD2AP.

    Evidence CD2AP−/− mice with kidney-specific rescue transgene, sodium fluorescein extravasation

    PMID:26358779

    Open questions at the time
    • Cell type mediating BBB defect (endothelial, pericyte, astrocyte) not identified
    • Molecular mechanism at the BBB not defined
  19. 2016 High

    Discovery that CD2AP complexes with TrkA and p85 and regulates NGF/AKT signaling through Rab5+ signaling endosomes to control axonal arborization extended CD2AP's RTK-adaptor function to neurotrophin signaling.

    Evidence Co-IP, siRNA, overexpression, neurite outgrowth and signaling assays

    PMID:27076424

    Open questions at the time
    • Whether CD2AP regulates other Trk family receptors untested
    • In vivo neuronal phenotype in CD2AP knockout brain not examined at this stage
  20. 2017 High

    Demonstrating that CD2AP directly binds ICAM-1 and is required for ICAM-1-triggered PI3K/Rac1 activation and cortactin recruitment in endothelial cells, with CD2AP loss shifting leukocyte transmigration from paracellular to transcellular, defined CD2AP as a mechanosensitive regulator of endothelial barrier function.

    Evidence Co-IP, siRNA, force application on ICAM-1, Rac1 and migration assays

    PMID:28484055

    Open questions at the time
    • Whether ICAM-1–CD2AP interaction occurs in other cell types unknown
    • Structural interface between CD2AP and ICAM-1 not mapped
  21. 2018 Medium

    Conditional knockout in CD4 T cells showing that CD2AP limits TCR signal duration and suppresses Tfh differentiation during chronic viral infection identified CD2AP as an immune checkpoint modulator distinct from CIN85.

    Evidence T cell-specific conditional knockout, LCMV infection, TCR signaling and Tfh assays

    PMID:29734372

    Open questions at the time
    • Molecular target through which CD2AP dampens TCR signaling not identified
    • Relevance to human chronic infections or autoimmunity not tested
  22. 2019 High

    Cross-species rescue experiments showing that VEGF-A–induced Y10 phosphorylation of CD2AP's SH3-1 domain is essential for glomerular barrier function, despite Y10A mutation enhancing nephrin binding, revealed a counterintuitive regulatory switch where phosphorylation tunes affinity to enable dynamic slit diaphragm remodeling.

    Evidence Site-directed mutagenesis, phospho-specific antibodies, zebrafish and Drosophila rescue

    PMID:31235616

    Open questions at the time
    • Kinase(s) responsible for Y10 phosphorylation in vivo not confirmed beyond VEGF-A context
    • Effect of Y10 phosphorylation on non-nephrin partners unknown
  23. 2019 High

    Demonstrating conserved synaptic phenotypes across Drosophila cindr mutants, Cd2ap null mice, and human brain tissue—including impaired vesicle recycling, altered ubiquitin-proteasome-mediated turnover of Synapsin and PMCA, and reduced cytosolic calcium—established CD2AP as a synaptic proteostasis regulator with relevance to neurodegeneration.

    Evidence Genetic mutants in fly and mouse, co-IP, electrophysiology, proteomics, calcium imaging, human postmortem correlation

    PMID:31412248

    Open questions at the time
    • Whether synaptic defects are cell-autonomous in mammalian neurons not fully resolved
    • Direct proteasome target of CD2AP regulation not identified
  24. 2019 High

    NMR characterization showing bivalent binding of CD2AP SH3-A and SH3-C to chikungunya nsP3 HVD, with SH3-B left free, defined a cooperative multidomain binding mode exploited by an alphavirus for replication.

    Evidence NMR chemical shift perturbation, mutagenesis, viral replication assays

    PMID:31493651

    Open questions at the time
    • Whether other RNA viruses exploit the same bivalent SH3 mechanism untested
    • Role of SH3-B during viral infection not identified
  25. 2024 High

    Neuron-specific Cd2ap deletion in APP/PS1 mice causing p38 MAPK-dependent tau hyperphosphorylation, synaptic loss, and cognitive decline—rescued by p38 inhibition—provided the first direct in vivo evidence that CD2AP loss drives Alzheimer's-relevant pathology through a defined kinase cascade.

    Evidence Conditional neuronal knockout in APP/PS1 mice, immunoblotting, electrophysiology, behavioral tests, p38 inhibitor rescue

    PMID:39696695

    Open questions at the time
    • Whether p38 activation is the primary or sole pathway downstream of neuronal CD2AP loss not established
    • Mechanism connecting CD2AP to p38 MAPK activation not molecularly defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CD2AP's barbed-end capping activity, SH3-mediated scaffolding, and phosphoregulation are coordinated in a single molecule to switch between its diverse cellular roles—podocyte slit diaphragm maintenance, RTK endocytosis, synaptic proteostasis, and immune signaling—remains the central open question.
  • No full-length CD2AP structure available
  • Allosteric communication between the three SH3 domains and the C-terminal coiled-coil region unexplored
  • Cell-type-specific regulatory mechanisms controlling CD2AP mode-switching not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 8 GO:0098772 molecular function regulator activity 5 GO:0008092 cytoskeletal protein binding 4
Localization
GO:0005886 plasma membrane 5 GO:0005856 cytoskeleton 4 GO:0005768 endosome 2 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-168256 Immune System 3
Partners
CBLFYNICAM1NPHS1NPHS2NTRK1SYNPOTGFBR1
Complex memberships
CD2AP–c-Cbl RTK endocytic complexnephrin–podocin–CD2AP slit diaphragm complexseptin 7–CD2AP–nephrin complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CD2AP localizes to the slit diaphragm in podocytes and interacts with nephrin via a novel C-terminal domain of CD2AP that binds the C-terminal portion of the nephrin cytoplasmic domain, as demonstrated by immunoelectron microscopy and co-immunoprecipitation from podocyte cell lines. Immunoelectron microscopy, co-immunoprecipitation, domain mapping The American Journal of Pathology High 11733379
2001 Podocin associates with CD2AP via its C-terminal domain and with nephrin, forming a ternary complex in lipid rafts at the slit diaphragm; direct interaction between podocin and CD2AP was confirmed in vitro by GST pull-down and co-immunoprecipitation from glomerular extracts. GST pull-down, co-immunoprecipitation, immunoelectron microscopy The Journal of Clinical Investigation High 11733557
2006 CD2AP associates with Fyn and synaptopodin in podocytes; bigenic heterozygosity of Cd2ap with either Synpo or Fyn (but not Neph1) leads to spontaneous proteinuria and FSGS-like glomerular damage, establishing a genetic and physical interaction network. Co-immunoprecipitation, bigenic mouse models, epistasis analysis The Journal of Clinical Investigation High 16628251
2004 CD2AP forms a ternary complex with c-Cbl and activated Flt-1 (VEGFR-1) upon VEGF stimulation, and wild-type CD2AP (but not a dominant-negative form) enhances VEGF-stimulated internalization and ubiquitination of Flt-1, promoting receptor endocytosis and degradation. Co-immunoprecipitation, dominant-negative overexpression, internalization assay, ubiquitination assay FASEB Journal High 15001553
2007 Dendrin directly binds to both nephrin and CD2AP at the slit diaphragm; upon glomerular injury or high-dose TGF-β1 stimulation, dendrin relocates from the slit diaphragm to the nucleus where it enhances apoptosis. Co-immunoprecipitation, immunofluorescence, nuclear import assay, apoptosis assay Proceedings of the National Academy of Sciences High 17537921
2009 CD2AP C-terminal region directly interacts with the cytoplasmic tail of TGF-β receptor type I (TβRI) in a kinase-dependent manner, and CD2AP is required for the interaction between TβRI and the p85 subunit of PI3K, thereby activating the antiapoptotic PI3K/AKT pathway independently of Smad2/3 signaling. Co-immunoprecipitation, CD2AP-deficient cell lines, genetic mouse models Journal of the American Society of Nephrology High 19679673
2011 CD2AP regulates TGF-β1-dependent translocation of dendrin from the slit diaphragm to the nucleus, where dendrin acts as a transcription factor inducing cytosolic cathepsin L (CatL) expression; CatL then proteolyzed dynamin and synaptopodin, reorganizing the podocyte microfilament system. CD2AP itself is proteolyzed by CatL in a feedback loop promoting sustained CatL expression and podocyte apoptosis. Loss-of-function mouse models, nuclear fractionation, in vitro proteolysis assays, cell biological assays The Journal of Clinical Investigation High 21911934
2012 CD2AP forms a complex with SHIP1, and upon BDCA2 cross-linking in plasmacytoid dendritic cells, this CD2AP/SHIP1 complex associates with the E3 ubiquitin ligase Cbl at the plasma membrane and inhibits its E3 ubiquitin ligase activity, thereby preventing degradation of Syk and FcεRIγ and sustaining ITAM signaling. Immunoprecipitation/mass spectrometry, knockdown (siRNA), ubiquitination assay, immunofluorescence Journal of Immunology High 22706086
2012 Septin 7 forms a complex with CD2AP and nephrin in podocytes; depletion of septin 7 increases VAMP2-nephrin interaction and glucose uptake, indicating that the septin 7/CD2AP/nephrin complex regulates GLUT4 storage vesicle trafficking. Co-immunoprecipitation, siRNA knockdown, subcellular fractionation, 2-deoxy-D-glucose uptake assay Molecular Biology of the Cell High 22809625
2013 CD2AP (FSGS3) functions as a barbed-end actin-capping protein at the adherens junction; knockdown of CD2AP compromises actin stability and accumulation at the adherens junction, reducing adhesive strength and disrupting barrier function. In vitro reconstitution biochemistry, cross-linking approach, siRNA knockdown, mechanical stress assay The Journal of Cell Biology High 24322428
2005 In podocytes, CD2AP colocalizes with cortactin and F-actin on motile vesicular spots; FRAP shows high turnover of CD2AP (half-time <10 s) at these spots, which depend on actin polymerization and are associated with a late endosomal-sorting compartment (Rab4-positive), implicating CD2AP in endosomal sorting/trafficking via actin assembly regulation. Confocal time-lapse microscopy, FRAP, microinjection of fluorescent G-actin, endosomal marker co-localization American Journal of Physiology – Renal Physiology High 15956777
2007 CD2AP deficiency in podocytes leads to diminished signal initiation and termination via receptor tyrosine kinases (RTKs); CIN85 expression is increased in CD2AP-/- podocytes, and repression of CIN85 restores RTK signaling (PI3K/AKT and ERK), establishing the CD2AP/CIN85 balance as a determinant of RTK signaling in podocytes. CD2AP-/- mouse and cell models, growth factor stimulation, siRNA knockdown of CIN85, signaling pathway assays The Journal of Biological Chemistry High 17213204
2014 CD2AP enhances Cbl-3/c-mediated ubiquitination and degradation of Ret51 (but not Ret9) isoform specifically; the SH3 domains of CD2AP are sufficient for this activity, while the coiled-coil C-terminal domain is dispensable; Ret51 ubiquitination requires functional ring finger and TKB domains in Cbl-3/c. siRNA knockdown, co-immunoprecipitation, ubiquitination assay, domain deletion/mutagenesis, site-directed mutagenesis of ubiquitination sites The Journal of Biological Chemistry High 24425877
2015 CD2AP forms a complex with GGA2 (a clathrin adaptor that sorts Glut4 to storage vesicles), connects clathrin to actin in the perinuclear region, and is required for clathrin recycling back to trans-Golgi membranes; CD2AP-/- podocytes fail to increase glucose uptake in response to insulin and show perinuclear clustering of Glut4. Co-immunoprecipitation, live-cell imaging, subcellular fractionation, 2-deoxy-D-glucose uptake assay, CD2AP-/- podocytes Journal of Cell Science High 26546360
2016 CD2AP forms a complex with tankyrases; in the absence of CD2AP, tankyrase-mediated PARylation and Wnt/β-catenin signaling (LEF1, fibronectin) are increased in podocytes, identifying CD2AP as a regulator of the Wnt/β-catenin pathway through control of tankyrase PARylation activity. Co-immunoprecipitation, CD2AP-/- podocytes, tankyrase inhibitor, zebrafish model Cell Death & Disease Medium 27441654
2017 CD2AP in endothelial cells binds directly to the receptor ICAM-1 and is required for ICAM-1-mediated PI3K activation, F-actin and cortactin recruitment, and Rac1 activation; loss of CD2AP increases ICAM-1 clustering, neutrophil adhesion, and promotes transcellular over paracellular diapedesis. Co-immunoprecipitation, siRNA knockdown, force application on ICAM-1, Rac1 activation assay, neutrophil adhesion/transmigration assay Journal of Immunology High 28484055
2016 CD2AP forms a complex with TrkA and the PI3K regulatory subunit p85 in neurons; CD2AP levels positively regulate TrkA:p85 association and NGF signaling through AKT (but not ERK), and regulate long-range signaling through TrkA+/RAB5+ signaling endosomes, controlling axon arbor growth and collateral sprouting. Co-immunoprecipitation, siRNA knockdown, overexpression, neurite outgrowth assay, signaling assays The Journal of Neuroscience High 27076424
2019 In Drosophila, loss of cindr (CD2AP ortholog) impairs synapse maturation, synaptic vesicle recycling and release; Cindr associates with and genetically interacts with 14-3-3ζ, regulates the ubiquitin-proteasome system, and affects turnover of Synapsin and PMCA; loss of cindr elevates PMCA and reduces cytosolic calcium. Cd2ap null mice show conserved synaptic proteostasis defects, and CD2AP protein levels are inversely related to Synapsin abundance in human postmortem brains. Genetic loss-of-function (Drosophila mutants, Cd2ap null mice), co-immunoprecipitation, electrophysiology, proteomics, calcium measurements Cell Reports High 31412248
2019 VEGF-A stimulation induces tyrosine phosphorylation of CD2AP in podocytes; phosphorylation at Y10 in the SH3-1 domain is indispensable for CD2AP function in vivo (shown by cross-species rescue in zebrafish and Drosophila). Absence of Y10 phosphorylation enhances nephrin binding affinity to CD2AP but paradoxically impairs glomerular filtration barrier function. Isoelectric focusing, site-directed mutagenesis, phospho-specific antibodies, cross-species rescue (zebrafish, Drosophila), western blot Journal of the American Society of Nephrology High 31235616
2011 NMR structural characterization of all three SH3 domains of CD2AP reveals that the N-terminal SH3 domain (SH3-A) is the most stable SH3 domain characterized, due to a more extensive intramolecular interaction network; the high stability is proposed to be crucial for maintaining proper conformation for target interaction. NMR spectroscopy, differential scanning calorimetry (DSC), FoldX structure-based analysis Journal of Biomolecular NMR Medium 21519904
2007 NMR high-resolution structure of the CD2AP SH3-C domain was determined, revealing all canonical SH3 features including the polyproline-binding site. NMR spectroscopy, triple-resonance experiments, NOESY Journal of Biomolecular NMR Medium 17922258
2013 NMR, ITC, and SAXS characterization shows that CD2AP SH3-A forms a type II dimer with CD2 and both type I and type II dimeric complexes with Cbl-b, revealing multimeric and differential binding modes that generate signaling diversity. NMR spectroscopy, isothermal titration calorimetry (ITC), small-angle X-ray scattering (SAXS) The FEBS Journal High 23663663
2018 PAWS1 interacts dynamically with CD2AP at lamellae; CRISPR/Cas9 knockout of CD2AP in U2OS cells causes defects in F-actin organization, lamellipodial organization, and impairs cell migration, phenocopying PAWS1-knockout cells. CRISPR/Cas9 knockout, co-immunoprecipitation, confocal microscopy, live-cell imaging, migration assay Journal of Cell Science Medium 29175910
2008 Cindr (Drosophila CD2AP ortholog) links E-cadherin and Roughest (IgCAM adhesion receptor) to actin-capping proteins (capping protein alpha and beta); reducing cindr activity disrupts normal localization of E-cadherin and Roughest and causes defects in local cell movement and tissue patterning. Genetic loss-of-function (Drosophila), co-immunoprecipitation, immunofluorescence, co-localization The Journal of Cell Biology High 18362180
2010 CD2AP is recruited to EPEC actin pedestals in a manner dependent on Tir Y474 phosphorylation, and CD2AP functions as a novel component of EPEC pedestal formation; CD2AP co-localizes with the endocytic machinery (clathrin) in pedestals. Immunofluorescence, genetic knockout/knockdown, pedestal formation assay Infection and Immunity Medium 20515931
2006 CFBP (CIN85/CD2AP family binding protein) is phosphorylated at tyrosine 204 upon EGF stimulation; its proline-rich motif is recognized by one of the three SH3 domains of CD2AP, with binding affinity regulated by tyrosine phosphorylation; CFBP accelerates EGF receptor down-regulation by facilitating Cbl recruitment to the CD2AP/CIN85 complex. Proteomic phosphorylation screen, co-immunoprecipitation, EGF receptor internalization assay, overexpression The Journal of Biological Chemistry Medium 16895919
2015 CD2AP loss maintains blood-brain barrier integrity; CD2AP-deficient mice (with kidney-specific CD2AP transgene) show reduced blood-brain barrier integrity measured by sodium fluorescein extravasation, independent of nephrotic syndrome. CD2AP-/- mouse model with kidney-specific rescue transgene, sodium fluorescein extravasation assay, seizure latency measurement Human Molecular Genetics Medium 26358779
2018 In chronic LCMV infection, CD2AP in CD4 T cells suppresses follicular helper (Tfh) differentiation; CD2AP-deficient CD4 T cells show extended TCR signaling duration and enhanced cytokine production specifically under TH1 conditions, promoting Tfh differentiation and germinal center responses. CIN85 shows non-overlapping/antagonistic roles. T cell-specific conditional knockout, LCMV infection model, TCR signaling assays, Tfh differentiation assays PLOS Pathogens Medium 29734372
2005 CD2AP co-localizes with F-actin in the leading edges of migrating gastric epithelial cells and co-immunoprecipitates with E-cadherin upon HGF stimulation; intracellular injection of anti-CD2AP antibody significantly retards cell migration speed. Co-immunoprecipitation, immunofluorescence, intracellular antibody injection, migration assay Biochemical and Biophysical Research Communications Medium 15910750
2008 EGF recruits c-fos and JunD (AP-1 components) to an AP-1-like element in the CD2AP gene promoter, increasing CD2AP expression and suppressing angiotensin II-induced apoptosis in renal tubular epithelial cells; CD2AP knockdown attenuates the antiapoptotic effect of EGF. Promoter deletion/mutation analysis, EMSA, chromatin immunoprecipitation, siRNA knockdown, apoptosis assay Gene Medium 19095050
2024 CD2AP deficiency in neurons activates p38 MAPK signaling, leading to increased tau phosphorylation, synaptic injury, neuronal apoptosis, and cognitive impairment in APP/PS1 mice; pharmacological inhibition of p38 MAPK ameliorates these phenotypes. Neuron-specific Cd2ap conditional knockout in APP/PS1 mice, immunoblotting, immunofluorescence, electrophysiology, behavioral tests, p38 inhibitor treatment Translational Neurodegeneration High 39696695
2024 CD2AP interacts with TRIM5 and its overexpression increases TRIM5 levels and NF-κB activity in glioblastoma cells; CD2AP promotes GBM cell proliferation, migration, invasion, and resistance to apoptosis through the TRIM5-NF-κB axis. Co-immunoprecipitation, overexpression/knockdown, NF-κB activity assay, in vitro proliferation/invasion/apoptosis assays, in vivo tumorigenesis Cell Death & Disease Medium 39353894
2003 CD2AP (CMS) binds the same highly conserved segment of the CD2 cytoplasmic tail as CIN85/CD2BP3 via its SH3 domains; unlike CIN85/CD2BP3, CD2AP co-localizes with F-actin and binds p130Cas; CD2AP and CIN85 activities are antagonistic in T cell adhesion and polarization. Interaction trap cloning, co-localization studies, protein interaction assays, T cell functional assays International Immunology Medium 12618476
2019 CD2AP interacts with CHIKV nsP3 HVD via its SH3-A and SH3-C domains simultaneously (bivalent interaction), as determined by NMR; this increases binding affinity through cooperativity and leaves SH3-B available for other partners; BIN1, CD2AP, and SH3KBP1 play redundant roles in initiation of CHIKV replication. NMR spectroscopy, chemical shift perturbation, mutagenesis, viral replication assays Virology High 31493651

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nature genetics 1626 21460840
2005 Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology 1281 16037678
2001 Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. The Journal of clinical investigation 474 11733557
2001 CD2AP localizes to the slit diaphragm and binds to nephrin via a novel C-terminal domain. The American journal of pathology 226 11733379
2016 Cytoplasmic male sterility (CMS) in hybrid breeding in field crops. Plant cell reports 148 26905724
2017 The immature electrophysiological phenotype of iPSC-CMs still hampers in vitro drug screening: Special focus on IK1. Pharmacology & therapeutics 128 28986101
2000 CD2AP is expressed with nephrin in developing podocytes and is found widely in mature kidney and elsewhere. American journal of physiology. Renal physiology 128 10997929
2011 CD2AP in mouse and human podocytes controls a proteolytic program that regulates cytoskeletal structure and cellular survival. The Journal of clinical investigation 124 21911934
2006 Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin. The Journal of clinical investigation 122 16628251
2007 Focal segmental glomerulosclerosis in a patient homozygous for a CD2AP mutation. Kidney international 102 17713465
2006 Autocrine VEGF-A system in podocytes regulates podocin and its interaction with CD2AP. American journal of physiology. Renal physiology 102 16597608
2009 CD2AP mutations are associated with sporadic nephrotic syndrome and focal segmental glomerulosclerosis (FSGS). Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 94 19131354
2007 Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes apoptosis of podocytes. Proceedings of the National Academy of Sciences of the United States of America 81 17537921
2004 The c-Cbl/CD2AP complex regulates VEGF-induced endocytosis and degradation of Flt-1 (VEGFR-1). FASEB journal : official publication of the Federation of American Societies for Experimental Biology 78 15001553
2019 Deciphering Role of Wnt Signalling in Cardiac Mesoderm and Cardiomyocyte Differentiation from Human iPSCs: Four-dimensional control of Wnt pathway for hiPSC-CMs differentiation. Scientific reports 76 31852937
2022 Asperosaponin VI ameliorates the CMS-induced depressive-like behaviors by inducing a neuroprotective microglial phenotype in hippocampus via PPAR-γ pathway. Journal of neuroinflammation 72 35610721
1980 Cytoplasmic Reversion of cms-S in Maize: Association with a Transpositional Event. Science (New York, N.Y.) 70 17747231
2010 The mitochondrial gene orfH79 plays a critical role in impairing both male gametophyte development and root growth in CMS-Honglian rice. BMC plant biology 64 20576097
2013 FSGS3/CD2AP is a barbed-end capping protein that stabilizes actin and strengthens adherens junctions. The Journal of cell biology 63 24322428
2008 The Drosophila CD2AP/CIN85 orthologue Cindr regulates junctions and cytoskeleton dynamics during tissue patterning. The Journal of cell biology 59 18362180
2013 Gender differences in CMS and the effects of antidepressant venlafaxine in rats. Neurochemistry international 58 24090637
2019 The role of CD2AP in the Pathogenesis of Alzheimer's Disease. Aging and disease 54 31440393
2014 Analyzing 54,936 Samples Supports the Association Between CD2AP rs9349407 Polymorphism and Alzheimer's Disease Susceptibility. Molecular neurobiology 54 25092125
2012 Septin 7 forms a complex with CD2AP and nephrin and regulates glucose transporter trafficking. Molecular biology of the cell 50 22809625
2022 Transient secretion of VEGF protein from transplanted hiPSC-CMs enhances engraftment and improves rat heart function post MI. Molecular therapy : the journal of the American Society of Gene Therapy 45 35982619
2022 Use of Human iPSC-CMs in Nonclinical Regulatory Studies for Cardiac Safety Assessment. Toxicological sciences : an official journal of the Society of Toxicology 43 36099065
2020 The Emergence of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) as a Platform to Model Arrhythmogenic Diseases. International journal of molecular sciences 42 31963859
2003 Alloplasmic male sterility in Brassica napus (CMS 'Tournefortii-Stiewe') is associated with a special gene arrangement around a novel atp9 gene. Molecular genetics and genomics : MGG 41 12898218
2015 The Alzheimer's disease risk factor CD2AP maintains blood-brain barrier integrity. Human molecular genetics 40 26358779
2012 CD2AP/SHIP1 complex positively regulates plasmacytoid dendritic cell receptor signaling by inhibiting the E3 ubiquitin ligase Cbl. Journal of immunology (Baltimore, Md. : 1950) 40 22706086
2009 TbetaRI independently activates Smad- and CD2AP-dependent pathways in podocytes. Journal of the American Society of Nephrology : JASN 39 19679673
2005 Association of CD2AP with dynamic actin on vesicles in podocytes. American journal of physiology. Renal physiology 39 15956777
2003 CD2BP3, CIN85 and the structurally related adaptor protein CMS bind to the same CD2 cytoplasmic segment, but elicit divergent functional activities. International immunology 39 12618476
2018 Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus. Viruses 38 29702546
2006 The relationship among nephrin, podocin, CD2AP, and alpha-actinin might not be a true 'interaction' in podocyte. Kidney international 38 16501493
2007 CD2AP/CIN85 balance determines receptor tyrosine kinase signaling response in podocytes. The Journal of biological chemistry 36 17213204
1995 URF13, a ligand-gated, pore-forming receptor for T-toxin in the inner membrane of cms-T mitochondria. Journal of bioenergetics and biomembranes 36 8595979
2021 Angiopoietin-1 enhanced myocyte mitosis, engraftment, and the reparability of hiPSC-CMs for treatment of myocardial infarction. Cardiovascular research 35 32666104
1994 Sequencing, processing, and localization of the petunia CMS-associated mitochondrial protein. The Plant journal : for cell and molecular biology 34 8019587
2020 Electrical stimulation applied during differentiation drives the hiPSC-CMs towards a mature cardiac conduction-like cells. Biochemical and biophysical research communications 32 32962862
2019 cindr, the Drosophila Homolog of the CD2AP Alzheimer's Disease Risk Gene, Is Required for Synaptic Transmission and Proteostasis. Cell reports 32 31412248
2018 Transcriptome, cytological and biochemical analysis of cytoplasmic male sterility and maintainer line in CMS-D8 cotton. Plant molecular biology 32 30066309
2018 PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP. Journal of cell science 29 29175910
2018 Comparative Transcriptome Analysis between Fertile and CMS Flower Buds in Wucai (Brassica campestris L.). BMC genomics 29 30541424
2017 Genome-wide comparative transcriptome analysis of CMS-D2 and its maintainer and restorer lines in upland cotton. BMC genomics 29 28595569
2016 The Adaptor Protein CD2AP Is a Coordinator of Neurotrophin Signaling-Mediated Axon Arbor Plasticity. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 27076424
2006 CFBP is a novel tyrosine-phosphorylated protein that might function as a regulator of CIN85/CD2AP. The Journal of biological chemistry 28 16895919
2020 Single-cell analysis reveals the purification and maturation effects of glucose starvation in hiPSC-CMs. Biochemical and biophysical research communications 25 33279112
2022 Green engineering of TMC-CMS nanoparticles decorated graphene sheets for targeting M. tuberculosis. Carbohydrate polymers 24 36657855
2020 CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly. Molecular carcinogenesis 24 31989722
2009 Analysis of recessive CD2AP and ACTN4 mutations in steroid-resistant nephrotic syndrome. Pediatric nephrology (Berlin, Germany) 24 19956976
2020 Genetic Association of FERMT2, HLA-DRB1, CD2AP, and PTK2B Polymorphisms With Alzheimer's Disease Risk in the Southern Chinese Population. Frontiers in aging neuroscience 23 32116649
2019 Tyrosine Phosphorylation of CD2AP Affects Stability of the Slit Diaphragm Complex. Journal of the American Society of Nephrology : JASN 22 31235616
2019 Viral expression of a SERCA2a-activating PLB mutant improves calcium cycling and synchronicity in dilated cardiomyopathic hiPSC-CMs. Journal of molecular and cellular cardiology 22 31751570
2015 Diabetic conditions downregulate the expression of CD2AP in podocytes via PI3-K/Akt signalling. Diabetes/metabolism research and reviews 21 24846128
2022 Chronic Cardiotoxicity Assays Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs). International journal of molecular sciences 20 35328619
2021 Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer. Cancers 20 34638407
2021 Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer's disease. Brain pathology (Zurich, Switzerland) 19 34514662
2019 Structural characterization and biological function of bivalent binding of CD2AP to intrinsically disordered domain of chikungunya virus nsP3 protein. Virology 19 31493651
2023 ROS accumulation-induced tapetal PCD timing changes leads to microspore abortion in cotton CMS lines. BMC plant biology 18 37308826
2022 Empagliflozin and Dapagliflozin Increase Na+ and Inward Rectifier K+ Current Densities in Human Cardiomyocytes Derived from Induced Pluripotent Stem Cells (hiPSC-CMs). Cells 18 36496967
2021 Colony-stimulating factor 3 signaling in colon and rectal cancers: Immune response and CMS classification in TCGA data. PloS one 18 33606788
2018 The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular helper T cells during chronic LCMV infection. PLoS pathogens 18 29734372
2017 Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy. Scientific reports 17 28814739
2016 A CD2AP Mutation Associated with Focal Segmental Glomerulosclerosis in Young Adulthood. Clinical medicine insights. Case reports 17 26997877
2016 Tankyrase inhibition aggravates kidney injury in the absence of CD2AP. Cell death & disease 17 27441654
2016 Allelism analysis of BrRfp locus in different restorer lines and map-based cloning of a fertility restorer gene, BrRfp1, for pol CMS in Chinese cabbage (Brassica rapa L.). TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 17 27896366
2015 Lack of CD2AP disrupts Glut4 trafficking and attenuates glucose uptake in podocytes. Journal of cell science 17 26546360
2021 Designing a 3D Printing Based Auxetic Cardiac Patch with hiPSC-CMs for Heart Repair. Journal of cardiovascular development and disease 16 34940527
2010 Role for CD2AP and other endocytosis-associated proteins in enteropathogenic Escherichia coli pedestal formation. Infection and immunity 16 20515931
2007 Mitochondrial nad2 gene is co-transcripted with CMS-associated orfB gene in cytoplasmic male-sterile stem mustard (Brassica juncea). Molecular biology reports 16 18046626
1995 Expression of the CMS-associated urfS sequence in transgenic petunia and tobacco. Plant molecular biology 16 7787190
2024 Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) for modeling cardiac arrhythmias: strengths, challenges and potential solutions. Frontiers in physiology 15 39328831
2017 Endothelial CD2AP Binds the Receptor ICAM-1 To Control Mechanosignaling, Leukocyte Adhesion, and the Route of Leukocyte Diapedesis In Vitro. Journal of immunology (Baltimore, Md. : 1950) 15 28484055
2024 CD2AP promotes the progression of glioblastoma multiforme via TRIM5-mediated NF-kB signaling. Cell death & disease 14 39353894
2021 Image-based assessment of extracellular mucin-to-tumor area predicts consensus molecular subtypes (CMS) in colorectal cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 14 34475526
2017 Inhibition of SHIP2 in CD2AP-deficient podocytes ameliorates reactive oxygen species generation but aggravates apoptosis. Scientific reports 14 28878342
2024 miR-590-3p Overexpression Improves the Efficacy of hiPSC-CMs for Myocardial Repair. JACC. Basic to translational science 13 38984045
2023 High-throughput longitudinal electrophysiology screening of mature chamber-specific hiPSC-CMs using optical mapping. iScience 13 37416454
2021 Anthracycline-Induced Cardiotoxicity: Molecular Insights Obtained from Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs). The AAPS journal 13 33719006
2020 Age-Dependent Maturation of iPSC-CMs Leads to the Enhanced Compartmentation of β2AR-cAMP Signalling. Cells 13 33053822
2019 Integrated Methylome and Transcriptome Analysis between the CMS-D2 Line ZBA and Its Maintainer Line ZB in Upland Cotton. International journal of molecular sciences 13 31810186
2018 Recessive mutation in CD2AP causes focal segmental glomerulosclerosis in humans and mice. Kidney international 13 30612599
2020 miR-188-5p Promotes Tumor Growth by Targeting CD2AP Through PI3K/AKT/mTOR Signaling in Children with Acute Promyelocytic Leukemia. OncoTargets and therapy 12 32764959
2019 Excessive apoptosis of podocytes caused by dysregulation of microRNA-182-5p and CD2AP confers to an increased risk of diabetic nephropathy. Journal of cellular biochemistry 12 31131477
2018 iTRAQ-Based Proteomic Analysis of Ogura-CMS Cabbage and Its Maintainer Line. International journal of molecular sciences 12 30326665
2014 CD2-associated protein (CD2AP) enhances casitas B lineage lymphoma-3/c (Cbl-3/c)-mediated Ret isoform-specific ubiquitination and degradation via its amino-terminal Src homology 3 domains. The Journal of biological chemistry 12 24425877
2012 Interactions between Drosophila IgCAM adhesion receptors and cindr, the Cd2ap/Cin85 ortholog. Developmental dynamics : an official publication of the American Association of Anatomists 12 23027549
2011 Solution structure, dynamics and thermodynamics of the three SH3 domains of CD2AP. Journal of biomolecular NMR 12 21519904
2007 The high resolution NMR structure of the third SH3 domain of CD2AP. Journal of biomolecular NMR 12 17922258
2005 CD2AP contributes to cell migration and adhesion in cultured gastric epithelium. Biochemical and biophysical research communications 12 15910750
1999 Nuclear genes from Tx CMS maintainer lines are unable to maintain atp6 RNA editing in any anther cell-type in the sorghum bicolor A3 cytoplasm. Current genetics 12 10447596
2021 Blebbistatin protects iPSC-CMs from hypercontraction and facilitates automated patch-clamp based electrophysiological study. Stem cell research 11 34638057
2018 Cytological and iTRAQ-based quantitative proteomic analyses of hau CMS in Brassica napus L. Journal of proteomics 11 30385414
2024 From Subtypes to Solutions: Integrating CMS Classification with Precision Therapeutics in Colorectal Cancer. Current treatment options in oncology 10 39589648
2024 CD2AP deficiency aggravates Alzheimer's disease phenotypes and pathology through p38 MAPK activation. Translational neurodegeneration 10 39696695
2022 Chloroplast Genes Are Involved in The Male-Sterility of K-Type CMS in Wheat. Genes 10 35205355
2013 Multimeric and differential binding of CIN85/CD2AP with two atypical proline-rich sequences from CD2 and Cbl-b*. The FEBS journal 10 23663663
2008 EGF-recruited JunD/c-fos complexes activate CD2AP gene promoter and suppress apoptosis in renal tubular epithelial cells. Gene 10 19095050
1998 Microsensor-aided measurements of cellular signalling and metabolism on tumor cells. The cell monitoring system (cms(R)). Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 10 9701728