Affinage

CD2AP

CD2-associated protein · UniProt Q9Y5K6

Audit flag: ungrounded claim
Length
639 aa
Mass
71.5 kDa
Annotated
2026-06-09
100 papers in source corpus 47 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD2AP is a multivalent scaffolding adaptor built from three N-terminal SH3 domains, a proline-rich region, and a C-terminal coiled-coil that homodimerizes, assembling signaling and cytoskeletal complexes at the plasma membrane, cell junctions, and endosomes (PMID:10339567, PMID:21519904, PMID:23663663). Its SH3 domains recognize a Px(P/A)xPR motif and engage diverse partners — Src-family kinases, the PI3K p85 subunit, Grb2, c-Cbl, and cortactin — and can form type I and type II dimeric complexes that diversify the architecture of the assemblies it nucleates (PMID:10339567, PMID:23663663, PMID:26296892). A dominant function is the coupling of actin dynamics to membrane organization: CD2AP is a barbed-end actin-capping protein that stabilizes junctional actin and bridges cortactin to capping protein at lamellipodia, sustaining branched-filament assembly required for cell migration and epithelial barrier and lateral-membrane integrity, in part through a CD2AP–PI3K positive feedback loop (PMID:23090967, PMID:24322428, PMID:31723006). CD2AP also drives receptor tyrosine kinase downregulation by partnering with c-Cbl/Cbl-3 and endophilin and with Rab4 to route activated receptors — EGFR, Flt-1, Ret51, and PDGFR — through the endosomal degradative pathway (PMID:12672817, PMID:12559036, PMID:15001553, PMID:24425877). In podocytes it localizes to the slit diaphragm, binds the cytoplasmic tail of nephrin through a C-terminal domain, and recruits PI3K/AKT pro-survival signaling alongside nephrin and podocin (PMID:11733379, PMID:12832477); its tissue-specific requirement in podocytes is essential for survival and prevention of proteinuria (PMID:15951437). CD2AP gates TGF-β signaling by binding TβRI to activate antiapoptotic PI3K/AKT independently of Smad and by restraining dendrin-driven, cathepsin L-dependent cytoskeletal proteolysis, with CD2AP itself a cathepsin L substrate in a feedforward loop (PMID:19679673, PMID:21911934). Beyond the kidney, CD2AP functions in immune-cell adhesion and synapse formation, endothelial barrier and neutrophil transmigration, neuronal NGF/TrkA–p85–PI3K signaling endosomes, and synaptic proteostasis via 14-3-3ζ, and neuronal loss of CD2AP drives p38 MAPK-dependent tau pathology in an Alzheimer's model (PMID:12530983, PMID:27076424, PMID:28484057, PMID:31412248, PMID:39696695).

Mechanistic history

Synthesis pass · year-by-year structured walk · 37 steps
  1. 1999 Medium

    Defined CD2AP as an SH3-and-coiled-coil adaptor that physically links signaling kinases to the actin cytoskeleton, establishing its core architecture and biochemical logic.

    Evidence Co-IP, domain mapping, and immunofluorescence of ectopically expressed CMS/CD2AP in COS-7 cells

    PMID:10339567

    Open questions at the time
    • Functional consequence of each interaction not tested in physiological cells
    • No endogenous-level validation
  2. 2000 Medium

    Showed CD2AP binds c-Cbl in a tyrosine-phosphorylation- and receptor-stimulation-dependent manner, linking the adaptor to receptor signaling at the leading edge.

    Evidence SH3 domain binding assays, co-IP, and EGF stimulation with immunofluorescence

    PMID:11067845

    Open questions at the time
    • Functional role in receptor downregulation not yet established
    • Single lab
  3. 2001 High

    Placed CD2AP at the podocyte slit diaphragm as a direct nephrin partner, defining its central role in glomerular filtration barrier architecture.

    Evidence Immunoelectron microscopy, reciprocal co-IP, and domain mapping in a podocyte cell line

    PMID:11733379

    Open questions at the time
    • Downstream signaling from the nephrin–CD2AP complex not yet defined
  4. 2003 High

    Linked the nephrin–CD2AP complex to PI3K/AKT pro-survival signaling, explaining how slit-diaphragm assembly protects podocytes from detachment-induced death.

    Evidence In vivo co-IP, PI3K recruitment and AKT/Bad phosphorylation readouts in podocytes

    PMID:12832477

    Open questions at the time
    • Stoichiometry of nephrin/podocin/CD2AP/PI3K complex unresolved
  5. 2003 High

    Established CD2AP as an endosomal trafficking adaptor by mapping interactions with Rab4, c-Cbl, and endophilin/cortactin that route activated receptors toward degradation.

    Evidence Yeast two-hybrid, in vitro binding, truncation mutants, and PDGFR/EGFR degradation assays

    PMID:12559036 PMID:12672817

    Open questions at the time
    • Direct demonstration of CD2AP on the degradative carriers limited to marker co-localization
  6. 2004 Medium

    Demonstrated a Flt-1/c-Cbl/CD2AP ternary complex required for VEGFR-1 internalization and ubiquitination, generalizing the receptor-downregulation function to angiogenic receptors.

    Evidence Co-IP, dominant-negative CD2AP, and endocytosis/ubiquitination assays

    PMID:15001553

    Open questions at the time
    • Relies on overexpression and dominant-negative; endogenous requirement untested
  7. 2005 High

    Pinpointed the essential, life-sustaining function of CD2AP to podocytes via tissue-specific transgenic rescue, separating its renal role from immune functions.

    Evidence Podocyte-specific transgenic rescue of CD2AP-null mice with histology and proteinuria readouts

    PMID:15951437

    Open questions at the time
    • Molecular basis of podocyte specificity not addressed
    • Testicular phenotype mechanism unexplored
  8. 2006 Medium

    Showed differential adaptor partnering of TβRI (CD2AP vs TAB1) routes TGF-β signaling through distinct MAPK outputs, introducing CD2AP as a TGF-β signaling determinant.

    Evidence Co-IP and in vivo TGF-β3 administration with p38/ERK readouts in Sertoli cells

    PMID:16617054

    Open questions at the time
    • Direct CD2AP–TβRI binding interface not mapped in this study
  9. 2007 Medium

    Defined the CD2AP/CIN85 balance as a rheostat for podocyte RTK signaling and identified dendrin as a CD2AP-bound proapoptotic slit-diaphragm factor.

    Evidence CD2AP-/- podocytes with growth-factor stimulation and CIN85-knockdown rescue; co-IP and nuclear translocation assays for dendrin

    PMID:17213204 PMID:17537921

    Open questions at the time
    • Mechanism by which CIN85 upregulation terminates RTK signaling not fully resolved
  10. 2008 High

    Extended the receptor-degradation role to neuronal Ret and revealed activity-dependent association/dissociation, establishing CD2AP as a negative regulator of GDNF/Ret survival signaling.

    Evidence Reciprocal co-IP, gain- and loss-of-function in sympathetic neurons with Ret degradation and survival assays

    PMID:18753381

    Open questions at the time
    • Isoform selectivity of Ret regulation not yet examined here
  11. 2008 Medium

    Used the Drosophila ortholog Cindr to show evolutionary conservation of CD2AP as a bridge between cadherin junctions and actin capping proteins controlling tissue patterning.

    Evidence Drosophila cindr genetics, co-IP, and epistasis in developing retina

    PMID:18362180

    Open questions at the time
    • Mammalian junctional capping role not yet demonstrated biochemically
  12. 2009 Medium

    Established CD2AP requirements in immune effector function, including NK-cell cytotoxicity through FasL-granule polarization.

    Evidence siRNA knockdown in NK92 cells, cytotoxicity/conjugate/degranulation assays, and CD2AP–FasL co-IP

    PMID:19945749

    Open questions at the time
    • Direct binding interface and reciprocal validation absent
    • Single lab
  13. 2009 High

    Resolved a direct, kinase-dependent CD2AP–TβRI interaction that recruits PI3K to activate antiapoptotic AKT independently of Smad, explaining CD2AP-loss hypersensitivity to TGF-β.

    Evidence Direct binding assay, CD2AP-/- and Smad-/- podocytes, apoptosis assay, and TGF-β1 transgenic mice

    PMID:19679673

    Open questions at the time
    • Phosphorylation event controlling the interaction not identified
  14. 2010 Medium

    Identified CD2AP as a Rac1-specific effector recruited to cell-cell contacts that links Rac1 to capping protein and cortactin for epithelial barrier control.

    Evidence Peptide pulldown/MS, domain mapping, siRNA, constitutively active Rac1, and barrier assays

    PMID:20404345

    Open questions at the time
    • Whether Rac1 binding is direct in cells vs via complexes not fully resolved
  15. 2011 High

    Defined the dendrin–cathepsin L cascade through which CD2AP gates actin-remodeling proteolysis, with CD2AP as both a regulator and a substrate in a feedforward loop.

    Evidence CD2AP KO podocytes and mice, nuclear fractionation, cathepsin L activity, and proteolysis assays

    PMID:21911934

    Open questions at the time
    • Trigger linking CD2AP loss to dendrin release not fully defined
  16. 2011 High

    Revealed CD2AP-dependent SUMOylation of its paralog CIN85 at Lys598 as a switch controlling competition for nephrin binding.

    Evidence SUMOylation assays, K598R mutagenesis, and binding assays in WT vs CD2AP-/- podocytes

    PMID:22203040

    Open questions at the time
    • SUMO E3 ligase and how CD2AP enhances SUMOylation unidentified
  17. 2011 Medium

    Provided NMR solution structures of all three SH3 domains, identifying the exceptionally stable N-terminal SH3 as a determinant of target recruitment.

    Evidence NMR, differential scanning calorimetry, and FoldX thermodynamic analysis

    PMID:21519904

    Open questions at the time
    • Functional consequence of stability inferred, not directly tested
  18. 2012 Medium

    Demonstrated CD2AP is required to colocalize capping protein with cortactin and to build lamellipodial branched actin for cell migration.

    Evidence siRNA, super-resolution microscopy, migration assay, and co-IP

    PMID:23090967

    Open questions at the time
    • Direct simultaneous binding of CP and cortactin by one CD2AP molecule not shown
  19. 2012 Medium

    Connected CD2AP/nephrin complexes to septin 7 and GLUT4-vesicle trafficking, implicating CD2AP in metabolic vesicle regulation in podocytes.

    Evidence Co-IP, siRNA, fractionation, and glucose uptake assays

    PMID:22809625

    Open questions at the time
    • Direct CD2AP–septin 7 interaction interface unmapped
  20. 2012 High

    Defined CD2AP/SHIP1 as positive regulators of BDCA2/FcεR1γ ITAM signaling that restrain Cbl-mediated degradation in plasmacytoid dendritic cells.

    Evidence Co-IP/MS, siRNA, ubiquitination and IFN assays, and membrane recruitment imaging

    PMID:22706086

    Open questions at the time
    • Structural basis of CD2AP–SHIP1–Cbl assembly not resolved
  21. 2013 High

    Established CD2AP as a bona fide barbed-end actin-capping protein that stabilizes adherens-junction actin under mechanical stress through in vitro reconstitution.

    Evidence In vitro reconstitution, barbed-end capping assay, siRNA, and mechanical-stress barrier assays

    PMID:24322428

    Open questions at the time
    • Regulation of capping activity in cells (on/off switch) not defined
  22. 2013 High

    Characterized the multimeric SH3 dimerization modes of CD2AP with CD2 and Cbl-b, explaining how the adaptor diversifies signaling complex assembly.

    Evidence NMR, isothermal titration calorimetry, and small-angle X-ray scattering

    PMID:23663663

    Open questions at the time
    • Cellular relevance of specific dimer modes not tested in vivo
  23. 2014 High

    Mapped isoform-selective Ret51 ubiquitination driven by CD2AP SH3 domains and Cbl-3/c, with Ret-induced CD2AP degradation as negative feedback.

    Evidence Co-IP, siRNA, ubiquitination assays, domain deletions, and substrate lysine mutagenesis

    PMID:24425877

    Open questions at the time
    • Mechanism of Ret9 vs Ret51 discrimination not fully explained
  24. 2015 High

    Defined the SH3 binding motif (Px(P/A)xPR) and solved high-resolution structures with RIN3 epitopes, showing RIN3 recruits CD2AP to Rab5+ early endosomes.

    Evidence Crystal structures, peptide arrays, ITC, co-IP, and immunofluorescence

    PMID:26296892

    Open questions at the time
    • Full repertoire of physiological motif-bearing partners not enumerated
  25. 2015 Medium

    Demonstrated CD2AP is required for blood-brain barrier integrity independently of nephrotic illness, broadening its barrier-maintenance role beyond the kidney.

    Evidence Fluorescein extravasation, EEG/behavior, in kidney-rescued CD2AP-/- mice

    PMID:26358779

    Open questions at the time
    • Molecular mechanism of CD2AP action in brain endothelium undefined
  26. 2015 High

    Established CD2AP control of GLUT4 storage-vesicle trafficking via GGA2 and clathrin–actin connection, linking it to insulin-responsive glucose uptake.

    Evidence CD2AP-/- podocytes, live imaging, fractionation, and co-IP

    PMID:26546360

    Open questions at the time
    • Direct vs indirect nature of CD2AP–GGA2 association unclear
  27. 2016 Medium

    Revealed CD2AP as a TrkA/p85 scaffold that promotes long-range NGF–AKT signaling endosomes and axon growth in sensory neurons.

    Evidence Co-IP, gain/loss-of-function, neurite morphology, AKT/ERK, and endosome imaging

    PMID:27076424

    Open questions at the time
    • Selectivity for AKT over ERK mechanism not explained
  28. 2016 Medium

    Connected CD2AP to tankyrase-regulated Wnt/β-catenin signaling in podocytes, with CD2AP loss elevating β-catenin activity and kidney injury.

    Evidence Co-IP, CD2AP-/- podocytes, XAV939, zebrafish KD, and β-catenin readouts

    PMID:27441654

    Open questions at the time
    • Direct biochemical link between CD2AP and tankyrase PARylation undefined
  29. 2017 High

    Showed CD2AP binds ICAM-1 and is a mechanosensitive node coupling endothelial ICAM-1 to PI3K/cortactin/Rac1 to govern neutrophil transmigration route.

    Evidence Co-IP, siRNA, transmigration, PI3K/Rac1 activation assays, and force application

    PMID:28484057

    Open questions at the time
    • Force-dependent conformational basis of CD2AP–ICAM-1 release not structurally resolved
  30. 2018 Medium

    Identified CD2AP as a host factor exploited by alphavirus nsP3 via cooperative bivalent SH3 binding, with redundancy among CD2AP/BIN1/SH3KBP1 in replication initiation.

    Evidence Quantitative proteomics, NMR, nsP3 mutagenesis, and viral replication assays

    PMID:29702546 PMID:31493651

    Open questions at the time
    • Cellular pathway co-opted by the CD2AP–nsP3 interaction not fully defined
  31. 2018 Medium

    Showed CD2AP restrains TCR signaling duration in CD4 T cells, limiting follicular helper differentiation during chronic infection.

    Evidence CD4-specific CD2AP KO, LCMV model, flow cytometry, and TCR signaling assays

    PMID:29734372

    Open questions at the time
    • Molecular target of CD2AP that shortens TCR signaling not identified
  32. 2019 High

    Demonstrated that VEGF-A-driven Y10 phosphorylation in SH3-1 tunes nephrin-binding affinity, with cross-species rescue showing this fine-tuning is functionally indispensable for the filtration barrier.

    Evidence Isoelectric focusing, mutagenesis, phospho-antibodies, and zebrafish/Drosophila rescue with filtration readouts

    PMID:31235616

    Open questions at the time
    • Kinase responsible for Y10 phosphorylation not definitively assigned
  33. 2019 Medium

    Defined a conserved CD2AP role in endosomal sorting of APP toward lysosomal degradation, linking CD2AP trafficking activity to APP processing.

    Evidence Gain/loss-of-function in cell lines and neurons, Rab5/Rab7 co-localization, and APP degradation assays

    PMID:31138646

    Open questions at the time
    • Direct effect on amyloidogenic vs non-amyloidogenic cleavage not resolved
  34. 2019 High

    Established a conserved synaptic role for CD2AP/Cindr in synapse maturation and proteostasis via 14-3-3ζ and the ubiquitin-proteasome system, validated in null mice.

    Evidence Drosophila cindr genetics, synaptic physiology, Cindr–14-3-3ζ co-IP, and CD2AP null mouse analysis

    PMID:31412248

    Open questions at the time
    • Direct substrates of CD2AP-regulated synaptic proteostasis incompletely defined
  35. 2020 High

    Identified a CD2AP–PI3K positive-feedback loop at lateral membranes that sets epithelial lateral membrane proportions through F-actin and PI3K activity.

    Evidence siRNA, PI3K inhibition, membrane-tethered domain rescue, and F-actin imaging in MDCK cells

    PMID:31723006

    Open questions at the time
    • How SH3-bound PI3K is locally activated mechanistically not fully resolved
  36. 2024 High

    Placed CD2AP upstream of p38 MAPK in neurons, where its loss promotes tau phosphorylation and cognitive decline, reversible by p38 inhibition.

    Evidence Neuron-specific Cd2ap KO in APP/PS1 mice, electrophysiology, behavior, and p38 inhibitor rescue

    PMID:39696695

    Open questions at the time
    • Direct molecular link from CD2AP loss to p38 activation not identified
  37. 2024 Medium

    Showed CD2AP can promote glioblastoma progression through a TRIM5–NF-κB axis, revealing a context-dependent pro-tumor role.

    Evidence Co-IP, gain/loss-of-function, NF-κB reporter, TRIM5-knockdown epistasis, and in vivo tumorigenesis

    PMID:39353894

    Open questions at the time
    • Mechanism of CD2AP-dependent TRIM5 stabilization undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CD2AP's actin-capping activity, receptor-degradation function, and PI3K/AKT scaffolding are coordinately switched by phosphorylation and partner availability in each tissue context remains unresolved.
  • No unified model integrating capping, trafficking, and signaling roles
  • Upstream kinases controlling CD2AP phosphostate largely unidentified
  • Quantitative competition among nephrin, CIN85, and other SH3/C-terminal partners not mapped in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005768 endosome 4 GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 4 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-392499 Metabolism of proteins 3
Partners
CBLCTTNNPHS1PSTPIP1RAB4ARAC1SH3KBP1TGFBR1
Complex memberships
GLUT4 storage vesicleslit diaphragm complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 CMS/CD2AP interacts with the focal adhesion protein p130(Cas) via its proline-rich sequences binding to the SH3 domains of p130(Cas); its SH3 domains also bind Src-family kinases, p85 subunit of PI3K, and Grb2. The C-terminal coiled-coil domain mediates homodimerization. CD2AP colocalizes with F-actin and p130(Cas) at membrane ruffles and leading edges, and ectopic expression alters actin cytoskeleton organization. Co-immunoprecipitation, domain mapping, immunofluorescence, ectopic expression in COS-7 cells Proceedings of the National Academy of Sciences of the United States of America Medium 10339567
2000 CD2AP binds the proto-oncogenic protein c-Cbl through its second SH3 domain interacting with the carboxyl terminus of c-Cbl; this interaction is dependent on tyrosine phosphorylation of CMS/CD2AP and is induced upon stimulation of cell-surface receptors (e.g., EGF). Both proteins colocalize at lamellipodia and leading edges of cells. SH3 domain binding assays, co-immunoprecipitation, immunofluorescence, EGF stimulation The Journal of biological chemistry Medium 11067845
2001 CD2AP localizes to the slit diaphragm of podocytes (demonstrated by immunoelectron microscopy), co-immunoprecipitates with nephrin from a podocyte cell line, and interacts with the cytoplasmic C-terminal domain of nephrin via a novel C-terminal domain of CD2AP. Immunoelectron microscopy, co-immunoprecipitation, domain mapping studies The American journal of pathology High 11733379
2001 In cultured podocytes, CD2AP colocalizes with F-actin at lamellipodia leading edges and in small spots associated with the Arp2/3 complex and cortactin (sites of dynamic actin assembly), whereas p130Cas localizes to focal adhesions. CD2AP thus associates with dynamic rather than stable actin structures in podocyte foot processes. Immunofluorescence, immunoelectron microscopy, co-localization with Arp2/3 and cortactin markers American journal of physiology. Renal physiology Medium 11553524
2003 Both nephrin and CD2AP interact with the p85 regulatory subunit of PI3K in vivo, recruit PI3K to the plasma membrane, and together with podocin stimulate PI3K-dependent AKT signaling in podocytes. AKT mediates phosphorylation of Bad, protecting podocytes from detachment-induced cell death. Co-immunoprecipitation in vivo, PI3K recruitment assay, AKT signaling readouts, phosphoserine 2D gel analysis, podocyte cell culture Molecular and cellular biology High 12832477
2003 CD2AP interacts constitutively with endophilin; EGF stimulation induces transient association of Cbl and EGFR with the CD2AP-endophilin complex. CD2AP binds cortactin via its second proline-rich region, and cortactin binds CD2AP through its SH3 domain. This links EGFR endocytosis to actin polymerization via the Arp2/3 complex. CD2AP and cortactin co-localize in EGF-induced membrane ruffles. Proteomics-based co-purification, co-immunoprecipitation at endogenous levels, domain mapping, immunofluorescence The Journal of biological chemistry Medium 12672817
2003 CD2AP/CMS interacts with GTP-bound Rab4 (Rab4-Q67L) via yeast two-hybrid and in vitro binding. Co-expression of Rab4-Q67L with CD2AP induces enlargement of EEA1-positive early endosomes. CD2AP also interacts with c-Cbl, and early endosome enlargement requires CD2AP to interact with both Rab4 and c-Cbl. A truncated CD2AP that binds Rab4 but not c-Cbl inhibits PDGF receptor degradation, placing CD2AP in the early-to-late endosome trafficking/degradative pathway. Yeast two-hybrid, in vitro binding, co-expression, truncation mutant analysis, fluorescence microscopy, PDGF receptor degradation assay Traffic (Copenhagen, Denmark) High 12559036
2003 CD2AP functions downstream of CD2 and the PSTPIP1 adaptor to promote formation of the immunological synapse; PSTPIP1 coiled-coil domain binds both CD2 and CD2AP, and the PSTPIP1 proline-rich region interacts with WASp. Expression of coiled-coil domain-deleted PSTPIP1 disrupts co-localization at the synapse and CD2-induced actin polymerization in WASp-deficient T cells is impaired. Co-immunoprecipitation, dominant-negative PSTPIP1 expression, T cell:APC conjugate formation assay, immunofluorescence Immunity Medium 12530983
2004 VEGF stimulation induces formation of a ternary complex of Flt-1 (VEGFR-1), c-Cbl, and CD2AP in endocytic vesicles. Wild-type CD2AP enhances VEGF-stimulated internalization and ubiquitination of Flt-1, whereas dominant-negative CD2AP or mutated c-Cbl fails to do so, demonstrating that the c-Cbl/CD2AP complex is required for Flt-1 endocytosis and degradation. Co-immunoprecipitation, transient expression, immunofluorescence colocalization, endocytosis assay, ubiquitination assay, dominant-negative CD2AP FASEB journal Medium 15001553
2005 Podocyte-specific expression of CD2AP in CD2AP-null mice rescues lethality and prevents proteinuria, demonstrating that the essential function of CD2AP for survival is specifically in podocytes and not in immune or other renal cells. CD2AP-deficient mice show age-related testicular abnormalities. Transgenic rescue with podocyte-specific promoter, histological and functional analysis of CD2AP-null mice The Journal of biological chemistry High 15951437
2005 In living podocytes, CD2AP localizes to dynamic, motile actin-rich spots (≤0.5 μm) that are frequently associated with vesicles. These spots are enriched for cortactin and F-actin, belong to a Rab4-positive late endosomal compartment, and their motility depends on actin polymerization. CD2AP has a high turnover rate (FRAP half-time <10 s) in these spots. Confocal time-lapse microscopy (GFP-CD2AP), FRAP, G-actin microinjection, jasplakinolide treatment, marker co-localization American journal of physiology. Renal physiology Medium 15956777
2006 VEGF-A signaling in podocytes induces upregulation of podocin and increases the interaction between podocin and CD2AP, linking VEGFR2 signaling to modulation of the slit diaphragm complex composition. Co-immunoprecipitation, VEGFR2 neutralizing antibody, recombinant VEGF165 treatment, Western blot American journal of physiology. Renal physiology Low 16597608
2006 CD2AP forms a complex with TGF-beta receptor type I (TβRI) in Sertoli cells; when TβRI preferentially associates with CD2AP (rather than TAB1), only Sertoli-germ cell adhesion is disrupted without compromising the blood-testis barrier. This differential adaptor association routes TGF-β3 signaling selectively through p38 MAPK or ERK. Co-immunoprecipitation, in vivo TGF-β3 administration, p38/ERK signaling readouts, overexpression The Journal of biological chemistry Medium 16617054
2007 Dendrin is a constituent of the slit diaphragm complex that directly binds both nephrin and CD2AP. In experimental glomerulonephritis and under high-dose TGF-β1 stimulation, dendrin translocates from the slit diaphragm to the podocyte nucleus, where it promotes apoptosis. CD2AP can repress this proapoptotic TGF-β signaling. Co-immunoprecipitation, immunofluorescence, nuclear translocation assay, TGF-β1 stimulation, apoptosis assays Proceedings of the National Academy of Sciences of the United States of America Medium 17537921
2007 CD2AP deficiency in podocytes leads to diminished signaling initiation and termination of receptor tyrosine kinase (RTK) pathways (IGF-1, VEGF, FGF), with decreased PI3K/AKT and ERK signaling. CIN85, upregulated in CD2AP-deficient podocytes, contributes to RTK signaling termination; repression of CIN85 restores the RTK signaling response, indicating that CD2AP/CIN85 balance regulates podocyte RTK signaling. CD2AP-/- mouse podocytes, growth factor stimulation, Western blot for p-AKT/p-ERK, CIN85 knockdown rescue experiments The Journal of biological chemistry Medium 17213204
2008 CD2AP associates with Ret receptor tyrosine kinase under basal (unstimulated) conditions in sympathetic neurons and dissociates upon GDNF-induced Ret activation. CD2AP also forms a complex with Cbl-3/c upon GDNF stimulation. CD2AP overexpression enhances Ret degradation and inhibits GDNF-dependent survival; CD2AP knockdown blocks Ret degradation and promotes survival, identifying CD2AP as a regulator of Ret downregulation. Co-immunoprecipitation from neurons, CD2AP overexpression and siRNA knockdown, Ret degradation assay, neuronal survival assay The Journal of neuroscience High 18753381
2008 The Drosophila CD2AP/CIN85 ortholog Cindr links E-cadherin at cell junctions to multiple actin cytoskeleton components including capping protein alpha and capping protein beta. Reducing cindr activity causes defects in cell movement and tissue patterning. Cindr physically and functionally connects junction proteins and actin regulators. Drosophila genetics (cindr reduction), co-immunoprecipitation, genetic epistasis, fluorescence microscopy in developing retina The Journal of cell biology Medium 18362180
2009 CD2AP interacts directly with the cytoplasmic tail of TGF-beta receptor type I (TβRI) in a kinase-dependent manner, and this interaction is required for TβRI to recruit the p85 subunit of PI3K, thereby activating the antiapoptotic PI3K/AKT pathway independently of Smad2/3 signaling. CD2AP-deficient podocytes are hypersensitive to TGF-β-induced apoptosis, while Smad3 deficiency is protective. Direct binding assay (C-terminal CD2AP with TβRI cytoplasmic tail), co-immunoprecipitation, CD2AP-/- and Smad-/- podocytes, apoptosis assay, TGF-β1 transgenic mouse model Journal of the American Society of Nephrology High 19679673
2010 CD2AP specifically interacts with the C-terminal hypervariable domain of Rac1 (but not other Rho family members), requiring both the proline-rich domain and the poly-basic region of Rac1 and at least two of the three N-terminal SH3 domains of CD2AP. Constitutively active Rac1 recruits CD2AP to cell-cell contacts in epithelial cells, where CD2AP controls epithelial barrier function and links Rac1 to CAPZ and cortactin. Peptide-based pulldown with mass spectrometry, co-immunoprecipitation, siRNA knockdown, constitutively active Rac1 expression, barrier function assay The Journal of biological chemistry Medium 20404345
2011 CD2AP regulates the TGF-β1-dependent translocation of dendrin from the slit diaphragm to the podocyte nucleus. Nuclear dendrin acts as a transcription factor promoting expression of cytosolic cathepsin L (CatL), which proteolytically cleaves dynamin and synaptopodin, reorganizing the podocyte actin cytoskeleton. CD2AP itself is a CatL substrate, creating a feedforward loop. Loss of CD2AP increases apoptotic susceptibility to TGF-β1. CD2AP KO mouse and human podocytes, nuclear fractionation, transcription factor reporter assay, cathepsin L activity assay, proteolysis assays, mouse model The Journal of clinical investigation High 21911934
2011 CD2AP regulates SUMOylation of its paralog CIN85 in podocytes: full-length CIN85 is SUMOylated by SUMO-1, -2, and -3 in wild-type podocytes and this SUMOylation is enhanced in the presence of CD2AP. SUMOylation at Lys598 prevents CIN85 from binding nephrin; K598R mutation abolishes SUMOylation and increases CIN85-nephrin binding. Co-immunoprecipitation, SUMOylation assay, site-directed mutagenesis (K598R), Western blot in CD2AP-/- vs WT podocytes Molecular and cellular biology High 22203040
2011 CD2AP NMR solution structures of all three SH3 domains were determined. The N-terminal SH3 domain of CD2AP (and CIN85) is the most stable SH3 domain characterized, driven by an extensive intramolecular interaction network; this high stability is proposed to be critical for maintaining the conformation needed for target recruitment. NMR spectroscopy, differential scanning calorimetry (DSC), FoldX structure-based thermodynamic analysis Journal of biomolecular NMR Medium 21519904
2012 CD2AP links cortactin and actin capping protein (CP) at the cell periphery; loss of CD2AP reduces colocalization of CP and cortactin and impairs formation of short branched actin filaments characteristic of lamellipodia, resulting in defective cell migration. Super-resolution microscopy confirmed that CD2AP is required for efficient colocalization of CP and cortactin. siRNA knockdown, super-resolution fluorescence microscopy, cell migration assay, co-immunoprecipitation Molecular and cellular biology Medium 23090967
2012 Septin 7 forms a complex with CD2AP and nephrin (co-immunoprecipitation) and also with VAMP2. The filamentous localization of septin 7 depends on CD2AP and intact actin. Knockdown of septin 7 facilitates glucose uptake and increases the interaction of VAMP2 with nephrin and syntaxin 4, suggesting septin 7 (in a CD2AP-containing complex) hinders GLUT4 storage vesicle trafficking. Co-immunoprecipitation, siRNA knockdown, subcellular fractionation, 2-deoxy-D-glucose uptake assay, immunofluorescence Molecular biology of the cell Medium 22809625
2012 CD2AP positively regulates BDCA2/FcεR1γ receptor signaling in plasmacytoid dendritic cells by forming a complex with SHIP1 that inhibits the E3 ubiquitin ligase Cbl. CD2AP/SHIP1 knockdown reduces ITAM signaling, enhances ubiquitination and degradation of Syk and FcεR1γ, and blocks inhibition of TLR9-mediated type I IFN production. Upon BDCA2 cross-linking, the CD2AP/SHIP1/Cbl complex recruits to the plasma membrane. Co-immunoprecipitation, mass spectrometry, siRNA knockdown, ubiquitination assay, IFN production assay, immunofluorescence Journal of immunology High 22706086
2013 CD2AP (FSGS3) is a barbed-end actin capping protein that stabilizes actin at the adherens junction. Identified by in vitro reconstitution biochemistry with cross-linking approach; CD2AP colocalizes with E-cadherin and α-actinin-4 at the apical junction of MDCK cells. CD2AP knockdown reduces actin accumulation and stability at the adherens junction and compromises adhesive strength and barrier function under mechanical stress. In vitro reconstitution, actin barbed-end capping assay, siRNA knockdown, mechanical stress apparatus, barrier function assay, immunofluorescence The Journal of cell biology High 24322428
2013 CD2AP SH3-A forms a type II dimer with CD2 and both type I and type II dimeric complexes with Cbl-b, as characterized by NMR, isothermal titration calorimetry (ITC), and small-angle X-ray scattering. This multimeric binding mode enables high diversity in signaling complex assembly. NMR, isothermal titration calorimetry, small-angle X-ray scattering The FEBS journal High 23663663
2014 CD2AP enhances Cbl-3/c-mediated ubiquitination and degradation of Ret51 (but not Ret9) isoform specifically. The SH3 domains of CD2AP are sufficient to drive Cbl-3/c-dependent Ret51 ubiquitination; the coiled-coil domain of CD2AP is dispensable. Two major ubiquitination sites in Ret51 are Lys1060 and Lys1107. Activated Ret induces CD2AP degradation as a negative feedback. Co-immunoprecipitation, siRNA knockdown, ubiquitination assay, domain deletion mutants, site-directed mutagenesis of Ret lysines The Journal of biological chemistry High 24425877
2015 CD2AP SH3 domains 1 and 2 show similar binding preferences; SH3-3 binds more weakly and recognizes an extended sequence in ALIX. Preferred binding motif is Px(P/A)xPR. Crystal structures of SH3-1 and SH3-2 in complex with RIN3 epitopes determined at 1.65 Å and 1.11 Å resolution. RIN3 recruits CD2AP to RAB5a-positive early endosomes via two SH3-binding sites. Crystal structure determination, peptide array screen, isothermal titration calorimetry, permutation arrays, co-immunoprecipitation, immunofluorescence The Journal of biological chemistry High 26296892
2015 CD2AP is required for blood-brain barrier integrity in mice: CD2AP-deficient mice show increased sodium fluorescein extravasation (reduced BBB integrity) independent of nephrotic syndrome severity, and CD2AP is expressed in brain-adjacent endothelial cells. CD2AP-/- mice also show shorter latency to pentylenetetrazol-induced seizures. Sodium fluorescein extravasation assay, EEG, behavioral testing, CD2AP-/- mice with kidney-specific CD2AP rescue transgene Human molecular genetics Medium 26358779
2015 CD2AP deficiency in podocytes disrupts GLUT4 (SLC2A4) trafficking: CD2AP-/- podocytes fail to increase glucose uptake in response to insulin, and HA-Glut4-GFP clusters perinuclearly rather than trafficking dynamically. CD2AP co-fractionates with GLUT4, IRAP, and sortilin on GLUT4 storage vesicles (GSVs), forms a complex with GGA2 (a clathrin adaptor sorting Glut4 to GSVs), and connects clathrin to actin in the perinuclear region. CD2AP-/- podocytes, live-cell imaging (HA-Glut4-GFP), 2-deoxy-D-glucose uptake assay, subcellular fractionation, co-immunoprecipitation Journal of cell science High 26546360
2016 CD2AP adaptor protein forms a novel complex with the NGF receptor TrkA and the PI3K regulatory subunit p85 in sensory neurons; CD2AP levels positively regulate the degree of TrkA:p85 association. CD2AP regulates NGF signaling through AKT (but not ERK) and regulates long-range NGF signaling through TrkA+/RAB5+ signaling endosomes. CD2AP functions as a positive regulator of axon growth and neurite complexity. Co-immunoprecipitation, siRNA knockdown and overexpression, neurite morphology assay, AKT/ERK signaling assays, endosome imaging The Journal of neuroscience Medium 27076424
2016 CD2AP mediates internalization of the exosome cargo protein GPRC5B following cell surface delivery, contributing to Golgi accumulation of GPRC5B in parallel with biosynthetic trafficking. Inducible GPRC5B expression system, GPRC5B trafficking assay, siRNA knockdown of CD2AP The Journal of biological chemistry Low 27765817
2017 In endothelial cells, CD2AP interacts with ICAM-1 and limits ICAM-1 clustering dynamics. Loss of CD2AP increases ICAM-1 complex formation, increases neutrophil adhesion, decreases crawling, and shifts neutrophil transmigration preference from paracellular to transcellular. Mechanistically, CD2AP is required for ICAM-1-mediated PI3K activation, cortactin/F-actin recruitment, and Rac1 recruitment and activation downstream of ICAM-1. Mechanical force on ICAM-1 impairs CD2AP binding to ICAM-1. Co-immunoprecipitation, CD2AP siRNA knockdown, neutrophil adhesion/transmigration assay, PI3K activation assay, Rac1 activation assay, mechanical force application Journal of immunology High 28484057
2018 Alphavirus (CHIKV) nsP3 HVD binds CD2AP via its SH3 domains; the interaction site was mapped to the second SH3-ligand-like element in nsP3 HVD. Mutation of the CD2AP-binding motif in nsP3 attenuates viral replication and abolishes co-localization of CD2AP with nsP3 and replication complexes. CD2AP binds nsP3 HVDs from many New and Old World alphaviruses. Quantitative proteomics, site-directed mutagenesis of nsP3, viral replication assay, immunofluorescence colocalization Viruses Medium 29702546
2018 CD2AP inactivation in CD4 T cells promotes follicular helper T cell (Tfh) differentiation during chronic LCMV infection, associated with extended TCR signaling duration and enhanced cytokine production specifically under TH1 conditions. CD2AP-deficient CD4 T cells show enhanced germinal center responses. CD4 T cell-specific CD2AP knockout, LCMV infection model, flow cytometry, TCR signaling duration assay PLoS pathogens Medium 29734372
2018 PAWS1 (FAM83G) interacts dynamically with CD2AP at lamellae. PAWS1 knockout causes F-actin disorganization, lamellipodial defects, and impaired cell migration. CD2AP knockout in U2OS cells produces similar actin and migration defects, consistent with the two proteins acting in the same cytoskeletal pathway. CRISPR/Cas9 knockout of PAWS1 and CD2AP, confocal microscopy, live-cell actin imaging, co-immunoprecipitation (interaction with CD2AP) Journal of cell science Medium 29175910
2019 CD2AP overexpression accelerates transfer of APP from Rab5-positive early endosomes to Rab7-positive late endosomes, stimulating lysosomal APP degradation. CD2AP knockdown has the opposite effect. This trafficking role is conserved in primary cortical neurons from mice. CD2AP overexpression and siRNA knockdown in COS-7, HEK293 cells, and primary cortical neurons; Rab5/Rab7 co-localization; APP degradation assay; nutrient starvation The Journal of biological chemistry Medium 31138646
2019 VEGF-A stimulation induces tyrosine phosphorylation of CD2AP in podocytes. Phosphorylation of Y10 in the SH3-1 domain is indispensable for CD2AP function in vivo: the Y10 phosphorylation increases nephrin binding affinity to CD2AP, but this enhanced affinity paradoxically impairs glomerular filtration barrier function rather than stabilizing it, as demonstrated by cross-species rescue in cd2ap-knockdown zebrafish and Drosophila cindr mutants. Isoelectric focusing, site-directed mutagenesis, phospho-CD2AP antibodies, zebrafish cd2ap KD rescue, Drosophila cindr mutant rescue Journal of the American Society of Nephrology High 31235616
2019 NMR structural analysis of CHIKV nsP3 HVD shows two SH3-binding sites; CD2AP interacts with HVD using its SH3-A and SH3-C domains, leaving SH3-B available for other partners. The cooperative bivalent interaction increases binding affinity. BIN1, CD2AP, and SH3KBP1 play redundant roles in initiation of CHIKV replication. NMR spectroscopy, chemical shift perturbation, point mutations in HVD binding sites, viral replication assay Virology High 31493651
2019 The Drosophila CD2AP ortholog Cindr is expressed in neurons and present at synaptic terminals. cindr mutants show impairments in synapse maturation and synaptic vesicle recycling/release. Cindr associates and genetically interacts with 14-3-3ζ, regulates the ubiquitin-proteasome system, and affects turnover of Synapsin and PMCA. Loss of cindr elevates PMCA levels and reduces cytosolic calcium. CD2AP null mice show conserved synaptic proteostasis defects. Drosophila cindr mutant analysis, synaptic physiology assays, co-immunoprecipitation (Cindr–14-3-3ζ), ubiquitin-proteasome assay, CD2AP null mouse analysis Cell reports High 31412248
2020 CD2AP is a critical determinant of epithelial lateral membrane proportions: depletion of CD2AP or PI3K inhibition causes loss of F-actin and expansion of apical-basal domains at the expense of lateral membrane height in MDCK cells. The SH3 domains of CD2AP bind PI3K and are necessary for PI3K activity along lateral membranes. Tethering CD2AP SH3 domains or p110γ to the membrane rescues CD2AP-KD phenotypes. CD2AP and PI3K form a positive feedback loop linking actin assembly to PI3K activation at lateral membranes. siRNA knockdown, PI3K inhibition, domain rescue experiments (membrane-tethered SH3/p110γ), F-actin imaging in MDCK cells The Journal of cell biology High 31723006
2020 CD2AP inhibits gastric cancer cell metastasis by promoting cellular adhesion and cytoskeletal assembly; interaction with the F-actin capping protein CAPZA1 was demonstrated by immunofluorescence and is proposed as a mechanistic basis for CD2AP effects on cytoskeleton. CD2AP overexpression and knockdown in GC cells, migration/invasion assay, immunofluorescence showing CAPZA1 interaction, IHC of patient samples Molecular carcinogenesis Low 31989722
2009 CD2AP is indispensable for NK cell cytotoxicity: CD2AP knockdown reduces NK92 cell cytotoxicity, impairs conjugate formation with target cells, and prevents FasL-bearing granule polarization toward the contact site. CD2AP associates with FasL by co-immunoprecipitation and colocalizes with FasL-bearing granules near the cell contact site during killing. siRNA knockdown in NK92 cells, cytotoxicity assay, conjugate formation assay, degranulation assay, co-immunoprecipitation (CD2AP–FasL), immunofluorescence Molecular immunology Medium 19945749
2016 Tankyrases interact with CD2AP and regulate Wnt/β-catenin signaling in podocytes. In the absence of CD2AP, tankyrase-mediated PARylation is increased and β-catenin activity is elevated. CD2AP-deficient podocytes show upregulation of LEF1 and fibronectin, downstream targets of Wnt/β-catenin. In zebrafish, tankyrase inhibition in CD2AP-depleted larvae aggravates kidney injury. Co-immunoprecipitation (tankyrase–CD2AP), CD2AP-/- podocytes, tankyrase inhibitor XAV939, zebrafish cd2ap knockdown model, β-catenin activity assay Cell death & disease Medium 27441654
2024 Neuronal knockout of Cd2ap in APP/PS1 mice activates p38 MAPK signaling, leading to increased tau phosphorylation, synaptic injury, neuronal apoptosis, and cognitive impairment. Treatment with a p38 MAPK inhibitor ameliorates these phenotypes, placing CD2AP upstream of p38 MAPK in a pathway regulating tau pathology. Neuron-specific Cd2ap knockout in APP/PS1 mice, immunoblotting, immunofluorescence, electrophysiology, behavioral tests, p38 MAPK inhibitor treatment, stable CD2AP-KD SH-SY5Y cells Translational neurodegeneration High 39696695
2024 CD2AP promotes glioblastoma progression by interacting with TRIM5, an NF-κB modulator. CD2AP overexpression increases TRIM5 levels and NF-κB activity; CD2AP knockdown has opposite effects. Downregulation of TRIM5 reverses elevated NF-κB activity in CD2AP-overexpressing cells, and NF-κB inhibition attenuates malignant features induced by CD2AP overexpression. Co-immunoprecipitation (CD2AP–TRIM5), CD2AP overexpression and knockdown in GBM cells, NF-κB reporter assay, TRIM5 knockdown epistasis, in vivo tumorigenesis Cell death & disease Medium 39353894

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 1635 21460840
2005 Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology 1290 16037678
2003 Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling. Molecular and cellular biology 311 12832477
2001 CD2AP localizes to the slit diaphragm and binds to nephrin via a novel C-terminal domain. The American journal of pathology 226 11733379
2003 A Cortactin-CD2-associated protein (CD2AP) complex provides a novel link between epidermal growth factor receptor endocytosis and the actin cytoskeleton. The Journal of biological chemistry 178 12672817
2002 CIN85/CMS family of adaptor molecules. FEBS letters 163 12354621
2003 The Wiskott-Aldrich syndrome protein acts downstream of CD2 and the CD2AP and PSTPIP1 adaptors to promote formation of the immunological synapse. Immunity 159 12530983
2016 Cytoplasmic male sterility (CMS) in hybrid breeding in field crops. Plant cell reports 150 26905724
1999 CMS: an adapter molecule involved in cytoskeletal rearrangements. Proceedings of the National Academy of Sciences of the United States of America 129 10339567
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 125 21911934
2003 CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl. Traffic (Copenhagen, Denmark) 115 12559036
2006 Autocrine VEGF-A system in podocytes regulates podocin and its interaction with CD2AP. American journal of physiology. Renal physiology 102 16597608
2013 CD2AP mRNA in urinary exosome as biomarker of kidney disease. Clinica chimica acta; international journal of clinical chemistry 98 24144866
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 95 19131354
2006 Differential interactions between transforming growth factor-beta3/TbetaR1, TAB1, and CD2AP disrupt blood-testis barrier and Sertoli-germ cell adhesion. The Journal of biological chemistry 87 16617054
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
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 79 31852937
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
2001 CD2AP and p130Cas localize to different F-actin structures in podocytes. American journal of physiology. Renal physiology 78 11553524
2000 The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl through a tyrosine phosphorylation-regulated Src homology 3 domain interaction. The Journal of biological chemistry 78 11067845
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 74 35610721
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
2012 CD2AP links cortactin and capping protein at the cell periphery to facilitate formation of lamellipodia. Molecular and cellular biology 57 23090967
2019 The role of CD2AP in the Pathogenesis of Alzheimer's Disease. Aging and disease 55 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
2005 CD2-associated protein (CD2AP) expression in podocytes rescues lethality of CD2AP deficiency. The Journal of biological chemistry 50 15951437
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 46 35982619
2016 Adaptor Protein CD2AP and L-type Lectin LMAN2 Regulate Exosome Cargo Protein Trafficking through the Golgi Complex. The Journal of biological chemistry 46 27765817
2022 Use of Human iPSC-CMs in Nonclinical Regulatory Studies for Cardiac Safety Assessment. Toxicological sciences : an official journal of the Society of Toxicology 44 36099065
2010 Rac1 recruits the adapter protein CMS/CD2AP to cell-cell contacts. The Journal of biological chemistry 41 20404345
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
2006 The relationship among nephrin, podocin, CD2AP, and alpha-actinin might not be a true 'interaction' in podocyte. Kidney international 39 16501493
2005 Association of CD2AP with dynamic actin on vesicles in podocytes. American journal of physiology. Renal physiology 39 15956777
2019 CD2-associated protein (CD2AP) overexpression accelerates amyloid precursor protein (APP) transfer from early endosomes to the lysosomal degradation pathway. The Journal of biological chemistry 38 31138646
2018 Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus. Viruses 38 29702546
2015 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). The Journal of biological chemistry 36 26296892
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
2019 CircRNA Expression Pattern and ceRNA and miRNA-mRNA Networks Involved in Anther Development in the CMS Line of Brassica campestris. International journal of molecular sciences 35 31569708
2019 cindr, the Drosophila Homolog of the CD2AP Alzheimer's Disease Risk Gene, Is Required for Synaptic Transmission and Proteostasis. Cell reports 33 31412248
2020 Electrical stimulation applied during differentiation drives the hiPSC-CMs towards a mature cardiac conduction-like cells. Biochemical and biophysical research communications 32 32962862
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
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
2011 CD2AP regulates SUMOylation of CIN85 in podocytes. Molecular and cellular biology 22 22203040
2008 CD2AP and Cbl-3/Cbl-c constitute a critical checkpoint in the regulation of ret signal transduction. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 18753381
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
2024 Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) for modeling cardiac arrhythmias: strengths, challenges and potential solutions. Frontiers in physiology 19 39328831
2022 Empagliflozin and Dapagliflozin Increase Na+ and Inward Rectifier K+ Current Densities in Human Cardiomyocytes Derived from Induced Pluripotent Stem Cells (hiPSC-CMs). Cells 19 36496967
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
2021 Colony-stimulating factor 3 signaling in colon and rectal cancers: Immune response and CMS classification in TCGA data. PloS one 18 33606788
2018 Identification and characterisation of a Theileria annulata proline-rich microtubule and SH3 domain-interacting protein (TaMISHIP) that forms a complex with CLASP1, EB1, and CD2AP at the schizont surface. Cellular microbiology 18 29520916
2018 The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular helper T cells during chronic LCMV infection. PLoS pathogens 18 29734372
2016 A CD2AP Mutation Associated with Focal Segmental Glomerulosclerosis in Young Adulthood. Clinical medicine insights. Case reports 18 26997877
2017 Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy. Scientific reports 17 28814739
2016 Tankyrase inhibition aggravates kidney injury in the absence of CD2AP. Cell death & disease 17 27441654
2015 Lack of CD2AP disrupts Glut4 trafficking and attenuates glucose uptake in podocytes. Journal of cell science 17 26546360
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 15 34475526
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
2017 Inhibition of SHIP2 in CD2AP-deficient podocytes ameliorates reactive oxygen species generation but aggravates apoptosis. Scientific reports 15 28878342
1994 Expression of CMS-unique and flanking mitochondrial DNA sequences in Phaseolus vulgaris L. Current genetics 15 7923411
2024 CD2AP promotes the progression of glioblastoma multiforme via TRIM5-mediated NF-kB signaling. Cell death & disease 14 39353894
2023 High-throughput longitudinal electrophysiology screening of mature chamber-specific hiPSC-CMs using optical mapping. iScience 14 37416454
2020 CD2AP links actin to PI3 kinase activity to extend epithelial cell height and constrain cell area. The Journal of cell biology 14 31723006
2019 DNA methylation profiling allows for characterization of atrial and ventricular cardiac tissues and hiPSC-CMs. Clinical epigenetics 14 31186048
2024 miR-590-3p Overexpression Improves the Efficacy of hiPSC-CMs for Myocardial Repair. JACC. Basic to translational science 13 38984045
2024 CD2AP deficiency aggravates Alzheimer's disease phenotypes and pathology through p38 MAPK activation. Translational neurodegeneration 13 39696695
2021 Anthracycline-Induced Cardiotoxicity: Molecular Insights Obtained from Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs). The AAPS journal 13 33719006
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 iTRAQ-Based Proteomic Analysis of Ogura-CMS Cabbage and Its Maintainer Line. International journal of molecular sciences 13 30326665
2018 Recessive mutation in CD2AP causes focal segmental glomerulosclerosis in humans and mice. Kidney international 13 30612599
2021 Blebbistatin protects iPSC-CMs from hypercontraction and facilitates automated patch-clamp based electrophysiological study. Stem cell research 12 34638057
2018 Cytological and iTRAQ-based quantitative proteomic analyses of hau CMS in Brassica napus L. Journal of proteomics 12 30385414
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
2005 CD2AP contributes to cell migration and adhesion in cultured gastric epithelium. Biochemical and biophysical research communications 12 15910750
2024 Upregulation of utrophin improves the phenotype of Duchenne muscular dystrophy hiPSC-derived CMs. Molecular therapy. Nucleic acids 11 39035791
2024 From Subtypes to Solutions: Integrating CMS Classification with Precision Therapeutics in Colorectal Cancer. Current treatment options in oncology 11 39589648
2009 CD2AP is indispensable to multistep cytotoxic process by NK cells. Molecular immunology 11 19945749
1995 Characterization and expression of rpoC2 in CMS and fertile lines of sorghum. Plant molecular biology 11 7640353
2013 Multimeric and differential binding of CIN85/CD2AP with two atypical proline-rich sequences from CD2 and Cbl-b*. The FEBS journal 10 23663663

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