Affinage

SH3KBP1

SH3 domain-containing kinase-binding protein 1 · UniProt Q96B97

Length
665 aa
Mass
73.1 kDa
Annotated
2026-04-28
100 papers in source corpus 57 papers cited in narrative 56 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SH3KBP1 (CIN85) is a multivalent scaffold protein that coordinates receptor trafficking, immune signaling, cytoskeletal remodeling, and cytokinesis by assembling multiprotein complexes through its three SH3 domains, proline-rich region, and coiled-coil oligomerization domain. Its SH3 domains recognize atypical PX(P/A)XXR motifs to constitutively associate with endophilins, Hrs, and Dab2, and upon ligand stimulation it is recruited by Cbl/Cbl-b to activated receptor tyrosine kinases (EGFR, c-MET) and immune receptors (FcεRI, FcγRIIa, D2DR, TβRI), promoting their clathrin-mediated internalization, ESCRT-dependent endosomal sorting, and lysosomal degradation (PMID:11894095, PMID:20551902, PMID:21635887, PMID:26169354). CIN85 trimerizes via its coiled-coil domain to oligomerize the B cell adaptor SLP65 into pre-formed signalosome condensates that are essential for BCR-induced NF-κB and Ca²⁺ responses — an autoinhibitory intramolecular SH3C:PRM interaction gates this oligomerization and is regulated by serine phosphorylation — and germline SH3KBP1 loss in humans causes X-linked antibody deficiency (PMID:27353366, PMID:38111344, PMID:29636373). Beyond trafficking and immune signaling, CIN85 inhibits PHD2 prolyl hydroxylase to stabilize HIF-1α, enhances RIG-I antiviral signaling via TRIM25-mediated K63-ubiquitination, facilitates cytokinesis through anillin–SEPT9 interactions, and supports myofiber integrity through dynamin-2 and calnexin binding (PMID:31142511, PMID:39466846, PMID:36044846, PMID:40065183).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2000 Medium

    Establishing CIN85 as a Cbl-interacting adaptor resolved the question of how Cbl's endocytic function is coupled to downstream effectors beyond its E3 ligase activity.

    Evidence Co-immunoprecipitation and domain mapping in mammalian cells identifying SH3-domain-mediated Cbl binding

    PMID:10679202

    Open questions at the time
    • Functional consequence of CIN85–Cbl interaction on receptor trafficking not yet tested
    • No structural detail of binding interface
  2. 2002 High

    Two concurrent studies demonstrated that CIN85 constitutively complexes with endophilins and is recruited to activated EGFR via Cbl, revealing a mechanistically distinct internalization pathway separable from Cbl's ubiquitin ligase activity.

    Evidence Reciprocal Co-IPs, dominant-negative interference, and EGFR internalization assays in mammalian cells by two independent laboratories

    PMID:11894095 PMID:11894096 PMID:12177062

    Open questions at the time
    • Whether CIN85 functions in initial internalization versus endosomal sorting was unresolved
    • Structural basis of PXXXPR recognition unknown
  3. 2002 High

    Discovery that Cbl monoubiquitinates CIN85 and that monoubiquitinated CIN85 is co-degraded with polyubiquitinated EGFR in lysosomes established a feedback mechanism linking the scaffold to receptor fate.

    Evidence In vivo ubiquitination assays with RING-domain and ubiquitin-acceptor-site mutagenesis, lysosomal inhibitor rescue

    PMID:12218189

    Open questions at the time
    • Identity of the monoubiquitinated lysine residue in CIN85 not mapped
    • Physiological relevance of CIN85 co-degradation unclear
  4. 2003 High

    Definition of the PX(P/A)XXR consensus for CIN85 SH3 domains and demonstration that tandem SH3 domains cluster multiple Cbl molecules explained how CIN85 valency drives ligand-induced complex stabilization and receptor downregulation.

    Evidence Iterative peptide library screening, in vitro affinity measurements, mutagenesis, and functional clustering assays in mammalian cells; identification of new partners synaptojanin-1, PAK2, and Dab2

    PMID:12829691 PMID:12874286 PMID:14596919

    Open questions at the time
    • High-resolution structure of SH3:PXXXPR complex not determined
    • How ligand-gated switching between Dab2 and Cbl binding is regulated remained unclear
  5. 2003 Medium

    Linking CIN85 to the actin cytoskeleton through direct CAPZ binding and to focal adhesions through FAK/PYK-2 expanded its role beyond endocytosis to cell adhesion and actin dynamics.

    Evidence BIAcore quantitative binding to CD2/CAPZ, F-actin bundling assays, ECIS adhesion assays, and co-localization with focal adhesion markers

    PMID:12690097 PMID:12771190

    Open questions at the time
    • In vivo relevance of CIN85–CAPZ axis to T cell function not tested
    • Whether F-actin bundling is CIN85-specific or shared with CMS not resolved
  6. 2004 High

    Identification of a broad spectrum of PXXXPR-containing endocytic effectors (SHIP-1, ASAP1, ARAP3, Hip1R) binding CIN85, and conservation of the CIN85–endophilin–ubiquitin ligase axis in yeast (Sla1–Rvs167–Rsp5), established CIN85 as an evolutionarily conserved endocytic scaffold hub.

    Evidence Co-IPs and pulldowns with PXXXPR-mutant controls in mammalian cells; in vitro reconstitution of Rsp5-mediated Rvs167 ubiquitination in yeast

    PMID:14761940 PMID:15090612

    Open questions at the time
    • Hierarchy and competition among multiple PXXXPR partners for CIN85 SH3 occupancy undefined
    • Whether yeast Sla1 and mammalian CIN85 are true functional orthologs debated
  7. 2005 High

    Sprouty2 and Alix were identified as negative regulators that compete at the Cbl–CIN85 interface, providing a mechanistic basis for fine-tuning EGFR downregulation through antagonistic complex formation.

    Evidence Domain mutagenesis, ternary complex Co-IPs, and reciprocal gain/loss-of-function EGFR internalization assays

    PMID:15456872 PMID:15962011

    Open questions at the time
    • Physiological contexts in which Sprouty2 versus Alix dominate are unknown
    • Whether antagonism extends to non-EGFR receptors not tested
  8. 2005 Medium

    Demonstrating CIN85 recruitment to FcεRI via Cbl in mast cells and its role in receptor internalization/sorting extended the Cbl–CIN85 trafficking paradigm to immune receptors beyond RTKs.

    Evidence Co-IP, confocal sorting assays, and degranulation functional readout in mast cells

    PMID:16177060

    Open questions at the time
    • Whether CIN85 also controls FcεRI signaling amplitude independently of internalization unclear
    • No genetic loss-of-function in mast cells
  9. 2008 High

    NMR-based discovery that CIN85 SH3 domains bind ubiquitin at the same surface used for PXXXPR ligands revealed a competition mechanism that auto-regulates Cbl-mediated ubiquitination, and Drosophila Cindr genetics confirmed conserved roles in adhesion receptor localization.

    Evidence NMR structural modeling with mutagenesis and ubiquitination assays; genetic loss-of-function in Drosophila with E-cadherin/Roughest localization phenotypes

    PMID:18362180 PMID:18680311

    Open questions at the time
    • Relative affinities of ubiquitin versus PXXXPR for each SH3 domain not quantified in cells
    • How ubiquitin competition is resolved temporally during trafficking unknown
  10. 2010 High

    CIN85-knockout mice showed impaired D2 dopamine receptor endocytosis, hyperactivity, and elevated striatal dopamine, providing the first in vivo genetic evidence that CIN85 is a non-redundant endocytic regulator in the brain.

    Evidence Conditional exon-2 knockout mouse with receptor internalization assays, neurochemistry, and behavioral analysis

    PMID:20551902

    Open questions at the time
    • Whether CD2AP compensates partially in other tissues not addressed
    • Molecular mechanism linking CIN85 loss to elevated dopamine release undefined
  11. 2010 High

    Binding of CIN85 to dynamin-2 at late endosomes was shown to prevent aberrant tubulation and sustained signaling, identifying a distinct late-endocytic membrane-scission role for CIN85 beyond early internalization.

    Evidence Co-IP, dominant-negative disruption, confocal imaging of elongated endosomal tubules, and signaling assays

    PMID:20711168

    Open questions at the time
    • Whether CIN85 directly stimulates dynamin-2 GTPase activity or acts as a scaffold not resolved
    • Relative contribution of late-endosomal versus early-endocytic CIN85 to EGFR fate unclear
  12. 2011 High

    CIN85 was established as a core component of the BCR primary transducer module: it constitutively associates with SLP65, and B-cell-specific CIN85 deletion abrogates IKK-β activation and T-cell-independent antibody responses, placing CIN85 upstream of NF-κB in humoral immunity.

    Evidence Quantitative MS interactome, live-cell imaging, conditional Mb1-cre knockout with IKK-β rescue, and in vivo immunization

    PMID:21708930 PMID:21822214

    Open questions at the time
    • How CIN85 specifically promotes IKK-β activation mechanistically undefined
    • Contribution of CIN85 to germinal center reactions not examined
  13. 2011 High

    Refined trafficking analysis showed CIN85 depletion delays EGFR degradation and increases recycling without blocking initial internalization, repositioning CIN85's primary function to endosomal sorting rather than plasma-membrane uptake; concurrently, CIN85 was linked to FcγRIIa and Syk degradation in neutrophils and mast cells.

    Evidence RNAi versus dominant-negative comparison with EGFR recycling/degradation assays; siRNA in neutrophils with phagocytosis readout

    PMID:17675467 PMID:21372129 PMID:21635887

    Open questions at the time
    • Whether the sorting versus internalization distinction applies to all CIN85-regulated receptors not tested
    • Mechanism by which CIN85 recruits ESCRT machinery not defined
  14. 2011 High

    Discovery that CD2AP promotes CIN85 SUMOylation at K598 and that SUMOylation reduces CIN85 binding to nephrin established a post-translational switch controlling slit-diaphragm receptor availability in podocytes.

    Evidence SUMO modification assays with K598R mutagenesis and Co-IP with nephrin

    PMID:22203040

    Open questions at the time
    • Identity of the SUMO E3 ligase not determined
    • In vivo relevance of K598 SUMOylation to podocyte function not tested
  15. 2012 High

    Src-mediated tyrosine phosphorylation of CIN85 was identified as a signal directing CIN85 to Rab5-positive early endosomes for EGFR MVB sorting, linking kinase signaling to CIN85's endosomal sorting function.

    Evidence Phosphorylation assays, Rab5 Co-IP, Src inhibitor experiments, and MVB sorting assays

    PMID:22833562

    Open questions at the time
    • Specific tyrosine residue(s) phosphorylated by Src not mapped
    • Whether Src phosphorylation of CIN85 affects non-EGFR cargoes unknown
  16. 2015 High

    CIN85 was shown to promote TβRI surface recycling via Rab11 rather than degradation, revealing that CIN85 can direct receptors toward recycling in a context-dependent manner, opposite to its role in EGFR downregulation.

    Evidence Co-IP, siRNA, dominant-negative Rab11, surface biotinylation, and Smad2 phosphorylation assays

    PMID:26169354

    Open questions at the time
    • What determines whether CIN85 routes a receptor for degradation versus recycling unresolved
    • Role of TRAF6 in CIN85 recruitment to TβRI not fully dissected
  17. 2016 High

    Structural and biochemical demonstration that CIN85 trimerizes via its coiled-coil domain and oligomerizes SLP65 into condensates through multivalent SH3:PRM interactions explained how pre-formed signaling clusters enable rapid BCR signal initiation; separately, CIN85 was shown to inhibit PP2A catalytic activity in platelets, affecting platelet spreading.

    Evidence NMR structural analysis, oligomerization reconstitution, B cell signaling assays; yeast two-hybrid, in vitro PP2A activity assay, cell-permeable peptide disruption

    PMID:27334924 PMID:27353366

    Open questions at the time
    • Whether CIN85-driven condensates undergo true liquid-liquid phase separation in vivo not proven
    • In vivo platelet phenotype of CIN85 loss not characterized
  18. 2016 High

    CIN85 knockout in diabetic mice preserved nephrin surface expression and reduced proteinuria, while zebrafish overexpression disrupted the filtration barrier, providing direct in vivo evidence for CIN85 as a driver of nephrin internalization and diabetic nephropathy pathogenesis.

    Evidence Knockout mouse model (diabetic), zebrafish overexpression, nephrin surface quantification, proteinuria measurement

    PMID:27531950

    Open questions at the time
    • Whether CIN85-mediated nephrin internalization is Cbl-dependent in vivo not determined
    • Applicability to non-diabetic nephropathies untested
  19. 2018 High

    Identification of germline SH3KBP1 loss in humans causing X-linked antibody deficiency with defective NF-κB activation established a non-redundant, disease-causing role for CIN85 in human humoral immunity.

    Evidence Human genetic analysis with B cell functional assays (NF-κB, CD86) from affected individuals

    PMID:29636373

    Open questions at the time
    • Precise mutation(s) and their structural consequences not fully characterized
    • Whether T cell or myeloid defects contribute to clinical phenotype not fully resolved
  20. 2019 High

    CIN85 was shown to directly inhibit PHD2 hydroxylase activity, stabilizing HIF-1α, and to limit T cell activation via the phosphatase Sts-2, revealing non-trafficking functions of CIN85 as an enzyme inhibitor and signaling attenuator.

    Evidence PHD2 enzymatic activity assay, CRISPR editing, xenograft tumor model; T cell conditional KO with Zap70/SLP76/ERK phosphorylation and Sts-2 Co-IP

    PMID:30723173 PMID:31142511

    Open questions at the time
    • Structural basis of PHD2 inhibition by CIN85 SH3 domains not determined
    • How CIN85 recruits Sts-2 to the TCR complex mechanistically undefined
  21. 2022 High

    Discovery that CIN85 localizes to the intercellular bridge during cytokinesis and directly binds anillin and SEPT9 to facilitate septin filament membrane recruitment revealed a cell-division role entirely distinct from endocytic trafficking.

    Evidence Direct in vitro binding reconstitution, live cell imaging of cytokinesis, siRNA loss-of-function

    PMID:36044846

    Open questions at the time
    • Whether CIN85 condensate/oligomerization properties contribute to septin assembly unknown
    • Upstream signal recruiting CIN85 to the ICB not identified
  22. 2023 High

    NMR resolution of an intramolecular SH3C:PRM autoinhibitory interaction within CIN85, regulated by serine phosphorylation, explained how CIN85 valency toward SLP65 is gated, controlling condensate formation and BCR-induced Ca²⁺ signaling.

    Evidence High-resolution NMR, phospho-mimetic mutagenesis, B cell Ca²⁺ flux and membrane recruitment assays

    PMID:38111344

    Open questions at the time
    • Identity of the kinase phosphorylating the regulatory serine not established
    • Whether autoinhibition regulates CIN85 interactions with non-SLP65 partners untested
  23. 2024 High

    SH3KBP1 was shown to enhance RIG-I antiviral signaling by promoting TRIM25-mediated K63-ubiquitination, and Sh3kbp1-knockout mice showed increased susceptibility to VSV, expanding CIN85's role to innate antiviral immunity.

    Evidence Co-IP, ubiquitination assays, knockout mouse VSV infection model, IFN-β measurement

    PMID:39466846

    Open questions at the time
    • Whether CIN85 scaffolds TRIM25–RIG-I or allosterically activates TRIM25 not distinguished
    • Relevance to RNA viruses beyond VSV/PRRSV unknown
  24. 2025 Medium

    Recent studies expanded CIN85 functions to muscle biology (myoblast fusion, triad formation via dynamin-2/calnexin), tubular recycling endosomes (CD98 recycling via MICAL-L1), podosome assembly in macrophages (via MYO1F), and bleb-neck signaling (septin–PI3K phase separation conferring anoikis resistance).

    Evidence siRNA screens in myotubes with Dnm2-mutant mouse; live imaging of TRE recycling; proximity labelling proteomics in macrophages; phase-separation and PI assays with anoikis readout

    PMID:40065183 PMID:40445717 PMID:40740057 PMID:41208482

    Open questions at the time
    • In vivo muscle phenotype of CIN85 loss not fully characterized
    • Whether TRE and bleb-neck functions depend on CIN85 oligomerization unknown
    • Phase-separation behavior awaits reconstitution with purified components

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of CIN85 SH3 selectivity among dozens of PXXXPR partners, the kinase(s) controlling autoinhibitory phosphorylation, how CIN85 switches between degradative and recycling sorting of different cargoes, and the full physiological spectrum of CIN85 loss in humans beyond antibody deficiency.
  • No high-resolution crystal/cryo-EM structure of full-length CIN85 or CIN85–Cbl complex
  • Kinase phosphorylating the autoinhibitory serine unknown
  • Decision logic routing receptors to degradation versus recycling not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0008092 cytoskeletal protein binding 4 GO:0008289 lipid binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005768 endosome 5 GO:0005856 cytoskeleton 3 GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 7 R-HSA-168256 Immune System 5 R-HSA-9609507 Protein localization 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 1
Partners
ANLNCBLCBLBDNM2EGFRPHD2SH3GL2SLP65
Complex memberships
CIN85–SLP65 BCR signalosomeCIN85–endophilin complexCbl–CIN85–endophilin ternary complex

Evidence

Reading pass · 56 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 CIN85 forms a constitutive complex with endophilins via their SH3 domains, and is recruited by Cbl to activated EGF receptors upon EGF stimulation; disruption of the Cbl–CIN85–endophilin complex blocks EGFR internalization and delays receptor degradation without affecting Cbl-directed receptor ubiquitination, demonstrating that this is a mechanistically distinct pathway from ubiquitin ligase activity. Co-immunoprecipitation, dominant-negative interference, internalization assays Nature High 11894095 11894096
2002 CIN85 binds to Cbl/Cbl-b via a novel polyproline-arginine motif (PXXXPR) in the C-terminus of Cbl; this interaction is enhanced by ligand-induced phosphorylation of Cbl and is required for Cbl-b-mediated internalization of EGFR and PDGFR but is dispensable for receptor polyubiquitination. Co-immunoprecipitation, deletion/mutation analysis, internalization assays The Journal of biological chemistry High 12177062 12874286
2000 CIN85 was identified as a novel c-Cbl-interacting protein; the second SH3 domain of CIN85 mediates constitutive association with c-Cbl, which is enhanced after EGF stimulation correlating with c-Cbl tyrosine phosphorylation. Co-immunoprecipitation, domain mapping Biochemical and biophysical research communications Medium 10679202
2000 CIN85 associates with BLNK/SLP65 through its SH3 domains; CIN85 also self-associates through its coiled-coil domain to form tetramers; both the coiled-coil and SH3 domains are required for subcellular localization. Yeast two-hybrid, co-immunoprecipitation, immunostaining Biochemical and biophysical research communications Medium 11071869
2002 Cbl and Cbl-b monoubiquitinate CIN85 after EGF stimulation; monoubiquitination requires direct CIN85–Cbl interaction, an intact RING finger domain, and a ubiquitin acceptor site in the CIN85 C-terminus; monoubiquitinated CIN85 is degraded in the lysosome together with polyubiquitinated EGFR. In vivo ubiquitination assays, mutagenesis of RING domain and ubiquitin acceptor site, lysosomal inhibitor experiments Proceedings of the National Academy of Sciences of the United States of America High 12218189
2003 CIN85 SH3 domains specifically recognize the PXXXPR motif; individual SH3 domains bind with micromolar affinity while tandem SH3 domains bind with higher stoichiometry; full-length CIN85 simultaneously clusters multiple Cbl molecules, which is essential for ligand-induced stabilization of CIN85–Cbl–EGFR complexes and EGFR lysosomal degradation. Binding assays, peptide competition, affinity measurements, clustering assays in mammalian cells The Journal of biological chemistry High 12874286
2003 The atypical SH3-domain recognition consensus of CIN85 is PX(P/A)XXR; this consensus was validated by mutagenesis and in vitro binding, and allowed identification of novel binding partners synaptojanin 1 and PAK2 confirmed by GST pulldown and Far Western blotting. Target-assisted iterative peptide library screening, mutagenesis, in vitro binding, GST pulldown The Journal of biological chemistry High 12829691
2004 CIN85 associates with multiple endocytic effectors (SHIP-1, synaptojanin 2B1, ASAP1, ARAP3, Hip1R, STAP1, p115RhoGEF) all via PXXXPR motifs; CIN85 acts as a scaffold clustering these effectors into high-molecular-weight complexes; ASAP1 overexpression promotes EGFR recycling in a CIN85-binding-dependent manner. Co-immunoprecipitation, GST pulldown, functional recycling assay with PXXXPR mutants Molecular biology of the cell High 15090612
2004 Alix/AIP1, which binds CIN85 and endophilins, antagonizes the Cbl–CIN85 complex by weakening CIN85–Cbl interaction and reducing EGFR ubiquitination; Alix overexpression reduces EGFR internalization while siRNA knockdown of Alix promotes internalization and downregulation. Co-immunoprecipitation, siRNA knockdown, internalization assays Molecular and cellular biology High 15456872
2003 CIN85 and CMS link the T cell surface protein CD2 (via its proline-rich cytoplasmic tail) to the actin-capping protein CAPZ; N-terminal SH3 domains of CIN85 bind CD2 (KD ~100 µM) and CAPZ binds the C-terminal half of CIN85/CMS, providing a direct connection to the actin cytoskeleton. Peptide pulldown, BIAcore binding analysis, overexpression functional assays The Journal of biological chemistry High 12690097
2003 CIN85 (SETA) co-localizes with actin in microfilaments and focal adhesions and with microtubules; it interacts with focal adhesion kinase (FAK) and PYK-2 and promotes cell adhesion in ECIS assays; SETA dimerizes to interact with FAKs. Co-immunoprecipitation, ECIS cell adhesion assay, co-localization microscopy Journal of cell science Medium 12771190
2004 The yeast orthologue of CIN85, Sla1, directly binds the endophilin-like Rvs167; the ubiquitin ligase Rsp5 binds both Sla1 and Rvs167 and monoubiquitinates Rvs167 on Lys481 via its SH3 domain, providing conservation of the CIN85–endophilin–ubiquitin ligase axis. In vitro binding reconstitution, ubiquitination assay, mutagenesis (K481R) The Journal of biological chemistry High 14761940
2005 Sprouty2 binds CIN85 SH3 domains A and C via PXXXPR motifs and acts at the Cbl–CIN85 interface to inhibit EGFR endocytosis; intact Sprouty2–Cbl–CIN85 ternary complex is required for inhibition; Sprouty4, which lacks CIN85-binding motifs, does not inhibit EGFR downregulation. Co-immunoprecipitation, domain mutagenesis, EGFR internalization assays EMBO reports High 15962011
2005 CIN85 is recruited to the FcεRI signaling complex via Cbl after receptor engagement on mast cells and promotes ligand-induced receptor internalization, accelerated sorting into early endosomes and lysosomal delivery; CIN85-overexpressing mast cells are severely impaired in degranulation. Co-immunoprecipitation, confocal microscopy, degranulation assay Journal of immunology Medium 16177060
2005 CIN85 binds MEKK4 via three PXXXPR motifs in MEKK4; disrupting this interaction impairs CIN85-enhanced activation of MKK6 and p38 MAP kinase upon oxidative stress/growth factor stimulation; CIN85 also promotes multi-ubiquitination of MEKK4. Co-immunoprecipitation, kinase assays, ubiquitination assay, dominant-negative mutants Biochemical and biophysical research communications Medium 16256071
2007 CIN85 co-localizes with AMAP1 at invadopodia in breast cancer cells; CIN85–AMAP1 binding is required for invasive activity; Cbl monoubiquitinates AMAP1, and this monoubiquitination is required for invasion; siRNA knockdown of CIN85 or Cbl inhibits invasion. Co-immunoprecipitation, siRNA knockdown, invasion assays, ubiquitination assays The EMBO journal High 17255943
2008 All three SH3 domains of CIN85 bind ubiquitin; ubiquitin binding is at the canonical proline-rich ligand interaction surface and competes with PXXXPR ligands; disruption of ubiquitin binding leads to constitutive CIN85 ubiquitination and elevated basal EGFR ubiquitination, suggesting ubiquitin–SH3 competition regulates Cbl function. NMR structural model, binding assays, mutagenesis, ubiquitination assays Biochemistry High 18680311
2008 Drosophila Cindr (sole CD2AP/CIN85 family member) links E-cadherin and the adhesion receptor Roughest with actin-capping proteins (CPα and CPβ); reducing cindr causes defective E-cadherin and Roughest localization, impaired local cell movement, and tissue patterning defects. Genetic loss-of-function, immunofluorescence, protein interaction assays in Drosophila The Journal of cell biology High 18362180
2008 Endogenous CIN85/Ruk localizes predominantly to COPI-coated vesicles of the Golgi complex in a manner dependent on Golgi integrity and intact microtubules; only a small fraction is at clathrin-mediated endocytic compartments. Subcellular fractionation, immunofluorescence with organelle markers Traffic (Copenhagen, Denmark) Medium 18266907
2009 CIN85 associates with endosomal membranes through binding of its positively charged C-terminal coiled-coil domain to the fusogenic lipid phosphatidic acid; deletion of the coiled-coil domain ablates membrane association and CIN85–c-Cbl interaction, blocking EGFR downregulation. Lipid-binding assay, deletion mutants, EGFR downregulation assays, confocal microscopy Cell research Medium 19417776
2010 CIN85 directly binds the coiled-coil domain of nephrin and podocin; in podocytes CIN85 promotes FGF-4-stimulated nephrin ubiquitination and internalization; co-expression of CD2AP reduces CIN85 binding to nephrin/podocin, indicating functional competition. Binding assays with CIN85 domain mutants, co-immunoprecipitation, internalization assays The Journal of biological chemistry High 20457601
2010 CIN85 interacts with the HEV ORF3 protein, competing with formation of the Cbl–CIN85 complex at growth factor receptors; this reduces CIN85 ubiquitination and delays receptor trafficking to late endosomes/lysosomes, prolonging endomembrane signaling. Co-immunoprecipitation, competitive binding assays, EGFR/c-Met trafficking assays Journal of virology Medium 20130058
2010 CIN85 in striatal neurons co-clusters with D2 dopamine receptors and interacts with endocytic regulators dynamin and endophilins; CIN85-deficient (exon 2 knockout) mice show decreased D2DR endocytosis in striatal neurons, elevated striatal dopamine and D2DR levels, and hyperactivity. Conditional knockout mouse model, receptor internalization assay, co-immunoprecipitation, behavioral analysis The EMBO journal High 20551902
2010 The SH3 domains of CIN85 bind a PXXXPR motif near the C-terminus of tristetraprolin (TTP/hTTP); CIN85 co-expression leads to increased TTP phosphorylation at Ser66 and Ser93, possibly through co-recruitment of MEKK4. Yeast two-hybrid, co-immunoprecipitation, co-localization, phosphorylation analysis PloS one Medium 20221403
2011 CIN85 is constitutively associated with SLP65 in resting B cells; absence of the SLP65–CIN85 complex abrogates SLP65 phosphorylation, plasma membrane translocation, BCR-induced Ca2+ and NF-κB responses; live cell imaging confirmed both are components of the BCR primary transducer module. Mass spectrometry interactome, co-immunoprecipitation, live cell imaging, RNAi knockdown with functional signaling assays The EMBO journal High 21822214
2011 B cell-specific deletion of CIN85 impairs IKK-β activation and T cell-independent type II antibody responses; introduction of constitutively active IKK-β corrects the defect, placing CIN85 upstream of IKK-β in BCR-to-NF-κB signaling. Conditional knockout (Mb1-cre), in vivo immunization, in vitro IKK-β kinase assay, rescue experiment The Journal of experimental medicine High 21708930
2011 CIN85 depletion decreases EGF-induced EGFR ubiquitination and delays degradation while increasing EGF recycling; CIN85 is constitutively associated with Hrs; overexpression of a dominant-negative CIN85 (three SH3 domains) inhibits EGF internalization, whereas RNAi knockdown of CIN85 does not, suggesting CIN85 functions primarily in endosomal sorting rather than initial internalization. RNAi knockdown, dominant-negative overexpression, ubiquitination assays, recycling/degradation assays, co-immunoprecipitation Experimental cell research High 21635887
2011 CIN85 overexpression inhibits FcεRI-induced Syk signaling and reduces Syk protein levels via the ubiquitin-proteasome pathway through c-Cbl; CIN85 overexpression limits Cbl binding to the negative regulator Sts1, while CIN85 knockdown promotes Cbl–Sts1 complex formation. Overexpression/knockdown, proteasome inhibitor rescue, co-immunoprecipitation Journal of immunology Medium 17675467
2011 CIN85 modulates FcγRIIa downregulation in neutrophils in concert with c-Cbl; siRNA knockdown of CIN85 prevents FcγRIIa ubiquitination and degradation and increases IgG-mediated phagocytosis; CIN85 is a PKC substrate and classical PKCs positively regulate FcγRIIa ubiquitination and degradation. siRNA knockdown, co-immunoprecipitation, confocal microscopy, PKC inhibitor experiments The Journal of biological chemistry Medium 21372129
2011 CD2AP regulates SUMOylation of full-length CIN85 in podocytes; CIN85 is SUMOylated by SUMO-1, -2, and -3; SUMOylation is enhanced by CD2AP; mutation of Lys598 abolishes SUMOylation and increases CIN85 binding to nephrin. SUMO modification assays, mutagenesis (K598R), co-immunoprecipitation Molecular and cellular biology High 22203040
2011 SHKBP1 constitutively binds the SH3 domains of CIN85 via PXXXPR motifs, competing with c-Cbl; SHKBP1 binding prevents CIN85 translocation to EGFR-containing vesicles and reduces EGFR degradation, enhancing EGF-induced signaling. Co-immunoprecipitation, domain competition, EGFR trafficking/degradation assays Cell biochemistry and function Medium 21830225
2012 EGF stimulation induces Src-mediated tyrosine phosphorylation of CIN85; phospho-CIN85 interacts with Rab5-positive early endosomes and mediates EGFR sequestration into multivesicular bodies for degradation; disruption of Src-dependent CIN85 phosphorylation impairs EGFR ubiquitination and MVB sorting. Phosphorylation assays, co-immunoprecipitation with Rab5, dominant-negative and kinase inhibitor experiments, MVB sorting assays Molecular biology of the cell High 22833562
2010 CIN85 interacts with the CIN85-interacting protein dynamin 2 (Dyn2) in an EGF-stimulation-dependent manner; disruption of the CIN85–Dyn2 interaction causes internalized EGFR to accumulate in aberrantly elongated late endosomal tubules and sustains downstream signaling, identifying a novel late-endocytic role for CIN85. Co-immunoprecipitation, dominant-negative disruption, confocal microscopy, signaling assays The EMBO journal High 20711168
2007 CIN85/CIN85 and CMS can crosslink F-actin into bundles via their proline-rich and coiled-coil domains; removal of these domains reduces cell migration; CMS and CIN85 form heterotypic complexes via their coiled-coil domains. F-actin binding/bundling assays, domain deletion mutants, migration assays Journal of cell science Medium 17606992
2013 MUC1 associates with CIN85 at invadopodia-like structures; siRNA-mediated silencing of CIN85 reduces breast cancer cell migration and invasion in vitro and lung metastasis in vivo; MUC1 overexpression partially rescues CIN85-depletion-reduced invasion. Co-immunoprecipitation, siRNA knockdown, invasion/migration assays, in vivo metastasis model Oncotarget Medium 24072600
2015 TβRI interacts with CIN85 SH3 domains in a TGFβ- and TRAF6-dependent manner; CIN85 knockdown causes TβRI accumulation in intracellular compartments and diminishes Smad2 phosphorylation; CIN85 overexpression increases TβRI at the cell surface via a Rab11-dependent recycling pathway. Co-immunoprecipitation, siRNA knockdown, Rab11 dominant-negative, Smad2 phosphorylation assays, surface biotinylation The Journal of cell biology High 26169354
2016 CIN85 trimerizes via its C-terminal coiled-coil domain; trimeric CIN85 oligomerizes SLP65 via its multiple SH3 domains interacting with SLP65 PRMs, propagating condensate formation; this oligomeric signaling complex pre-assembles in resting B cells and is required for efficient BCR signal initiation. NMR structural analysis, biochemical oligomerization assays, B cell signaling functional assays Science signaling High 27353366
2016 CIN85/RukL knockout in diabetic mice prevents nephrin internalization, preserves nephrin surface expression on the slit diaphragm, and reduces proteinuria; conversely, CIN85 overexpression in zebrafish induces edema and filtration barrier disruption. Knockout mouse model (diabetic), zebrafish overexpression, nephrin surface expression, proteinuria measurement Diabetes High 27531950
2018 Germline deletion of CIN85 in humans causes X-linked antibody deficiency with intact immune cell development but intrinsic B cell defects in NF-κB activation and CD86 upregulation downstream of BCR, establishing non-redundant in vivo roles of CIN85 in humoral immunity. Human germline genetics, B cell functional assays (NF-κB activation, CD86 expression) The Journal of experimental medicine High 29636373
2019 CIN85 is a novel binding partner of PHD2 (but not PHD1 or PHD3); the N-terminal SH3 domains of CIN85 interact with the proline-arginine-rich N-terminus of PHD2, inhibiting PHD2 hydroxylase activity and thereby stabilizing HIF-1α; CRISPR disruption of the CIN85–PHD2 interaction in cells impairs tumor growth and migration. Co-immunoprecipitation, PHD2 enzymatic activity assay, CRISPR/Cas9 editing, in vivo xenograft Cancer research High 31142511
2019 After TCR stimulation, CIN85 is recruited to the TCR signaling complex and limits T cell activation; CIN85-deficient T cells show enhanced Zap70, SLP76, and ERK phosphorylation; the inhibitory function requires CIN85 SH3 and PR domains and involves association with the phosphatase Sts-2. T cell-specific conditional knockout, signaling analysis (phospho-western), co-immunoprecipitation, domain mutagenesis Science signaling High 30723173
2022 CIN85 localizes to the intercellular bridge during cytokinesis; CIN85 directly interacts with the N-terminal region of anillin and SEPT9, facilitating SEPT9-containing filament localization to the ICB plasma membrane; loss of CIN85 impairs cytokinesis timing and robustness. siRNA knockdown, co-immunoprecipitation, live cell imaging, direct in vitro binding Cell reports High 36044846
2023 ASAP2 directly binds CIN85, disrupting its interaction with c-MET and thereby antagonizing CIN85-induced c-MET internalization and lysosomal degradation; CIN85 knockdown rescues the inhibitory effects of ASAP2 knockdown on HGF/c-MET signaling. Co-immunoprecipitation, cycloheximide chase, siRNA epistasis knockdown experiments Experimental hematology & oncology Medium 37061723
2023 An intramolecular SH3C:PRM interaction within CIN85 (between C-terminal SH3 domain and adjacent PRM) autoinhibits CIN85 valency toward SLP65; phosphorylation of a serine residue adjacent to the PRM modulates this intramolecular interaction; disrupting it impairs SLP65/CIN85 condensate formation, membrane recruitment of CIN85, and BCR-induced Ca2+ mobilization. High-resolution NMR, mutagenesis, B cell functional assays (Ca2+ flux, membrane recruitment) Journal of the American Chemical Society High 38111344
2024 SH3KBP1 enhances RIG-I signal transduction by increasing K63-linked polyubiquitination through interaction with E3 ligase TRIM25; PRRSV NSP2 induces autophagic degradation of SH3KBP1 via the third PVPAPR motif in NSP2; Sh3kbp1−/− mice are more susceptible to VSV infection with reduced serum IFN-β. Co-immunoprecipitation, ubiquitination assays, knockout mouse model, VSV infection, autophagy assays PLoS pathogens High 39466846
2025 SH3KBP1 N-terminus binds dynamin-2 and C-terminus associates with ER through calnexin; SH3KBP1 is required for myoblast fusion, myonuclear positioning, and myotube elongation; SH3KBP1 contributes to triad formation and excitation-contraction coupling in mature muscle fibers. siRNA screen, co-immunoprecipitation, domain mapping, excitation-contraction coupling assays, Dnm2 mutant mouse model EMBO reports High 40065183
2025 CIN85 is recruited to tubular recycling endosomes (TREs) via SH3-domain interaction with MICAL-L1; depletion of CIN85 impairs recycling of CD98 cargo; CIN85 likely regulates TRE function through effects on the actin cytoskeleton. Co-immunoprecipitation, siRNA knockdown, fluorescence live imaging, recycling assays Traffic (Copenhagen, Denmark) Medium 40740057
2025 SH3KBP1 is recruited to bleb necks where it interacts with septins and recruits PI3K via liquid-liquid phase separation; the Septin–SH3KBP1–PI3K axis establishes differential PI(3,4,5)P3 enrichment at bleb membranes and confers anoikis resistance. Fluorescence microscopy, co-immunoprecipitation, phase-separation assays, PI assays, anoikis resistance functional assays American journal of physiology. Cell physiology Medium 40445717
2003 CIN85 associates with disabled-2 (Dab2) via all three SH3 domains binding the PKPAPR motif in Dab2; this association recruits CIN85 to clathrin-coated structures; upon growth factor stimulation, Dab2 and clathrin dissociate from CIN85, enabling Cbl binding to CIN85. Co-immunoprecipitation, domain mapping, clathrin association assays FEBS letters Medium 14596919
2004 Multiple domains of CIN85 (SH3 domains and coiled-coil) interact with the p85α regulatory subunit of PI3K; the SH3 domain of p85α is required to outcompete intramolecular SH3–PRR interaction within CIN85; homodimerization via coiled-coil affects both intra- and intermolecular CIN85 interactions. GST pulldown, domain deletion/mutation analyses, binding competition assays Journal of molecular biology Medium 15476827
2006 CIN85 is localized at synapses; its first SH3 domain and C-terminal region bind the proline-rich region and N-terminal region of dendrin, respectively; CIN85, dendrin, and S-SCAM form a ternary complex in vitro that facilitates recruitment of dendrin and S-SCAM to CIN85-positive vesicle-like structures. Yeast two-hybrid, co-immunoprecipitation, immunocytochemistry, subcellular fractionation, in vitro complex reconstitution Journal of biochemistry Medium 16751601
2009 Intersectin 1 (ITSN1) constitutively forms a complex with CIN85/Ruk independent of EGF stimulation; the interaction is mediated by ITSN1 SH3A domain and the third/fourth proline-rich blocks of CIN85; both proteins co-localize with c-Cbl in MCF-7 cells. Co-immunoprecipitation, domain mapping, confocal co-localization Cellular signalling Low 19166927
2014 Basic amino acids K645, K646, R648 and R650 in the CIN85 coiled-coil domain are required for interaction with both c-Cbl and phosphatidic acid; their mutation dissociates CIN85 from endosomes and prevents ESCRT assembly on endosomal membranes, blocking EGFR sorting for degradation. Mutagenesis, co-immunoprecipitation, phosphatidic acid binding assay, ESCRT co-IP, EGFR degradation assay BMC biochemistry Medium 25005938
2016 CIN85 interacts with the catalytic subunit of PP2A via a PPKKPRP motif (P3 block) in its proline-rich region; purified PP2Ac-CIN85 complex exhibits suppressed phosphatase activity; disruption of PP2Ac-CIN85 interaction by cell-permeable P3 peptide reduces platelet spreading on fibrinogen and thrombus-related functions. Yeast two-hybrid, mutagenesis, in vitro PP2A phosphatase activity assay, cell-permeable peptide, ECIS cell adhesion The Journal of biological chemistry High 27334924
2011 SOX10 binds a highly conserved element within an alternative promoter of the Sh3kbp1 locus in Schwann cells; mutation of the SOX10 binding site ablates promoter activity; ectopic SOX10 expression drives endogenous Sh3kbp1 expression in SOX10-negative cells. Reporter gene assay, electrophoretic mobility shift/ChIP-equivalent, ectopic SOX10 expression, mutagenesis Molecular and cellular neurosciences Medium 22037207
2025 SH3KBP1 co-localizes with MYO1F, CD2AP, ASAP1, and SH3BP2 at podosomes and phagocytic cups in macrophages/microglia; structural modelling and mutagenesis confirmed multivalent proline-rich motif interactions between SH3KBP1 and the MYO1F SH3 domain. Proximity labelling proteomics, structural modelling, mutagenesis, immunofluorescence Journal of cell science Medium 41208482

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors. Nature 470 11894095
2002 The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met. Nature 370 11894096
2002 CIN85/CMS family of adaptor molecules. FEBS letters 163 12354621
2000 Cloning and characterization of a novel adaptor protein, CIN85, that interacts with c-Cbl. Biochemical and biophysical research communications 133 10679202
2002 Cbl-directed monoubiquitination of CIN85 is involved in regulation of ligand-induced degradation of EGF receptors. Proceedings of the National Academy of Sciences of the United States of America 125 12218189
2003 Identification of a novel proline-arginine motif involved in CIN85-dependent clustering of Cbl and down-regulation of epidermal growth factor receptors. The Journal of biological chemistry 106 12874286
2004 CIN85 associates with multiple effectors controlling intracellular trafficking of epidermal growth factor receptors. Molecular biology of the cell 104 15090612
2004 Alix/AIP1 antagonizes epidermal growth factor receptor downregulation by the Cbl-SETA/CIN85 complex. Molecular and cellular biology 101 15456872
2002 CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases. The Journal of biological chemistry 101 12177062
2003 Linking the T cell surface protein CD2 to the actin-capping protein CAPZ via CMS and CIN85. The Journal of biological chemistry 96 12690097
2003 SETA/CIN85/Ruk and its binding partner AIP1 associate with diverse cytoskeletal elements, including FAKs, and modulate cell adhesion. Journal of cell science 80 12771190
2004 The Rsp5 ubiquitin ligase binds to and ubiquitinates members of the yeast CIN85-endophilin complex, Sla1-Rvs167. The Journal of biological chemistry 71 14761940
2000 Characterization of the CIN85 adaptor protein and identification of components involved in CIN85 complexes. Biochemical and biophysical research communications 68 11071869
2005 Sprouty2 acts at the Cbl/CIN85 interface to inhibit epidermal growth factor receptor downregulation. EMBO reports 62 15962011
2011 The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85. The EMBO journal 59 21822214
2008 The Drosophila CD2AP/CIN85 orthologue Cindr regulates junctions and cytoskeleton dynamics during tissue patterning. The Journal of cell biology 59 18362180
2007 CIN85, a Cbl-interacting protein, is a component of AMAP1-mediated breast cancer invasion machinery. The EMBO journal 54 17255943
2010 CIN85/RukL is a novel binding partner of nephrin and podocin and mediates slit diaphragm turnover in podocytes. The Journal of biological chemistry 51 20457601
2003 Atypical recognition consensus of CIN85/SETA/Ruk SH3 domains revealed by target-assisted iterative screening. The Journal of biological chemistry 51 12829691
2010 The ORF3 protein of hepatitis E virus delays degradation of activated growth factor receptors by interacting with CIN85 and blocking formation of the Cbl-CIN85 complex. Journal of virology 46 20130058
2007 Structure and function analysis of the CMS/CIN85 protein family identifies actin-bundling properties and heterotypic-complex formation. Journal of cell science 45 17606992
2010 A Dyn2-CIN85 complex mediates degradative traffic of the EGFR by regulation of late endosomal budding. The EMBO journal 44 20711168
2010 Emerging roles of Ruk/CIN85 in vesicle-mediated transport, adhesion, migration and malignancy. Traffic (Copenhagen, Denmark) 41 20331533
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
2005 Herpes simplex virus 1 infected cell protein 0 forms a complex with CIN85 and Cbl and mediates the degradation of EGF receptor from cell surfaces. Proceedings of the National Academy of Sciences of the United States of America 38 15824310
2016 CIN85 Deficiency Prevents Nephrin Endocytosis and Proteinuria in Diabetes. Diabetes 36 27531950
2007 CD2AP/CIN85 balance determines receptor tyrosine kinase signaling response in podocytes. The Journal of biological chemistry 36 17213204
2005 CIN85 regulates the ligand-dependent endocytosis of the IgE receptor: a new molecular mechanism to dampen mast cell function. Journal of immunology (Baltimore, Md. : 1950) 36 16177060
2009 Proteins recruited by SH3 domains of Ruk/CIN85 adaptor identified by LC-MS/MS. Proteome science 35 19531213
2013 Altered glycosylation of MUC1 influences its association with CIN85: the role of this novel complex in cancer cell invasion and migration. Oncotarget 33 24072600
2010 CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice. The EMBO journal 33 20551902
2003 Dab2 links CIN85 with clathrin-mediated receptor internalization. FEBS letters 33 14596919
2006 CFBP is a novel tyrosine-phosphorylated protein that might function as a regulator of CIN85/CD2AP. The Journal of biological chemistry 28 16895919
2012 TRAIL/MEKK4/p38/HSP27/Akt survival network is biphasically modulated by the Src/CIN85/c-Cbl complex. Cellular signalling 25 23085457
2011 CIN85 drives B cell responses by linking BCR signals to the canonical NF-kappaB pathway. The Journal of experimental medicine 25 21708930
2009 CIN85 associates with endosomal membrane and binds phosphatidic acid. Cell research 25 19417776
2008 Interactions between the three CIN85 SH3 domains and ubiquitin: implications for CIN85 ubiquitination. Biochemistry 25 18680311
2018 Germline deletion of CIN85 in humans with X chromosome-linked antibody deficiency. The Journal of experimental medicine 23 29636373
2011 CIN85 interacting proteins in B cells-specific role for SHIP-1. Molecular & cellular proteomics : MCP 23 21725061
2010 Phosphorylation of human tristetraprolin in response to its interaction with the Cbl interacting protein CIN85. PloS one 23 20221403
2016 The adaptor protein CIN85 assembles intracellular signaling clusters for B cell activation. Science signaling 22 27353366
2011 SH3KBP1-binding protein 1 prevents epidermal growth factor receptor degradation by the interruption of c-Cbl-CIN85 complex. Cell biochemistry and function 22 21830225
2004 CIN85 associates with TNF receptor 1 via Src and modulates TNF-alpha-induced apoptosis. Experimental cell research 22 15707590
2011 CD2AP regulates SUMOylation of CIN85 in podocytes. Molecular and cellular biology 21 22203040
2005 CIN85 regulates the ability of MEKK4 to activate the p38 MAP kinase pathway. Biochemical and biophysical research communications 20 16256071
2011 ARAP1 association with CIN85 affects epidermal growth factor receptor endocytic trafficking. Biology of the cell 19 21275903
2007 The adaptor molecule CIN85 regulates Syk tyrosine kinase level by activating the ubiquitin-proteasome degradation pathway. Journal of immunology (Baltimore, Md. : 1950) 19 17675467
2006 CIN85 is localized at synapses and forms a complex with S-SCAM via dendrin. Journal of biochemistry 19 16751601
2015 Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis. Cancers 18 25675408
2012 CIN85 phosphorylation is essential for EGFR ubiquitination and sorting into multivesicular bodies. Molecular biology of the cell 18 22833562
2015 CIN85 modulates TGFβ signaling by promoting the presentation of TGFβ receptors on the cell surface. The Journal of cell biology 17 26169354
2011 CIN85 modulates the down-regulation of Fc gammaRIIa expression and function by c-Cbl in a PKC-dependent manner in human neutrophils. The Journal of biological chemistry 17 21372129
2009 Intersectin 1 forms a complex with adaptor protein Ruk/CIN85 in vivo independently of epidermal growth factor stimulation. Cellular signalling 17 19166927
2007 Abl-SH3 binding protein 2, 3BP2, interacts with CIN85 and HIP-55. FEBS letters 17 17306257
2019 Inhibition of T cell activation and function by the adaptor protein CIN85. Science signaling 16 30723173
2011 CIN85 regulates ubiquitination and degradative endosomal sorting of the EGF receptor. Experimental cell research 16 21635887
2010 Significance of PTPRZ1 and CIN85 expression in cervical carcinoma. Archives of gynecology and obstetrics 16 20882291
2008 Adaptor protein Ruk/CIN85 is associated with a subset of COPI-coated membranes of the Golgi complex. Traffic (Copenhagen, Denmark) 16 18266907
2004 Multiple domains of Ruk/CIN85/SETA/CD2BP3 are involved in interaction with p85alpha regulatory subunit of PI 3-kinase. Journal of molecular biology 16 15476827
2023 ASAP2 interrupts c-MET-CIN85 interaction to sustain HGF/c-MET-induced malignant potentials in hepatocellular carcinoma. Experimental hematology & oncology 15 37061723
2012 CIN85 is required for Cbl-mediated regulation of antigen receptor signaling in human B cells. Blood 15 22262777
2022 An anillin-CIN85-SEPT9 complex promotes intercellular bridge maturation required for successful cytokinesis. Cell reports 14 36044846
2021 E3 ligase-inactivation rewires CBL interactome to elicit oncogenesis by hijacking RTK-CBL-CIN85 axis. Oncogene 14 33627783
2013 Inhibition of CIN85-mediated invasion by a novel SH3 domain binding motif in the lysyl oxidase propeptide. PloS one 14 24167568
2007 Regulation of the interaction of Disabled-1 with CIN85 by phosphorylation with Cyclin-dependent kinase 5. Genes to cells : devoted to molecular & cellular mechanisms 14 18076569
2014 Cbl-family ubiquitin ligases and their recruitment of CIN85 are largely dispensable for epidermal growth factor receptor endocytosis. The international journal of biochemistry & cell biology 13 25449262
2012 Increased levels of the HER1 adaptor protein Rukl/CIN85 contribute to breast cancer malignancy. Carcinogenesis 13 22791810
2011 SOX10 regulates expression of the SH3-domain kinase binding protein 1 (Sh3kbp1) locus in Schwann cells via an alternative promoter. Molecular and cellular neurosciences 13 22037207
2019 The Pro-Oncogenic Adaptor CIN85 Acts as an Inhibitory Binding Partner of Hypoxia-Inducible Factor Prolyl Hydroxylase 2. Cancer research 12 31142511
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
2009 Novel insights into the mechanisms of CIN85 SH3 domains binding to Cbl proteins: solution-based investigations and in vivo implications. Journal of molecular biology 12 19268472
2006 Expression of adaptor protein Ruk/CIN85 isoforms in cell lines of various tissue origins and human melanoma. Experimental oncology 12 17285110
2024 Porcine reproductive and respiratory syndrome virus nonstructural protein 2 promotes the autophagic degradation of adaptor protein SH3KBP1 to antagonize host innate immune responses by enhancing K63-linked polyubiquitination of RIG-I. PLoS pathogens 11 39466846
2014 The basic amino acids in the coiled-coil domain of CIN85 regulate its interaction with c-Cbl and phosphatidic acid during epidermal growth factor receptor (EGFR) endocytosis. BMC biochemistry 11 25005938
2004 Studying protein isoforms of the adaptor SETA/CIN85/Ruk with monoclonal antibodies. Biochemical and biophysical research communications 11 15522216
2021 SH3KBP1 Promotes Glioblastoma Tumorigenesis by Activating EGFR Signaling. Frontiers in oncology 10 33643898
2013 Dab1-mediated colocalization of multi-adaptor protein CIN85 with Reelin receptors, ApoER2 and VLDLR, in neurons. Genes to cells : devoted to molecular & cellular mechanisms 10 23506116
2013 Multimeric and differential binding of CIN85/CD2AP with two atypical proline-rich sequences from CD2 and Cbl-b*. The FEBS journal 10 23663663
2018 Biochemical and Structural Studies of the Interaction between ARAP1 and CIN85. Biochemistry 9 29589748
2011 Simulating EGFR-ERK signaling control by scaffold proteins KSR and MP1 reveals differential ligand-sensitivity co-regulated by Cbl-CIN85 and endophilin. PloS one 9 21829671
2023 Autoinhibition in the Signal Transducer CIN85 Modulates B Cell Activation. Journal of the American Chemical Society 8 38111344
2013 Adaptor protein complex of FRS2β and CIN85/CD2AP provides a novel mechanism for ErbB2/HER2 protein downregulation. Cancer science 7 23279575
2020 High expression of CIN85 promotes proliferation and invasion of human esophageal squamous cell carcinoma. Molecular medicine reports 6 33179079
2023 The Rab GTPase-binding protein EHBP1L1 and its interactors CD2AP/CIN85 negatively regulate the length of primary cilia via actin remodeling. The Journal of biological chemistry 5 36754282
2011 Making ends meet: the importance of the N- and C-termini for the structure, stability, and function of the third SH3 domain of CIN85. Biochemistry 5 21446695
2010 The adaptor protein Ruk/CIN85 activates plasminogen activator inhibitor-1 (PAI-1) expression via hypoxia-inducible factor-1alpha. Thrombosis and haemostasis 5 20216986
2024 Quantitative description of the phase-separation behavior of the multivalent SLP65-CIN85 complex. PNAS nexus 4 38463037
2021 In Silico Identification of Potential Druggable Binding Sites on CIN85 SH3 Domain. International journal of molecular sciences 4 33430321
2016 A Novel Interaction of the Catalytic Subunit of Protein Phosphatase 2A with the Adaptor Protein CIN85 Suppresses Phosphatase Activity and Facilitates Platelet Outside-in αIIbβ3 Integrin Signaling. The Journal of biological chemistry 4 27334924
2012 Dab1 stabilizes its interaction with Cin85 by suppressing Cin85 phosphorylation at serine 587. FEBS letters 4 23178720
2005 Overexpression of CIN85 suppresses the growth of herpes simplex virus in HeLa cells. Experimental cell research 4 16223483
2025 SH3KBP1 promotes skeletal myofiber formation and functionality through ER/SR architecture integrity. EMBO reports 3 40065183
2025 Feature gene selection and functional validation of SH3KBP1 in infantile hemangioma using machine learning. Biochemical and biophysical research communications 2 39955954
2025 Blebs regulate phosphoinositide distribution and promote cell survival through the Septin-SH3KBP1-PI3K axis. American journal of physiology. Cell physiology 2 40445717
2025 The MYO1F interactome reveals ASAP1, CD2AP and SH3KBP1 as novel adaptor proteins in podosomes and phagosomes. Journal of cell science 2 41208482
2025 CIN85 and CD2AP Are Novel Constituents of Dynamic Tubular Recycling Endosomes That Regulate Recycling Upon Recruitment by MICAL-L1. Traffic (Copenhagen, Denmark) 1 40740057
2021 Exploring Molecular Contacts of MUC1 at CIN85 Binding Interface to Address Future Drug Design Efforts. International journal of molecular sciences 1 33672244
2014 Multiple molecular forms of adaptor protein Ruk/CIN85 specifically associate with different subcellular compartments in human breast adenocarcinoma MCF-7 cells. Ukrainian biochemical journal 1 25816594
2011 Lentiviral vector-mediated siRNA knockdown and concurrent rescue of Murine CIN85. Journal of biochemical and molecular toxicology 1 21400643