Affinage

Showing SH3KBP1 — CIN85 is a alias.

SH3KBP1

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

Length
665 aa
Mass
73.1 kDa
Annotated
2026-06-10
100 papers in source corpus 57 papers cited in narrative 58 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SH3KBP1 (CIN85) is a multidomain adaptor that organizes receptor downregulation and assembly of multiprotein signaling complexes through its three SH3 domains, proline-rich region, and self-associating coiled-coil (PMID:11894095, PMID:10679202, PMID:12874286). Its SH3 domains recognize an atypical PX(P/A)XXR/PXXXPR proline-arginine motif, allowing it to bind Cbl/Cbl-b and a wide array of endocytic effectors and to cluster them into high-molecular-weight complexes; full-length CIN85 can simultaneously engage multiple Cbl molecules to promote receptor degradation (PMID:12874286, PMID:12829691, PMID:15090612). Upon growth factor stimulation it is recruited by Cbl to activated RTKs, where together with constitutively bound endophilins it controls internalization and lysosomal degradation of EGFR and c-Met (PMID:11894095, PMID:11894096). CIN85 couples to the endocytic and sorting machinery through stimulation-induced binding to dynamin-2 at late endosomes and Src-dependent phosphorylation that drives ubiquitinated EGFR into multivesicular bodies, while its coiled-coil/basic C-terminus binds phosphatidic acid on endosomal membranes to enable ESCRT assembly and cargo sorting (PMID:20711168, PMID:22833562, PMID:19417776, PMID:25005938). It is itself a substrate of regulatory modification, being monoubiquitinated by Cbl/Cbl-b and competing with ubiquitin for its own SH3 ligand-binding surface, with disruption of ubiquitin binding causing constitutive CIN85 and EGFR ubiquitination (PMID:12218189, PMID:18680311). CIN85 broadly tunes receptor trafficking across many systems, mediating endocytosis of nephrin in podocytes, D2 dopamine receptors in striatal neurons, FcεRI in mast cells, FcγRIIa in neutrophils, and recycling of TβRI, and its activity is gated by competitive binding partners (Sprouty2, SHKBP1, ASAP2, Alix) that displace it from Cbl or its receptor targets (PMID:20457601, PMID:20551902, PMID:16177060, PMID:21372129, PMID:26169354, PMID:15962011, PMID:21830225, PMID:37061723, PMID:15456872). In B cells CIN85 constitutively pre-assembles with SLP65/BLNK into oligomeric, condensate-forming complexes via its coiled-coil and SH3 domains, an interaction gated by an intramolecular SH3C:proline-rich autoinhibition under serine-phosphorylation control, priming BCR signaling and linking the receptor to IKK-β–dependent NF-κB activation (PMID:21822214, PMID:27353366, PMID:38111344, PMID:21708930). Germline loss of CIN85 in humans causes an X-linked antibody deficiency with B cell-intrinsic defects in BCR-driven NF-κB activation (PMID:29636373). Beyond trafficking and lymphocyte signaling, CIN85 inhibits HIF prolyl hydroxylase PHD2 to stabilize HIF-α (PMID:31142511), activates p38 MAPK through MEKK4 (PMID:16256071), suppresses PP2Ac phosphatase activity (PMID:27334924), crosslinks F-actin (PMID:17606992), and acts in cytokinesis, myofiber formation, ciliary length control, and RIG-I innate immune signaling through interactions with septins/anillin, dynamin-2/calnexin, EHBP1L1, and TRIM25 respectively (PMID:36044846, PMID:40065183, PMID:36754282, PMID:39466846).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 Medium

    Established the core architecture and first partners: how CIN85 engages Cbl and self-associates, defining it as a clustering adaptor rather than a simple linker.

    Evidence Yeast two-hybrid, Co-IP, and domain-deletion mutagenesis in EGF-stimulated cells, identifying Cbl binding via the second SH3 domain and coiled-coil-mediated tetramerization, plus BLNK/Crk/PI3K associations

    PMID:10679202 PMID:11071869

    Open questions at the time
    • Functional consequence of self-association not yet defined
    • No structural basis for SH3-ligand recognition
  2. 2002 High

    Defined CIN85's central role in RTK downregulation by showing it forms an endophilin-Cbl-receptor complex that drives internalization, and that it is itself monoubiquitinated and co-degraded with the receptor.

    Evidence Reciprocal Co-IP, dominant-negative inhibition, EGFR/c-Met internalization and degradation assays (two independent labs), plus in vitro ubiquitination with Cbl RING and acceptor-site mutagenesis

    PMID:11894095 PMID:11894096 PMID:12177062 PMID:12218189

    Open questions at the time
    • Whether internalization requirement is cell-type dependent
    • Endosomal sorting steps downstream of internalization not resolved
  3. 2003 High

    Defined the molecular grammar of CIN85 recognition — an atypical PX(P/A)XXR proline-arginine motif — explaining how it binds many partners and clusters multiple Cbl molecules to promote receptor degradation.

    Evidence Peptide library screening, ITC, mutagenesis, Far Western and GST-pulldown mapping the motif across Cbl, BLNK, Alix, CD2 and identifying additional interactors; CD2/CAPZ link to actin

    PMID:12690097 PMID:12829691 PMID:12874286

    Open questions at the time
    • Stoichiometry of multivalent complexes in cells not measured
    • Selectivity among the three SH3 domains incompletely defined
  4. 2004 Medium

    Showed CIN85 functions as a scaffold clustering endocytic effectors and revealed antagonistic regulators and an intramolecular autoinhibition relieved by partners.

    Evidence Co-IP/pulldown identifying SHIP-1, synaptojanin, ASAP1, ARAP3, Hip1R partners; siRNA and Co-IP for Alix antagonism; in vitro binding showing p85α SH3 relieves CIN85 SH3:PR autoinhibition; yeast Sla1/Rvs167 ortholog ubiquitination

    PMID:14761940 PMID:15090612 PMID:15456872 PMID:15476827

    Open questions at the time
    • Physiological balance between scaffolding and antagonist binding unquantified
    • Autoinhibition regulation in cells not yet shown
  5. 2005 Medium

    Extended CIN85 regulation to receptor trafficking control by competitive inhibitors and to MAPK and death-receptor signaling beyond pure endocytosis.

    Evidence Co-IP, domain mutagenesis and functional EGFR/FcεRI/TNFR1 assays for Sprouty2 inhibition, MEKK4-p38 activation, FcεRI internalization, and Src-mediated TNFR1 association

    PMID:15707590 PMID:15962011 PMID:16177060 PMID:16256071

    Open questions at the time
    • Whether p38 and apoptosis roles are direct or trafficking-dependent unclear
    • Most based on overexpression rather than endogenous loss-of-function
  6. 2008 High

    Provided the structural basis for ubiquitin/proline-rich ligand competition and mapped the endogenous CIN85 pool to Golgi COPI vesicles, broadening its trafficking remit.

    Evidence NMR modeling, ITC, mutagenesis showing ubiquitin binds the SH3 PPII surface and competes with ligands; immunofluorescence/fractionation localizing CIN85 to COPI-Golgi membranes

    PMID:18266907 PMID:18680311

    Open questions at the time
    • Functional role of ubiquitin-binding in vivo not fully resolved
    • Golgi function of CIN85 not mechanistically connected to RTK role
  7. 2010 High

    Defined the membrane-targeting and late-endosomal steps and broadened receptor scope, showing CIN85 binds phosphatidic acid and dynamin-2 to route receptors through endosomal sorting, and controls nephrin and D2 dopamine receptor endocytosis in vivo.

    Evidence Lipid-binding and domain-deletion assays; Co-IP and dominant-negative dynamin-2 studies; CD2AP-knockout podocyte and CIN85-knockout mouse analyses with endocytosis and behavioral readouts

    PMID:19417776 PMID:20457601 PMID:20551902 PMID:20711168

    Open questions at the time
    • Direct PA-binding residues not yet pinpointed
    • Tissue-specific receptor selectivity mechanism unclear
  8. 2011 High

    Established CIN85 as a constitutive organizer of the B-cell SLP65/BLNK complex required for BCR-driven Ca2+ and NF-κB responses via IKK-β, and as a regulator of immunoreceptor degradation across mast cells, neutrophils and B cells.

    Evidence MS interactome, live imaging, Ca2+ flux, and B cell-specific conditional knockout with IKK-β rescue; siRNA/overexpression Co-IP studies of Syk and FcγRIIa ubiquitination

    PMID:17675467 PMID:21372129 PMID:21708930 PMID:21725061 PMID:21822214 PMID:21830225 PMID:22262777

    Open questions at the time
    • Direct link between SLP65 scaffolding and NF-κB output mechanistically incomplete
    • How CIN85 switches between negative (Syk degradation) and positive (NF-κB) roles unclear
  9. 2016 High

    Revealed the biophysical basis of B-cell priming — CIN85 oligomerizes SLP65 into pre-formed condensates via its trimeric coiled-coil and multiple SH3 domains — and linked CIN85 to PP2Ac suppression and nephrin endocytosis in vivo.

    Evidence Biochemical oligomerization and structure-function assays in B cells; phosphatase activity assay and platelet functional readouts for PP2Ac; CIN85-knockout mouse and zebrafish overexpression for nephrin filtration barrier

    PMID:27334924 PMID:27353366 PMID:27531950

    Open questions at the time
    • Quantitative properties of condensates in resting cells unresolved
    • Phase behavior in vivo not directly demonstrated
  10. 2019 High

    Showed CIN85 acts as a negative regulator of TCR signaling via Sts-2 recruitment and inhibits PHD2 to stabilize HIF-α, expanding its roles into T-cell tolerance and hypoxia/tumor biology.

    Evidence Conditional knockout T cells with signaling and IL-2 readouts and Sts-2 Co-IP; binding, PHD2 hydroxylase activity assay, and CRISPR knock-in with tumor xenograft

    PMID:30723173 PMID:31142511

    Open questions at the time
    • How CIN85 partitions between activating and inhibitory immunoreceptor roles unresolved
    • Structural basis of PHD2 inhibition not defined
  11. 2022 Medium

    Established cytoskeletal and developmental roles, placing CIN85 at the intercellular bridge in cytokinesis, in myofiber formation, ciliary length control, and RIG-I innate immune signaling.

    Evidence Direct binding and live-cell imaging for anillin/SEPT9 in cytokinesis; Co-IP, domain binding and Dnm2 mouse for dynamin-2/calnexin in myogenesis; siRNA/EHBP1L1 rescue for cilia; Co-IP, KO mouse and recombinant virus for TRIM25/RIG-I

    PMID:36044846 PMID:36754282 PMID:39466846 PMID:40065183

    Open questions at the time
    • Mechanistic connection between adaptor scaffolding and septin filament assembly incomplete
    • Whether these roles share a common biochemical activity unclear
  12. 2023 High

    Defined phosphorylation-gated intramolecular autoinhibition controlling CIN85 valency toward SLP65 and identified further trafficking modulators that displace CIN85 from receptors.

    Evidence NMR of multidomain constructs with phosphomimetic mutagenesis and B cell Ca2+/recruitment assays; Co-IP and epistasis for ASAP2-c-MET

    PMID:37061723 PMID:38111344

    Open questions at the time
    • Kinase responsible for the regulatory serine phosphorylation not identified
    • How autoinhibition is relieved in vivo unresolved
  13. 2025 High

    Tested necessity of CIN85/Cbl for EGFR internalization and extended its trafficking roles to tubular recycling endosomes and bleb-associated phosphoinositide patterning.

    Evidence Cbl/Cbl-b double-knockout MEFs with inducible CIN85 siRNA and quantitative EGF internalization assays; siRNA and Co-IP for MICAL-L1/TRE recycling; phase-separation and biosensor assays for septin-PI3K bleb axis

    PMID:25449262 PMID:40445717 PMID:40740057

    Open questions at the time
    • Reconciliation of dispensability for internalization with earlier dominant-negative data unaddressed
    • Bleb phase-separation role rests on indirect evidence (Low confidence)

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CIN85 selects among its dozens of partners to switch between promoting versus inhibiting a given receptor, and how its condensate/oligomerization behavior is controlled across the many cell types in which it acts, remain unresolved.
  • No unifying model for partner-selection logic
  • Cell-type-specific regulatory inputs (kinases, modifications) largely uncharacterized
  • In vivo significance of phase separation beyond B cells unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0008289 lipid binding 2
Localization
GO:0005768 endosome 5 GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1 GO:0005929 cilium 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 1
Partners
CBLCBLBDNM2ENDOPHILINPHD2/EGLN1SEPT9SLP65/BLNKTRIM25
Complex memberships
SLP65/CIN85 oligomeric condensateendophilin-CIN85-Cbl complex

Evidence

Reading pass · 58 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 CIN85 constitutively associates with endophilins via SH3 domain interactions, and is rapidly recruited by Cbl to form a trimeric complex with activated EGF receptors upon EGF stimulation, controlling receptor internalization independently of Cbl ubiquitin ligase activity. Inhibition of CIN85-Cbl or CIN85-endophilin interactions blocks EGFR internalization and delays receptor degradation. Co-immunoprecipitation, dominant-negative inhibition, EGF receptor internalization/degradation assays Nature High 11894095
2002 The endophilin-CIN85-Cbl complex controls HGF receptor (c-Met) internalization; Cbl ubiquitinates activated c-Met and recruits the endophilin-CIN85 complex to regulate receptor internalization. Inhibition of complex formation blocks HGF receptor internalization and enhances HGF-induced signaling. Co-immunoprecipitation, dominant-negative inhibition, HGF receptor internalization assays Nature High 11894096
2000 CIN85 binds to c-Cbl via its second SH3 domain; this association is basally present and enhanced after EGF stimulation correlating with Cbl tyrosine phosphorylation. CIN85 self-associates through its coiled-coil region to form tetramers, and both SH3 domains and coiled-coil region contribute to subcellular localization. Co-immunoprecipitation, yeast two-hybrid, domain deletion mutagenesis, EGF stimulation assay Biochemical and biophysical research communications Medium 10679202
2000 CIN85 associates with BLNK (B cell linker protein) via its SH3 domains, with both proteins co-localizing in the cytoplasm, implicating CIN85 in BCR-mediated signaling. CIN85 also forms complexes with Crk-I, Crk-II, p130Cas, p85-PI3K, Grb2, and Sos1. Yeast two-hybrid screen, co-immunoprecipitation, immunostaining Biochemical and biophysical research communications Medium 11071869
2002 CIN85 and its homologue CMS are monoubiquitinated by Cbl/Cbl-b after EGF stimulation. Monoubiquitination requires direct CIN85-Cbl interaction, intact RING finger domain of Cbl, and a ubiquitin acceptor site in the CIN85 C-terminus. Cbl-b and monoubiquitinated CIN85 are degraded together with polyubiquitinated EGFRs in the lysosome. Co-immunoprecipitation, ubiquitination assay, RING finger domain mutagenesis, lysosomal degradation assay Proceedings of the National Academy of Sciences of the United States of America High 12218189
2003 CIN85 SH3 domains specifically recognize a novel polyproline-arginine motif (PXXXPR) present in Cbl/Cbl-b. Individual SH3 domains bind with micromolar affinity, while extended two- or three-SH3-domain constructs bind with higher stoichiometry and affinity. This enables full-length CIN85 to simultaneously bind multiple Cbl molecules, promoting their clustering, which is important for EGFR degradation. Peptide binding assays, isothermal titration calorimetry, mutagenesis, co-immunoprecipitation, receptor degradation assay The Journal of biological chemistry High 12874286
2002 Cbl-b, but not Cbl-3, utilizes the same CIN85/endophilin pathway as Cbl to down-regulate multiple RTKs (EGFR, PDGFR). CIN85 binds to the C-terminus of Cbl-b; inhibiting CIN85-Cbl-b interaction impairs EGFR internalization but not receptor polyubiquitination. Co-immunoprecipitation, dominant-negative inhibition, EGFR internalization and ubiquitination assays The Journal of biological chemistry High 12177062
2004 CIN85 SH3 domains bind to PxxxPR motifs in multiple endocytic effectors including SHIP-1, synaptojanin 2B1, ASAP1, ARAP3, Hip1R, STAP1, and p115RhoGEF, functioning as a molecular scaffold that clusters these proteins into high-molecular-weight complexes. ASAP1 overexpression increases EGFR recycling, an effect dependent on its intact PxxxPR motif. Co-immunoprecipitation, pulldown, overexpression/mutant studies, EGFR recycling assay Molecular biology of the cell Medium 15090612
2003 CIN85 and CMS/CD2AP SH3 domains bind to the CD2 cytoplasmic tail proline-rich segment, and CIN85/CMS directly bind to the actin-capping protein CAPZ via their C-terminal half, providing a molecular link between CD2 and the actin cytoskeleton. Overexpression of CMS/CIN85 fragments in T cells enhanced IL-2 production and reduced TCR downmodulation. Peptide affinity chromatography, BIAcore surface plasmon resonance, co-immunoprecipitation, functional T cell assays The Journal of biological chemistry Medium 12690097
2004 Alix/AIP1 antagonizes the Cbl-CIN85 complex by weakening the CIN85-Cbl interaction and reducing Cbl-mediated ubiquitination of EGFR and CIN85, thereby diminishing EGFR internalization. siRNA knockdown of Alix promoted EGFR internalization, confirming the inhibitory role. Co-immunoprecipitation, siRNA knockdown, ubiquitination assay, EGFR internalization assay Molecular and cellular biology Medium 15456872
2003 CIN85 SH3 domains bind to an atypical recognition consensus PX(P/A)XXR, confirmed by mutagenesis and in vitro binding. This motif maps CIN85-binding sites in c-Cbl, Cbl-b, BLNK, AIP1/Alix, and CD2. Novel interactors synaptojanin 1, PAK2, ZO-2, and TAFII70 were identified by GST-pulldown from brain lysates. Target-assisted iterative peptide library screening, mutagenesis, in vitro binding assays, GST pulldown, Far Western blotting The Journal of biological chemistry High 12829691
2003 Disabled-2 (Dab2) associates with all three SH3 domains of CIN85 via a PKPAPR motif and recruits CIN85 to the clathrin coat. This association is modulated by growth factor stimulation, whereby Dab2 and clathrin dissociate from CIN85 after growth factor treatment, enabling Cbl to bind. Co-immunoprecipitation, peptide binding, stimulation-dependent association studies FEBS letters Medium 14596919
2004 Yeast Sla1 is a functional ortholog of CIN85, with similar domain structure and direct binding to endophilin-like Rvs167. Rsp5 (yeast ubiquitin ligase) directly binds and monoubiquitinates Rvs167 at Lys481 in its SH3 domain, mediated through Rsp5 WW domains and PXY motifs in Rvs167. Genetic analysis, in vitro binding, ubiquitination assay, mutagenesis The Journal of biological chemistry Medium 14761940
2008 All three SH3 domains of CIN85 bind to ubiquitin at the canonical proline-rich ligand-binding surface, with ubiquitin mimicking a PPII helix. Ubiquitin and proline-rich ligands compete for the same binding surface. Disruption of ubiquitin binding results in constitutive CIN85 ubiquitination and elevated basal EGFR ubiquitination in the absence of EGF. NMR structural modeling, ITC, mutagenesis, EGFR ubiquitination assay Biochemistry High 18680311
2010 CIN85 binds to the coiled-coil domain of nephrin and podocin (not via SH3 domains), mediates nephrin internalization after FGF-4 stimulation, and promotes nephrin ubiquitination. CD2AP competes with CIN85 for binding to nephrin/podocin. In CD2AP-deficient podocytes, CIN85 accumulation correlates with increased nephrin ubiquitination. Co-immunoprecipitation, binding assays with domain mutants, immunofluorescence, internalization assay, CD2AP knockout mouse analysis The Journal of biological chemistry High 20457601
2010 CIN85 directly interacts with dynamin 2 (Dyn2) in a manner induced by EGFR stimulation; this interaction occurs late in the endocytic process at late endosomes. Disruption of CIN85-Dyn2 interaction causes accumulation of internalized EGFR in aberrantly elongated late endosomal tubules and sustained downstream signaling. Co-immunoprecipitation, dominant-negative studies, fluorescence microscopy of EGFR trafficking The EMBO journal Medium 20711168
2005 Sprouty2 associates with CIN85 via SH3 domains A and C binding proline-arginine motifs in Sprouty2, and acts at the Cbl-CIN85 interface to inhibit EGFR endocytosis and degradation. Sprouty4, which lacks CIN85-binding sites, does not inhibit EGFR downregulation. Co-immunoprecipitation, EGFR endocytosis/degradation assay, PC12 differentiation assay, domain mutagenesis EMBO reports Medium 15962011
2011 CIN85 constitutively associates with SLP65 (BLNK) in a stimulation-independent manner in B cells, which is required for SLP65 phosphorylation and inducible plasma membrane translocation. In the absence of a stable SLP65/CIN85 complex, BCR-induced Ca2+ and NF-κB responses are abrogated. Mass spectrometry interactome, co-immunoprecipitation, live cell imaging, loss-of-function studies, Ca2+ flux assay The EMBO journal High 21822214
2011 CIN85 links the BCR to IKK-β activation to drive canonical NF-κB signaling in B cells. B cell-specific CIN85 knockout mice show impaired T cell-independent type II antibody responses, diminished IKK-β activation, and defective BCR cross-linking responses, rescued by constitutively active IKK-β. B cell-specific conditional knockout mouse (Mb1-cre), in vivo antibody responses, IKK-β activation assay, constitutively active IKK-β rescue The Journal of experimental medicine High 21708930
2016 CIN85 oligomerizes SLP-65 in B cells through its trimeric coiled-coil domain and multiple SH3 domains, forming large signaling condensates/oligomeric complexes. This pre-formed oligomeric complex in resting B cells is required for efficient BCR signaling initiation. Biochemical oligomerization assays, co-immunoprecipitation, structure-function analysis with domain mutants, B cell functional assays Science signaling High 27353366
2010 CIN85 deficiency in mice (CIN85Δex2) leads to insufficient endophilin-D2 dopamine receptor (D2DR) complex formation in the striatum and decreased D2DR endocytosis in striatal neurons in response to dopamine, resulting in elevated striatal D2DR levels and dopamine, and hyperactive behavior. CIN85 localizes to the post-synaptic compartment of striatal neurons and co-clusters with D2DRs. Conditional knockout mouse, receptor endocytosis assay in striatal neurons, co-immunoprecipitation, immunofluorescence localization, behavioral analysis The EMBO journal High 20551902
2008 Drosophila Cindr (CD2AP/CIN85 ortholog) links E-cadherin and Roughest (IgCAM adhesion receptor) at cell junctions with actin cytoskeletal components including capping protein alpha and beta. Reduction of cindr activity causes defects in E-cadherin and Roughest localization, local cell movement, tissue patterning, and cell death in the developing retina. Drosophila genetics (loss-of-function), immunofluorescence, protein interaction studies, tissue phenotype analysis The Journal of cell biology High 18362180
2007 CIN85 colocalizes with AMAP1 at invadopodia in breast cancer cells; binding of AMAP1 to CIN85 is required for invasive activity including matrix degradation. CIN85 siRNA silencing inhibits invasion. Cbl monoubiquitinates AMAP1, and this monoubiquitination is important for AMAP1's role in invasion. siRNA knockdown, co-immunoprecipitation, invasion assay, immunofluorescence The EMBO journal Medium 17255943
2005 CIN85 associates with the TNFR1 signaling complex via Src family kinases (not directly with TNFR1 cytoplasmic domain); Src binds directly to TNFR1. Ectopic CIN85 expression increases susceptibility to TNF-α-induced apoptosis 10-fold. The three SH3 domains and proline-rich regions of CIN85 are essential for this pro-apoptotic effect. Co-immunoprecipitation, overexpression, apoptosis assay, domain deletion mutagenesis Experimental cell research Medium 15707590
2005 CIN85 overexpression in mast cells drives IgE receptor (FcεRI) internalization into early endosomes and lysosomes, reduces FcεRI expression levels, and dramatically impairs mast cell degranulation after antigen stimulation. Overexpression, confocal microscopy, receptor internalization/degradation assay, degranulation assay Journal of immunology Medium 16177060
2009 CIN85 associates with endosomal membranes through its positively charged C-terminus binding to phosphatidic acid (PA), with the coiled-coil domain essential for this protein-lipid interaction. Deletion of the coiled-coil domain abolishes membrane association, reduces c-Cbl interaction, and blocks EGFR downregulation. A significant pool of CIN85 localizes to EEA1-positive endosomal compartments. Lipid binding assay, domain deletion mutagenesis, subcellular fractionation, immunofluorescence, EGFR degradation assay Cell research Medium 19417776
2011 SHIP-1 constitutively associates with all three SH3 domains of CIN85 in B cells via a 79-amino acid region near the SHIP-1 C-terminus, identified by systematic pulldown proteomics. Pulldown proteomics, co-immunoprecipitation, domain mapping Molecular & cellular proteomics Medium 21725061
2012 Src kinase mediates tyrosine phosphorylation of CIN85 following EGFR activation; phospho-CIN85 interacts with Rab5-positive early endosomes and mediates sequestration of ubiquitinated EGFR into multivesicular bodies (MVBs). CIN85 knockdown decreases EGF-induced EGFR ubiquitination and reduces EGFR sorting to MVBs. siRNA knockdown, Src inhibition, phospho-specific analysis, co-immunoprecipitation, subcellular fractionation, immunofluorescence Molecular biology of the cell Medium 22833562
2015 CIN85 interacts with TβRI (TGFβ receptor type I) SH3 domains in a TRAF6-dependent manner upon TGFβ stimulation. CIN85 knockdown causes accumulation of TβRI in intracellular compartments and diminished Smad2 phosphorylation. CIN85 overexpression increases TβRI at the cell surface by promoting receptor recycling via a Rab11-dependent pathway, enhancing TGFβ-stimulated Smad2 phosphorylation, transcriptional responses, and cell migration. siRNA knockdown, overexpression, dominant-negative Rab11, Smad2 phosphorylation assay, transcriptional reporter, cell migration assay, Co-IP The Journal of cell biology Medium 26169354
2011 CIN85 regulates Syk protein levels in mast cells by promoting c-Cbl-mediated Syk ubiquitination and proteasomal degradation. CIN85 overexpression limits Cbl binding to Sts1 (a negative regulator of Cbl), while CIN85 knockdown favors Cbl/Sts1 complex formation, reducing Cbl-directed Syk ubiquitination. Overexpression, siRNA knockdown, co-immunoprecipitation, proteasome inhibition, ubiquitination assay Journal of immunology Medium 17675467
2011 In human B cells, CIN85 is constitutively associated with c-Cbl and Cbl-b, and increases c-Cbl phosphorylation. CIN85 overexpression inhibits BCR-induced calcium flux and phosphorylation of Syk and PLCγ2, correlating with increased Syk ubiquitination and degradation. CIN85 knockdown enhances BCR-induced survival, growth, and differentiation-associated gene expression. Overexpression, siRNA knockdown, co-immunoprecipitation, calcium flux assay, phosphorylation analysis, ubiquitination assay Blood Medium 22262777
2007 CMS/CIN85 can crosslink filamentous actin (F-actin) into bundles, a function dependent on the proline-rich region and coiled-coil domain. CMS/CIN85 are found in podosomes. CMS and CIN85 can form heterotypic complexes via their coiled-coil domains. Removal of these actin-bundling domains reduces cell migration. F-actin binding/bundling assays, domain deletion mutagenesis, cell migration assay, immunofluorescence Journal of cell science Medium 17606992
2011 CIN85 co-localizes with actin at focal adhesions and with microtubules, and CIN85 interacts with focal adhesion kinases FAK and PYK-2. CIN85 promotes cell adhesion as assessed by ECIS. Immunofluorescence co-localization, co-immunoprecipitation, ECIS (electrical cell-substrate impedance sensing) adhesion assay Journal of cell science Low 12771190
2006 CIN85 forms a complex with S-SCAM and dendrin at synapses; the first SH3 domain and the C-terminal region of CIN85 bind the proline-rich and N-terminal regions of dendrin, respectively. CIN85 localizes to synaptic compartments as shown by immunocytochemistry and subcellular fractionation. Yeast two-hybrid, co-immunoprecipitation, immunocytochemistry, subcellular fractionation, in vitro binding assay Journal of biochemistry Medium 16751601
2004 CIN85 interacts with the p85α regulatory subunit of PI3K through multiple domains: CIN85 SH3 domains are required and sufficient for binding full-length p85α, but the SH3 domain of p85α is required to activate this interaction by relieving an intramolecular autoinhibitory interaction between CIN85 SH3 domains and its proline-rich region. Co-immunoprecipitation, domain deletion/mutagenesis, in vitro binding assays Journal of molecular biology Medium 15476827
2009 Intersectin 1 (ITSN1) forms a constitutive complex with CIN85 mediated by the SH3A domain of ITSN1 and the third or fourth proline-rich blocks of CIN85, independent of EGF stimulation. Co-immunoprecipitation, domain mapping, immunofluorescence co-localization Cellular signalling Low 19166927
2008 CIN85 is distributed in multiple membrane trafficking compartments in human cells; the major endogenous pool associates with COPI-coated vesicles of the Golgi complex involved in retrograde ER-Golgi transport. This localization depends on Golgi complex integrity and intact microtubules. Immunofluorescence with compartment markers, subcellular fractionation, antibody characterization, Golgi disruption experiments Traffic (Copenhagen, Denmark) Medium 18266907
2010 CIN85 binds the catalytic subunit of protein phosphatase 2A (PP2Ac) via the P3 block (PAIPPKKPRP) in CIN85's proline-rich region; this interaction suppresses PP2Ac phosphatase activity. Disruption of PP2Ac-CIN85 interaction decreases platelet spreading and fibrin clot retraction and reduces phosphorylation of Src and GSK3β. Yeast two-hybrid, truncation/alanine mutagenesis, in vitro phosphatase activity assay, cell adhesion assay, clot retraction assay, cell-permeable peptide The Journal of biological chemistry Medium 27334924
2005 CIN85 SH3 domains interact with MEKK4 via three PxxxPR motifs; disruption of this interaction demonstrates that CIN85 binding to MEKK4 enhances MKK6 and p38 MAP kinase activation following oxidative stress and growth factor stimulation. CIN85 also regulates MEKK4 activation by GADD45 proteins and promotes MEKK4 multi-ubiquitination. Co-immunoprecipitation, dominant-negative inhibition, kinase activation assays, ubiquitination assay Biochemical and biophysical research communications Medium 16256071
2010 CD2AP regulates SUMOylation of CIN85 in podocytes; full-length CIN85 is SUMOylated by SUMO-1, -2, and -3, and SUMOylation is enhanced in the presence of CD2AP. Mutation of lysine 598 to arginine abolishes CIN85 SUMOylation and leads to increased CIN85 binding to nephrin. SUMOylation assay, site-directed mutagenesis (K598R), co-immunoprecipitation, podocyte cell culture Molecular and cellular biology Medium 22037207
2016 CIN85 (RukL isoform) deficiency in mice preserves nephrin surface expression on the slit diaphragm and reduces proteinuria under diabetic conditions; CIN85/RukL overexpression in zebrafish causes severe edema and disruption of the filtration barrier. CIN85/RukL mediates nephrin endocytosis via ubiquitination in podocytes. CIN85 knockout mouse under diabetic conditions, zebrafish overexpression, nephrin surface expression assay, proteinuria measurement Diabetes High 27531950
2014 Basic amino acids K645, K646, R648, and R650 in the CIN85 coiled-coil domain are required for both phosphatidic acid binding and c-Cbl interaction but not endophilin interaction. CIN85 also interacts with ESCRT components, and mutations in the coiled-coil domain dissociate CIN85 from endosomes and prevent ESCRT assembly on endosomal membranes, inhibiting EGFR sorting. Site-directed mutagenesis, lipid binding assay, co-immunoprecipitation, EGFR sorting/degradation assay, immunofluorescence BMC biochemistry Medium 25005938
2011 CIN85 depletion by siRNA in neutrophils prevents FcγRIIa ubiquitination and degradation by c-Cbl following receptor cross-linking, increases IgG-mediated phagocytosis, and disrupts proper FcγRIIa endosomal sorting. CIN85 is a substrate of classical PKCs, which positively regulate FcγRIIa ubiquitination/degradation. siRNA knockdown, co-immunoprecipitation, ubiquitination assay, phagocytosis assay, PKC inhibition, confocal microscopy The Journal of biological chemistry Medium 21372129
2019 CIN85 inhibits T cell activation by being recruited to the TCR signaling complex upon stimulation; CIN85-deficient T cells show enhanced TCR signaling (Zap70, SLP76, Erk phosphorylation) and increased IL-2 production. The inhibitory function requires CIN85 SH3 and PR regions, which associate with the phosphatase Sts-2 after TCR stimulation. Conditional knockout T cells, T cell activation assays, signaling phosphorylation analysis, co-immunoprecipitation, domain mutant studies Science signaling High 30723173
2018 Germline deletion of CIN85 in humans with X-linked antibody deficiency causes B cell-intrinsic defects in BCR effector pathways, most notably NF-κB activation and CD86 upregulation, without affecting immune cell compartment development. Human genetic analysis, functional B cell assays (NF-κB activation, CD86 upregulation), immune cell phenotyping The Journal of experimental medicine High 29636373
2019 CIN85 binds directly to PHD2 (the main HIF prolyl hydroxylase) via CIN85 N-terminal SH3 domains interacting with the proline-arginine-rich N-terminus of PHD2, but not PHD1 or PHD3. This interaction inhibits PHD2 hydroxylase activity and HIF degradation. CRISPR/Cas9 disruption of the CIN85-PHD2 interaction in cells affects growth, migration, and tumor growth in mice. Co-immunoprecipitation, PHD2 hydroxylase activity assay, CRISPR/Cas9 knock-in, tumor xenograft Cancer research High 31142511
2022 CIN85 interacts directly with the N-terminal region of anillin and with SEPT9 to facilitate SEPT9-containing septin filament localization to the intercellular bridge (ICB) plasma membrane during cytokinesis. CIN85 is required for robust and timely cytokinesis and ICB elongation and maturation. Co-immunoprecipitation, direct binding assay, siRNA knockdown, live-cell imaging of cytokinesis, immunofluorescence Cell reports High 36044846
2023 An intramolecular autoinhibitory interaction occurs between the CIN85 SH3C domain and an adjacent proline-rich motif (PRM) in the linker region. Phosphorylation of a serine adjacent to this PRM regulates the intramolecular SH3:PRM interaction, modulating CIN85 valency toward SLP65. Disruption of this interaction impairs SLP65/CIN85 condensate formation, CIN85 membrane recruitment, and Ca2+ mobilization in B cells. NMR spectroscopy of multidomain constructs, phosphomimetic mutagenesis, B cell functional assays (Ca2+ flux, membrane recruitment) Journal of the American Chemical Society High 38111344
2025 SH3KBP1 N-terminus binds directly to dynamin-2 and C-terminus associates with the ER through calnexin; these interactions control myonuclei dynamics and ER integrity respectively during myofiber formation. SH3KBP1 is required for myoblast fusion, myonuclear positioning, myotube elongation, triad formation, and efficient excitation-contraction coupling. siRNA screen, co-immunoprecipitation (dynamin-2, calnexin), domain binding assays, live-cell imaging, functional excitation-contraction coupling assay, Dnm2R465W/+ mouse model EMBO reports Medium 40065183
2025 SH3KBP1 recruits PI3K to bleb necks via liquid-liquid phase separation through interactions with septin, forming a Septin-SH3KBP1-PI3K axis that establishes differential phosphoinositide (PI3P/PIP2) distribution at bleb vs non-bleb membrane and confers anoikis resistance. Phase separation assay, co-immunoprecipitation, immunofluorescence with phosphoinositide biosensors, anoikis assay American journal of physiology. Cell physiology Low 40445717
2023 ASAP2 directly binds CIN85, disrupting the CIN85-c-MET interaction and preventing CIN85-induced c-MET internalization and lysosomal degradation, thereby sustaining HGF/c-MET signaling. CIN85 knockdown rescues the inhibitory effect of ASAP2 knockdown on c-MET signaling. Co-immunoprecipitation, cycloheximide chase, siRNA knockdown (ASAP2, CIN85), c-MET signaling assays Experimental hematology & oncology Medium 37061723
2011 SH3KBP1-binding protein 1 (SHKBP1) constitutively binds to CIN85 SH3 domains via its two PXXXPR motifs, competing with c-Cbl for CIN85 binding. This competition prevents CIN85 translocation to EGFR-containing vesicles, reduces EGFR degradation, and enhances EGF-induced signaling. Co-immunoprecipitation, dominant-negative inhibition, EGFR degradation assay, reporter gene assay Cell biochemistry and function Medium 21830225
2025 CIN85 and CD2AP are recruited to tubular recycling endosomes (TREs) via interactions with MICAL-L1 through their SH3 domains. Depletion of either CIN85 or CD2AP impairs receptor recycling (CD98 cargo), demonstrating their roles in TRE function. siRNA knockdown, co-immunoprecipitation, live-cell fluorescence imaging of TRE dynamics, recycling assays Traffic (Copenhagen, Denmark) Medium 40740057
2011 Cbl/Cbl-b double knockout MEFs retain largely normal EGFR internalization, and inducible siRNA knockdown of CIN85 in WT or Cbl/Cbl-b DKO MEFs has no impact on EGFR internalization. This demonstrates that endogenous CIN85, Cbl, and Cbl-b are largely dispensable for initial EGFR internalization, while Cbl is required for EGFR ubiquitination and degradation. Cbl/Cbl-b double-knockout MEFs, inducible siRNA knockdown of CIN85, 125I-EGF and fluorescent EGF internalization assay The international journal of biochemistry & cell biology High 25449262
2024 SH3KBP1 enhances RIG-I signal transduction by promoting K63-linked polyubiquitination through interaction with E3 ubiquitin ligase TRIM25. PRRSV NSP2 induces autophagic degradation of SH3KBP1 via its third polyproline-arginine motif (453PVPAPR458), counteracting innate immune signaling. Sh3kbp1 knockout mice show increased susceptibility to VSV with reduced IFN-β. Co-immunoprecipitation, mass spectrometry, ubiquitination assay, autophagy assay, knockout mouse, recombinant virus with motif deletion PLoS pathogens Medium 39466846
2010 HEV ORF3 protein (pORF3) interacts with CIN85 and thereby competes with growth factor receptor-Cbl-CIN85 complex formation, resulting in reduced CIN85 ubiquitination and delayed trafficking of the growth factor receptor complex to late endosomes/lysosomes. Co-immunoprecipitation, receptor trafficking assay, ubiquitination assay, pORF3 mutant analysis Journal of virology Medium 20130058
2011 SOX10 transcription factor directly regulates expression of an alternative CIN85 isoform in Schwann cells via a highly conserved SOX10 binding site within an alternative promoter at the Sh3kbp1 locus. Mutation of the SOX10 binding site ablates promoter activity, and ectopic SOX10 promotes endogenous Sh3kbp1 expression. ChIP, promoter reporter assay, site-directed mutagenesis, ectopic SOX10 expression Molecular and cellular neurosciences Medium 22037207
2023 The EHBP1L1-CIN85/CD2AP axis controls ciliary length via actin network remodeling; CIN85 and CD2AP localize to the ciliary sheath in an EHBP1L1-dependent manner, and their depletion causes elongated cilia with actin nucleation and branching defects around the ciliary base. siRNA knockdown, immunofluorescence microscopy, co-immunoprecipitation, rescue with EHBP1L1 mutants The Journal of biological chemistry Medium 36754282

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 471 11894095
2002 The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met. Nature 371 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 97 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 60 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) 42 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
2011 CIN85 interacting proteins in B cells-specific role for SHIP-1. Molecular & cellular proteomics : MCP 24 21725061
2018 Germline deletion of CIN85 in humans with X chromosome-linked antibody deficiency. The Journal of experimental medicine 23 29636373
2016 The adaptor protein CIN85 assembles intracellular signaling clusters for B cell activation. Science signaling 23 27353366
2010 Phosphorylation of human tristetraprolin in response to its interaction with the Cbl interacting protein CIN85. PloS one 23 20221403
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
2011 CD2AP regulates SUMOylation of CIN85 in podocytes. Molecular and cellular biology 22 22203040
2004 CIN85 associates with TNF receptor 1 via Src and modulates TNF-alpha-induced apoptosis. Experimental cell research 22 15707590
2005 CIN85 regulates the ability of MEKK4 to activate the p38 MAP kinase pathway. Biochemical and biophysical research communications 20 16256071
2015 Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis. Cancers 19 25675408
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
2023 ASAP2 interrupts c-MET-CIN85 interaction to sustain HGF/c-MET-induced malignant potentials in hepatocellular carcinoma. Experimental hematology & oncology 18 37061723
2012 CIN85 phosphorylation is essential for EGFR ubiquitination and sorting into multivesicular bodies. Molecular biology of the cell 18 22833562
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 18 21372129
2015 CIN85 modulates TGFβ signaling by promoting the presentation of TGFβ receptors on the cell surface. The Journal of cell biology 17 26169354
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
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 16 39466846
2022 An anillin-CIN85-SEPT9 complex promotes intercellular bridge maturation required for successful cytokinesis. Cell reports 16 36044846
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
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 15 25449262
2012 CIN85 is required for Cbl-mediated regulation of antigen receptor signaling in human B cells. Blood 15 22262777
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
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
2021 SH3KBP1 Promotes Glioblastoma Tumorigenesis by Activating EGFR Signaling. Frontiers in oncology 11 33643898
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
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
2023 Autoinhibition in the Signal Transducer CIN85 Modulates B Cell Activation. Journal of the American Chemical Society 9 38111344
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
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 Feature gene selection and functional validation of SH3KBP1 in infantile hemangioma using machine learning. Biochemical and biophysical research communications 3 39955954
2025 SH3KBP1 promotes skeletal myofiber formation and functionality through ER/SR architecture integrity. EMBO reports 3 40065183
2025 Blebs regulate phosphoinositide distribution and promote cell survival through the Septin-SH3KBP1-PI3K axis. American journal of physiology. Cell physiology 3 40445717
2025 CIN85 and CD2AP Are Novel Constituents of Dynamic Tubular Recycling Endosomes That Regulate Recycling Upon Recruitment by MICAL-L1. Traffic (Copenhagen, Denmark) 3 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
2026 Adaptor protein CIN85 potentiates the motility of osteosarcoma cells via the Akt/mTOR and MMP2-COL3A1 axis. Molecular oncology 0 41998852
2025 Herpes simplex virus diverts CIN85 endosomal cargo for exocytosis to evade antiviral responses: a novel role for the viral immediate-early protein ICP0. mBio 0 40990523

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