Affinage

SRCIN1

SRC kinase signaling inhibitor 1 · UniProt Q9C0H9

Length
1183 aa
Mass
127.1 kDa
Annotated
2026-04-28
73 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SRCIN1 (p140Cap) is a multidomain scaffold protein that coordinates Src family kinase inhibition, actin cytoskeleton remodeling, and membrane organization in both epithelial cells and neurons. In cancer cells, p140Cap recruits and activates Csk through Abl-phosphorylated EPLYA/EGLYA tyrosine motifs, thereby inhibiting Src and downstream Ras/Erk, STAT3, and Rac1/Tiam1 signaling; it additionally stabilizes the β-catenin destruction complex and promotes mevalonate pathway flux to modulate cholesterol-dependent membrane dynamics, collectively suppressing tumor growth, invasion, and metastasis (PMID:17525734, PMID:23383002, PMID:37169737, PMID:38123597). At synapses, p140Cap localizes to both pre- and postsynaptic compartments where it controls dendritic spine maturation through interactions with SNAP-25, cortactin, Citron-N, endophilin A1, and SNX17, organizes GluN2A/PSD-95 complexes into lipid rafts, and restrains GABAergic vesicle release; loss of p140Cap in mice impairs LTP/LTD, object recognition, and female fertility through reduced glutamatergic innervation of GnRH neurons (PMID:24453341, PMID:35953295, PMID:29161354, PMID:35237119).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2000 High

    The initial discovery that p140Cap/SNIP directly binds SNAP-25 via coiled-coil domains and inhibits Ca²⁺-dependent exocytosis established it as a regulator linking exocytic machinery to the cortical actin cytoskeleton, opening the question of its broader signaling roles.

    Evidence Yeast two-hybrid, biochemical pulldown, deletion mapping, and Ca²⁺-dependent exocytosis assay in PC12 cells

    PMID:10625663

    Open questions at the time
    • Whether SNAP-25 interaction is relevant in neurons in vivo was untested
    • Mechanism of actin cytoskeleton linkage undefined
    • No kinase regulatory function yet identified
  2. 2003 High

    Identification of p140Cap as a tyrosine-phosphorylated p130Cas-associated protein that delays cell spreading on fibronectin linked it to integrin/growth factor signaling and cytoskeletal regulation, beyond its exocytic role.

    Evidence Affinity chromatography, mass spectrometry identification, co-immunoprecipitation, cell spreading assay on fibronectin

    PMID:14657239

    Open questions at the time
    • Kinase responsible for tyrosine phosphorylation unknown
    • Direct mechanism of spreading inhibition unresolved
  3. 2007 High

    Demonstration that p140Cap inhibits Src kinase activity by activating Csk, with silencing increasing and overexpression decreasing Src-dependent migration/invasion and in vivo tumor growth, established the central tumor-suppressive mechanism.

    Evidence RNAi and overexpression in multiple breast cancer lines, kinase activity assays, co-IP, in vivo xenograft tumor growth

    PMID:17525734

    Open questions at the time
    • Phosphorylation sites mediating Csk recruitment not yet mapped
    • Src-independent tumor suppressive mechanisms not addressed
  4. 2008 High

    Localization of p140Cap to pre- and postsynaptic sites in brain and identification of vinexin as a synaptic partner extended the protein's function from cancer biology into neurobiology.

    Evidence Subcellular fractionation, electron microscopy, co-IP from rat brain synaptosomes with domain mapping

    PMID:18662323

    Open questions at the time
    • Functional synaptic consequence of p140Cap loss not yet tested
    • Relationship between Src inhibition and synaptic function unclear
  5. 2010 High

    Showing that p140Cap stabilizes E-cadherin at the membrane and independently inhibits both Src-dependent EGFR signaling and Ras/Erk pathway activation revealed dual control over epithelial cell proliferation and scattering.

    Evidence Gain/loss of function in breast and colon cancer cells, Ras activity assay, Erk phosphorylation, E-cadherin localization

    PMID:20453886

    Open questions at the time
    • Mechanism of Src-independent Ras inhibition not fully resolved
    • Direct versus indirect E-cadherin stabilization unclear
  6. 2011 High

    Mapping the cortactin SH3 domain as the direct binding interface and showing that p140Cap suppresses cortactin Y421 phosphorylation—with rescue by a phosphomimetic mutant—defined the molecular basis for metastasis suppression (80% reduction in lung metastases).

    Evidence Orthotopic transplantation in immunodeficient mice, co-IP, domain mapping, EGF-stimulated phosphorylation, phosphomimetic rescue

    PMID:21725361

    Open questions at the time
    • Whether cortactin inhibition operates through Src or an alternative kinase in vivo not fully distinguished
  7. 2013 High

    Identification of Abl as the kinase phosphorylating the EPLYA/EGLYA motifs and demonstration that these phosphotyrosines are required for Csk binding resolved how p140Cap activates Csk to inhibit Src, completing the upstream regulatory circuit.

    Evidence In vivo mass spectrometry phosphosite mapping, site-directed mutagenesis, in vitro kinase assay with Abl, Far Western, co-IP in HEK-293 cells

    PMID:23383002 PMID:23841028

    Open questions at the time
    • Whether Abl phosphorylation of p140Cap is regulated by specific upstream signals in tumors is undefined
    • Structural basis of p140Cap–Csk interaction unknown
  8. 2013 High

    Discovery that postsynaptic SNAP-25 binding to p140Cap is required for dendritic spine morphogenesis established a neuronal function beyond the original exocytosis role.

    Evidence shRNA knockdown and overexpression in neurons, spine morphology quantification, co-localization with PSD-95

    PMID:23868368

    Open questions at the time
    • Downstream signaling from SNAP-25–p140Cap to actin in spines not elucidated
  9. 2014 High

    p140Cap knockout mice showed impaired LTP/LTD, reduced mushroom spines, and disrupted object recognition; mechanistically, p140Cap locally inhibits RhoA and cortactin/cofilin through Src inhibition and Citron-N scaffolding, establishing it as a master organizer of synaptic actin dynamics.

    Evidence KO mouse model, behavioral testing, electrophysiology, phalloidin staining, co-IP with Citron-N, kinase assays

    PMID:24453341

    Open questions at the time
    • Relative contribution of Src-dependent versus Src-independent pathways in spine regulation not quantified
    • Role at presynaptic terminals in excitatory synapses not addressed
  10. 2015 High

    Identification of endophilin A1 as a direct upstream partner that regulates p140Cap distribution into spines revealed how p140Cap is recruited to postsynaptic sites to control cortactin and F-actin.

    Evidence GST pulldown, co-IP, shRNA knockdown with spine morphology and synaptic function readouts

    PMID:25771685

    Open questions at the time
    • Structural determinants of endophilin A1–p140Cap binding not resolved
    • Whether endophilin A1 also modulates p140Cap in non-neuronal cells unknown
  11. 2017 High

    Three parallel advances—(i) p140Cap dampening ERBB2/Rac1 signaling to suppress EMT and metastasis in vivo, (ii) presynaptic β-catenin requiring p140Cap to enhance excitatory transmission, and (iii) a synaptic interactome of 351 proteins—broadened p140Cap's role to Rac GTPase control in cancer and trans-synaptic signaling in brain.

    Evidence NeuT mouse model with Rac1 assays; conditional β-catenin expression with electrophysiology; co-IP/MS from synaptosomes

    PMID:28300085 PMID:28641114 PMID:28713243

    Open questions at the time
    • Mechanism linking presynaptic β-catenin–p140Cap to vesicle release probability not defined
    • Which of the 351 synaptic interactors are functionally required is unknown
  12. 2019 High

    Extension of the Src/STAT3 inhibitory mechanism to neuroblastoma, with demonstration that p140Cap increases chemosensitivity, generalized the tumor-suppressive activity beyond breast cancer and identified STAT3 as an additional downstream effector.

    Evidence SRCIN1 overexpression/silencing in neuroblastoma cells, xenograft models, Src/STAT3 activity assays, drug sensitivity assays

    PMID:31285546

    Open questions at the time
    • Whether p140Cap-mediated chemosensitization is solely through Src/STAT3 or involves additional pathways not resolved
  13. 2019 High

    Conditional knockout showed p140Cap is present in presynaptic GABAergic terminals and restrains inhibitory synaptogenesis and vesicle release, with loss causing increased seizure susceptibility, revealing a previously unknown role in inhibitory circuit homeostasis.

    Evidence Global and interneuron-specific conditional KO mice, patch-clamp electrophysiology, vesicle pool assays, seizure models, immunohistochemistry

    PMID:29161354

    Open questions at the time
    • Molecular target through which p140Cap restricts GABA vesicle release probability not identified
    • Whether Src inhibition mediates the presynaptic GABAergic phenotype untested
  14. 2020 High

    Mapping the N-terminal domain (1–287) as sufficient to bind Tiam1 and directly inhibit its GEF activity toward Rac1 provided a Src-independent mechanism for p140Cap's suppression of Rac1 signaling and E-cadherin stabilization.

    Evidence Domain truncation analysis, co-IP, Tiam1 GEF activity assay, E-cadherin immunofluorescence

    PMID:33415001

    Open questions at the time
    • Whether the Tiam1-binding and Csk-binding functions are coordinately regulated is unknown
    • No structural data for the N-terminal domain
  15. 2022 High

    Demonstrating that p140Cap directly binds GluN2A and is required for GluN2A/PSD-95 assembly in synaptic lipid rafts, with rescue in KO neurons, established a postsynaptic scaffolding function for NMDAR organization that explains the LTP/LTD deficits.

    Evidence Co-IP, synaptosome and lipid raft fractionation, gated-STED super-resolution microscopy, KO rescue, electrophysiology

    PMID:35953295

    Open questions at the time
    • How p140Cap promotes lipid raft recruitment of GluN2A/PSD-95 mechanistically is unclear
    • Relationship between cholesterol regulation (mevalonate pathway) and raft organization in neurons not tested
  16. 2022 High

    KO female mice showed severe hypofertility with reduced GnRH neurons and diminished glutamatergic synapses onto GnRH neurons, extending p140Cap's synaptic function to neuroendocrine reproductive control.

    Evidence KO mouse, immunohistochemistry for GnRH/VGLUT, hormone measurements, kisspeptin challenge

    PMID:35237119

    Open questions at the time
    • Whether p140Cap acts cell-autonomously in GnRH neurons or in their presynaptic partners is unresolved
    • Mechanism of GnRH neuron loss not determined
  17. 2023 High

    Two new tumor-suppressive mechanisms were defined: p140Cap stabilizes the β-catenin destruction complex to restrict tumor-initiating cell self-renewal and immunosuppressive G-CSF release, and it promotes mevalonate pathway flux to increase membrane cholesterol, reducing lipid raft Rac1 signaling and migration.

    Evidence Co-IP of destruction complex, β-catenin reporter, in vivo models, HMGCR activity/expression assays, cholesterol imaging, lipid raft fractionation, Rac1 assay

    PMID:37169737 PMID:38123597

    Open questions at the time
    • Whether β-catenin destruction complex stabilization and mevalonate regulation are mechanistically linked is unknown
    • Transcriptional versus post-translational contribution to HMGCR regulation not fully separated
  18. 2023 Medium

    Identification of SNX17 as a p140Cap interactor required for dendritic spine maturation added an endosomal trafficking component to the synaptic scaffold network.

    Evidence GST pulldown, interactome analysis, Snx17 haploinsufficient mice, spine morphology, electrophysiology

    PMID:37704928

    Open questions at the time
    • Direct mechanistic link between SNX17–p140Cap and spine actin remodeling not established
    • Whether SNX17 regulates p140Cap trafficking or vice versa is unclear
  19. 2025 High

    Quantitative biophysical mapping of the BIN1 SH3 domain–p140Cap interaction (KD 7.7 µM) and demonstration that a rare BIN1 coding variant disrupts this binding connected p140Cap to Alzheimer's disease-associated BIN1 biology.

    Evidence Surface plasmon resonance, alanine-scanning mutagenesis, proximity ligation assay in mouse brain, co-IP, confocal microscopy

    PMID:40889683

    Open questions at the time
    • Functional consequence of BIN1–p140Cap interaction at synapses not yet demonstrated
    • Whether the rare BIN1 variant affects synaptic p140Cap function in vivo is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of p140Cap's multivalent scaffold function, whether its cholesterol/mevalonate regulation in cancer cells operates in neurons to control lipid raft NMDAR assembly, and whether Src-dependent actin remodeling underlies its putative role in ciliogenesis.
  • No high-resolution structure for any p140Cap domain or complex
  • Integration of mevalonate/cholesterol regulation with synaptic lipid raft function untested
  • Ciliogenesis role reported only in a preprint and not independently validated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 7 GO:0098772 molecular function regulator activity 5 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 4 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-112316 Neuronal System 6 R-HSA-1500931 Cell-Cell communication 3 R-HSA-1430728 Metabolism 1
Partners
BIN1CITCSKCTNNB1CTTNGRIN2ASNAP25TIAM1
Complex memberships
β-catenin destruction complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 SRCIN1/p140Cap (identified as SNIP) was discovered as a novel SNAP-25-interacting protein; the interaction is mediated via coiled-coil domains, and overexpression of SNIP or its SNAP-25-interacting domain inhibits Ca2+-dependent exocytosis from PC12 cells. SNIP co-localizes with SNAP-25 and cortical actin cytoskeleton, suggesting it links SNAP-25 to the submembranous cytoskeleton. Yeast two-hybrid / biochemical pulldown, deletion analysis, co-localization by immunofluorescence, Ca2+-dependent exocytosis assay in PC12 cells The Journal of biological chemistry High 10625663
2003 p140Cap (SRCIN1) was identified as a p130Cas-associated protein that is tyrosine-phosphorylated upon integrin-mediated cell adhesion and EGF stimulation; it co-immunoprecipitates with p130Cas via its carboxy-terminal region, co-localizes with cortical actin and actin stress fibers (but not focal adhesions), and its expression delays cell spreading on fibronectin. Affinity chromatography, mass spectrometry, co-immunoprecipitation, immunofluorescence, cell spreading assay on fibronectin Molecular biology of the cell High 14657239
2007 p140Cap/SRCIN1 was characterized as a novel Src-binding protein that inhibits Src kinase activity through activation of C-terminal Src kinase (Csk). p140Cap silencing increases cell spreading, migration, and Src activity; increased p140Cap expression activates Csk, inhibits Src and downstream signaling, impairs cell motility/invasion, and suppresses in vivo breast cancer cell growth. RNAi silencing, overexpression, kinase activity assays, co-immunoprecipitation, in vivo tumor growth assay The EMBO journal High 17525734
2008 p140Cap is expressed in rat brain in a developmentally regulated manner, enriched in the synaptic plasma membrane fraction, localizes to pre- and post-synaptic sites by electron microscopy, and forms a complex with vinexin (via its third SH3 domain binding to the C-terminal Pro-rich motif of p140Cap) and with synaptophysin, suggesting roles in neurotransmitter release and synapse formation. Subcellular fractionation, immunohistochemistry, electron microscopy, co-immunoprecipitation from COS7 cells and rat brain, interaction domain mapping Journal of neurochemistry High 18662323
2010 p140Cap/SRCIN1 immobilizes E-cadherin at the cell membrane and inhibits EGFR and Erk1/2 signaling, blocking scatter and proliferation of cancer cells; this E-cadherin/EGFR cross-talk regulation is dependent on Src kinase inhibition. Additionally, p140Cap impairs Erk1/2 phosphorylation independently of Src by affecting Ras activity downstream of EGFR. Gain and loss of function (overexpression and silencing), western blotting for signaling molecules, cell motility assays, Ras activity assay Oncogene High 20453886
2011 p140Cap suppresses metastasis in vivo (80% reduction in lung metastases) and inhibits directional migration by associating with cortactin via its second proline-rich domain binding to the cortactin SH3 domain, inhibiting cortactin tyrosine phosphorylation (Y421) in response to EGF; a phosphomimetic cortactin Y421 mutant rescues migration in p140Cap-overexpressing cells. Orthotopic transplantation in Rag2-/-γc-/- mice, co-immunoprecipitation, domain binding mapping, EGF stimulation/phosphorylation assays, rescue with phosphomimetic mutant Oncogene High 21725361
2013 SNAP-25 binds p140Cap at the plasma membrane in postsynaptic compartments, and this interaction is required for spine morphogenesis; acute reduction of SNAP-25 leads to immature dendritic spines, while overexpression increases density of mature PSD-95-positive spines in a manner dependent on SNAP-25 binding to both the plasma membrane and p140Cap. shRNA knockdown, overexpression, immunofluorescence, co-localization, spine morphology analysis Nature communications High 23868368
2013 p140Cap is phosphorylated in vivo on tyrosine within the EGLYA motif (by mass spectrometry); mutagenesis of both EPLYA/EGLYA tyrosines abolishes tyrosine phosphorylation and eliminates binding to Csk. The Abelson (Abl) kinase is identified as the major kinase phosphorylating p140Cap on EPLYA and EGLYA sequences both in vitro and in HEK-293 cells. Mass spectrometry phosphoproteomics, site-directed mutagenesis, in vitro kinase assay, co-immunoprecipitation, Far Western analysis PloS one High 23383002
2013 The TER (Tyrosine Enriched Region) and CT (Carboxy Terminal) domains of p140Cap are each sufficient to associate with Csk and Src, inhibit Src activation, inhibit FAK phosphorylation, and impair in vitro and in vivo tumor cell migration and proliferation; the functional activity resides specifically on the two EPLYA/EGLYA tyrosines in TER and the second proline-rich stretch in CT. Stable cell line expression of truncation/point-mutant constructs, co-immunoprecipitation, kinase activity assays, in vitro migration assays, in vivo tumor growth American journal of cancer research High 23841028
2014 p140Cap knockout mice show impaired object recognition, LTP, and LTD; p140Cap-/- primary neurons have reduced mushroom spines and abnormal F-actin. p140Cap regulates spine actin organization through local inhibition of RhoA and cortactin/cofilin signaling, mediated by its ability to directly inhibit Src kinase activation and by binding to the scaffold protein Citron-N. Knockout mouse model, behavioral tests (object recognition), electrophysiology (LTP/LTD), phalloidin staining of F-actin, co-immunoprecipitation with Citron-N, kinase activity assays The Journal of neuroscience High 24453341
2015 Endophilin A1 localizes to dendritic spines and regulates spine morphogenesis through a direct downstream interaction with p140Cap; disruption of endophilin A1-p140Cap interaction impairs spine formation and maturation. Endophilin A1 regulates the distribution of p140Cap and its effector cortactin, as well as F-actin enrichment in spines. GST pulldown, co-immunoprecipitation, shRNA knockdown, immunofluorescence, spine morphology analysis, synaptic function assays Cell research High 25771685
2017 Presynaptic β-catenin expression stabilizes functional synapses and spines via anterograde signaling; p140Cap was identified as a β-catenin-interacting protein required in the presynaptic locus for mediating enhanced excitatory synaptic transmission, increased dendritic spine density, and elevated release probability of glutamatergic synapses. Co-immunoprecipitation, conditional expression of stabilized β-catenin in specific neuron layers, electrophysiology, spine density analysis Neuron High 28641114
2017 p140Cap/SRCIN1 dampens ERBB2-positive tumor cell progression by interfering with ERBB2-dependent activation of Rac GTPase-controlled circuitries, impairing tumor onset and growth in the NeuT mouse model and counteracting EMT to decrease metastasis formation. NeuT mouse tumor model, gain/loss of function, Rac1 activity assays, EMT markers, in vivo tumor growth and metastasis assessment Nature communications High 28300085
2017 p140Cap synaptic interactome (351 proteins) identified by co-immunoprecipitation from mouse synaptosomes followed by mass spectrometry; interactors cluster to postsynaptic density sub-complexes involved in synaptic transmission, actin cytoskeleton remodeling, and cell-cell junction organization. Co-immunoprecipitation from crude synaptosomes, mass spectrometry-based proteomics, bioinformatics network analysis Frontiers in molecular neuroscience High 28713243
2019 p140Cap/SRCIN1 negatively regulates Src and STAT3 signaling in neuroblastoma, suppresses anchorage-independent growth and migration, inhibits in vivo tumor growth and spontaneous lung metastasis formation, and increases sensitivity to doxorubicin/etoposide and Src inhibitors. Gain/loss of function (SRCIN1 overexpression and silencing), in vivo xenograft and spontaneous metastasis models, kinase activity assays (Src, STAT3), drug sensitivity assays Cell death and differentiation High 31285546
2019 p140Cap/SRCIN1 regulates GABAergic synaptogenesis: p140Cap is present in presynaptic GABAergic terminals, and its genetic depletion results in a larger synaptic vesicle readily releasable pool, increased mIPSC frequency without amplitude change, premature/enhanced network synchronization, increased susceptibility to seizures, and increased number of inhibitory synapses and parvalbumin/somatostatin interneurons. Specific deletion in forebrain interneurons recapitulates these phenotypes. p140Cap knockout mice, whole-cell patch-clamp electrophysiology, synaptic vesicle pool assays, in vitro and in vivo seizure models, immunohistochemistry, conditional interneuron-specific KO Cerebral cortex High 29161354
2020 The N-terminal domain of p140Cap (residues 1-287) is sufficient to interact with Tiam1 (full-length and truncated catalytic domain), causing Tiam1 redistribution to apicobasal junctions and decreased Tiam1 GEF activity toward Rac1, with concomitant increase of E-cadherin at the cell membrane. Co-immunoprecipitation, domain truncation/deletion analysis, GEF activity assay for Tiam1/Rac1, immunofluorescence of E-cadherin localization American journal of cancer research High 33415001
2022 p140Cap directly binds the GluN2A subunit of NMDA receptors and modulates the GluN2A-associated molecular network; in p140Cap KO mice, GluN2A association with PSD95 is reduced in synaptosomes and hippocampal neurons, and GluN2A/PSD95 are less recruited into synaptic lipid rafts. p140Cap KO rescue experiments restore GluN2A-PSD95 colocalization. Co-immunoprecipitation, synaptosome fractionation, lipid raft isolation, gated-STED microscopy, KO rescue, electrophysiology The Journal of neuroscience High 35953295
2022 p140Cap KO female mice exhibit severe hypofertility, delayed puberty, altered estrus cycle, reduced ovulation, and defective LH/estradiol production during proestrus; adult KO mice show loss of GnRH-ir neurons and reduced GnRH projections to the median eminence, without changes in kisspeptin signaling, but with significantly reduced density of glutamatergic (VGLUT-ir) synapses on GnRH neurons, indicating p140Cap controls female fertility via glutamatergic input to hypothalamic GnRH neurons. p140Cap KO mouse model, immunohistochemistry, hormone measurements (LH, estradiol), in vivo kisspeptin challenge, VGLUT immunostaining, GnRH neuron counting Frontiers in neuroscience High 35237119
2023 p140Cap inhibits β-Catenin by localizing in and stabilizing the β-Catenin destruction complex, promoting enhanced β-Catenin inactivation, thereby restricting tumorigenicity and self-renewal of tumor-initiating cells, limiting G-CSF release, and impairing polymorphonuclear myeloid-derived suppressor cell function. Transcriptomic analysis, co-immunoprecipitation of destruction complex components, β-Catenin activity reporter assays, in vivo preclinical models, cytokine measurement Nature communications High 37169737
2023 p140Cap promotes increased flux through the mevalonate pathway by positively regulating HMGCR via transcriptional and post-translational mechanisms; this leads to enhanced cholesterol efflux, increased cholesterol in the plasma membrane, reduction of lipid raft-associated Rac1 signaling, impaired membrane fluidity and cell migration in a cholesterol-dependent manner. In vitro and in vivo metabolic flux analysis, HMGCR expression/activity assays, cholesterol localization imaging, lipid raft fractionation, Rac1 activity assay, statin sensitivity assay Cell death & disease High 38123597
2023 SNX17 interacts with p140Cap (identified by GST pulldown and interactome analysis); this interaction is required for dendritic spine maturation, as Snx17 haploinsufficiency reduces spine maturation and impairs synaptic transmission. GST pulldown, interactome analysis, Snx17 knockout/haploinsufficient mice, spine morphology analysis, electrophysiology Molecular neurobiology Medium 37704928
2025 BIN1 SH3 domain directly binds p140Cap via two class II proline-rich motifs (KD = 7.7 μM by surface plasmon resonance); alanine-scanning mutagenesis maps the binding residues. BIN1 and p140Cap colocalize and are within molecular distance in cultured cells and mouse brain by confocal microscopy and proximity ligation assay. A rare BIN1 coding variant (rs138047593) significantly reduces p140Cap (and tau) binding. Surface plasmon resonance, alanine-scanning mutagenesis, confocal microscopy, proximity ligation assay, co-immunoprecipitation, GST pulldown The Journal of biological chemistry High 40889683
2025 p140Cap and its paralog KIAA1217/SKT are centrosomal proteins; loss of p140Cap or KIAA1217 impairs ciliogenesis (fewer and shorter cilia), and these defects are rescued by inhibiting actin polymerization or Src family kinase activity, indicating p140Cap regulates ciliogenesis through Src-dependent actin remodeling. BioID proximity labeling, ciliogenesis assays, actin polymerization inhibitors, Src inhibitors, domain mapping for centrosomal targeting bioRxivpreprint Medium bio_10.1101_2025.10.30.685566

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Breast cancer cell-derived exosomal miR-20a-5p promotes the proliferation and differentiation of osteoclasts by targeting SRCIN1. Cancer medicine 95 31385464
2000 SNIP, a novel SNAP-25-interacting protein implicated in regulated exocytosis. The Journal of biological chemistry 84 10625663
2018 MicroRNA-181a promotes angiogenesis in colorectal cancer by targeting SRCIN1 to promote the SRC/VEGF signaling pathway. Cell death & disease 80 29739921
2007 p140Cap protein suppresses tumour cell properties, regulating Csk and Src kinase activity. The EMBO journal 75 17525734
2014 miR-374a promotes cell proliferation, migration and invasion by targeting SRCIN1 in gastric cancer. FEBS letters 69 25554419
2015 miR-873 induces lung adenocarcinoma cell proliferation and migration by targeting SRCIN1. American journal of translational research 66 26807196
2013 SNAP-25 regulates spine formation through postsynaptic binding to p140Cap. Nature communications 63 23868368
2003 P130Cas-associated protein (p140Cap) as a new tyrosine-phosphorylated protein involved in cell spreading. Molecular biology of the cell 56 14657239
2010 p140Cap dual regulation of E-cadherin/EGFR cross-talk and Ras signalling in tumour cell scatter and proliferation. Oncogene 49 20453886
2014 p140Cap regulates memory and synaptic plasticity through Src-mediated and citron-N-mediated actin reorganization. The Journal of neuroscience : the official journal of the Society for Neuroscience 46 24453341
2016 MiR-346 promotes the biological function of breast cancer cells by targeting SRCIN1 and reduces chemosensitivity to docetaxel. Gene 41 27913185
2017 A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex. Neuron 40 28641114
2015 miR-211 promotes non-small cell lung cancer proliferation by targeting SRCIN1. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 40 26277787
2015 Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap. Cell research 37 25771685
2018 MiR-150 promotes angiogensis and proliferation of endothelial progenitor cells in deep venous thrombosis by targeting SRCIN1. Microvascular research 36 30315850
2022 How bacteria utilize sialic acid during interactions with the host: snip, snatch, dispatch, match and attach. Microbiology (Reading, England) 34 35316172
2017 Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study. Translational psychiatry 33 29064472
2008 Characterization of a multidomain adaptor protein, p140Cap, as part of a pre-synaptic complex. Journal of neurochemistry 30 18662323
2023 Ginsenoside Rh2 suppresses colon cancer growth by targeting the miR-150-3p/SRCIN1/Wnt axis. Acta biochimica et biophysica Sinica 25 36916297
2019 miR-150-5p promotes the proliferation and epithelial-mesenchymal transition of cervical carcinoma cells via targeting SRCIN1. Pathology, research and practice 25 30679084
2018 Hepatitis B virus promotes proliferation and metastasis in male Chinese hepatocellular carcinoma patients through the LEF-1/miR-371a-5p/SRCIN1/pleiotrophin/Slug pathway. Experimental cell research 24 29928866
2017 Synaptic Interactome Mining Reveals p140Cap as a New Hub for PSD Proteins Involved in Psychiatric and Neurological Disorders. Frontiers in molecular neuroscience 23 28713243
2010 Survey of Neonates in Pomerania (SNiP): a population-based birth study--objectives, design and population coverage. Paediatric and perinatal epidemiology 23 20415776
2015 Genetic Sources of Subcomponents of Event-Related Potential in the Dimension of Psychosis Analyzed From the B-SNIP Study. The American journal of psychiatry 22 25615564
2019 MicroRNA-665 promotes the proliferation of ovarian cancer cells by targeting SRCIN1. Experimental and therapeutic medicine 19 32010277
2016 SRCIN1 Suppressed Osteosarcoma Cell Proliferation and Invasion. PloS one 19 27513473
2013 Identification of two regions in the p140Cap adaptor protein that retain the ability to suppress tumor cell properties. American journal of cancer research 19 23841028
2011 p140Cap suppresses the invasive properties of highly metastatic MTLn3-EGFR cells via impaired cortactin phosphorylation. Oncogene 19 21725361
2011 The adaptor proteins p140CAP and p130CAS as molecular hubs in cell migration and invasion of cancer cells. American journal of cancer research 19 21994904
2019 Role of microRNA-150-5p/SRCIN1 axis in the progression of breast cancer. Experimental and therapeutic medicine 18 30867707
2019 The SRCIN1/p140Cap adaptor protein negatively regulates the aggressiveness of neuroblastoma. Cell death and differentiation 17 31285546
2017 The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled circuitries. Nature communications 17 28300085
2019 p140Cap Regulates GABAergic Synaptogenesis and Development of Hippocampal Inhibitory Circuits. Cerebral cortex (New York, N.Y. : 1991) 16 29161354
2018 Comparison of PCR Methods for Onchocerca volvulus Detection in Skin Snip Biopsies from the Tshopo Province, Democratic Republic of the Congo. The American journal of tropical medicine and hygiene 15 29611501
2017 Overexpression of Srcin1 contributes to the growth and metastasis of colorectal cancer. International journal of oncology 14 28393242
2013 Mapping of p140Cap phosphorylation sites: the EPLYA and EGLYA motifs have a key role in tyrosine phosphorylation and Csk binding, and are substrates of the Abl kinase. PloS one 14 23383002
2020 SRCIN1 Regulated by circCCDC66/miR-211 Is Upregulated and Promotes Cell Proliferation in Non-Small-Cell Lung Cancer. BioMed research international 13 32964035
2019 MicroRNA-374a promotes pancreatic cancer cell proliferation and epithelial to mesenchymal transition by targeting SRCIN1. Pathology, research and practice 13 30890278
2004 3'-End polishing of the kinetoplastid spliced leader RNA is performed by SNIP, a 3'-->5' exonuclease with a Motley assortment of small RNA substrates. Molecular and cellular biology 13 15542846
2023 p140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response. Nature communications 12 37169737
2023 p140Cap modulates the mevalonate pathway decreasing cell migration and enhancing drug sensitivity in breast cancer cells. Cell death & disease 12 38123597
2017 [ARTICLE WITHDRAWN] Downregulation of SRC Kinase Signaling Inhibitor 1 (SRCIN1) Expression by MicroRNA-32 Promotes Proliferation and Epithelial-Mesenchymal Transition in Human Liver Cancer Cells. Oncology research 12 28550679
2020 LincRNA00494 Suppresses Non-small Cell Lung Cancer Cell Proliferation by Regulating SRCIN1 Expression as a ceRNA. Frontiers in oncology 11 32117734
2018 VEGFA GENE variation influences hallucinations and frontotemporal morphology in psychotic disorders: a B-SNIP study. Translational psychiatry 11 30310054
2021 Real-time facial emotion recognition deficits across the psychosis spectrum: A B-SNIP Study. Schizophrenia research 10 34887147
2019 miR-373 promotes neuroblastoma cell proliferation, migration, and invasion by targeting SRCIN1. OncoTargets and therapy 9 31417287
2002 Comparison between the skin snip test and simple dot blot assay as potential rapid assessment tools for Onchocerciasis in the postcontrol era in Ghana. Clinical and diagnostic laboratory immunology 9 12204952
2023 Effect of genetic polymorphisms on outcomes following nivolumab for advanced renal cell carcinoma in the SNiP-RCC trial. Cancer immunology, immunotherapy : CII 8 36729213
2021 p130Cas/BCAR1 and p140Cap/SRCIN1 Adaptors: The Yin Yang in Breast Cancer? Frontiers in cell and developmental biology 8 34708040
2020 The p140Cap adaptor protein as a molecular hub to block cancer aggressiveness. Cellular and molecular life sciences : CMLS 7 33079227
2019 Dissecting the Shared and Context-Dependent Pathways Mediated by the p140Cap Adaptor Protein in Cancer and in Neurons. Frontiers in cell and developmental biology 7 31681758
1999 A novel pancreatic model: the snip method of pancreatic isolation for in vitro study. Pancreas 7 10547198
2022 p140Cap Regulates the Composition and Localization of the NMDAR Complex in Synaptic Lipid Rafts. The Journal of neuroscience : the official journal of the Society for Neuroscience 6 35953295
2020 The N-terminal domain of the adaptor protein p140Cap interacts with Tiam1 and controls Tiam1/Rac1 axis. American journal of cancer research 5 33415001
2013 Localization of multidomain adaptor proteins, p140Cap and vinexin, in the pancreatic islet of a spontaneous diabetes mellitus model, Otsuka Long-Evans Tokushima Fatty rats. Medical molecular morphology 5 23325552
2023 SNX17 Mediates Dendritic Spine Maturation via p140Cap. Molecular neurobiology 4 37704928
2022 miR-657 Targets SRCIN1 via the Slug Pathway to Promote NSCLC Tumor Growth and EMT Induction. Disease markers 4 36033827
2020 Correction to: The SRCIN1/p140Cap adaptor protein negatively regulates the aggressiveness of neuroblastoma. Cell death and differentiation 4 31488891
2016 Role of the Mdm2 SNIP 309 Polymorphism in Gastric Mucosal Morphologic Patterns of Patients with Helicobacter pylori Associated Gastritis. Asian Pacific journal of cancer prevention : APJCP 4 27039725
2024 Effect of HLA Genotype on Anti-PD-1 Antibody Treatment for Advanced Renal Cell Carcinoma in the SNiP-RCC Study. Journal of immunology (Baltimore, Md. : 1950) 3 38758119
2023 Clinical factors for tumor response, progression, and survival in nivolumab for advanced renal cell carcinoma in the SNiP-RCC study. International journal of urology : official journal of the Japanese Urological Association 3 37528632
2015 Correlation between Patterns of Mdm2 SNIP 309 and Histopathological Severity of Helicobacter pylori Associated Gastritis in Thailand. Asian Pacific journal of cancer prevention : APJCP 3 26625797
1997 [Endothelial cell loss after phacoemulsification with the "reversed tip and snip" technique compared with the "divide and conquer" technique]. Klinische Monatsblatter fur Augenheilkunde 3 9229600
2018 Author Correction: The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled circuitries. Nature communications 2 29600801
2017 Semi-automated Tip Snip cloning of restriction fragments into and out of plasmid polylinkers. BioTechniques 2 28298176
2023 Hsa_circ_0046430 promotes the progression of colorectal cancer by targeting miR-6785-5p/SRCIN1 axis as a ceRNA. Medicine 1 36827049
2022 p140Cap Controls Female Fertility in Mice Acting via Glutamatergic Afference on Hypothalamic Gonadotropin-Releasing Hormone Neurons. Frontiers in neuroscience 1 35237119
1998 [Experiences with "reversed tip and snip" phacoemulsification]. Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft 1 9738377
2025 Predictive Model of Objective Response to Nivolumab Monotherapy for Advanced Renal Cell Carcinoma by Machine Learning Using Genetic and Clinical Data: The SNiP-RCC Study. JCO clinical cancer informatics 0 40279530
2025 "Snip, snip, cure"? Philosophical, legal and biomedical perspectives on novel somatic genomic therapies. Medicine, health care, and philosophy 0 40788566
2025 SRCIN1 promotes thyroid carcinoma growth by activating Wnt signaling pathway. Scientific reports 0 40849352
2025 A biophysical and molecular characterization of the interaction between the Alzheimer risk factor BIN1 and the neuronal scaffold protein p140Cap. The Journal of biological chemistry 0 40889683
2009 GEN-SNiP: an online tool to find polymorphisms in a genome. In silico biology 0 22430435