Affinage

CADM1

Cell adhesion molecule 1 · UniProt Q9BY67

Length
442 aa
Mass
48.5 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CADM1 (SynCAM 1) is a transmembrane immunoglobulin superfamily adhesion molecule that organizes cell–cell contacts across neuronal synapses, epithelia, spermatids, mast cells, and endocrine tissues through Ca²⁺-independent homophilic and heterophilic trans-interactions and lateral cis-oligomerization via its Ig domains (PMID:21926970, PMID:18615557). Its cytoplasmic PDZ-binding tail scaffolds complexes containing 4.1B, MPP/MAGuK proteins, Par-3, PI3K (p85), and PTPN13, coupling adhesion to actin cytoskeleton remodeling, epithelial polarity, and signaling through Akt/Rac1, Rb-E2F, and ErbB4 pathways (PMID:19854157, PMID:24503895, PMID:23769722); this same tail is co-opted by HTLV-1 Tax and KSHV vFLIP/vGPCR to sustain NF-κB activation in virally transformed cells (PMID:25774694, PMID:29698475). Post-translational regulation—including N-glycan–dependent modulation of adhesive strength, polysialylation by ST8SiaII that abolishes homophilic binding, and alternative splicing–controlled O-glycosylation gating of ADAM-mediated ectodomain shedding—tunes CADM1 function during synapse development and cortical critical-period plasticity, where CADM1 in parvalbumin-positive interneurons controls thalamocortical input number and feedforward inhibition maturation (PMID:20479255, PMID:22908220, PMID:28393893, PMID:30625321, PMID:27413156). Somatic gain-of-function intramembranous CADM1 mutations cause aldosterone-producing adenomas and reversible hypertension by disrupting gap junction communication and de-repressing CYP11B2 (PMID:37291193).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2005 High

    Whether a single adhesion molecule could instruct presynaptic assembly was unknown; demonstrating that CADM1 expressed in non-neuronal cells induces functional presynaptic terminals via its cytoplasmic tail established CADM1 as a synaptogenic organizer.

    Evidence Co-culture synapse induction assay with electrophysiology and chimeric constructs in neurons

    PMID:15634790

    Open questions at the time
    • Identity of cytoplasmic binding partners mediating synaptogenic signaling not determined
    • Whether CADM1 is required (not just sufficient) for synapse formation in vivo was untested
  2. 2006 High

    Whether CADM1 adhesion serves non-neuronal tissue morphogenesis was unclear; knockout mice revealed CADM1 is essential for spermatid maturation and retention within Sertoli cell invaginations, broadening its role to germ cell–somatic cell adhesion.

    Evidence CADM1 knockout mouse with testicular histology and immunofluorescence

    PMID:16382161

    Open questions at the time
    • Molecular partners at the spermatid–Sertoli junction were uncharacterized
    • Whether heterophilic ligands contribute to spermatid adhesion was unknown
  3. 2007 Medium

    How CADM1 organizes polarity in spermatids was unknown; identification of a Par-3-mediated ternary complex linking CADM1 to JAM-C, lost in knockout spermatids, established CADM1 as a polarity scaffold in male germ cells.

    Evidence Co-immunoprecipitation of CADM1/Par-3/JAM-C ternary complex, immunofluorescence in KO testis

    PMID:18055550

    Open questions at the time
    • Single-lab co-IP without reciprocal validation from an independent group
    • Whether Par-3 interaction applies at neuronal synapses was untested
  4. 2008 Medium

    The heterophilic binding code of the SynCAM family was undefined; systematic cell overlay experiments mapped SynCAM 1/2, 2/4, and 3/4 as the dominant trans-heterophilic pairs, defining how SynCAM diversity generates contact specificity.

    Evidence Cell overlay adhesion assay using extracellular domain constructs, in situ hybridization

    PMID:18615557

    Open questions at the time
    • Affinities not quantified
    • In vivo relevance of heterophilic pairs at specific synapses not demonstrated
  5. 2009 High

    How CADM1's cytoplasmic domain controls epithelial architecture was poorly understood; identification of the CADM1–4.1B–MPP2/MPP3 tripartite complex and demonstration that CADM1 knockdown causes loss of epithelial polarity markers established CADM1 as a membrane-proximal scaffold for polarity and junction organization.

    Evidence Co-immunoprecipitation of tripartite complex, siRNA knockdown in HEK293 cells with immunofluorescence

    PMID:19854157

    Open questions at the time
    • Whether the tripartite complex operates identically at neuronal synapses was unknown
    • Structural basis of 4.1B–MPP2 recruitment not resolved
  6. 2010 High

    Three concurrent advances resolved how CADM1 functions in vivo and how glycosylation tunes its adhesion: transgenic/KO mice showed CADM1 maintains excitatory synapse number and modulates LTD and spatial learning; polysialylation on N-glycans of Ig1 was shown to abolish homophilic binding; and site-specific N-glycosylation was demonstrated to strengthen trans-synaptic interactions and be required for synapse induction.

    Evidence Transgenic overexpression/KO mice with electrophysiology and behavior; in vitro polysialylation and binding assays; crystal structure with mutagenesis and synapse induction assay

    PMID:20479255 PMID:20739279 PMID:21145003

    Open questions at the time
    • Which polysialyltransferase acts on CADM1 in vivo was unresolved (both ST8SiaII and ST8SiaIV active in vitro)
    • Whether polysialylation regulates synapse number in vivo was untested
  7. 2010 High

    CADM1's role at growth cones was unknown; live imaging showed CADM1 rapidly clusters at nascent axo-dendritic contacts, restricts filopodial complexity, and associates with FAK, linking adhesion to growth cone morphogenesis.

    Evidence Live imaging, siRNA/overexpression in neurons, FAK co-immunoprecipitation

    PMID:20368431

    Open questions at the time
    • Whether FAK is a direct or indirect CADM1 interactor was not resolved
    • Upstream signals triggering CADM1 clustering were undefined
  8. 2011 High

    Whether CADM1 acts as monomers or oligomers was unresolved; biochemical and mutagenesis studies showed cis-oligomerization through Ig2–Ig3 domains is required for adhesive clustering and synaptogenic activity, and restricts synaptic size at mature contacts.

    Evidence Biochemical oligomerization assays, domain mutagenesis, synapse induction in differentiating neurons

    PMID:21926970

    Open questions at the time
    • Stoichiometry and structure of cis oligomers not determined
    • Relationship between cis-oligomerization and polysialylation regulation unclear
  9. 2012 High

    Multiple 2012 studies resolved isoform-specific functions and in vivo polysialylation: ST8SiaII was identified as the exclusive in vivo polysialyltransferase requiring both Ig1 and Ig2 domains; CADM1 isoforms were shown to differentially control mast cell survival (via Mcl-1) and homotypic adhesion; and CADM1 was identified as a metastasis suppressor dependent on host CD8⁺ T cell immunity.

    Evidence ST8SiaII/IV KO mice with in vitro polysialylation; mast cell isoform-specific KD/OE with caspase and adhesion assays; CADM1 KO with CD8 depletion epistasis in metastasis model

    PMID:22438059 PMID:22908220 PMID:23028344

    Open questions at the time
    • How CADM1 loss evades CD8⁺ T cell recognition mechanistically was unknown
    • Whether mast cell isoform effects apply in vivo was not shown
  10. 2012 Medium

    How mast cells adhere to neurons was poorly defined; co-culture experiments showed CADM1-mediated homophilic adhesion drives mast cell–neuron attachment, degranulation, and IL-6 secretion, while heterophilic binding to nectin-3 on DRG neurons was identified as an additional trans-ligand.

    Evidence CADM1 siRNA and blocking peptide in BMMC–DRG co-culture; nectin-3 neutralizing antibody with calcium imaging

    PMID:22703826 PMID:31275114

    Open questions at the time
    • Relative contributions of homophilic vs. nectin-3 heterophilic adhesion not quantified in vivo
    • Whether mast cell–neuron CADM1 adhesion is polysialylation-regulated was unknown
  11. 2013 Medium

    How CADM1 influences inhibitory circuit development was unclear; identification of CADM1–ErbB4 interaction in PV⁺ interneurons, with PTPN13 as a cytoplasmic phosphatase recruited to CADM1 that suppresses Nrg1/ErbB4-driven excitatory synapse formation, revealed CADM1 as a negative modulator of ErbB4 signaling in GABAergic neurons.

    Evidence Co-immunoprecipitation of CADM1–ErbB4, siRNA knockdown, PTPN13 overexpression, phospho-ErbB4 assay

    PMID:23769722

    Open questions at the time
    • PTPN13 interaction with CADM1 not confirmed by reciprocal IP or structural data
    • In vivo relevance in PV⁺ interneuron development not demonstrated
  12. 2014 High

    The signaling pathway downstream of CADM1 trans-adhesion was undefined; reconstitution showed CADM1 activates PI3K through a CADM1–MPP3–Dlg–p85 complex, driving Akt/Rac1-dependent actin reorganization and epithelial spreading.

    Evidence Spreading assay on recombinant CADM1, chemical inhibitor screen, co-immunoprecipitation of quaternary complex

    PMID:24503895

    Open questions at the time
    • Whether PI3K signaling mediates CADM1's synaptogenic activity was untested
    • Direct vs. bridged interaction between CADM1 and p85 not resolved
  13. 2015 High

    How viral oncoproteins hijack CADM1 was unknown; HTLV-1 Tax was shown to require CADM1's PDZ-binding tail to recruit Ubc13 for K63-linked polyubiquitination in lipid rafts, activating IKK and sustaining NF-κB signaling while inactivating A20.

    Evidence Co-IP, ubiquitination assays, lipid raft fractionation, CADM1 KO and PDZ-motif deletion mutants

    PMID:25774694

    Open questions at the time
    • Whether CADM1 scaffolding of NF-κB occurs in non-infected cells was unknown
    • Structural basis of Tax–CADM1 interaction not resolved
  14. 2016 High

    Multiple 2016 discoveries broadened CADM1's circuit and signaling roles: in hippocampus, CADM1 KO reduced mossy fiber–PV⁺ interneuron synapses and GluA1 causing CA3 disinhibition; in squamous carcinoma, CADM1 formed a surface complex with HER2/integrin-α6β4 to suppress STAT3-driven proliferation and metastasis; and in pancreatic β-cells, transcellular CADM1 interactions constrained insulin secretion via exocytic site and actin network organization.

    Evidence KO electrophysiology and synapse counting; co-IP of CADM1/HER2/integrin complex with xenograft; CADM1 KD/OE in INS-1 cells and primary islets with insulin secretion assay

    PMID:27035095 PMID:27072493 PMID:27413156

    Open questions at the time
    • Whether the HER2/integrin complex exists at synapses or only in carcinoma cells was unknown
    • Whether β-cell CADM1 is polysialylated was not addressed
  15. 2017 High

    How CADM1 ectodomain shedding is regulated was undefined; alternative splicing was shown to insert a non-glycosylatable spacer between protective O-glycans and the ADAM cleavage site, revealing a glycan-gated shedding switch that controls CADM1 surface levels.

    Evidence Shedding assays with splicing variants and O-glycosylation mutants, ADAM metalloprotease inhibitors

    PMID:28393893

    Open questions at the time
    • Which ADAM family member is the primary sheddase in vivo was not identified
    • Functional consequence of shedding for synapse remodeling was not tested
  16. 2018 High

    Whether KSHV exploits the same CADM1 scaffold as HTLV-1 was unknown; vFLIP and vGPCR were shown to interact with CADM1's PDZ-binding motif in lipid rafts to activate IKK/NF-κB, establishing CADM1 as a shared viral oncogenic platform.

    Evidence Co-IP, lipid raft fractionation, CADM1 KD and PDZ-motif deletion in PEL cells

    PMID:29698475

    Open questions at the time
    • Whether other oncogenic viruses use the same mechanism was untested
    • Structural basis of vFLIP–CADM1 PDZ interaction not resolved
  17. 2019 High

    Whether CADM1 regulates critical-period cortical plasticity was unknown; cell-type-specific KD in adult PV⁺ interneurons restored juvenile-like ocular dominance plasticity by reducing thalamocortical inputs and impairing feedforward inhibition maturation, establishing CADM1 as a molecular brake on critical-period closure.

    Evidence Conditional SynCAM 1 KO/KD in PV⁺ cells, monocular deprivation assay, synapse counting

    PMID:30625321

    Open questions at the time
    • Downstream signaling linking CADM1 loss to plasticity reopening was not identified
    • Whether polysialylation of CADM1 contributes to critical-period timing was not tested
  18. 2021 High

    How measles virus spreads transsynaptically in receptor-negative neurons was unexplained; CADM1 and CADM2 were identified as cis-acting cofactors that trigger MeV fusion protein on the same membrane, enabling cell–cell fusion and viral transmission between neurons.

    Evidence siRNA KD, cell fusion assay, co-IP of CADM1 with MeV H protein in cis

    PMID:33910952

    Open questions at the time
    • Whether cis-interaction is direct or involves intermediary membrane proteins was not fully resolved
    • In vivo validation in animal MeV infection model lacking
  19. 2023 High

    Whether CADM1 mutations could cause endocrine disease was unknown; somatic intramembranous gain-of-function mutations (V380D, G379D) in aldosterone-producing adenomas were shown to upregulate CYP11B2 by disrupting gap junction communication, establishing CADM1 as a causal gene in primary aldosteronism.

    Evidence WES of aldosterone-producing adenomas, mutant CADM1 transduction in H295R cells, gap junction dye transfer assay, Gap27 pharmacological blockade, patient adrenalectomy cure

    PMID:37291193

    Open questions at the time
    • How intramembranous mutations mechanistically disrupt gap junctions (direct pore interaction vs. trafficking defect) was not resolved
    • Whether wild-type CADM1 regulates aldosterone in normal adrenal physiology was not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of CADM1 cis-oligomers and their regulation by polysialylation; identification of the ADAM sheddase responsible in vivo and how shedding feeds back on synapse remodeling; the mechanism by which CADM1 loss permits immune evasion of metastases; and whether CADM1's diverse tissue-specific functions (synapse, spermatid, mast cell, β-cell, adrenal) rely on shared or distinct cytoplasmic signaling complexes.
  • No high-resolution structure of CADM1 cis or trans complexes
  • In vivo ADAM sheddase identity unknown
  • Mechanism of CD8⁺ T cell sensitization by CADM1 undefined
  • Tissue-specific complex composition not systematically compared

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 8 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 9 GO:0005856 cytoskeleton 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1500931 Cell-Cell communication 5 R-HSA-112316 Neuronal System 4 R-HSA-1643685 Disease 3 R-HSA-1266738 Developmental Biology 2 R-HSA-168256 Immune System 1
Partners
EPB41L3ERBB4MPP2MPP3NECTIN3PARD3PTK2PTPN13
Complex memberships
CADM1–4.1B–MPP2/MPP3 polarity complexCADM1–HER2–integrin-α6β4 surface complexCADM1–MPP3–Dlg–PI3K(p85) signaling complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 SynCAM 1 (CADM1) expressed in non-neuronal cells specifically induces presynaptic differentiation in co-cultured neurons, forming artificial synapses capable of both spontaneous and evoked neurotransmitter release; the dominant-positive effect on synaptic function in developing neurons is mediated by its intracellular cytoplasmic tail. Co-culture synapse induction assay, electrophysiology (mEPSC recording), chimeric molecule analysis The Journal of neuroscience High 15634790
2010 SynCAM 1 (CADM1) overexpression in transgenic mice increases excitatory synapse number, while knockout reduces excitatory synapses; SynCAM 1 also regulates long-term depression and spatial learning, demonstrating it maintains synapses and modulates plasticity in vivo. Transgenic overexpression and knockout mouse models, electrophysiology, behavioral testing (spatial learning) Neuron High 21145003
2010 SynCAM 1 (CADM1) is a target for polysialylation in postnatal mouse brain; both polysialyltransferases ST8SiaII and ST8SiaIV polysialylate SynCAM 1 in vitro on N-glycans of the first Ig domain, and polysialylation completely abolishes homophilic SynCAM 1 binding. Affinity purification, peptide mass fingerprinting (glycoproteomics), in vitro polysialylation assay, homophilic binding assay Proceedings of the National Academy of Sciences of the United States of America High 20479255
2010 SynCAM 1 (CADM1) localizes to neuronal growth cones and, upon contact with target neurites, rapidly assembles into stable adhesive clusters; SynCAM 1 restricts filopodial number and growth cone morphological complexity; focal adhesion kinase (FAK) is a binding partner implicated in these morphogenetic activities. Live imaging, immunofluorescence localization, siRNA knockdown and overexpression in neurons, FAK co-immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America High 20368431
2011 SynCAM 1 (CADM1) self-assembles laterally (cis oligomerization) via its extracellular membrane-proximal Ig domains 2 and 3; this cis oligomerization generates SynCAM oligomers with increased adhesive capacity, promotes adhesive clustering at new axo-dendritic contacts, is required for synaptogenic activity, and restricts synaptic size at mature synapses. Biochemical oligomerization assays, mutagenesis of Ig domains, immunofluorescence in differentiating neurons, synapse induction assay The EMBO journal High 21926970
2010 Site-specific N-glycosylation differentially modulates SynCAM adhesion: N-glycan on SynCAM 2 Asn60 reduces adhesion, while N-glycans on SynCAM 1 Asn70/Asn104 (which flank the Ig1 binding interface) increase interactions; sialylation of SynCAM 1 contributes to glycan-dependent strengthening; N-glycosylation promotes trans-synaptic SynCAM 1 interactions and is required for synapse induction. X-ray crystallography (SynCAM 2 Ig1 domain), mass spectrometry, site-directed mutagenesis, adhesion assay, synapse induction assay The Journal of biological chemistry High 20739279
2009 CADM1 associates with actin-binding protein 4.1B/DAL-1 and scaffold proteins MPP1/p55, MPP2/DLG2, and MPP3/DLG3, forming a tripartite complex; MPP2 is recruited to the CADM1-4.1B complex during early adhesion; siRNA knockdown of CADM1 in HEK293 cells causes loss of epithelial-like structure, flat morphology, and mislocalization of 4.1B, MPP2, E-cadherin, and ZO-1 from the membrane. Co-immunoprecipitation, siRNA knockdown, immunofluorescence Biochemical and biophysical research communications High 19854157
2014 Trans-homophilic interaction of CADM1 activates PI3K signaling; MPP3 and Dlg (MAGuK-family proteins) connect CADM1 with the p85 subunit of PI3K forming a multi-protein complex at the cell periphery; PI3K inhibition suppresses CADM1-mediated cell spreading, and downstream Akt and Rac1 partially mediate this effect on actin cytoskeleton reorganization and epithelial structure formation. Cell-based spreading assay on recombinant CADM1-coated substrate, chemical inhibitor screen (104 inhibitors), co-immunoprecipitation of CADM1/MPP3/Dlg/p85 complex PloS one High 24503895
2015 HTLV-1 Tax requires membrane-associated CADM1 as a scaffold: CADM1 recruits Ubc13 to Tax causing K63-linked polyubiquitination of Tax and IKK complex activation in plasma membrane lipid rafts; the PDZ-binding motif in CADM1's cytoplasmic tail is critical; in the absence of CADM1, Tax fails to inactivate the A20 ubiquitin-editing enzyme complex and cannot activate IKK, abolishing persistent NF-κB signaling. Co-immunoprecipitation, ubiquitination assays, lipid raft fractionation, CADM1 knockdown/knockout, PDZ-motif deletion mutants PLoS pathogens High 25774694
2018 KSHV oncoproteins vFLIP and vGPCR interact with CADM1; the PDZ-binding motif at the C-terminus of CADM1 is essential for both vGPCR- and vFLIP-mediated chronic NF-κB activation; lipid raft-associated CADM1 interaction with vFLIP is critical for IKK complex initiation; CADM1 is required for survival of KSHV-associated PEL cells. Co-immunoprecipitation, lipid raft fractionation, CADM1 knockdown, PDZ-motif deletion analysis, cell viability assays PLoS pathogens High 29698475
2016 CADM1 inhibits squamous cell carcinoma proliferation and invasion by forming a cell-surface complex with HER2 and integrin α6β4 that disrupts downstream STAT3 activity; this requires the extracellular domain of CADM1; JAK/STAT inhibition mimics CADM1 restoration in preventing SqCC growth and metastasis. Gene transduction, co-immunoprecipitation (CADM1/HER2/integrin α6β4 complex), xenograft tumor assay, STAT3 phosphorylation assays Scientific reports High 27035095
2006 Knockout of RA175/CADM1 in male mice causes infertility due to failure of elongating spermatids (steps 9–12) to mature and translocate to the adluminal surface; CADM1 is expressed at cell junctions of spermatocytes and elongating spermatids and is required for retaining them in Sertoli cell invaginations. Gene knockout mouse model, histological analysis of testis, immunofluorescence localization Molecular and cellular biology High 16382161
2007 Par-3 (a cell polarity protein with PDZ domains) binds the cytoplasmic region of RA175/CADM1 in testis; RA175 forms a ternary complex with JAM-C via Par-3 interaction; in RA175-knockout elongating spermatids, Par-3 is absent and JAM-C is absent or mislocalized, indicating that CADM1 organizes polarity machinery in spermatids. Co-immunoprecipitation (ternary complex), immunofluorescence in RA175-KO vs wildtype testis The American journal of pathology Medium 18055550
2008 Two missense mutations in CADM1 (H246N and Y251S) located in the third Ig domain, identified in ASD patients, result in reduced high-molecular-weight (mature oligosaccharide-containing) forms, defective trafficking to the cell surface, and increased susceptibility to cleavage/degradation; the third Ig domain is essential for trans-active interaction. Patient mutation identification, Western blot (glycoform analysis), cell surface biotinylation, degradation assays Biochemical and biophysical research communications Medium 18957284
2012 CADM1-mediated homophilic adhesion of mast cells to neurons is required for mast cell degranulation and IL-6 secretion enhancement; knockdown of CADM1 in bone marrow-derived mast cells or application of a CADM1 blocking peptide significantly decreased BMMC attachment to sensory neurites and abolished enhanced secretory responses. CADM1 siRNA knockdown, blocking peptide, BMMC-DRG neuron co-culture, β-hexosaminidase degranulation assay, cytokine ELISA Frontiers in cellular neuroscience Medium 31275114
2012 On mast cells, CADM1 promotes attachment to dorsal root ganglion (DRG) neurites through heterophilic binding to nectin-3 expressed on DRG neurons; neutralizing antibody to nectin-3 inhibits both mast cell attachment and subsequent calcium responses, despite low CADM1 expression on DRG. Adhesion assay, neutralizing antibody blocking, calcium imaging, immunofluorescence of nectin-3 at cell-cell contacts Journal of neuroimmunology Medium 22703826
2014 CADM1 controls actin cytoskeleton assembly in human mast cells; downregulation of CADM1 in HMC-1 cells reduces surface KIT levels, alters cortical F-actin polymerization, elongates cortical actin filaments, increases cell rigidity, and reduces ECM adhesion indirectly through regulation of integrin function. siRNA knockdown, flow cytometry (surface KIT), confocal microscopy (F-actin), atomic force microscopy (cell rigidity), adhesion assays PloS one Medium 24465823
2012 CADM1 polysialylation in mouse brain is exclusively mediated by ST8SiaII in vivo (not ST8SiaIV); polysialylation requires both Ig1 (which contains the glycosylation site) and Ig2 (which serves as a docking site for ST8SiaII), as Ig1 alone is insufficient as an acceptor. ST8SiaII and ST8SiaIV single knockout mouse analysis, domain-deletion constructs, in vitro polysialylation assay The Journal of biological chemistry High 22908220
2013 CADM1 (Necl-2) interacts with ErbB4 receptor tyrosine kinase in parvalbumin-positive GABAergic neurons; Necl-2 knockdown enhances Nrg1-induced ErbB4 phosphorylation; overexpression of PTPN13 (a tyrosine phosphatase bound to the cytoplasmic tail of Necl-2) suppresses Nrg1-induced excitatory synapse development in GABAergic neurons through inhibition of ErbB4 activity. Co-immunoprecipitation (Necl-2/ErbB4), siRNA knockdown, PTPN13 overexpression, phospho-ErbB4 assay, synapse morphology analysis Molecular and cellular neurosciences Medium 23769722
2019 TWIST1 transcription factor directly binds the CADM1 promoter (shown by ChIP and promoter assays) to repress CADM1 expression; restored CADM1 expression inhibits melanoma cell motility and invasion, and induces caspase-independent cell death in non-adherent conditions associated with loss of mitochondrial membrane potential. Chromatin immunoprecipitation (ChIP), promoter reporter assay, CADM1 overexpression, migration/invasion assay, apoptosis assays Cell death & disease Medium 30911007
2016 CADM1 regulates G1/S cell cycle transition in hepatocellular carcinoma; ectopic CADM1 expression increases Retinoblastoma (Rb) protein levels, inhibits cell growth, and suppresses tumorigenicity in vitro and in vivo, implicating the Rb-E2F pathway in CADM1-mediated tumor suppression. Cell cycle analysis, EdU incorporation, colony formation assay, in vivo xenograft, Western blot (Rb protein levels) Hepatobiliary & pancreatic diseases international Medium 27298105
2017 CADM1 ectodomain shedding susceptibility is determined by alternative splicing and O-glycosylation: a 33-bp alternative exon inserts five non-glycosylatable amino acids between O-glycans (which normally block ADAM-family metalloprotease access) and the cleavage site, conferring shedding susceptibility; O-glycans adjacent to the cleavage site thus interfere with shedding. Shedding assays with CADM1 splicing variants, O-glycosylation mutants, ADAM metalloprotease inhibitors Scientific reports High 28393893
2019 SynCAM 1/CADM1 acts cell-autonomously in parvalbumin-positive (PV+) interneurons to regulate thalamocortical synapse number onto PV+ cells and restrict cortical plasticity; selective knockdown of SynCAM 1 in adult PV+ interneurons restores juvenile-like plasticity in visual cortex, and SynCAM 1 loss reduces thalamocortical inputs onto PV+ cells impairing feedforward inhibition maturation. Conditional and cell-type-specific SynCAM 1 KO/knockdown, monocular deprivation plasticity assay, immunofluorescence synapse counting Cell reports High 30625321
2016 SynCAM 1 (CADM1) loss reduces excitatory mossy fiber inputs onto parvalbumin-positive interneurons in hippocampal CA3, decreases postsynaptic GluA1 expression in these interneurons, and causes CA3 disinhibition; SynCAM 1 KO also reduces excitatory synapse number in nucleus accumbens and impairs mossy fiber refinement in CA3. SynCAM 1 knockout mice, DTI-MRI, electrophysiology (feedforward inhibition), immunofluorescence synapse counting, Western blot (GluA1) The Journal of neuroscience High 27413156
2023 Somatic gain-of-function CADM1 mutations (p.Val380Asp, p.Gly379Asp) in aldosterone-producing adenomas cause reversible hypertension; these intramembranous mutations markedly upregulate CYP11B2 (aldosterone synthase) 10–25-fold; CADM1 mutation or knockdown inhibits gap junction-permeable dye transfer, and gap junction blockade by Gap27 increases CYP11B2 similarly to CADM1 mutation, revealing that CADM1 normally suppresses aldosterone production via gap junction communication. Whole exome sequencing, H295R cell transduction with mutant CADM1, gene expression profiling, gap junction dye transfer assay, Gap27 pharmacological blockade, adrenalectomy cure in patients Nature genetics High 37291193
2012 CADM1 suppresses metastasis in a manner that requires the host's adaptive immune system; loss of CADM1 metastasis suppression is recapitulated by depletion of CD8+ T cells in immune-competent mice, indicating CADM1 sensitizes tumor cells to immune surveillance without affecting tumor-cell-autonomous proliferation or invasion. Genetic screen (complex cross), CADM1 KO mouse models, CD8+ T cell depletion, metastasis assay (lung colonization) PLoS genetics Medium 23028344
2016 CADM1 regulates TNFα-induced migration of endothelial progenitor cells; TNFα activates NF-κB, which upregulates CADM1 expression; inhibition of NF-κB or CADM1 knockdown significantly decreases EPC migration and incorporation into vessel-like structures in vitro. siRNA knockdown, NF-κB inhibitor, migration/incorporation co-culture assay, genomic and proteomic approaches Stem cells Medium 26867147
2021 CADM1 and CADM2 act in cis (on the same cell membrane as the viral protein, not in trans) with the measles virus attachment protein on neurons lacking canonical MeV receptors, triggering the fusion protein and enabling membrane fusion and transsynaptic MeV spread; knockdown of CADM1 and CADM2 inhibits syncytium formation and virus transmission between neurons. siRNA knockdown, cell fusion assays, expression of hyperfusogenic MeV F protein, co-immunoprecipitation of CADM1 with MeV H protein in cis Journal of virology High 33910952
2016 Extracellular CADM1 interactions in pancreatic β-cells constrain insulin secretion; CADM1 expression decreases after prolonged glucose stimulation; transcellular CADM1 interactions promote exocytic site assembly and actin network formation in β-cells, paralleling its role at CNS synapses. CADM1 overexpression and siRNA knockdown in INS-1 insulinoma cells and primary rat/human islet β-cells, insulin secretion assay, co-culture model, actin and syntaxin-1 imaging American journal of physiology. Endocrinology and metabolism Medium 27072493
2012 CADM1 isoforms differentially regulate human mast cell survival and homotypic adhesion; CADM1 is the sole receptor mediating mast cell aggregation (knockdown abolishes homotypic adhesion); CADM1 downregulation reduces viability and Mcl-1(L) expression, increasing caspase-3/7 activity; SP4 isoform augments homotypic adhesion more than SP1. siRNA knockdown (complete abolition of aggregation), isoform-specific overexpression, cell viability assay, caspase-3/7 activity, Western blot (Mcl-1) Cellular and molecular life sciences Medium 22438059
2008 SynCAM family members engage in specific heterophilic adhesion interactions: SynCAMs 1/2, 2/4, and 3/4 mediate the three prominent trans-interactions, as shown by cell overlay experiments using extracellular domains. Cell overlay adhesion experiments with SynCAM extracellular domain constructs, in situ hybridization, immunohistochemistry The Journal of comparative neurology Medium 18615557
2010 Cadm1 knockout mice exhibit impaired social interaction, increased anxiety-related behavior, and impaired motor coordination, demonstrating that CADM1-mediated synaptic adhesion is required for normal emotional, social, and motor behaviors. Cadm1 knockout mice, open-field test, light-dark transition test, social interaction/memory/recognition tests, rotarod, footprint analysis Biochemical and biophysical research communications Medium 20450890

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Selective capability of SynCAM and neuroligin for functional synapse assembly. The Journal of neuroscience : the official journal of the Society for Neuroscience 147 15634790
2002 AID-dependent somatic hypermutation occurs as a DNA single-strand event in the BL2 cell line. Nature immunology 143 12145648
2010 SynCAM 1 adhesion dynamically regulates synapse number and impacts plasticity and learning. Neuron 135 21145003
2010 Synaptic cell adhesion molecule SynCAM 1 is a target for polysialylation in postnatal mouse brain. Proceedings of the National Academy of Sciences of the United States of America 133 20479255
2011 Combined promoter methylation analysis of CADM1 and MAL: an objective triage tool for high-risk human papillomavirus DNA-positive women. Clinical cancer research : an official journal of the American Association for Cancer Research 118 21389098
2013 CADM1 and MAL promoter methylation levels in hrHPV-positive cervical scrapes increase proportional to degree and duration of underlying cervical disease. International journal of cancer 107 23456988
2005 Bioinformatic characterization of the SynCAM family of immunoglobulin-like domain-containing adhesion molecules. Genomics 97 16311015
2005 Regulation of methane oxidation in the facultative methanotroph Methylocella silvestris BL2. Molecular microbiology 91 16238619
2013 Polysialic acid: versatile modification of NCAM, SynCAM 1 and neuropilin-2. Neurochemical research 90 23354723
2011 Combined CADM1 and MAL promoter methylation analysis to detect (pre-)malignant cervical lesions in high-risk HPV-positive women. International journal of cancer 89 21190187
2014 CADM1, MAL and miR124-2 methylation analysis in cervical scrapes to detect cervical and endometrial cancer. Journal of clinical pathology 86 25281766
2018 Exosomes of glioma cells deliver miR-148a to promote proliferation and metastasis of glioblastoma via targeting CADM1. Bulletin du cancer 85 29921422
2014 MicroRNA-1246 enhances migration and invasion through CADM1 in hepatocellular carcinoma. BMC cancer 85 25159494
2012 MicroRNA-10b promotes migration and invasion through CADM1 in human hepatocellular carcinoma cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 85 22528944
1998 Purification and characterization of L-methionine gamma-lyase from brevibacterium linens BL2. Applied and environmental microbiology 84 9726878
2017 miR-21 enhances cardiac fibrotic remodeling and fibroblast proliferation via CADM1/STAT3 pathway. BMC cardiovascular disorders 79 28335740
2008 Mutations in the gene encoding CADM1 are associated with autism spectrum disorder. Biochemical and biophysical research communications 79 18957284
2006 Oligo-astheno-teratozoospermia in mice lacking RA175/TSLC1/SynCAM/IGSF4A, a cell adhesion molecule in the immunoglobulin superfamily. Molecular and cellular biology 75 16382161
2011 Aberrant expression of tumor suppressors CADM1 and 4.1B in invasive lesions of primary breast cancer. Breast cancer (Tokyo, Japan) 68 21526423
2019 Down-regulated lncRNA DLX6-AS1 inhibits tumorigenesis through STAT3 signaling pathway by suppressing CADM1 promoter methylation in liver cancer stem cells. Journal of experimental & clinical cancer research : CR 66 31171015
2008 Expression and adhesion profiles of SynCAM molecules indicate distinct neuronal functions. The Journal of comparative neurology 66 18615557
2012 Cadm1 is a metastasis susceptibility gene that suppresses metastasis by modifying tumor interaction with the cell-mediated immunity. PLoS genetics 63 23028344
2005 Heterotypic interaction of CRTAM with Necl2 induces cell adhesion on activated NK cells and CD8+ T cells. International immunology 63 16091383
2009 Tumor suppressor CADM1 is involved in epithelial cell structure. Biochemical and biophysical research communications 61 19854157
2001 Expression of error-prone polymerases in BL2 cells activated for Ig somatic hypermutation. Proceedings of the National Academy of Sciences of the United States of America 60 11427727
2010 SynCAM 1 participates in axo-dendritic contact assembly and shapes neuronal growth cones. Proceedings of the National Academy of Sciences of the United States of America 57 20368431
2011 Lateral assembly of the immunoglobulin protein SynCAM 1 controls its adhesive function and instructs synapse formation. The EMBO journal 56 21926970
2016 CADM1/TSLC1 Identifies HTLV-1-Infected Cells and Determines Their Susceptibility to CTL-Mediated Lysis. PLoS pathogens 51 27105228
2010 N-glycosylation at the SynCAM (synaptic cell adhesion molecule) immunoglobulin interface modulates synaptic adhesion. The Journal of biological chemistry 51 20739279
1984 Preparation and characterization of monoclonal antibodies recognizing three distinct differentiation antigens (BL1, BL2, BL3) on human B lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 51 6429242
2014 TGF-β upregulates miR-182 expression to promote gallbladder cancer metastasis by targeting CADM1. Molecular bioSystems 49 24445397
2014 HPV-positive oropharyngeal squamous cell carcinoma is associated with TIMP3 and CADM1 promoter hypermethylation. Cancer medicine 48 25065733
2010 Impairment of social and emotional behaviors in Cadm1-knockout mice. Biochemical and biophysical research communications 47 20450890
2012 Clinical significance of CADM1/TSLC1/IgSF4 expression in adult T-cell leukemia/lymphoma. Leukemia 46 22289924
2001 Incorporation of [(15)N] ammonia by the cellulolytic ruminal bacteria Fibrobacter succinogenes BL2, Ruminococcus albus SY3, and Ruminococcus flavefaciens 17. Applied and environmental microbiology 46 11375199
2019 CADM1 is a TWIST1-regulated suppressor of invasion and survival. Cell death & disease 43 30911007
2014 The SynCAM synaptic cell adhesion molecules are involved in sensory axon pathfinding by regulating axon-axon contacts. Journal of cell science 43 25335893
2008 Large clonal outbreak of multidrug-resistant CC17 ST17 Enterococcus faecium containing Tn5382 in a Spanish hospital. The Journal of antimicrobial chemotherapy 43 19001448
2023 Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production. Nature genetics 42 37291193
2015 Human T-cell leukemia virus type 1 (HTLV-1) tax requires CADM1/TSLC1 for inactivation of the NF-κB inhibitor A20 and constitutive NF-κB signaling. PLoS pathogens 41 25774694
2014 Combined CADM1/MAL methylation and cytology testing for colposcopy triage of high-risk HPV-positive women. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 41 24962840
2010 CADM1/TSLC1 inactivation by promoter hypermethylation is a frequent event in colorectal carcinogenesis and correlates with late stages of the disease. International journal of cancer 40 20340131
2021 Functional and Clinical Characteristics of Cell Adhesion Molecule CADM1 in Cancer. Frontiers in cell and developmental biology 39 34395444
2019 Synapse-Selective Control of Cortical Maturation and Plasticity by Parvalbumin-Autonomous Action of SynCAM 1. Cell reports 39 30625321
2018 Circular RNAs hsa_circ_0032462, hsa_circ_0028173, hsa_circ_0005909 are predicted to promote CADM1 expression by functioning as miRNAs sponge in human osteosarcoma. PloS one 39 30153287
2015 Polysialic acid on SynCAM 1 in NG2 cells and on neuropilin-2 in microglia is confined to intracellular pools that are rapidly depleted upon stimulation. Glia 39 25752299
2003 IGSF4: a new intercellular adhesion molecule that is called by three names, TSLC1, SgIGSF and SynCAM, by virtue of its diverse function. Histology and histopathology 39 12973698
2018 miR-214-3p promotes the proliferation, migration and invasion of osteosarcoma cells by targeting CADM1. Oncology letters 37 30013657
2009 Role of the spermatogenic-Sertoli cell interaction through cell adhesion molecule-1 (CADM1) in spermatogenesis. Anatomical science international 37 19337787
2012 Polysialylation of the synaptic cell adhesion molecule 1 (SynCAM 1) depends exclusively on the polysialyltransferase ST8SiaII in vivo. The Journal of biological chemistry 36 22908220
2007 The adhesion molecule Necl-3/SynCAM-2 localizes to myelinated axons, binds to oligodendrocytes and promotes cell adhesion. BMC neuroscience 36 17967169
2015 CADM1 and MAL methylation status in cervical scrapes is representative of the most severe underlying lesion in women with multiple cervical biopsies. International journal of cancer 35 26219541
2014 Trans-homophilic interaction of CADM1 activates PI3K by forming a complex with MAGuK-family proteins MPP3 and Dlg. PloS one 35 24503895
2016 CADM1 inhibits squamous cell carcinoma progression by reducing STAT3 activity. Scientific reports 34 27035095
2015 Methylation Levels of CADM1, MAL, and MIR124-2 in Cervical Scrapes for Triage of HIV-Infected, High-Risk HPV-Positive Women in Kenya. Journal of acquired immune deficiency syndromes (1999) 34 26473640
2012 Increased tumorigenesis associated with loss of the tumor suppressor gene Cadm1. Molecular cancer 34 22553910
2016 MYCN-mediated miR-21 overexpression enhances chemo-resistance via targeting CADM1 in tongue cancer. Journal of molecular medicine (Berlin, Germany) 33 27055844
2016 Antiobesity Effect of Garlic Extract Fermented by Lactobacillus plantarum BL2 in Diet-Induced Obese Mice. Journal of medicinal food 33 27627701
2012 CADM1/TSLC1 is a novel cell surface marker for adult T-cell leukemia/lymphoma. Journal of clinical and experimental hematopathology : JCEH 33 22706526
2011 Rapid detection of "highly virulent" Group B Streptococcus ST-17 and emerging ST-1 clones by MALDI-TOF mass spectrometry. Journal of microbiological methods 33 21663770
2019 MicroRNA-155-3p promotes breast cancer progression through down-regulating CADM1. OncoTargets and therapy 32 31579252
2019 Secretion of Mast Cell Inflammatory Mediators Is Enhanced by CADM1-Dependent Adhesion to Sensory Neurons. Frontiers in cellular neuroscience 31 31275114
2011 Development of a system for genetic manipulation of the facultative methanotroph Methylocella silvestris BL2. Methods in enzymology 30 21419918
2008 CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23. BMC cancer 29 18559103
2017 Human Papillomavirus Genotypes and Methylation of CADM1, PAX1, MAL and ADCYAP1 Genes in Epithelial Ovarian Cancer Patients. Asian Pacific journal of cancer prevention : APJCP 28 28240513
2017 Mechanistic insights into ectodomain shedding: susceptibility of CADM1 adhesion molecule is determined by alternative splicing and O-glycosylation. Scientific reports 28 28393893
2016 Tumor Necrosis Factor α Regulates Endothelial Progenitor Cell Migration via CADM1 and NF-kB. Stem cells (Dayton, Ohio) 28 26867147
2009 Necl2 regulates epidermal adhesion and wound repair. Development (Cambridge, England) 28 19783739
2016 Excitatory Synaptic Drive and Feedforward Inhibition in the Hippocampal CA3 Circuit Are Regulated by SynCAM 1. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 27413156
2007 Loss of partitioning-defective-3/isotype-specific interacting protein (par-3/ASIP) in the elongating spermatid of RA175 (IGSF4A/SynCAM)-deficient mice. The American journal of pathology 27 18055550
2014 CADM1 controls actin cytoskeleton assembly and regulates extracellular matrix adhesion in human mast cells. PloS one 26 24465823
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2004 Distribution of RA175/TSLC1/SynCAM, a member of the immunoglobulin superfamily, in the developing nervous system. Brain research. Developmental brain research 26 15707673
2022 Phenotypic and Genotypic Characterization of a Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae ST17-KL38 Clinical Isolate Harboring the Carbapenemase IMP-4. Microbiology spectrum 25 35225687
2021 Differential Contribution of Cadm1-Cadm3 Cell Adhesion Molecules to Peripheral Myelinated Axons. The Journal of neuroscience : the official journal of the Society for Neuroscience 25 33397712
2006 Direct interaction between nerves and mast cells mediated by the SgIGSF/SynCAM adhesion molecule. Journal of pharmacological sciences 25 16936456
2023 Concerted roles of LRRTM1 and SynCAM 1 in organizing prefrontal cortex synapses and cognitive functions. Nature communications 24 36709330
2021 CADM1 and CADM2 Trigger Neuropathogenic Measles Virus-Mediated Membrane Fusion by Acting in cis. Journal of virology 24 33910952
2020 MiR-423-5p aggravates lung adenocarcinoma via targeting CADM1. Thoracic cancer 24 33205911
2020 The Role of Cell Adhesion Molecule 1 (CADM1) in Cutaneous Malignancies. International journal of molecular sciences 24 33419290
2017 Decreased expression of CADM1 and CADM4 are associated with advanced stage breast cancer. Oncology letters 24 29434950
2012 Cell adhesion molecule 1 (CADM1) on mast cells promotes interaction with dorsal root ganglion neurites by heterophilic binding to nectin-3. Journal of neuroimmunology 24 22703826
2012 The synaptic adhesion molecule SynCAM 1 contributes to cocaine effects on synapse structure and psychostimulant behavior. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 24 23169347
2017 MicroRNA-196b inhibits late apoptosis of pancreatic cancer cells by targeting CADM1. Scientific reports 23 28904340
2013 Necl-4/SynCAM-4 is expressed in myelinating oligodendrocytes but not required for axonal myelination. PloS one 23 23700466
2012 Expression of a splicing variant of the CADM1 specific to small cell lung cancer. Cancer science 23 22429880
2018 CADM1 is essential for KSHV-encoded vGPCR-and vFLIP-mediated chronic NF-κB activation. PLoS pathogens 22 29698475
2017 Regulation of PI-2b Pilus Expression in Hypervirulent Streptococcus agalactiae ST-17 BM110. PloS one 22 28107386
2016 Performance of CADM1/MAL-methylation analysis for monitoring of women treated for high-grade CIN. Gynecologic oncology 22 27430395
2016 CADM1 regulates the G1/S transition and represses tumorigenicity through the Rb-E2F pathway in hepatocellular carcinoma. Hepatobiliary & pancreatic diseases international : HBPD INT 21 27298105
2013 Necl-2/CADM1 interacts with ErbB4 and regulates its activity in GABAergic neurons. Molecular and cellular neurosciences 21 23769722
2012 Cadm1-expressing synapses on Purkinje cell dendrites are involved in mouse ultrasonic vocalization activity. PloS one 21 22272290
2015 MicroRNA-126 regulates migration and invasion of gastric cancer by targeting CADM1. International journal of clinical and experimental pathology 20 26464628
2012 CADM1 isoforms differentially regulate human mast cell survival and homotypic adhesion. Cellular and molecular life sciences : CMLS 20 22438059
2008 Six cadm/SynCAM genes are expressed in the nervous system of developing zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists 20 18095341
2022 Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia. Scientific reports 19 35241698
2018 Methylation of CADM1 and MAL together with HPV status in cytological cervical specimens serves an important role in the progression of cervical intraepithelial neoplasia. Oncology letters 19 30546453
2016 ΔNp63 regulates cell proliferation, differentiation, adhesion, and migration in the BL2 subtype of basal-like breast cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 18 26825981
2016 Extracellular CADM1 interactions influence insulin secretion by rat and human islet β-cells and promote clustering of syntaxin-1. American journal of physiology. Endocrinology and metabolism 18 27072493
2012 CADM1 is expressed as multiple alternatively spliced functional and dysfunctional isoforms in human mast cells. Molecular immunology 18 23063768