Affinage

CADM1

Cell adhesion molecule 1 · UniProt Q9BY67

Length
442 aa
Mass
48.5 kDa
Annotated
2026-06-09
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CADM1 (SynCAM 1, Necl-2/RA175) is an immunoglobulin-superfamily transmembrane cell adhesion molecule that organizes cell-cell contacts and, most prominently, induces presynaptic differentiation through homophilic trans-adhesion coupled to intracellular PDZ-scaffold recruitment (PMID:12202822, PMID:15634790). Its adhesive output is tuned by its extracellular architecture: membrane-proximal Ig domains 2-3 mediate cis-oligomerization that increases adhesive capacity and is required for synaptogenic activity (PMID:21926970), while site-specific N-glycosylation of the Ig1 domain (Asn70/Asn104) strengthens binding (PMID:20739279) and stimulus-regulated polysialylation of Ig1 by ST8SiaII—using Ig2 as an enzyme docking site—dynamically abolishes homophilic binding (PMID:20479255, PMID:22908220, PMID:25752299). Through its cytoplasmic PDZ-binding tail CADM1 assembles signaling scaffolds: it binds 4.1B/MPP-family MAGuKs (PMID:19854157) and the Rac-GEF Tiam1 (PMID:20215110), and trans-homophilic engagement nucleates an MPP3-Dlg-p85 complex that activates PI3K-Akt-Rac1 signaling to remodel the actin cytoskeleton and drive cell spreading (PMID:24503895), with FAK contributing to growth-cone morphogenesis (PMID:20368431). In parallel, cis-association of its extracellular region with ErbB3 or ErbB4 recruits the tyrosine phosphatase PTPN13 to its tail to suppress receptor tyrosine kinase signaling (PMID:19561085, PMID:23769722). In vivo, SynCAM 1 sets excitatory synapse number and plasticity, cell-autonomously promoting maturation of thalamocortical and excitatory inputs onto parvalbumin interneurons to control cortical critical-period and feedforward inhibition (PMID:21145003, PMID:30625321, PMID:27413156), and acting synergistically with LRRTM1 in prefrontal circuit assembly (PMID:36709330). Beyond the brain, CADM1 is required for spermatid-Sertoli junctions during spermatogenesis via a Par-3/JAM-C ternary complex (PMID:16382161, PMID:18055550), mediates mast cell adhesion to neurons and stromal cells to potentiate degranulation (PMID:22703826, PMID:31275114), constrains beta-cell insulin secretion by organizing exocytic sites (PMID:27072493), and is processed by ADAM10 followed by gamma-secretase to release an intracellular domain (PMID:22172944). Somatic intramembranous gain-of-function mutations (p.Val380Asp, p.Gly379Asp) in aldosterone-producing adenomas impair gap-junction communication and drive aldosterone overproduction, establishing that CADM1 normally suppresses aldosterone synthesis (PMID:37291193).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2002 High

    Establishing that a single adhesion molecule can instruct presynaptic assembly answered whether trans-cellular adhesion alone organizes synapses; SynCAM 1 was shown sufficient and its cytoplasmic tail necessary.

    Evidence Heterologous cell-neuron co-culture synapse induction, dominant-negative tail expression, reconstituted glutamatergic transmission

    PMID:12202822

    Open questions at the time
    • Did not identify the intracellular scaffolds bound by the tail
    • Did not resolve the trans-adhesive interface structurally
  2. 2005 High

    Comparing SynCAM 1 to neuroligin-1 distinguished synapse formation from synapse function, showing SynCAM 1 uniquely promotes functional maturation of immature excitatory synapses via its cytoplasmic tail.

    Evidence Co-culture induction, chimeric molecule expression in neurons, electrophysiology

    PMID:15634790

    Open questions at the time
    • Downstream effectors of the dominant-positive tail not defined
  3. 2006 High

    Knockout phenotyping in testis extended CADM1 function beyond brain, showing its adhesion is required to retain maturing spermatids at Sertoli cell junctions.

    Evidence RA175 knockout mice, testis histology and immunostaining, fertility assays

    PMID:16382161

    Open questions at the time
    • Counter-receptor on Sertoli cells not identified in this study
    • Intracellular junction machinery not yet mapped
  4. 2008 Medium

    Mapping CADM1's adhesive interface to Ig3 and linking trans-binding to surface trafficking and cleavage susceptibility connected extracellular structure to protein stability.

    Evidence Missense mutant expression, Western blot, cell surface trafficking assays

    PMID:18957284

    Open questions at the time
    • Single lab
    • No structural confirmation of the Ig3 interaction interface
  5. 2010 High

    Multiple studies established how glycosylation tunes CADM1 adhesion and how the cytoplasmic tail couples to actin signaling, defining the molecule as a dynamically regulated adhesion-signaling hub.

    Evidence Crystallography of SynCAM 2 Ig1, MS glycosite mapping and mutagenesis, in vitro polysialylation, FAK and Tiam1 Co-IP, Rac assays, neuronal imaging, transgenic/knockout mice

    PMID:19561085 PMID:20215110 PMID:20368431 PMID:20479255 PMID:20739279 PMID:21145003

    Open questions at the time
    • How glycan-state switching is regulated in vivo
    • Quantitative contribution of each scaffold to synaptogenesis unresolved
  6. 2011 High

    Demonstrating cis-oligomerization via Ig2-3 and regulated intramembrane proteolysis by ADAM10/gamma-secretase revealed two layers of post-assembly control over CADM1 adhesion.

    Evidence Oligomer biochemistry, domain deletions, dominant-negative cis mutants, synapse induction; LC/MS/MS cleavage mapping, ADAM10 siRNA, gamma-secretase inhibition

    PMID:21926970 PMID:22172944

    Open questions at the time
    • Function of the released intracellular domain not established
    • Triggers of shedding in vivo unknown
  7. 2013 Medium

    Linking CADM1-PTPN13 to ErbB4 suppression in parvalbumin interneurons placed CADM1 in inhibitory-circuit control of neuregulin signaling.

    Evidence Co-IP, co-localization, siRNA, PTPN13 overexpression, ErbB4 phosphorylation assay

    PMID:23769722

    Open questions at the time
    • Single lab
    • In vivo requirement for the CADM1-PTPN13-ErbB4 axis not tested genetically here
  8. 2014 Medium

    Identifying the MPP3-Dlg-p85 scaffold linking trans-homophilic CADM1 to PI3K-Akt-Rac1 provided the signaling route from adhesion to actin reorganization, and cis-interactions with SynCAM 2 were shown to guide axon pathfinding and actin assembly in mast cells.

    Evidence Spreading assays, inhibitor screen, complex Co-IP, Akt/Rac assays; chick in ovo knockdown; mast cell knockdown with AFM and phalloidin

    PMID:24465823 PMID:24503895 PMID:25335893

    Open questions at the time
    • Single labs for each finding
    • Direct demonstration that PI3K activation drives in vivo synaptogenesis missing
  9. 2019 High

    Cell-type-specific manipulation showed SynCAM 1 in parvalbumin interneurons gates cortical critical-period plasticity, and CADM1 adhesion was shown necessary for mast cell-neuron functional coupling.

    Evidence Knockout and PV-specific AAV knockdown, electrophysiology, ocular dominance plasticity; mast cell-DRG co-culture with blocking peptide and secretion assays

    PMID:30625321 PMID:31275114

    Open questions at the time
    • Molecular link between PV-cell SynCAM 1 and plasticity machinery incomplete
    • Mast cell intracellular signaling from CADM1 not fully resolved
  10. 2023 High

    Discovery of somatic intramembranous gain-of-function CADM1 mutations in aldosterone-producing adenomas established a Mendelian-type disease mechanism in which CADM1 normally suppresses aldosterone via gap-junction communication.

    Evidence Whole exome sequencing across cohorts, mutant expression in H295R cells, CYP11B2 expression, gap-junction dye transfer, Gap27 blockade

    PMID:37291193

    Open questions at the time
    • How an intramembranous adhesion molecule controls connexin function molecularly unresolved
    • Whether the same mechanism operates in non-adrenal tissue unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how CADM1's glycan-state, cis/trans adhesion, proteolytic processing, and scaffold recruitment are integrated into a single regulatory logic that selects among its divergent tissue-specific outputs.
  • No unified structural model coupling adhesion state to intracellular signaling output
  • Function of the released ICD undetermined
  • Mechanism connecting CADM1 to gap-junction regulation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 5 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2
Partners
CRTAMERBB3ERBB4FAKMPP3PAR-3PTPN13TIAM1
Complex memberships
CADM1-4.1B-MPP2/MPP3 scaffold complexCADM1-HER2-integrin alpha6beta4 complexCADM1-Par-3-JAM-C ternary complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 SynCAM 1 (CADM1) is a brain-specific immunoglobulin domain-containing protein that functions as a homophilic cell adhesion molecule at synapses, binds intracellular PDZ-domain proteins via its cytoplasmic tail, and expression in nonneuronal cells is sufficient to induce functional presynaptic differentiation in cocultured hippocampal neurons. Expression of the isolated cytoplasmic tail in neurons inhibited synapse assembly (dominant-negative effect). Heterologous cell co-culture synapse induction assay, neuronal dominant-negative overexpression, reconstitution of glutamatergic transmission with coexpressed glutamate receptors Science High 12202822
2005 SynCAM 1 (CADM1) and neuroligin-1 (NL1) both specifically induce presynaptic differentiation in co-culture assays; only SynCAM 1 (not NL1) increased synaptic function in immature developing excitatory neurons, and this dominant-positive effect was mediated by its intracellular cytoplasmic tail. Heterologous cell co-culture synapse induction, electrophysiology, chimeric molecule expression in neurons The Journal of neuroscience High 15634790
2008 Two missense mutations in CADM1 (C739A/H246N and A755C/Y251S) located in the third immunoglobulin domain impair trans-active interaction; mutant CADM1 shows reduced high-molecular-weight glycosylated forms, defective trafficking to the cell surface, and increased susceptibility to cleavage/degradation. Mutant protein expression in cells, Western blot, cell surface trafficking assays Biochemical and biophysical research communications Medium 18957284
2010 SynCAM 1 (CADM1) is a target for polysialylation in postnatal mouse brain; polySia is added on N-glycans of the first Ig domain by both ST8SiaII and ST8SiaIV in vitro, and polysialylation of SynCAM 1 completely abolishes its homophilic binding activity. Glycoproteomics affinity purification from Ncam−/− brain, peptide mass fingerprinting, in vitro polysialylation assay, binding assay after polySia modification Proceedings of the National Academy of Sciences of the United States of America High 20479255
2010 SynCAM 1 (CADM1) overexpression in transgenic mice promotes excitatory synapse number; loss of SynCAM 1 results in fewer excitatory synapses. SynCAM 1 also regulates long-term depression (LTD) at mature synapses and affects spatial learning, with knockout mice learning better. Transgenic overexpression and knockout mice, synapse counting, electrophysiology (LTD), spatial learning behavioral assays Neuron High 21145003
2010 SynCAM 1 (CADM1) localizes to growth cones of developing neurons and is required and sufficient to restrict active filopodia number, negatively regulating growth cone morphological complexity. Focal adhesion kinase (FAK) is a binding partner of SynCAM 1 and is implicated in its morphogenetic activities. Live imaging of developing neurons, SynCAM 1 overexpression/knockdown, FAK co-immunoprecipitation, filopodia quantification Proceedings of the National Academy of Sciences of the United States of America High 20368431
2010 N-glycosylation at specific sites on the SynCAM 1 Ig1 domain (Asn70/Asn104) modulates its adhesive interactions: these N-glycans increase adhesion and are required for synapse induction. In contrast, N-glycosylation of SynCAM 2 at Asn60 reduces adhesion. Sialic acid modification contributes to the glycan-dependent strengthening of SynCAM 1 binding. Crystallographic analysis of SynCAM 2 Ig1 domain, mass spectrometry of glycosylation sites, site-directed mutagenesis of glycosylation sites, adhesion assays, synapse induction assay The Journal of biological chemistry High 20739279
2011 SynCAM 1 (CADM1) self-assembles laterally (cis-oligomerization) via its extracellular membrane-proximal Ig domains 2 and 3, generating oligomers with increased adhesive capacity. Cis assembly promotes adhesive clustering at new axo-dendritic contacts and is required for synaptogenic activity; lateral oligomerization also restricts synaptic size at later stages. Biochemical characterization of SynCAM oligomers, domain deletion constructs, neuronal overexpression with dominant-negative cis-assembly mutants, synapse induction assays, imaging The EMBO journal High 21926970
2009 CADM1 interacts with actin-binding protein 4.1B/DAL-1 and scaffold protein MPP3/DLG3. MPP1/p55 and MPP2/DLG2 form a tripartite complex with CADM1 and 4.1B. MPP2 is recruited to the CADM1–4.1B complex during early adhesion. siRNA-mediated suppression of CADM1 disrupts epithelia-like cell structure and mislocalizes 4.1B, MPP2, E-cadherin, and ZO-1 from the membrane. Co-immunoprecipitation, siRNA knockdown in HEK293 cells, immunofluorescence localization Biochemical and biophysical research communications Medium 19854157
2010 The cytoplasmic PDZ-binding motif of CADM1 directly interacts with the PDZ domain of Tiam1 (a Rac-specific GEF), inducing lamellipodia formation through Rac activation in HTLV-I-transformed and ATL cell lines, promoting an invasive phenotype. Co-immunoprecipitation of CADM1 cytoplasmic domain with Tiam1 PDZ domain, Rac activation assay, lamellipodia formation assay in cell lines The Journal of biological chemistry High 20215110
2009 CADM1 (Necl-2) interacts in cis with the extracellular region of ErbB3 (but not ErbB2), reducing ligand-induced ErbB2-catalyzed tyrosine phosphorylation of ErbB3 and inhibiting subsequent ErbB3-mediated activation of Rac and Akt. These inhibitory effects are mediated by PTPN13, a protein-tyrosine phosphatase that interacts with the cytoplasmic tail of CADM1. Co-immunoprecipitation (cis interaction), receptor phosphorylation assays, Rac and Akt activity assays, siRNA knockdown, PTPN13 interaction mapping The Journal of biological chemistry High 19561085
2013 CADM1 (Necl-2) interacts with ErbB4 in parvalbumin-positive GABAergic neurons (co-localizing at excitatory synapses). Knockdown of CADM1 enhances Nrg1-induced ErbB4 phosphorylation. Overexpression of PTPN13, which binds the cytoplasmic tail of CADM1, suppresses Nrg1-induced excitatory synapse development in GABAergic neurons via inhibition of ErbB4 activity. Co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown, PTPN13 overexpression, ErbB4 phosphorylation assay Molecular and cellular neurosciences Medium 23769722
2006 CADM1 (RA175) is expressed at spermatocyte and elongating/elongated spermatid cell junctions in testes. Knockout mice lacking RA175 are male-infertile (oligo-astheno-teratozoospermia): elongating spermatids (steps 9–12) fail to mature and translocate to the adluminal surface and are phagocytosed by Sertoli cells, demonstrating that CADM1-mediated cell junction is necessary for retaining elongating spermatids in Sertoli cell invaginations during maturation. Gene knockout mice, histology, immunostaining in testes, fertility assays Molecular and cellular biology High 16382161
2007 CADM1 (RA175) interacts with Par-3 (a PDZ-domain cell polarity protein) via its cytoplasmic region in testis, and forms a ternary complex with JAM-C via Par-3. In RA175-knockout elongating spermatids, Par-3 is absent and JAM-C is absent or abnormally localized, indicating this ternary complex is required for maintaining specialized adhesion structures in spermatid differentiation. Co-immunoprecipitation from testis, immunostaining of knockout vs. wildtype testes The American journal of pathology Medium 18055550
2011 CADM1 is cleaved by ADAM10 (a disintegrin and metalloprotease) at a membrane-proximal site (identified by LC/MS/MS), and the resulting membrane-bound fragment is subsequently cleaved by γ-secretase to generate a CADM1 intracellular domain (ICD) via regulated intramembrane proteolysis (RIP). ADAM10 mediates endogenous CADM1 shedding as shown by siRNA knockdown. LC/MS/MS cleavage site mapping, siRNA knockdown of ADAM10, γ-secretase inhibitor, cell-based cleavage assays Biochemical and biophysical research communications High 22172944
2012 Polysialylation of SynCAM 1 (CADM1) in perinatal brain is exclusively mediated by ST8SiaII (not ST8SiaIV) in vivo. The minimal polypeptide required for ST8SiaII-dependent polysialylation contains both Ig1 (the polySia acceptor site) and Ig2 (a docking site for ST8SiaII); Ig1 alone is insufficient. Analysis of ST8SiaII and ST8SiaIV single-knockout mice, domain deletion constructs transfected in cell culture, polySia immunoblot The Journal of biological chemistry High 22908220
2014 Trans-homophilic interaction of CADM1 activates PI3K by forming a multi-protein complex with MAGuK family proteins MPP3 and Dlg at the cell periphery; these scaffold proteins connect CADM1 to the p85 regulatory subunit of PI3K. PI3K activation downstream leads to Akt and Rac1 activity, reorganizing the actin cytoskeleton and promoting epithelial cell spreading. Cell-based CADM1 trans-homophilic spreading assay, chemical inhibitor screen (104 inhibitors), co-immunoprecipitation of CADM1–MPP3–Dlg–p85 complex, Akt and Rac1 activity assays PloS one Medium 24503895
2016 CADM1 inhibits squamous cell carcinoma proliferation and invasion by forming a complex at the cell surface with HER2 and integrin α6β4 via its extracellular domain, which disrupts downstream STAT3 activity. This effect is dependent on the extracellular domain of CADM1. Gene transduction (CADM1 overexpression), domain deletion constructs, co-immunoprecipitation of CADM1–HER2–integrin α6β4 complex, STAT3 activity assays, xenograft tumor assays Scientific reports Medium 27035095
2005 CADM1 (Necl-2) mediates heterotypic cell adhesion with CRTAM (class I-restricted T cell-associated molecule) expressed on activated NK cells and CD8+ T cells. The heterotypic CRTAM–Necl-2 interaction has higher affinity than homotypic Necl-2 interaction and mediates tight heterotypic cell binding without altering cytotoxic function. Expression-cloning identification of Necl-2 as CRTAM ligand, binding affinity measurements, cell adhesion/aggregation assays, CRTAM-Ig fusion protein blocking International immunology Medium 16091383
2008 SynCAM proteins (including SynCAM 1/CADM1) exhibit specific heterophilic adhesion patterns: SynCAM 1 interacts with SynCAM 2, SynCAM 2 interacts with SynCAM 4, and SynCAM 3 interacts with SynCAM 4, as demonstrated by cell overlay experiments using extracellular domains. Cell overlay adhesion assays with extracellular domain-expressing cells, expression profiling by ISH and immunohistology The Journal of comparative neurology Medium 18615557
2012 CADM1 is a key adhesion receptor in human mast cells mediating homotypic (mast cell–mast cell) adhesion as the sole receptor for MC aggregation; CADM1 isoform SP4 promotes survival via upregulation of pro-survival protein Mcl-1(L). CADM1 downregulation reduces Mcl-1(L) expression and increases caspase-3/7 activity, while SP1 isoform overexpression compromises survival compared to SP4. Adenoviral CADM1 knockdown, isoform-specific cDNA overexpression, homotypic adhesion assays, Western blot (Mcl-1L, Bcl-2, Bcl-XL), caspase-3/7 activity assay Cellular and molecular life sciences Medium 22438059
2013 CADM1 (SP4 isoform) is the key receptor mediating human mast cell adhesion to human lung fibroblasts (HLFs) and airway smooth muscle cells (HASMCs). HLFs express both CADM1 and nectin-3 as CADM1 counter-receptors, while HASMCs express only nectin-3. SP4 overexpression specifically increases adhesion to HLFs. CADM1-mediated adhesion accounts for up to 67% of MC adhesion to HLFs. Adenoviral shRNA knockdown and isoform-specific cDNA overexpression, adhesion assays, counter-receptor expression analysis PloS one Medium 23620770
2012 CADM1 on mast cells promotes heterophilic adhesion to dorsal root ganglion (DRG) neurites via binding to nectin-3 (expressed on DRG neurons). A nectin-3 neutralizing antibody inhibits both mast cell attachment to DRG neurites and subsequent calcium responses in mast cells, demonstrating functional consequence of this heterophilic interaction. Co-culture adhesion assay, nectin-3 neutralizing antibody blocking, calcium imaging Journal of neuroimmunology Medium 22703826
2014 CADM1 controls actin cytoskeleton assembly in human mast cells: CADM1 downregulation reduces cortical F-actin polymerization, elongates cortical actin filaments, and increases cell rigidity. CADM1 accounts for ~46% of surface KIT levels and ~31% of F-actin in HMC-1 cells, and regulates phosphotyrosine signaling and KIT tyrosine autophosphorylation. siRNA/shRNA CADM1 knockdown, flow cytometry (surface KIT), phalloidin staining (F-actin quantification), atomic force microscopy (cell rigidity), phosphotyrosine western blot PloS one Medium 24465823
2019 CADM1-mediated adhesion between mast cells and sensory neurons is necessary and sufficient for enhanced mast cell degranulation and IL-6 secretion in response to neuronal activation and antigen stimulation. A CADM1 blocking peptide or CADM1 knockdown in mast cells significantly decreases mast cell attachment to sensory neurites and abolishes enhanced secretory responses. Bone marrow-derived mast cell/DRG neuron co-culture, CADM1 blocking peptide, shRNA knockdown, degranulation and cytokine secretion assays Frontiers in cellular neuroscience Medium 31275114
2019 SynCAM 1 (CADM1) in parvalbumin (PV+) interneurons limits visual cortex plasticity: loss of SynCAM 1 selectively reduces thalamocortical inputs onto PV+ interneurons, impairing feedforward inhibition maturation. Brief PV+-cell-specific knockdown of SynCAM 1 in adult visual cortex restores juvenile-like plasticity, demonstrating a cell-autonomous role. SynCAM 1 knockout mice, conditional PV+-specific AAV-mediated knockdown, synaptic quantification, electrophysiology, ocular dominance plasticity assay Cell reports High 30625321
2016 SynCAM 1 (CADM1) loss reduces the number of excitatory terminals onto parvalbumin-positive interneurons in hippocampal CA3, reduces postsynaptic GluA1 in these interneurons, and impairs mossy fiber refinement and thorny excrescence size in CA3 pyramidal neurons, resulting in CA3 disinhibition and impaired feedforward inhibition. SynCAM 1 knockout mice, diffusion tensor MRI, immunostaining and synapse quantification, electrophysiology, memory behavioral tasks The Journal of neuroscience High 27413156
2023 Somatic gain-of-function mutations in CADM1 (intramembranous p.Val380Asp or p.Gly379Asp) in aldosterone-producing adenomas cause 10- to 25-fold upregulation of CYP11B2 (aldosterone synthase). Mutant CADM1 inhibits gap junction-permeable dye transfer, and pharmacological gap junction blockade (Gap27) increases CYP11B2 similarly, revealing that CADM1 normally suppresses aldosterone production through promoting gap junction communication. Whole exome sequencing, H295R cell transduction with mutant/wildtype CADM1, CYP11B2 gene expression, gap junction dye transfer assay, Gap27 pharmacological blockade Nature genetics High 37291193
2018 CADM1 and CADM2 act as host factors enabling neuropathogenic measles virus (MeV) to spread between neurons via hyperfusogenic F proteins. CADM1/CADM2 interact in cis (on the same cell membrane) with the MeV attachment protein, triggering the fusion protein and causing membrane fusion — a receptor-mimicking cis-acting mechanism. Knockdown of CADM1 and CADM2 inhibits syncytium formation and virus transmission between neurons. siRNA knockdown of CADM1/CADM2 in neurons, co-immunoprecipitation of cis interaction with MeV attachment protein, syncytium formation assay, virus transmission assay Journal of virology Medium 33910952
2018 CADM1 is upregulated in KSHV-infected PEL cells. Both KSHV oncoproteins vFLIP and vGPCR interact with CADM1, and the PDZ-binding motif at the carboxyl terminus of CADM1 is essential for vGPCR and vFLIP to maintain chronic NF-κB activation. Membrane lipid raft-associated CADM1 interaction with vFLIP is critical for IKK kinase complex initiation and NF-κB activation. Co-immunoprecipitation of vFLIP/vGPCR with CADM1, PDZ-binding motif deletion mutants, NF-κB reporter assays, lipid raft fractionation, IKK kinase assay PLoS pathogens Medium 29698475
2016 CADM1 regulates the G1/S transition in hepatocellular carcinoma cells; ectopic CADM1 expression increases Retinoblastoma (Rb) protein levels, and CADM1-mediated tumor suppression is associated with the Rb-E2F pathway. CADM1 overexpression in HCC cell lines, cell cycle analysis (flow cytometry), EdU incorporation, colony formation, in vivo xenograft tumorigenicity, Western blot (Rb protein) Hepatobiliary & pancreatic diseases international Medium 27298105
2019 TWIST1 directly represses CADM1 expression by physically interacting with the CADM1 promoter, as shown by ChIP and promoter assays. Increased CADM1 expression inhibits melanoma cell motility/invasiveness and elicits caspase-independent cell death in non-adherent conditions associated with loss of mitochondrial membrane potential. Chromatin immunoprecipitation (ChIP), promoter assays, CADM1 overexpression, invasion assay, anoikis assay, mitochondrial membrane potential measurement Cell death & disease Medium 30911007
2016 CADM1 loss in the nucleus accumbens (NAc) reduces excitatory synapse number on medium spiny neurons. Cocaine administration increases stubby spine density in NAc, and maintaining this structural increase requires SynCAM 1. SynCAM 1 knockout mice show altered behavioral responses to acute and repeated cocaine administration. SynCAM 1 knockout mice, NAc spine morphology analysis, cocaine administration paradigm, behavioral psychostimulant assays Neuropsychopharmacology Medium 23169347
2014 SynCAM 1 (CADM1) and SynCAM 2 engage in heterophilic cis-interactions in addition to homophilic interactions; these cis-interactions modulate SynCAM trans-binding interactions and are required for correct sensory axon pathfinding in vivo in the chick embryo. In vitro cis-interaction assays (cell aggregation), in ovo SynCAM knockdown in chick embryo, sensory axon pathfinding analysis Journal of cell science Medium 25335893
2021 In the peripheral nervous system, Cadm1 acts redundantly with Cadm2 and Cadm3 as axonal ligands for glial Cadm4. Genetic ablation of all three (Cadm1/2/3 triple KO) phenocopies Cadm4 null abnormalities in Caspr and Kv1 channel distribution. Cadm3 is the main axonal ligand for Cadm4, and its loss can be compensated by combined Cadm2 and Cadm1 action. Single, double, and triple Cadm knockout mice, immunostaining of Caspr and Kv1 channels at paranodes/juxtaparanodes The Journal of neuroscience High 33397712
2023 SynCAM 1 (CADM1) controls excitatory synapse number in the prefrontal cortex (PFC) and is upregulated upon LRRTM1 loss. Combined deletion of LRRTM1 and SynCAM 1 reduces PFC dendritic spine number more than the sum of single knockouts (synergistic interaction), reduces Neurexin puncta in PFC, impairs PFC network activity (fMRI/electrophysiology), and causes deficits in social interaction and cognition. LRRTM1 and SynCAM 1 single and double knockout mice, spine morphology analysis, fMRI, electrophysiology, behavioral testing Nature communications High 36709330
2016 Extracellular CADM1 interactions in pancreatic β-cells constrain insulin secretion; CADM1 expression decreases after prolonged glucose stimulation. CADM1 promotes assembly of exocytic sites and actin network formation in β-cells, similar to its role in presynaptic assembly. CADM1 also influences insulin secretion in a transcellular (trans-interaction) manner in co-culture. INS-1 and primary islet β-cell knockdown/overexpression, insulin secretion assays, co-culture transcellular assay, F-actin and exocytic site imaging American journal of physiology. Endocrinology and metabolism Medium 27072493
2012 In tongue cancer cells, CADM1 interacts with BMI1 to inhibit its nuclear translocation. MYCN transcriptionally upregulates miR-21, which directly targets and reduces CADM1 expression, thereby releasing BMI1 to translocate to the nucleus and promote chemo-resistance. Co-immunoprecipitation of CADM1 with BMI1, nuclear/cytoplasmic fractionation, luciferase reporter assay (miR-21 targeting CADM1 3'UTR), MYCN ChIP at miR-21 promoter Journal of molecular medicine Medium 27055844
2015 PolySia on SynCAM 1 in NG2 cells is confined to the Golgi compartment under basal conditions and is transiently recruited to the cell surface in response to depolarization. The polySia is exclusively on N-glycans and synthesized by ST8SIA2 in NG2 cells. This stimulus-dependent surface translocation indicates polySia-SynCAM 1 is dynamically regulated. Murine glial cultures, immunostaining with Golgi markers and polySia antibodies, depolarization assay (KCl), glycan analysis (N- vs O-glycan), ST8SiaII/ST8SiaIV knockout cultures Glia Medium 25752299

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 SynCAM, a synaptic adhesion molecule that drives synapse assembly. Science (New York, N.Y.) 630 12202822
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
2014 CADM1 expression and stepwise downregulation of CD7 are closely associated with clonal expansion of HTLV-I-infected cells in adult T-cell leukemia/lymphoma. Clinical cancer research : an official journal of the American Association for Cancer Research 109 24727323
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 98 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
2008 Mutations in the gene encoding CADM1 are associated with autism spectrum disorder. Biochemical and biophysical research communications 81 18957284
2017 miR-21 enhances cardiac fibrotic remodeling and fibroblast proliferation via CADM1/STAT3 pathway. BMC cardiovascular disorders 80 28335740
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
2008 Expression and adhesion profiles of SynCAM molecules indicate distinct neuronal functions. The Journal of comparative neurology 66 18615557
2005 Heterotypic interaction of CRTAM with Necl2 induces cell adhesion on activated NK cells and CD8+ T cells. International immunology 63 16091383
2010 CADM1 interacts with Tiam1 and promotes invasive phenotype of human T-cell leukemia virus type I-transformed cells and adult T-cell leukemia cells. The Journal of biological chemistry 62 20215110
2009 Tumor suppressor CADM1 is involved in epithelial cell structure. Biochemical and biophysical research communications 62 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
2019 CADM1 inhibits ovarian cancer cell proliferation and migration by potentially regulating the PI3K/Akt/mTOR pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 53 31865146
2016 CADM1/TSLC1 Identifies HTLV-1-Infected Cells and Determines Their Susceptibility to CTL-Mediated Lysis. PLoS pathogens 52 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 50 24445397
2009 Silencing of ErbB3/ErbB2 signaling by immunoglobulin-like Necl-2. The Journal of biological chemistry 50 19561085
2010 Impairment of social and emotional behaviors in Cadm1-knockout mice. Biochemical and biophysical research communications 49 20450890
2012 Clinical significance of CADM1/TSLC1/IgSF4 expression in adult T-cell leukemia/lymphoma. Leukemia 47 22289924
2023 Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production. Nature genetics 46 37291193
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
2018 HPV E4 expression and DNA hypermethylation of CADM1, MAL, and miR124-2 genes in cervical cancer and precursor lesions. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 42 30135508
2007 Expression of the tumour suppressor gene CADM1 is associated with favourable outcome and inhibits cell survival in neuroblastoma. Oncogene 41 18084322
2021 Functional and Clinical Characteristics of Cell Adhesion Molecule CADM1 in Cancer. Frontiers in cell and developmental biology 40 34395444
2019 Synapse-Selective Control of Cortical Maturation and Plasticity by Parvalbumin-Autonomous Action of SynCAM 1. Cell reports 40 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
2013 CADM1 is a key receptor mediating human mast cell adhesion to human lung fibroblasts and airway smooth muscle cells. PloS one 38 23620770
2009 Role of the spermatogenic-Sertoli cell interaction through cell adhesion molecule-1 (CADM1) in spermatogenesis. Anatomical science international 37 19337787
2014 Trans-homophilic interaction of CADM1 activates PI3K by forming a complex with MAGuK-family proteins MPP3 and Dlg. PloS one 36 24503895
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
2019 Secretion of Mast Cell Inflammatory Mediators Is Enhanced by CADM1-Dependent Adhesion to Sensory Neurons. Frontiers in cellular neuroscience 34 31275114
2016 CADM1 inhibits squamous cell carcinoma progression by reducing STAT3 activity. Scientific reports 34 27035095
2012 Increased tumorigenesis associated with loss of the tumor suppressor gene Cadm1. Molecular cancer 34 22553910
2011 Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ-secretase complex. Biochemical and biophysical research communications 34 22172944
2019 CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions. International journal of molecular sciences 33 31067838
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
2019 MicroRNA-155-3p promotes breast cancer progression through down-regulating CADM1. OncoTargets and therapy 32 31579252
2008 Nerve-mast cell and smooth muscle-mast cell interaction mediated by cell adhesion molecule-1, CADM1. Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi 29 18552455
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
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
2020 MiR-423-5p aggravates lung adenocarcinoma via targeting CADM1. Thoracic cancer 26 33205911
2019 CD4+ CADM1+ cell percentage predicts disease progression in HTLV-1 carriers and indolent adult T-cell leukemia/lymphoma. Cancer science 26 31642546
2014 CADM1 controls actin cytoskeleton assembly and regulates extracellular matrix adhesion in human mast cells. PloS one 26 24465823
2006 Direct interaction between nerves and mast cells mediated by the SgIGSF/SynCAM adhesion molecule. Journal of pharmacological sciences 26 16936456
2006 Down-regulation of DNA polymerase beta accompanies somatic hypermutation in human BL2 cell lines. DNA repair 26 17127106
2004 Distribution of RA175/TSLC1/SynCAM, a member of the immunoglobulin superfamily, in the developing nervous system. Brain research. Developmental brain research 26 15707673
2023 Concerted roles of LRRTM1 and SynCAM 1 in organizing prefrontal cortex synapses and cognitive functions. Nature communications 25 36709330
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
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 25 22703826
2021 CADM1 and CADM2 Trigger Neuropathogenic Measles Virus-Mediated Membrane Fusion by Acting in cis. Journal of virology 24 33910952
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 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
2018 CADM1 is a diagnostic marker in early-stage mycosis fungoides: Multicenter study of 58 cases. Journal of the American Academy of Dermatology 23 29928911
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
2016 CADM1 regulates the G1/S transition and represses tumorigenicity through the Rb-E2F pathway in hepatocellular carcinoma. Hepatobiliary & pancreatic diseases international : HBPD INT 22 27298105
2016 Performance of CADM1/MAL-methylation analysis for monitoring of women treated for high-grade CIN. Gynecologic oncology 22 27430395
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
2022 Combined Liquid Biopsy Methylation Analysis of CADM1 and MAL in Cervical Cancer Patients. Cancers 20 36010947
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
2019 The Implicated Roles of Cell Adhesion Molecule 1 (CADM1) Gene and Altered Prefrontal Neuronal Activity in Attention-Deficit/Hyperactivity Disorder: A "Gene-Brain-Behavior Relationship"? Frontiers in genetics 18 31616473
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
2015 Polysialic acid modification of the synaptic cell adhesion molecule SynCAM 1 in human embryonic stem cell-derived oligodendrocyte precursor cells. Stem cell research 18 25863442
2012 CADM1 is expressed as multiple alternatively spliced functional and dysfunctional isoforms in human mast cells. Molecular immunology 18 23063768
2022 Evidence of islet CADM1-mediated immune cell interactions during human type 1 diabetes. JCI insight 17 35133983
2019 lncRNA CADM1-AS1 inhibits cell-cycle progression and invasion via PTEN/AKT/GSK-3β axis in hepatocellular carcinoma. Cancer management and research 17 31118799
2013 miR-214 and hypoxia down-regulate Necl-2/CADM1 and enhance ErbB2/ErbB3 signaling. Genes to cells : devoted to molecular & cellular mechanisms 17 23301758

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