Affinage

NCAM1

Neural cell adhesion molecule 1 · UniProt P13591

Round 2 corrected
Length
858 aa
Mass
94.6 kDa
Annotated
2026-04-29
130 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NCAM1 is a multifunctional immunoglobulin-superfamily cell adhesion molecule that mediates homophilic and heterophilic cell–cell interactions critical for neural development, synaptic plasticity, and immune cell cytotoxicity. Its extracellular region contains five Ig-like domains that form cis-dimers and zipper-like trans-interactions, with adhesion strength negatively regulated by polysialylation (catalyzed by ST8SIA2 and ST8SIA4) through steric and ionic repulsion (PMID:10802736, PMID:15504723, PMID:17986444). The NCAM140 isoform, whose lipid-raft association depends on palmitoylation, recruits RPTPα to activate Fyn and FAK, triggering Ras→MEK→ERK1/2 and CREB phosphorylation to drive neurite outgrowth; NCAM additionally signals through direct binding to FGFR1 via its fibronectin type III modules and serves as a RET-independent GDNF co-receptor via GFRα1, activating Fyn/FAK in Schwann cells and neurons (PMID:9079653, PMID:10084688, PMID:12791257, PMID:12837245, PMID:11980923). Beyond the nervous system, NCAM1 promotes NK-cell lytic granule exocytosis through Pyk2 signaling and sustains leukemic stem cell survival in AML via constitutive MAPK activation (PMID:32510326, PMID:30814062).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1987 High

    Molecular cloning resolved NCAM's domain architecture—five Ig-like extracellular domains shared by three major isoforms (120, 140, 180 kDa)—and established that homophilic binding resides in the Ig domains while isoform diversity arises from alternative splicing of cytoplasmic segments, providing the structural framework for all subsequent signaling studies.

    Evidence cDNA cloning and amino acid sequencing of CNBr/proteolytic fragments, Northern blot; additional tissue-specific (muscle MSD1) and secreted isoforms identified by cDNA cloning

    PMID:2887295 PMID:3203385 PMID:3576199

    Open questions at the time
    • Three-dimensional structure of the full extracellular domain was not yet determined
    • Cytoplasmic signaling partners unknown
  2. 1988 High

    Functional experiments demonstrated that polysialic acid (PSA) on NCAM generates steric exclusion that inhibits membrane apposition and cell–cell contact, establishing PSA as a negative regulator of NCAM-mediated adhesion rather than a binding enhancer.

    Evidence Cell adhesion assays with enzymatic PSA removal and antibody blocking

    PMID:3281256

    Open questions at the time
    • Identity of polysialyltransferase(s) unknown
    • Quantitative biophysical characterization of repulsion pending
  3. 1993 High

    Discovery that NCAM's fourth Ig domain binds L1 glycans in cis via a lectin-like motif, and that transmembrane NCAM isoforms regulate MMP secretion, expanded NCAM's role beyond simple adhesion to heterophilic cis-signaling and extracellular matrix remodeling.

    Evidence Co-IP, recombinant domain binding, peptide inhibition of L1–NCAM, neurite outgrowth assay; transfection of glioma cells with isoform-specific constructs and MMP zymography

    PMID:8265575 PMID:8509458

    Open questions at the time
    • Structural basis of L1–NCAM cis-complex unresolved
    • Downstream effectors linking NCAM to MMP gene regulation unknown
  4. 1995 High

    Cloning of polysialyltransferases PST-1 and ST8SIA2 and reconstitution of PSA synthesis on NCAM in vitro identified the enzymes responsible for NCAM polysialylation, enabling subsequent genetic dissection of PSA function.

    Evidence Expression cloning, in vitro enzymatic reconstitution with defined NCAM substrates, stable transfection in NCAM-expressing cell lines

    PMID:7624364 PMID:7854457 PMID:8805371

    Open questions at the time
    • Relative contributions of the two polysialyltransferases in vivo not yet resolved
    • Chain-length control mechanism unknown
  5. 1997 High

    Identification of p59fyn and p125FAK as isoform-selective (NCAM140-specific) signaling effectors, together with the demonstration that NCAM-knockout mice have severe mossy fiber pathfinding defects, connected NCAM to intracellular kinase cascades and established its in vivo requirement for axon guidance.

    Evidence Co-IP from neonatal brain and transfected cells, tyrosine phosphorylation assays; NCAM-knockout mouse histology and tract tracing

    PMID:9073395 PMID:9079653

    Open questions at the time
    • Mechanism linking Fyn/FAK to cytoskeletal remodeling unknown
    • How NCAM140 selectively recruits Fyn (not NCAM180 or 120) unclear
  6. 1999 High

    Full Ras→MEK→ERK1/2→CREB pathway downstream of NCAM140 was mapped, and MEK inhibition selectively blocked NCAM-driven neurite outgrowth, establishing MAPK as the principal effector cascade for NCAM-dependent neuritogenesis.

    Evidence NCAM antibody clustering, specific MEK/Ras inhibitors, phospho-kinase assays, cerebellar neuron neurite outgrowth

    PMID:10084688

    Open questions at the time
    • Parallel PI3K/Akt and cGMP branches not yet placed in signaling hierarchy
    • Nuclear transcriptional targets of CREB downstream of NCAM undefined
  7. 2000 High

    Crystal structure of the two N-terminal Ig domains revealed antiparallel cis-dimers that assemble into zipper-like trans-arrays, providing the first atomic model of homophilic NCAM recognition; concurrently, PSA-NCAM was shown to bind BDNF and modulate hippocampal LTP via TrkB.

    Evidence X-ray crystallography at 1.85 Å; NCAM-KO and Endo-N-treated hippocampal slices with BDNF rescue and TrkB phosphorylation

    PMID:10760298 PMID:10802736

    Open questions at the time
    • Structure of full-length extracellular region (all five Ig + FNIII domains) not determined
    • Direct PSA–BDNF binding site unmapped
  8. 2002 High

    Two parallel signaling axes were delineated: palmitoylation-dependent lipid-raft localization of NCAM140 was shown essential for Fyn/FAK/ERK activation, and NCAM was identified as a RET-independent co-receptor for GDNF via GFRα1, activating Fyn/FAK in RET-null cells to promote Schwann cell migration and axon growth.

    Evidence Palmitoylation-site mutagenesis, raft disruption (MβCD), FGFR inhibitor in NCAM-null hippocampal neurons; co-IP and kinase assays in RET-deficient cells, migration and neurite outgrowth assays

    PMID:11980923 PMID:12837245

    Open questions at the time
    • Whether GDNF–NCAM and FGFR–NCAM pathways converge or remain independent unclear
    • Palmitoylation enzyme(s) for NCAM not identified
  9. 2003 High

    NMR and SPR experiments mapped the direct NCAM–FGFR1 binding interface to NCAM FNIII modules 1–2 and FGFR1 Ig2–3, and revealed that extracellular ATP competes for the same NCAM surface, acting as a molecular switch that inhibits NCAM–FGFR signaling and neurite outgrowth.

    Evidence NMR structure of NCAM F3 module 2, surface plasmon resonance, FGFR phosphorylation and neurite outgrowth assays

    PMID:12791257

    Open questions at the time
    • Physiological regulation of local ATP concentration at the NCAM–FGFR interface unknown
    • Whether ATP regulation applies to all NCAM-expressing cell types untested
  10. 2003 High

    NCAM signals through a spectrin–PKCβ2 scaffold that is redistributed to lipid rafts in an FGFR-dependent manner; disrupting this scaffold with dominant-negative βI spectrin blocked neurite outgrowth, linking cytoskeletal adaptor assembly to NCAM function.

    Evidence Co-IP, lipid raft fractionation, dominant-negative βI spectrin transfection, FGFR inhibitor, neurite outgrowth assay in hippocampal neurons

    PMID:12743109

    Open questions at the time
    • How spectrin crosslinking mechanically couples to growth cone advance not defined
    • Structural basis of NCAM180–spectrin interaction unknown
  11. 2004 High

    Quantitative biophysical force measurements showed that PSA overwhelms both NCAM homophilic and cadherin-mediated attraction at physiological ionic strength, while RPTPα was identified as the direct bridge linking NCAM140 to Fyn activation, with RPTPα-knockout neurons losing NCAM-dependent signaling.

    Evidence Surface force apparatus on reconstituted membranes; RPTPα-KO neurons, dominant-negative RPTPα, co-IP, lipid raft fractionation, neurite outgrowth

    PMID:15504723 PMID:15623578

    Open questions at the time
    • Crystal structure of NCAM–RPTPα complex not determined
    • Whether PSA removal fully restores adhesive strength in vivo unclear
  12. 2007 High

    In vivo analysis of ST8SiaII and ST8SiaIV knockout mice resolved their relative contributions: both enzymes modify NCAM glycosylation sites 5 and 6, but synergize to produce long polySia chains, with ST8SiaIV as the dominant modifier.

    Evidence Polysialyltransferase-KO mice, glycopeptide mass spectrometry, polySia chain-length analysis

    PMID:17986444

    Open questions at the time
    • Determinants of site-specific polysialyltransferase recruitment unresolved
    • Chain-length termination mechanism unknown
  13. 2008 High

    A Ca²⁺-dependent signaling branch was uncovered: NCAM clustering opens T/L-type Ca²⁺ channels, activating CaMKIIα, which phosphorylates RPTPα at Ser180/204 to boost its phosphatase activity, establishing a parallel Ca²⁺→CaMKII→RPTPα→Fyn cascade for neurite outgrowth.

    Evidence NCAM clustering, Ca²⁺ channel co-IP, CaMKIIα activation, RPTPα serine-phosphorylation mutants, neurite outgrowth in hippocampal neurons

    PMID:18809727

    Open questions at the time
    • Identity of T/L-type channel subunits complexed with NCAM not defined
    • How this Ca²⁺ branch integrates with Ras–MAPK signaling quantitatively unknown
  14. 2009 High

    Activity-dependent alternative splicing of NCAM exon 18 was shown to be governed by intragenic epigenetic changes: membrane depolarization induces H3K9 hyperacetylation at the exon 18 locus, altering RNA Pol II elongation rate and exon inclusion, establishing a novel chromatin-based splicing switch.

    Evidence Neuronal depolarization, RT-PCR splicing, slow Pol II mutant, ChIP for H3K9ac/H3K36me3, HDAC inhibitor TSA; later confirmed by intragenic repressive marks (H3K9me2, H3K27me3) and intronic siRNA-directed chromatin remodeling during differentiation

    PMID:19251664 PMID:23892457

    Open questions at the time
    • Chromatin reader and splicing factor that interpret the marks not identified
    • Whether this mechanism operates in non-neuronal NCAM-expressing cells unknown
  15. 2006 High

    ADAM metalloprotease-mediated ectodomain shedding of NCAM140, regulated by ERK1/2, was identified as a physiological modulator of neurite outgrowth and connectivity, with a transgenic shedding model showing impaired neuronal connectivity.

    Evidence Pharmacological inhibitors, metalloprotease inhibitors, transgenic NCAM-shedding mouse, neurite outgrowth assay

    PMID:16967505

    Open questions at the time
    • Specific ADAM family member(s) responsible not identified
    • Whether shed NCAM acts as a soluble ligand or simply removes receptor unknown
  16. 2019 High

    In AML, NCAM1 was found to sustain leukemia-initiating cell survival via constitutive MAPK activation; genetic depletion induced differentiation or death and sensitized blasts to chemotherapy, repositioning NCAM1 as a therapeutic target outside the nervous system.

    Evidence Genetic knockdown/KO, phosphoproteomics, transcriptomics, murine transplantation leukemia model, MEK1/2 inhibitor sensitization

    PMID:30814062

    Open questions at the time
    • Mechanism of constitutive MAPK activation by NCAM1 in AML (ligand-independent?) unclear
    • Whether anti-NCAM1 therapy is effective without chemotherapy combination unknown
  17. 2020 High

    Two non-neural roles were established: NCAM1 was identified as a Zika virus entry receptor by chemical proteomics, and CRISPR knockout in NK cells demonstrated that NCAM1 drives lytic granule exocytosis and immunological synapse polarization via Pyk2 Tyr402 phosphorylation.

    Evidence Photocrosslinking chemical proteomics, NCAM1 overexpression/KO infection assays (Zika); CRISPR-Cas9 KO in NK92 cells with CD56 rescue, phospho-Pyk2 immunoblot, granule exocytosis and synapse assays

    PMID:32510326 PMID:32753727

    Open questions at the time
    • ZIKV binding site on NCAM1 extracellular domain not mapped
    • Whether Pyk2 binds NCAM1 directly or via an adaptor unknown
  18. 2022 High

    Patient-derived anti-NCAM1 autoantibodies disrupted homophilic binding, GDNF interaction, and Fyn signaling, and when introduced intrathecally in mice, reduced FAK/MEK/ERK phosphorylation, spine/synapse density, and caused schizophrenia-related behaviors, providing causal evidence linking NCAM1 signaling disruption to psychiatric disease.

    Evidence Patient autoantibody characterization, in vitro interaction blocking, intracerebrospinal injection in mice, spine/synapse immunofluorescence, pre-pulse inhibition and cognitive behavioral assays

    PMID:35492247

    Open questions at the time
    • Epitope specificity of pathogenic autoantibodies not mapped at residue level
    • Whether anti-NCAM1 autoantibodies are causative or secondary in schizophrenia patients unresolved
  19. 2023 High

    KLK8 serine protease was identified as a novel extracellular protease that cleaves NCAM1, reducing surface expression in hippocampal neurons; NCAM1 overexpression or a mimetic peptide rescued KLK8-driven neuronal apoptosis and depression-like behavior.

    Evidence KLK8 transgenic/KO mice, CUMS model, protease cleavage assay, co-IP, adenoviral NCAM1 overexpression and mimetic peptide rescue

    PMID:37076499

    Open questions at the time
    • KLK8 cleavage site on NCAM1 not determined
    • Whether KLK8-mediated NCAM1 shedding generates a bioactive soluble fragment unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length extracellular domain structure in a membrane context, how NCAM1's multiple signaling arms (FGFR, GFRα1/GDNF, RPTPα/Fyn, Ca²⁺/CaMKII, Pyk2) are integrated spatiotemporally, the identity and regulation of palmitoylation enzymes for NCAM, the structural basis of the NCAM1–Pyk2 connection in NK cells, and whether NCAM1 can be therapeutically targeted in AML or as a viral entry receptor without neurological consequences.
  • No full-length ectodomain structure in lipid bilayer context
  • Quantitative model integrating parallel signaling cascades lacking
  • Therapeutic window for NCAM1 targeting in cancer/infection versus neural side effects undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098631 cell adhesion mediator activity 4 GO:0048018 receptor ligand activity 2 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 6 GO:0005576 extracellular region 2
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-112316 Neuronal System 4 R-HSA-1266738 Developmental Biology 4 R-HSA-1500931 Cell-Cell communication 4 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 1
Partners
FGFR1FYNGFRA1L1CAMPTK2PTK2BPTPRASPTBN1

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 NCAM is a member of the immunoglobulin superfamily with five contiguous Ig-like domains in its extracellular region. Three major polypeptide isoforms (120, 140, 180 kDa) share an identical extracellular region but differ in their membrane-associated and cytoplasmic domains through alternative RNA splicing. Homophilic binding is mediated by interactions among the Ig-like domains, and regulation is achieved not by changes in binding-site sequence but by cell surface modulation events (PSA content, prevalence, mobility) and alternative splicing that alter isoform-specific cytoplasmic interactions. cDNA cloning, amino acid sequencing of CNBr/proteolytic fragments, Northern blot Science High 3576199
1987 A muscle-specific sequence domain (MSD1) of 37 amino acids is present in the extracellular region of the 5.2 and 4.3 kb NCAM isoforms expressed during myotube formation but absent from transmembrane isoforms in myoblasts and from brain NCAM, demonstrating tissue-specific alternative splicing within the extracellular domain. cDNA cloning, Northern blot, sequencing Cell High 2887295
1988 A secreted isoform of NCAM is generated by alternative splicing that inserts a novel exon into the extracellular domain, introducing an in-frame stop codon; stable transfectants expressing this isoform accumulate it intracellularly and secrete it into the medium, contrasting with GPI-anchored NCAM that is expressed at the cell surface. cDNA cloning, genomic analysis, stable transfection, immunoprecipitation Cell High 3203385
1988 NCAM regulates membrane-membrane contact required for diverse intercellular events. When NCAM carries low polysialic acid (PSA), adhesion is increased and contact-dependent signaling is triggered; when PSA content is high, the large excluded volume of PSA sterically inhibits membrane apposition and cell-cell interactions. Cell adhesion assays, enzymatic PSA removal, antibody blocking Science High 3281256
1990 Mouse myoblasts transfected to constitutively express the human muscle-specific 125 kDa GPI-linked NCAM isoform fuse more readily to form myotubes than controls, demonstrating that NCAM promotes myoblast fusion and that the isoform switch (transmembrane to GPI-linked) may promote this function. Stable transfection of myoblasts, fusion assay Nature High 2179732
1993 The fourth Ig-like domain of NCAM contains a carbohydrate recognition domain (with sequence homology to C-type lectins) that mediates binding to oligomannosidic glycans on L1, forming a heterophilic cis-complex. A peptide from this domain disrupts L1-NCAM association and inhibits neurite outgrowth, demonstrating that carbohydrate-mediated cis-association between L1 and NCAM modulates their functional properties. Co-immunoprecipitation, carbohydrate inhibition assays, recombinant domain binding, peptide inhibition, neurite outgrowth assay The Journal of cell biology High 8509458
1993 Expression of the transmembrane NCAM-B isoform (but not GPI-linked NCAM-C) in NCAM-negative rat glioma cells induces down-regulation of 92-kDa gelatinase (MMP-9) and interstitial collagenase (MMP-1) secretion, indicating that transmembrane NCAM signaling regulates extracellular matrix metalloproteinase production. Transfection of NCAM isoforms into glioma cells, metalloproteinase zymography/activity assay Proceedings of the National Academy of Sciences of the United States of America High 8265575
1994 The VASE exon (10 amino acids inserted into the fourth Ig domain) in NCAM receptors specifically inhibits NCAM-stimulated neurite outgrowth. Both the 140- and 180-kDa isoforms without VASE are functional receptors for neurite outgrowth; a VASE-containing peptide inhibits NCAM-dependent but not integrin-, N-cadherin-, or L1-dependent neurite outgrowth, suggesting that VASE prevents NCAM from engaging the FGF receptor. PC12 transfection with NCAM isoforms ± VASE, synthetic peptide inhibition, neurite outgrowth assay The Journal of cell biology High 8163558
1995 Polysialylation of NCAM is catalyzed by a single enzyme, PST-1 (polysialyltransferase-1), as demonstrated by reconstitution of PSA synthesis on incompletely glycosylated NCAM variants in vitro using soluble recombinant enzyme. Terminal sialylation of the N-glycan core is sufficient to generate the PSA acceptor site. In vitro reconstitution with recombinant PST-1, incompletely glycosylated NCAM variants Current biology High 8805371
1995 Molecular cloning of eukaryotic polysialyltransferase-1 (PST-1) and demonstration that expression of this single enzyme is sufficient to induce PSA synthesis on all NCAM-expressing cell lines in reconstitution experiments, establishing that polycondensation of α-2,8-linked sialic acids on NCAM is the result of a single enzymatic activity. Expression cloning, transfection, reconstitution in NCAM-expressing cell lines Nature High 7854457
1995 Expression cloning of a human polysialyltransferase (ST8SIA2/STX) that forms polysialylated NCAM present in embryonic brain. HeLa cells stably expressing polysialic acid and NCAM promoted neurite outgrowth and sprouting, indicating that polysialylated NCAM is critical for neural plasticity. Expression cloning, FACS sorting, stable transfection, neurite outgrowth assay Proceedings of the National Academy of Sciences of the United States of America High 7624364
1997 NCAM140 selectively co-immunoprecipitates with p59(fyn) from neonatal mouse cerebellum and transfected cells (NCAM180 and NCAM120 do not). NCAM activation (via antibody clustering or soluble NCAM fusion protein) recruits p125(fak) to the NCAM140-p59(fyn) complex and induces rapid transient tyrosine phosphorylation (activation) of both kinases, initiating a signaling cascade linked to growth cone migration. Co-immunoprecipitation from brain tissue and transfected cells, tyrosine phosphorylation assays The Journal of biological chemistry High 9079653
1997 NCAM-deficient mice show severely impaired fasciculation and pathfinding of hippocampal mossy fiber axons, with alterations in mossy fiber terminal distribution, demonstrating that NCAM is essential for axonal growth, fasciculation, and maintenance of plasticity in the mature nervous system. Analysis of NCAM knockout mice (all isoforms), histology, axon tract tracing Molecular and cellular neurosciences High 9073395
1999 Clustering of the NCAM140 isoform stimulates activation (dual phosphorylation) of ERK1/2 through a pathway involving p125fak, p59fyn, Ras, and MEK, and also induces phosphorylation of CREB at Ser133. Inhibition of the MAPK pathway selectively reduces NCAM-stimulated neurite outgrowth in cerebellar neurons. NCAM antibody clustering, kinase phosphorylation assays, specific pathway inhibitors, cerebellar neuron culture neurite outgrowth assay Journal of neurobiology High 10084688
2000 Crystal structure (1.85 Å) of the two N-terminal extracellular Ig-like domains of NCAM reveals a cross-shaped antiparallel dimer in molecular packing, providing the structural basis for homophilic trans-cellular recognition: NCAM forms cis-dimers that mediate low-affinity trans-interactions between cells in zipper-like arrays. X-ray crystallography Nature structural biology High 10802736
2002 NCAM functions as a signaling receptor for GDNF family ligands independent of RET. NCAM associates with GFRα1 (GPI-anchored GDNF receptor), enabling high-affinity GDNF binding to p140(NCAM) and rapid activation of cytoplasmic kinases Fyn and FAK in RET-deficient cells. GDNF stimulates Schwann cell migration and hippocampal/cortical axonal growth via NCAM-Fyn activation. Co-immunoprecipitation, binding assays, kinase activation assays in RET-null cells, migration assay, neurite outgrowth assay Cell High 12837245
2002 Lipid raft association of NCAM140 is required for activation of the non-receptor tyrosine kinase pathway and neurite outgrowth. Mutation of NCAM140 palmitoylation sites or destruction of lipid rafts attenuates activation of FAK and ERK1/2, completely blocking neurite outgrowth. Cosignaling via both raft-associated kinases and the FGF receptor is essential for neuritogenesis. Hippocampal neuron transfection in NCAM-null mice, palmitoylation-site mutagenesis, methyl-β-cyclodextrin raft disruption, FGFR inhibitor, phospho-kinase assays, neurite outgrowth assay The Journal of cell biology High 11980923
2003 NCAM (120, 140, 180 isoforms) forms Triton X-100-insoluble complexes with βI spectrin in hippocampal neurons. βI spectrin binds directly to the intracellular domain of NCAM180 (and via lipid rafts to NCAM120). PKCβ2 forms complexes with NCAM140/NCAM180 and spectrin; NCAM activation enhances this complex and redistributes it to lipid rafts via FGFR. Dominant-negative βI spectrin fragment disrupts the complex and inhibits NCAM-induced neurite outgrowth. Co-immunoprecipitation, lipid raft fractionation, dominant-negative transfection, FGFR inhibitor, neurite outgrowth assay The Journal of cell biology High 12743109
2003 Direct interaction between NCAM fibronectin type III modules 1 and 2 and FGFR1 Ig modules 2 and 3 demonstrated by surface plasmon resonance. NMR structure of NCAM F3 module 2 shows overlapping binding sites for FGFR1 and ATP; ATP inhibits the NCAM-FGFR interaction and inhibits NCAM-induced neurite outgrowth, revealing ATP as a molecular switch regulating NCAM-FGFR signaling. Surface plasmon resonance, NMR structure determination, FGFR phosphorylation assay, neurite outgrowth assay Structure High 12791257
2004 NCAM polysialylation increases intermembrane repulsion quantitatively by steric/ionic mechanisms, overwhelming both homophilic NCAM and cadherin-mediated attraction at physiological ionic strength. The repulsion is ionic-strength dependent and PSA-dose dependent, revealing the molecular mechanism by which PSA-NCAM regulates cell adhesion. Molecular force measurements (surface force apparatus) on membrane-bound NCAM The Journal of biological chemistry High 15504723
2004 NCAM140 directly interacts with the intracellular domain of RPTPα, a known activator of p59fyn. NCAM activation promotes Ca2+-dependent spectrin-mediated crosslinking of NCAM and RPTPα and redistributes the complex to lipid rafts. RPTPα-deficient neurons lose NCAM-p59fyn association and NCAM-mediated p59fyn activation, blocking NCAM-dependent neurite outgrowth. Co-immunoprecipitation, RPTPα-knockout neurons, dominant-negative RPTPα, lipid raft fractionation, neurite outgrowth assay The Journal of cell biology High 15623578
2006 Metalloprotease-induced ectodomain shedding of NCAM140 releases a 115-kDa soluble fragment. Shedding is induced by the tyrosine phosphatase inhibitor pervanadate via an ADAM metalloprotease regulated by ERK1/2. Metalloprotease inhibitor GM6001 increases NCAM-dependent neurite branching and outgrowth; a transgenic NCAM-shedding mouse model shows impaired neuronal connectivity. NCAM transfection in L-fibroblasts, pharmacological inhibitors, metalloprotease inhibitors, transgenic mouse model, neurite outgrowth assay Journal of neurobiology High 16967505
2007 ST8SiaIV is the major regulator of NCAM polysialylation in vivo. Analysis of mice lacking ST8SiaII or ST8SiaIV shows that both enzymes polysialylate N-glycosylation sites 5 and 6 of NCAM with the same glycan sets, but ST8SiaII and ST8SiaIV act synergistically to produce long polySia chains at site 5; ST8SiaIV alone yields shorter chains. Analysis of polysialyltransferase knockout mice, glycopeptide mass spectrometry, polySia chain-length analysis The Journal of biological chemistry High 17986444
2008 NCAM clustering at the cell surface is coupled to Ca2+ influx via T- and L-type voltage-dependent Ca2+ channels associated with NCAM, activation of CaMKIIα, and serine phosphorylation of RPTPα at Ser180 and Ser204, increasing RPTPα phosphatase activity. Mutation of these serine residues interferes with NCAM-induced neurite outgrowth, establishing a novel NCAM→Ca2+ channel→CaMKIIα→RPTPα→neurite outgrowth cascade. NCAM clustering assay, Ca2+ channel co-IP, CaMKIIα activation assay, RPTPα serine phosphorylation, dominant-negative/mutant transfection, neurite outgrowth assay The Journal of cell biology High 18809727
2008 GAP-43 phosphorylation by PKC or CKII potentiates NCAM-180/spectrin-mediated neurite outgrowth. In the presence of GAP-43, NCAM-180/spectrin/GAP-43 association is required; in its absence, the NCAM-140/Fyn pathway dominates. GAP-43 thus acts as a molecular switch that determines the predominant NCAM signaling mechanism. GAP-43 overexpression, phosphorylation mutants, dominant-negative betaI spectrin, neurite outgrowth assay in PC12 and hippocampal neurons Journal of neurochemistry Medium 17212696
2008 NCAM-mediated ERK phosphorylation requires FGFR, Src-family kinases, MEK, and Gi/G0-proteins; NCAM-mediated CREB phosphorylation requires Src-family kinases and MEK; NCAM-mediated Akt phosphorylation requires cGMP and PI3K. These pathways are independent of PLC, PKC, PKA, and CaMKII, revealing a specific signaling hierarchy downstream of NCAM. NCAM ligand (C3d peptide) stimulation of cerebellar granule neurons, specific pathway inhibitors, phospho-kinase assays Neurochemistry international Medium 18656513
2009 Neuronal membrane depolarization triggers skipping of NCAM exon 18, independently of the CaMKIV pathway. This splicing change is regulated by RNA Pol II elongation rate and is accompanied by H3K9 hyper-acetylation restricted to the intragenic region surrounding exon 18, without promoter acetylation changes; effects are reversible and potentiated by HDAC inhibitor TSA. Neuronal depolarization, RT-PCR splicing assay, slow Pol II mutant, ChIP for H3K9ac and H3K36me3, HDAC inhibitor Proceedings of the National Academy of Sciences of the United States of America High 19251664
2011 NCAM promotes ovarian cancer cell migration and peritoneal metastasis via direct interaction with FGFR. FGFR signaling is required for NCAM-induced cell motility, and a monoclonal antibody targeting the NCAM/FGFR interplay abolishes metastatic dissemination in mice. In vitro migration/invasion assays, FGFR inhibition, anti-NCAM monoclonal antibody, mouse peritoneal metastasis model EMBO molecular medicine High 21739604
2013 Intragenic repressive chromatin marks (H3K9me2, H3K27me3) increase along the NCAM gene body during neuronal differentiation, correlating with inhibition of Pol II elongation in the exon 18 region and increased exon 18 inclusion. Intronic siRNAs targeting NCAM intron 18 induce H3K9me2 and promote E18 inclusion in undifferentiated cells, confirming that intragenic chromatin deployment is sufficient to alter NCAM alternative splicing. ChIP for H3K9me2/H3K27me3, 5-azacytidine and BIX01294 inhibition, intronic siRNA-directed chromatin changes, RT-PCR splicing assay The EMBO journal High 23892457
2013 NeuroD1 transcriptionally regulates NCAM expression in neuroendocrine lung carcinomas; impaired NeuroD1 expression mirrors loss of NCAM, and NCAM is a downstream target of NeuroD1 that promotes tumor cell survival and metastasis. NeuroD1 knockdown/overexpression, gene expression analysis, cell survival and migration assays Proceedings of the National Academy of Sciences of the United States of America Medium 23553831
2017 GFRα1 directly interacts with NCAM in embryonic Purkinje cells. Genetic reduction of NCAM expression enhances wild-type Purkinje cell migration and rescues delayed migration in Gfra1 mutants, demonstrating that NCAM restricts Purkinje cell migration and that GFRα1 promotes migration by limiting NCAM function in cis and trans. Co-immunoprecipitation, Gfra1/NCAM genetic mutants, in vitro migration assays Cell reports High 28076782
2017 TGFβ1 induces NCAM1 expression in cardiomyocytes via a p38-dependent pathway; selective targeting of NCAM1 rescues the cell-cell adhesion defect caused by TGFβ1. NCAM1 protein levels correlate with TGFβ1 activity in human cardiomyopathy samples. Cardiac-specific TGFβ1 transgenic mice, electron microscopy, p38 inhibition, NCAM1 siRNA, immunostaining Journal of molecular and cellular cardiology Medium 28870505
2018 Peripheral nerve injury activates the anterior cingulate cortex (ACC) and increases turnover of NCAM1 at synapses. NCAM1 mediates dendritic spine reorganization in the ACC and contributes to behavioral sensitization after nerve injury through a mechanism parallel to NMDA-receptor- and protein-synthesis-dependent LTP. Peripheral nerve injury model, synaptic protein turnover analysis, spine morphology, behavioral assays Cell reports Medium 29346771
2019 NCAM1 regulates AML cell survival and stress resistance. Loss of NCAM1 induces cell death or differentiation and sensitizes blasts to genotoxic agents. NCAM1 expression is associated with constitutive activation of the MAPK pathway; MEK1/2 inhibition specifically sensitizes NCAM1+ AML cells to chemotherapy. Depletion of Ncam1 in a murine leukemia model reduced leukemia-initiating cells and prolonged disease latency. Genetic knockdown/knockout (NCAM1), phosphoproteomics, transcriptomics, in vitro cytotoxicity assays, murine transplantation model Blood High 30814062
2020 NCAM1 functions as a receptor for Zika virus (ZIKV) entry. Chemical proteomic photocrosslinking identified NCAM1 as a ZIKV-interacting protein; overexpression of NCAM1 enhanced ZIKV infection while knockout and inhibition reduced it in Vero and U-251 MG cells. Chemical proteomics (photocrosslinking + biotin enrichment + MS), NCAM1 overexpression, knockout, and inhibition, infection assays Nature communications High 32753727
2020 CD56 (NCAM1) deletion in NK92 cells impairs cytotoxic function, lytic granule exocytosis, and immunological synapse polarization. Phosphorylation of the FAK family member Pyk2 at Tyr402 is decreased in CD56-KO cells; reintroduction of CD56 rescues cytotoxicity, exocytosis, and Pyk2 phosphorylation, establishing a functional link between NCAM1 and Pyk2 signaling in NK cell cytotoxicity. CRISPR-Cas9 knockout of CD56 in NK92, lytic granule exocytosis assay, immunological synapse assay, phospho-Pyk2 immunoblot, CD56 rescue transfection eLife High 32510326
2022 Anti-NCAM1 autoantibodies from schizophrenia patients disrupt NCAM1-NCAM1 homophilic binding, NCAM1-GDNF, and NCAM1-Fyn interactions. Intracerebrospinal introduction into mice inhibits FAK, MEK1, and ERK1 phosphorylation, reduces spine and synapse number in frontal cortex, and induces schizophrenia-related behavior (deficient pre-pulse inhibition, cognitive impairment). Cell-based autoantibody assay, ELISA, in vitro interaction blocking assays, intrathecal antibody injection in mice, immunofluorescence (spine/synapse density), behavioral assays Cell reports. Medicine High 35492247
2023 KLK8 (a serine protease) proteolytically cleaves the extracellular domain of NCAM1 in hippocampal neurons, decreasing NCAM1 surface expression. Transgenic KLK8 overexpression exacerbates CUMS-induced hippocampal neuronal apoptosis and depression-like behavior; KLK8 deficiency prevents NCAM1 loss. Both NCAM1 overexpression and an NCAM1 mimetic peptide rescue KLK8-overexpressing neurons from apoptosis. KLK8 transgenic and KO mice, CUMS model, adenoviral NCAM1 overexpression, co-immunoprecipitation, protease cleavage assay, NCAM1 mimetic peptide rescue, immunofluorescence Cell death & disease High 37076499
2000 PSA-NCAM directly interacts with BDNF. Enzymatic removal of PSA (Endo-N) or NCAM knockout reduces LTP in hippocampal CA1 and reduces TrkB phosphorylation. Exogenous BDNF restores deficient LTP in both NCAM-KO and Endo-N-treated slices, suggesting that PSA-NCAM sensitizes pyramidal neurons to BDNF to modulate activity-dependent synaptic plasticity. NCAM knockout mice, Endo-N enzymatic PSA removal, organotypic hippocampal slice LTP recordings, BDNF rescue, TrkB phosphorylation assay, PSA-NCAM binding to BDNF Proceedings of the National Academy of Sciences of the United States of America High 10760298

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
1987 Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing. Science (New York, N.Y.) 1087 3576199
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
1993 Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2. Science (New York, N.Y.) 772 8493579
1988 The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions. Science (New York, N.Y.) 758 3281256
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2010 Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education. Blood 615 20696944
2010 CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. Blood 609 20733159
2003 The neural cell adhesion molecule NCAM is an alternative signaling receptor for GDNF family ligands. Cell 475 12837245
1989 Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. The Journal of experimental medicine 467 2471777
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2006 PSA-NCAM in mammalian structural plasticity and neurogenesis. Progress in neurobiology 352 17029752
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2002 Clinical and biologic features of CD4(+)CD56(+) malignancies. Blood 317 11861268
2006 The phenotypes of pluripotent human hepatic progenitors. Stem cells (Dayton, Ohio) 263 16627685
1995 Molecular characterization of eukaryotic polysialyltransferase-1. Nature 263 7854457
1997 NCAM is essential for axonal growth and fasciculation in the hippocampus. Molecular and cellular neurosciences 244 9073395
2004 CD56bright NK cells are enriched at inflammatory sites and can engage with monocytes in a reciprocal program of activation. Journal of immunology (Baltimore, Md. : 1950) 232 15528382
2002 Cosignaling of NCAM via lipid rafts and the FGF receptor is required for neuritogenesis. The Journal of cell biology 228 11980923
1988 Alternative splicing generates a secreted form of N-CAM in muscle and brain. Cell 227 3203385
2009 Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing. Proceedings of the National Academy of Sciences of the United States of America 223 19251664
2003 Structural basis for a direct interaction between FGFR1 and NCAM and evidence for a regulatory role of ATP. Structure (London, England : 1993) 222 12791257
1997 NCAM140 interacts with the focal adhesion kinase p125(fak) and the SRC-related tyrosine kinase p59(fyn). The Journal of biological chemistry 218 9079653
1987 Human muscle neural cell adhesion molecule (N-CAM): identification of a muscle-specific sequence in the extracellular domain. Cell 214 2887295
1995 Expression cloning of a human polysialyltransferase that forms the polysialylated neural cell adhesion molecule present in embryonic brain. Proceedings of the National Academy of Sciences of the United States of America 210 7624364
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2021 Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders. Nature genetics 204 34741163
2009 CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK-cell subsets. Blood 196 19897577
1993 The fourth immunoglobulin-like domain of NCAM contains a carbohydrate recognition domain for oligomannosidic glycans implicated in association with L1 and neurite outgrowth. The Journal of cell biology 192 8509458
1999 NCAM stimulates the Ras-MAPK pathway and CREB phosphorylation in neuronal cells. Journal of neurobiology 190 10084688
2013 Mutations in GATA2 cause human NK cell deficiency with specific loss of the CD56(bright) subset. Blood 188 23365458
2004 Direct evidence that neural cell adhesion molecule (NCAM) polysialylation increases intermembrane repulsion and abrogates adhesion. The Journal of biological chemistry 181 15504723
2017 The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs. Nature communications 176 28685749
2000 Brain-derived neurotrophic factor restores long-term potentiation in polysialic acid-neural cell adhesion molecule-deficient hippocampus. Proceedings of the National Academy of Sciences of the United States of America 176 10760298
2004 Zippers make signals: NCAM-mediated molecular interactions and signal transduction. Neurochemical research 162 15662836
1998 The neural cell adhesion molecule (NCAM) in development and plasticity of the nervous system. Experimental gerontology 161 9951628
2006 Haplotype spanning TTC12 and ANKK1, flanked by the DRD2 and NCAM1 loci, is strongly associated to nicotine dependence in two distinct American populations. Human molecular genetics 157 17085484
1990 Enhanced myogenesis in NCAM-transfected mouse myoblasts. Nature 139 2179732
2003 What is CD4+CD56+ malignancy and how should it be treated? Bone marrow transplantation 138 13130309
1994 High expression of CD56 (N-CAM) in a patient with cutaneous CD4-positive lymphoma. American journal of hematology 137 7526680
2005 Structural biology of NCAM homophilic binding and activation of FGFR. Journal of neurochemistry 136 16045455
2007 CD4+/CD56+ hematodermic tumor: the features of an evolving entity and its relationship to dendritic cells. American journal of clinical pathology 116 17439829
2007 Dissecting polysialic acid and NCAM functions in brain development. Journal of neurochemistry 115 17986140
2001 Revisiting the function of PSA-NCAM in the nervous system. Molecular neurobiology 115 11831554
2003 Neural cell adhesion molecule (NCAM) association with PKCbeta2 via betaI spectrin is implicated in NCAM-mediated neurite outgrowth. The Journal of cell biology 112 12743109
1992 NCAM: structural diversity, function and regulation of expression. Seminars in cell biology 111 1623208
2007 Association of haplotypic variants in DRD2, ANKK1, TTC12 and NCAM1 to alcohol dependence in independent case control and family samples. Human molecular genetics 104 17761687
2000 Structural basis of cell-cell adhesion by NCAM. Nature structural biology 102 10802736
1991 Expression of cytoadhesion molecules (CD56, CD54, CD18 and CD29) by myeloma plasma cells. British journal of haematology 99 1721526
2004 RPTPalpha is essential for NCAM-mediated p59fyn activation and neurite elongation. The Journal of cell biology 96 15623578
2006 Metalloprotease-induced ectodomain shedding of neural cell adhesion molecule (NCAM). Journal of neurobiology 91 16967505
2013 Polysialic acid: versatile modification of NCAM, SynCAM 1 and neuropilin-2. Neurochemical research 90 23354723
2013 NeuroD1 regulates survival and migration of neuroendocrine lung carcinomas via signaling molecules TrkB and NCAM. Proceedings of the National Academy of Sciences of the United States of America 87 23553831
2002 Differential expression of CD56 and CD44 in the evolution of extramedullary myeloma. British journal of haematology 85 11841427
1997 Increased intermale aggression and neuroendocrine response in mice deficient for the neural cell adhesion molecule (NCAM). The European journal of neuroscience 84 9215693
2008 Neural cell adhesion molecule (NCAM) marks adult myogenic cells committed to differentiation. Experimental cell research 81 18308302
2008 Haplotypic variants in DRD2, ANKK1, TTC12, and NCAM1 are associated with comorbid alcohol and drug dependence. Alcoholism, clinical and experimental research 81 18828801
2019 NCAM1 (CD56) promotes leukemogenesis and confers drug resistance in AML. Blood 78 30814062
2013 Intragenic epigenetic changes modulate NCAM alternative splicing in neuronal differentiation. The EMBO journal 76 23892457
2004 Molecular mechanisms of NCAM function. Frontiers in bioscience : a journal and virtual library 74 15353284
1993 Transmembrane neural cell-adhesion molecule (NCAM), but not glycosyl-phosphatidylinositol-anchored NCAM, down-regulates secretion of matrix metalloproteinases. Proceedings of the National Academy of Sciences of the United States of America 67 8265575
2011 The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling. EMBO molecular medicine 66 21739604
1996 Polysialylation of NCAM by a single enzyme. Current biology : CB 66 8805371
1994 Expression of NCAM containing VASE in neurons can account for a developmental loss in their neurite outgrowth response to NCAM in a cellular substratum. The Journal of cell biology 65 8163558
1997 Expression of neural cell adhesion molecule (NCAM) characterizes a subpopulation of type 1 astrocytes in human optic nerve head. Glia 61 9215735
2006 GAP-43 regulates NCAM-180-mediated neurite outgrowth. Journal of neurochemistry 60 17212696
2013 ANKK1, TTC12, and NCAM1 polymorphisms and heroin dependence: importance of considering drug exposure. JAMA psychiatry 58 23303482
1993 Neural cell adhesion molecule (NCAM) and perineural invasion in bile duct cancer. Journal of surgical oncology 57 8501910
2002 Cadherins and NCAM as potential targets in metal toxicity. Toxicology and applied pharmacology 55 12183105
2007 Enzyme-dependent variations in the polysialylation of the neural cell adhesion molecule (NCAM) in vivo. The Journal of biological chemistry 54 17986444
2004 NCAM mimetic peptides: Pharmacological and therapeutic potential. Journal of molecular neuroscience : MN 54 14742908
1995 Neural cell adhesion molecule (NCAM) as a quantitative marker in synaptic remodeling. Neurochemical research 54 7643959
1991 Expression of the neural cell adhesion molecule (CD56) by human myeloma cells. Clinical and experimental immunology 54 1706237
2015 L1-CAM and N-CAM: From Adhesion Proteins to Pharmacological Targets. Trends in pharmacological sciences 52 26478212
2023 Identification of human exTreg cells as CD16+CD56+ cytotoxic CD4+ T cells. Nature immunology 50 37563308
2013 The dendritic spines of interneurons are dynamic structures influenced by PSA-NCAM expression. Cerebral cortex (New York, N.Y. : 1991) 50 23780867
2020 CD56 regulates human NK cell cytotoxicity through Pyk2. eLife 49 32510326
1996 A novel population of CD4+CD56+ myelin-reactive T cells lyses target cells expressing CD56/neural cell adhesion molecule. Journal of immunology (Baltimore, Md. : 1950) 49 8752917
2020 Chemical proteomics tracks virus entry and uncovers NCAM1 as Zika virus receptor. Nature communications 48 32753727
1994 Regional changes in expression of NCAM, GFAP, and S100 in aging rat brain. Neurobiology of aging 47 7824058
2005 CD56/NCAM-positive Langerhans cell sarcoma: a clinicopathologic study of 4 cases. International journal of hematology 46 15914364
2018 Rapid Turnover of Cortical NCAM1 Regulates Synaptic Reorganization after Peripheral Nerve Injury. Cell reports 44 29346771
2007 Papillary carcinoma of the thyroid: low expression of NCAM (CD56) is associated with downregulation of VEGF-D production by tumour cells. The Journal of pathology 43 17573672
2004 Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56-/+dim chronic natural killer cell large granular lymphocytosis. The American journal of pathology 43 15466379
1993 Abnormal expression of N-CAM (CD56) adhesion molecule on myeloid and progenitor cells from chronic myeloid leukemia. Leukemia 41 7692192
1993 NCAM (CD56)-positive malignant lymphoma. Leukemia & lymphoma 40 7512851
2008 Neural cell adhesion molecule (NCAM) isoform expression is associated with neuroblastoma differentiation status. Pediatric blood & cancer 38 18213713
2008 NCAM induces CaMKIIalpha-mediated RPTPalpha phosphorylation to enhance its catalytic activity and neurite outgrowth. The Journal of cell biology 38 18809727
1996 The neural cell adhesion molecule (NCAM) provides clues to the development of testicular Leydig cells. Journal of andrology 38 8792212
1993 A functional role for the middle extracellular region of the neural cell adhesion molecule (NCAM) in axonal fasciculation and orientation. Developmental biology 38 8462735
2009 Specific detection of CD56 (NCAM) isoforms for the identification of aggressive malignant neoplasms with progressive development. The American journal of pathology 37 19246644
2004 Ex vivo expansion of CD8+CD56+ and CD8+CD56- natural killer T cells specific for MUC1 mucin. Cancer research 37 14871854
2002 The role of NCAM in remyelination. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 37 11976973
2005 Mycosis fungoides with a CD56+ immunophenotype. Journal of the American Academy of Dermatology 36 15965442
2000 Neural cell adhesion molecule (NCAM) and myoblast fusion. Developmental biology 36 10772795
2000 Control of NCAM polysialylation by the differential expression of polysialyltransferases ST8SiaII and ST8SiaIV. European journal of cell biology 35 11089916
2020 Upregulation of Neural Cell Adhesion Molecule 1 (NCAM1) by hsa-miR-141-3p Suppresses Ameloblastoma Cell Migration. Medical science monitor : international medical journal of experimental and clinical research 33 32269209
2007 Alteration of serum and tumoral neural cell adhesion molecule (NCAM) isoforms in patients with brain tumors. Journal of neuro-oncology 32 17216340
1995 Expression of N-CAM (CD56) on acute leukemia cells: relationship with disease characteristics and outcome. Leukemia & lymphoma 32 8535222
1991 Expression of neural cell adhesion molecule (NCAM) isoforms in neuroblastoma. Journal of clinical pathology 32 1856291
2022 NCAM1 and GDF15 are biomarkers of Charcot-Marie-Tooth disease in patients and mice. Brain : a journal of neurology 31 35148379
2005 SNPs in the neural cell adhesion molecule 1 gene (NCAM1) may be associated with human neural tube defects. Human genetics 31 15883837
2001 Genetic deletions of NCAM and PSA impair circadian function in the mouse. Physiology & behavior 31 11399310
2020 Deep phenotypical characterization of human CD3+ CD56+ T cells by mass cytometry. European journal of immunology 30 33231295
1994 CD56 (NCAM)-positive malignant lymphoma. Leukemia & lymphoma 30 7522719
2023 Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1. Cell death & disease 29 37076499
2017 TGF-β1 affects cell-cell adhesion in the heart in an NCAM1-dependent mechanism. Journal of molecular and cellular cardiology 29 28870505
2014 Direct involvement of CD56 in cytokine-induced killer-mediated lysis of CD56+ hematopoietic target cells. Experimental hematology 29 25201755
2001 CD2- CD4+ CD56+ hematodermic/hematolymphoid malignancy. Journal of the American Academy of Dermatology 29 11174380
2014 Characterisation of genetic variation in ST8SIA2 and its interaction region in NCAM1 in patients with bipolar disorder. PloS one 28 24651862
2022 Autoantibodies against NCAM1 from patients with schizophrenia cause schizophrenia-related behavior and changes in synapses in mice. Cell reports. Medicine 27 35492247
2015 Promotion of cell migration by neural cell adhesion molecule (NCAM) is enhanced by PSA in a polysialyltransferase-specific manner. PloS one 27 25885924
2016 NCAM1 Polysialylation: The Prion Protein's Elusive Reason for Being? ASN neuro 25 27879349
2008 Relative role of upstream regulators of Akt, ERK and CREB in NCAM- and FGF2-mediated signalling. Neurochemistry international 25 18656513
1993 Expression of neural cell adhesion molecule (NCAM) during the first molar development in the mouse. Anatomy and embryology 25 8470821
2004 CD56+ lymphoma with skin involvement: clinicopathologic features and classification. Archives of dermatology 24 15096371
1993 Expression of NCAM mRNA and polypeptides in aging rat brain. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 24 8488756
2022 Human NK cells responses are enhanced by CD56 engagement. European journal of immunology 23 35775327
2016 Pharmacological approach for targeting dysfunctional brain plasticity: Focus on neural cell adhesion molecule (NCAM). Pharmacological research 23 27095082
2014 NCAM1-TTC12-ANKK1-DRD2 variants and smoking motives as intermediate phenotypes for nicotine dependence. Psychopharmacology 23 25273375
2017 GFRα1 Regulates Purkinje Cell Migration by Counteracting NCAM Function. Cell reports 22 28076782
2012 Human natural killer cell maturation defect supports in vivo CD56(bright) to CD56(dim) lineage development. PloS one 22 23240056
2004 Clinicopathologic differences between 22 cases of CD56-negative and CD56-positive subcutaneous panniculitis-like lymphoma in Japan. Human pathology 22 14991542
2000 CD56 directly interacts in the process of NCAM-positive target cell-killing by NK cells. Cell biology international 22 10772769
2022 Comprehensive Immune Profiling Reveals CD56+ Monocytes and CD31+ Endothelial Cells Are Increased in Severe COVID-19 Disease. Journal of immunology (Baltimore, Md. : 1950) 21 34987111
2017 Reduction in CD16/CD56 and CD16/CD3/CD56 Natural Killer Cells in Coronary Artery Disease. Immunological investigations 21 28414590