Affinage

JAM3

Junctional adhesion molecule C · UniProt Q9BX67

Length
310 aa
Mass
35.0 kDa
Annotated
2026-06-10
86 papers in source corpus 40 papers cited in narrative 40 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

JAM3 (JAM-C) is a two-Ig-domain junctional adhesion molecule whose defining biochemical activity is heterophilic engagement of its counter-receptor JAM-B (JAM2): JAM-C was first identified as the 43-kDa counter-receptor mediating JAM-B adhesion to T cells (PMID:11590146), and JAM-B reciprocally stabilizes junctional JAM-C while soluble JAM-B dissociates JAM-C homodimers into higher-affinity heterodimers, releasing JAM-C for leukocyte engagement (PMID:16093349). Through this adhesive system JAM-C organizes epithelial and endothelial junctions and cell polarity, binding the polarity protein PAR-3 and the scaffold ZO-1 via PDZ-domain interactions (PMID:12953056) and requiring a cytoplasmic serine (S281) for junctional localization, polarity establishment, and restraint of beta1/beta3 integrin activation (PMID:17099249). At endothelial junctions JAM-C maintains a unidirectional barrier that sets the directionality of neutrophil transendothelial migration, such that loss or imbalance of JAM-C promotes reverse migration (PMID:21706006, PMID:27442505); it also tunes vascular permeability by associating with alphavbeta3 integrin and signaling through the GTPase Rap1b (PMID:19461049), and its junctional turnover is controlled by CBL-mediated ubiquitylation and lysosomal degradation during angiogenic remodeling (PMID:31790392). Beyond leukocytes, JAM-C serves as a counter-receptor for the Mac-1 (CD11b/CD18) integrin to drive transmigration and platelet–leukocyte interactions (PMID:15194813, PMID:17379836), and its trans JAM-B/JAM-C interaction is essential for myocyte fusion (PMID:22180726) and for hematopoietic stem/progenitor retention in the marrow stromal niche (PMID:24357068). In neural development JAM-C acts in a Pard3-dependent pathway to promote DCC surface recruitment and germinal-zone exit of cerebellar granule neurons (PMID:39774925, PMID:33259808), and its polarized localization in spermatids requires PDZ-mediated binding to GRASP55 (PMID:28617811). JAM-C is processed by ADAM10 (PMID:35535899) and is genetically required for peripheral nerve paranodal integrity (PMID:22090315), cerebrospinal fluid drainage (PMID:23029139), and lens fiber/epithelial homeostasis (PMID:36048019, PMID:38095908, PMID:41173413). In cancer, JAM-C dimerization drives pro-metastatic behavior (PMID:29378216), and JAM3 supports leukemia-initiating-cell self-renewal through a junction-independent LRP5/PDK1/AKT/beta-catenin/CCND1 axis (PMID:29584620).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2001 High

    Establishing JAM-C's binding partner was the foundational question; identifying it as the counter-receptor for JAM-B defined the molecular adhesion pair around which all later function is organized.

    Evidence Ectodomain binding, JAM2-Fc pulldown, and static adhesion assays in CHO cells

    PMID:11590146

    Open questions at the time
    • Affinity and stoichiometry of the interaction not quantified
    • Cytoplasmic signaling consequences not addressed
  2. 2002 High

    Resolved how JAM-C couples to integrin-mediated leukocyte adhesion, showing JAM-C/JAM-B engagement is a prerequisite for JAM-B binding to alpha4beta1 integrin and confirming JAM-C as the functional leukocyte receptor.

    Evidence Antibody blockade, alpha4 inhibitor, soluble JAM-C competition, JAM2 mutagenesis; adhesion assays with T/NK/dendritic cells

    PMID:11823489 PMID:12070135

    Open questions at the time
    • Whether JAM-C directly contacts integrin or only positions JAM-B not fully resolved
  3. 2003 High

    Connected JAM-C to junctional architecture by identifying PDZ-mediated binding to PAR-3 and ZO-1, placing it in the cell polarity and tight junction machinery.

    Evidence Direct PDZ binding assays, domain mutagenesis, ectopic expression in CHO cells

    PMID:12953056

    Open questions at the time
    • Functional consequence of each interaction in vivo not separated
  4. 2004 High

    Broadened JAM-C's adhesive repertoire by demonstrating direct binding to the Mac-1 (CD11b/CD18) integrin and a role in PMN transepithelial migration, with localization to desmosomes rather than tight junctions in intestinal epithelium.

    Evidence Junction disruption, transmigration assays, direct CD11b/CD18 binding

    PMID:15194813

    Open questions at the time
    • Cell-type variability of subcellular localization unexplained
  5. 2005 High

    Defined the regulatory logic of the JAM-B/JAM-C system, showing soluble JAM-B converts JAM-C homodimers into heterodimers and liberates JAM-C for integrin engagement, linking junctional state to leukocyte adhesion.

    Evidence Co-IP, soluble competition, antibody blockade, adhesion assays

    PMID:16093349

    Open questions at the time
    • In vivo trigger for homodimer-to-heterodimer switching not identified
  6. 2006 High

    Identified the cytoplasmic determinant (S281) controlling junctional localization, polarity, and integrin restraint, providing a phosphoregulatable switch in JAM-C function.

    Evidence S281A mutagenesis with barrier, migration, and integrin activation readouts in carcinoma cells

    PMID:17099249

    Open questions at the time
    • Kinase responsible for S281 phosphorylation not identified
  7. 2009 High

    Mechanistically separated JAM-C's effects on vascular permeability into an alphavbeta3-association arm and a Rap1b-dependent beta1 integrin inhibition arm, with stimulus-dependent junctional translocation.

    Evidence siRNA/overexpression, Co-IP, Rap1 isoform-specific knockdown, permeability assays

    PMID:19461049

    Open questions at the time
    • Link between JAM-C and Rap1b activation upstream not defined
  8. 2011 High

    Demonstrated in vivo that junctional JAM-C levels set the directionality of neutrophil transendothelial migration, establishing reverse-TEM as a consequence of JAM-C loss.

    Evidence Intravital imaging, ischemia-reperfusion model, blocking antibody, endothelial JAM-C deletion

    PMID:21706006

    Open questions at the time
    • Molecular signal that imposes unidirectionality not defined
  9. 2011 High

    Extended JAM-C function beyond leukocytes by showing trans JAM-B/JAM-C interaction is required for myocyte fusion and that Schwann-cell JAM-C maintains peripheral nerve paranodal integrity.

    Evidence Zebrafish forward genetics and transplantation; Schwann-cell conditional knockout with electrophysiology and morphology

    PMID:22090315 PMID:22180726

    Open questions at the time
    • Downstream fusion machinery engaged by JAM-B/JAM-C not identified
    • Mechanism linking JAM-C to paranodal structure unresolved
  10. 2012 High

    Defined cell-type-specific physiological requirements for JAM-C, including non-endothelial control of CSF drainage and stromal control of lymph node chemokine secretion and T cell egress.

    Evidence JAM-C knockout with endothelial rescue (hydrocephalus); knockout/antibody blockade with chemokine and egress readouts; B-cell homing via JAM-B

    PMID:21685324 PMID:23029139 PMID:23221386

    Open questions at the time
    • Effector cell type for CSF phenotype not pinpointed
    • Mechanism linking JAM-C to chemokine secretion unknown
  11. 2014 High

    Established JAM-C's role in the hematopoietic niche, showing JAM-B/JAM-C interaction between HSPCs and mesenchymal stromal cells governs marrow homing and retention.

    Evidence Blocking antibody, bone marrow transplantation, mobilization assays, human CD34+ homing

    PMID:24357068

    Open questions at the time
    • Signaling downstream of niche JAM-B/JAM-C engagement not defined
  12. 2017 High

    Provided structural and functional insight into PDZ-driven polarized localization by identifying GRASP55 as a JAM-C partner whose interaction is required for spermatid acrosome formation and JAM-C polarization.

    Evidence Proteomics, knockout mice, crystal structures of GRASP55–JAM-C/JAM-B, and an in vivo PDZ-inhibitor (Graspin)

    PMID:28617811

    Open questions at the time
    • Generality of GRASP55-mediated polarization to other tissues untested
  13. 2018 High

    Uncovered a junction-independent signaling role in cancer, showing JAM3 associates with LRP5 to drive a PDK1/AKT/beta-catenin/CCND1 self-renewal program in leukemia-initiating cells, and that dimerization residues E66/K68 drive pro-metastatic behavior.

    Evidence Reciprocal Co-IP, Jam3 deletion in MLL-AF9 AML with serial transplantation; E66/K68 mutagenesis with in vitro and metastasis readouts

    PMID:29378216 PMID:29584620

    Open questions at the time
    • How LRP5 binding is regulated relative to junctional pools unknown
    • Whether dimerization couples to the LRP5 signaling axis untested
  14. 2019 High

    Defined the trafficking control of junctional JAM-C, identifying CBL-mediated ubiquitylation and lysosomal degradation as required for endothelial junctional remodeling and angiogenesis.

    Evidence Receptor mutagenesis, APEX-2/HRP proximity labeling, microscopy, ubiquitylation assays

    PMID:31790392

    Open questions at the time
    • Signal triggering CBL recruitment not defined
  15. 2022 Medium

    Identified ADAM10 as a JAM-C-processing protease coupling cleavage to Rap1GAP activity and neural stem cell compartment transit.

    Evidence ADAM10 manipulation, Rap1GAP activity assays, NSC localization analysis

    PMID:35535899

    Open questions at the time
    • Cleavage site and fate of fragments not mapped
    • Single lab
  16. 2025 Medium

    Resolved a developmental pathway in which Pard3 and JAM-C promote DCC surface recruitment to gate Netrin-1 repulsion and germinal-zone exit, antagonized by Siah2.

    Evidence In vivo cerebellar genetics, DCC surface recruitment assays, genetic epistasis (Siah2/Pard3/JamC/DCC)

    PMID:33259808 PMID:39774925

    Open questions at the time
    • Biochemical basis of JAM-C-driven DCC trafficking unclear
    • Single lab
  17. 2026 Medium

    Extended JAM-C's Mac-1 engagement to solid-tumor immunology, showing JAM3/Mac-1 interaction activates AKT to drive neutrophil migration and NET formation in meningioma.

    Evidence Co-IP, knockdown with AKT activator rescue, NET assays, xenograft model

    PMID:41500374

    Open questions at the time
    • Whether tumor JAM-C signals cell-autonomously or only via neutrophils unresolved
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How JAM-C's adhesive/junctional pools are biochemically switched to its junction-independent signaling roles (LRP5, NRF2/FSP1, Hippo, PI3K/AKT) reported across diverse cancers remains unresolved, as does whether these context-specific outputs share a unifying mechanism.
  • No structural model linking ectodomain engagement to intracellular signaling outputs
  • Tissue-context determinants of tumor-suppressive versus oncogenic roles unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 4 GO:0060089 molecular transducer activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1500931 Cell-Cell communication 3 R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2
Partners
CBLGORASP2ITGAMITGB3JAM2LRP5PARD3TJP1
Complex memberships
JAM-B/JAM-C heterodimertight junction

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 JAM3 (JAM-C) was identified as the counter-receptor for JAM2 (JAM-B); JAM3 ectodomain binds firmly to JAM2-Fc in heterotypic interactions, and JAM3 was demonstrated to be the previously uncharacterized 43-kDa counter-receptor mediating JAM2 adhesion to T cells. Ectodomain binding assays, JAM2-Fc pulldown, static adhesion assays with CHO cells expressing full-length JAM2, polyclonal anti-JAM3 serum The Journal of biological chemistry High 11590146
2002 JAM3 on T cells facilitates JAM2 engagement of alpha4beta1 integrin: prior adhesion of JAM2 to JAM3 is required for JAM2/alpha4beta1 interaction; neutralizing JAM3 serum or soluble JAM3 ectodomain blocked both JAM2/JAM3 and JAM2/alpha4beta1 interactions. The first Ig-like fold of JAM2 is competent for binding both JAM3 and alpha4beta1. Neutralizing integrin antibodies, alpha4-specific inhibitor TBC 772, soluble JAM3 ectodomain competition, mutagenesis of JAM2 Asp-82 The Journal of biological chemistry High 12070135
2002 VE-JAM/JAM2 interacts with T cells, NK cells, and dendritic cells through JAM3, identifying JAM3 as the functional receptor for JAM2-mediated leukocyte adhesion. Cloning and functional characterization; cell adhesion assays with J45 T cell line and primary immune cells Journal of immunology Medium 11823489
2003 JAM3 directly associates with the cell polarity protein PAR-3 through the first PDZ domain of PAR-3; JAM3 also associates with ZO-1 in a PDZ domain-dependent manner, implicating JAM3 in tight junction formation and endothelial cell polarity. Direct binding assays, PDZ domain interaction studies, ectopic expression of JAM-2 in CHO cells showing junctional localization regulated by serine phosphorylation and recruitment of endogenous PAR-3 and ZO-1 Journal of cell science High 12953056
2004 JAM-C localizes to desmosomes (not tight junctions) in intestinal epithelia and functions as a ligand for CD11b/CD18 (Mac-1) on neutrophils, mediating PMN transepithelial migration. Specific binding of JAM-C to CD11b/CD18 was demonstrated. Selective disruption of tight junctions and desmosomes, JAM-C mAb and JAM-C/Fc chimera inhibition of PMN transmigration assays, direct binding assays with CD11b/CD18 Molecular biology of the cell High 15194813
2005 JAM-C undergoes heterophilic interaction with JAM-B at cell-cell contacts; JAM-B stabilizes JAM-C in junctional complexes and soluble JAM-B dissociates JAM-C homodimers to form higher-affinity JAM-B/JAM-C heterodimers. JAM-C liberated from junctional JAM-B becomes available for interaction with leukocyte counter-receptor alphaM-beta2 integrin, modulating leukocyte adhesion. Co-immunoprecipitation, soluble protein competition assays, antibody blockade, cell adhesion assays Molecular biology of the cell High 16093349
2006 JAM-C regulates tight junctions and cell polarity through serine 281 in its cytoplasmic tail; mutation S281A abolishes junctional localization of JAM-C and establishment of cell polarity, and stimulates integrin-mediated cell migration and adhesion via modulation of beta1 and beta3 integrin activation. Transfection of JAM-C and serine-to-alanine mutant in carcinoma cells, tight junction barrier assays, cell migration/adhesion assays, integrin activation measurements The Journal of biological chemistry High 17099249
2006 CAR (coxsackievirus and adenovirus receptor) forms a complex with JAM-C in mouse testis, as demonstrated by co-immunoprecipitation in germ cells. Co-immunoprecipitation, RT-PCR, Western analysis, GST pulldown, indirect immunofluorescence Experimental cell research Medium 16410001
2007 Platelet JAM-C mediates firm adhesion of dendritic cells to platelets via CD11b/CD18 (Mac-1); soluble JAM-C reduced DC adhesion to platelets, and platelet/DC interaction resulted in DC apoptosis mediated by a JAM-C-dependent mechanism. Adhesion assays, preincubation with soluble JAM-C, in vivo carotid artery injury model, phagocytosis assays, apoptosis assays Arteriosclerosis, thrombosis, and vascular biology Medium 17379836
2009 JAM-C modulates endothelial permeability through association with alphavbeta3 integrin and regulation of its localization and activity; JAM-C also inhibits beta1 integrin activation (without direct association) through regulation of the small GTPase Rap1b (not Rap1a). Thrombin induces JAM-C localization to junctions increasing permeability; angiopoietin-1 prevents JAM-C translocation. siRNA knockdown, overexpression, co-immunoprecipitation with alphavbeta3, integrin activity assays, Rap1 isoform-specific knockdown, permeability assays Arteriosclerosis, thrombosis, and vascular biology High 19461049
2011 JAM-C at endothelial cell junctions regulates the directionality (polarity) of neutrophil transendothelial migration in vivo; lower JAM-C expression at EC junctions (or blockade/genetic deletion of JAM-C) promotes 'reverse' TEM of neutrophils back into the vasculature, contributing to systemic inflammation dissemination. Real-time confocal intravital imaging, ischemia-reperfusion inflammation model, JAM-C blocking antibodies, genetic deletion of JAM-C in ECs Nature immunology High 21706006
2011 Zebrafish orthologs Jamb and Jamc are essential for myocyte fusion during vertebrate skeletal muscle development; Jamb and Jamc physically interact and must act in trans between neighboring cells. Loss of either gene prevents myocyte fusion, producing mononuclear fast-twitch fibers. Ectopic jamc expression in slow muscle precursors causes inappropriate fusion. Forward genetic screen, heritable mutations in jamb and jamc, cell transplantation experiments, in vivo receptor interaction studies PLoS biology High 22180726
2011 JAM-C expressed in Schwann cells is required for the structural integrity and function of peripheral nerves: SC-specific JAM-C knockout mice show electrophysiological defects, muscular weakness, mechanical hypersensitivity, and morphological defects in the paranodal region with increased nodal length. Conditional knockout (Schwann cell-specific JAM-C deletion), electrophysiology, histomorphological analysis of paranodal regions FASEB journal High 22090315
2011 JAM-C in lymph node fibroblastic reticular cells (identified by thrombomodulin and PDGFRalpha) controls homeostatic chemokine secretion (CXCL12/SDF-1alpha, CCL21, CCL19); Jam-C-deficient mice and anti-JAM-C-treated mice show decreased intranodal content of these chemokines, correlated with reduced naive T cell egress from lymph nodes. JAM-C knockout mice, anti-JAM-C antibody treatment, chemokine measurement in lymph nodes, naive T cell egress assay Journal of immunology Medium 21685324
2012 JAM-B expressed by endothelial cells contributes to B16 melanoma cell metastasis through heterophilic interaction with JAM-C on tumor cells, mediating melanoma cell adhesion to lung microvascular endothelial cells; metastasis of B16 cells was reduced in Jam-b deficient mice. Jam-b knockout mice, in vivo metastasis assay, cell adhesion assays to primary lung microvascular endothelial cells FEBS letters Medium 23068611
2012 JAM-C is expressed on the apical surface of neural stem cells in embryonic and adult mouse brain and is asymmetrically distributed during cell divisions, enriched at the apical membrane. In vivo immunohistochemistry, live imaging of neural stem cells, subcellular localization during division Stem cells and development Medium 22114908
2012 JAM-C deficiency in C57BL/6 mice causes severe hydrocephalus associated with a block or reduction of CSF drainage from the lateral to the 3rd ventricle; endothelial re-expression of JAM-C failed to rescue the hydrocephalus, indicating the relevant JAM-C function is not endothelial but likely ependymal/choroid plexus epithelial. JAM-C knockout mice on C57BL/6 background, endothelial rescue experiments, CSF circulation analysis, immunohistochemistry PloS one High 23029139
2012 JAM-C on B lymphocytes mediates homing to bone marrow, lymph nodes, and spleen via heterophilic interaction with JAM-B on lymphatic endothelial cells (identified by plasmon resonance as the major JAM-C ligand, with homotypic JAM-C interactions at background levels). Anti-JAM-C antibodies blocked adhesion of JAM-C-expressing B cells to JAM-B and reduced lymphoma engraftment. Xenogeneic NOD/SCID mouse model, short- and long-term anti-JAM-C antibody treatment, plasmon resonance binding studies, immunofluorescence for JAM-B on endothelium Cancer research High 23221386
2014 JAM-B/JAM-C interaction between hematopoietic stem and progenitor cells (HSPC) and bone marrow stromal/mesenchymal cells is required for HSPC homing to bone marrow; anti-JAM-C blocking antibody inhibited hematopoietic reconstitution, progenitor homing, and induced HSPC mobilization in a JAM-B-dependent manner. This interaction occurs between HSPC and mesenchymal stem cells but not endothelial cells or osteoblasts. Blocking monoclonal antibodies, bone marrow transplantation, HSPC mobilization assays, human CD34+ hematopoietic progenitor homing in mouse BM Stem cells High 24357068
2017 GRASP55 interacts with JAM-C via PDZ-mediated interactions in developing germ cells (proteomic identification confirmed by crystal structure); GRASP55 knockout disrupts acrosome formation and polarized localization of JAM-C in spermatids. Crystal structures of GRASP55 in complex with JAM-C or JAM-B reveal that GRASP55 interaction induces a conformational change in GRASP55. A chemical compound (Graspin) inhibiting PDZ-mediated GRASP55/JAM interactions disrupted JAM-C polarized localization in spermatids in vivo. Proteomic pulldown, Gorasp2 knockout mice, crystal structure determination of GRASP55–JAM-C/JAM-B complexes, in silico pharmacophore/chemical inhibitor (Graspin), mouse treatment with Graspin PLoS genetics High 28617811
2018 JAM3 directly associates with LRP5 to activate the PDK1/AKT pathway, leading to GSK3beta downregulation and beta-catenin/CCND1 activation, maintaining leukemia-initiating cell (LIC) self-renewal and cell cycle entry. This function is independent of JAM3's canonical role in cell junctions and migration. Co-immunoprecipitation (JAM3–LRP5 association), Jam3 genetic deletion in MLL-AF9 AML model, serial transplantation, JAM3 knockdown in human leukemia cell lines and primary LICs, Western blotting for pathway components The Journal of clinical investigation High 29584620
2018 JAM-C dimerization sites E66 and K68 are critical for JAM-C/JAM-B interaction and correct junctional localization; mutations at these sites increase cell adhesion, reduce migration and proliferation, and abolish metastatic lung nodule formation in mice, demonstrating that JAM-C dimerization drives pro-metastatic behavior. Directed mutagenesis of E66 and K68, cell adhesion assays, migration/proliferation assays, in vivo lung metastasis model Biochimica et biophysica acta. Molecular cell research High 29378216
2019 Dynamic trafficking and lysosomal degradation of JAM-C, regulated by ubiquitylation via the E3 ligase CBL, are necessary for junctional remodelling during endothelial cell migration and angiogenesis. JAM-C co-traffics with VE-Cadherin and neuropilin-1/2 but not with leukocyte transmigration-associated junctional proteins. Receptor mutagenesis, HRP and APEX-2 proximity labelling, light and electron microscopy, co-trafficking analysis, CBL-mediated ubiquitylation assays PLoS biology High 31790392
2008 JAM-C localizes specifically to tight junctions in human retinal pigment epithelium (hfRPE); JAM-C knockdown disrupts N-cadherin and ZO-1 organization at cell contacts, delays hfRPE cell polarization (reduced apical ezrin), and significantly decreases chemokine-induced transmigration of granulocytes (but not monocytes) through the hfRPE monolayer. siRNA knockdown, immunofluorescence, Western blot, transepithelial migration assay Investigative ophthalmology & visual science Medium 19060272
2018 LPS reduces JAM-3 expression in renal tubular epithelial cells via the RhoT1/SMAD-4/JAM-3 pathway: LPS increases SMAD-4 (which suppresses JAM-3), and RhoT1 inhibits SMAD-4 to maintain JAM-3 expression; downregulation of SMAD-4 via RNAi increased JAM-3 levels in LPS-treated cells. siRNA knockdown of SMAD-4 and RhoT1, Western blot, transepithelial permeability and resistance assays, immunofluorescence International journal of medical sciences Medium 29725250
2020 In cerebellar granule cells, Pard3a and JamC operate in the same molecular pathway to regulate radial migration initiation from the external granule cell layer; normalizing expression of Pard3a and JamC in organotypic cerebellar slice cultures rescued both migratory and apoptotic defects caused by intrauterine growth restriction. Organotypic cerebellar slice cultures, gene expression normalization experiments, in vivo pig IUGR model with IHC/gene expression analysis Experimental neurology Medium 33259808
2017 JAM-C is required to maintain VEGFR2 expression in retinal pigment epithelial cells under oxidative stress; JAM-C knockdown decreased RPE cell survival, and overexpression of VEGFR2 partially restored impaired RPE survival caused by JAM-C knockdown. JAM-C regulates VEGFR2 expression and modulates downstream p38 phosphorylation. siRNA knockdown, overexpression rescue with VEGFR2, cell survival assays, Western blot for VEGFR2 and p-p38 Thrombosis and haemostasis Medium 28203682
2022 ADAM10 processes/cleaves JAM-C to increase Rap1GAP activity, promoting neural stem cell transit from the apical to basal compartment of the subventricular zone and subsequent lineage progression. ADAM10 conditional manipulation, RAP1GAP activity assays, neural stem cell localization and lineage analysis Neural regeneration research Medium 35535899
2022 JAM-C deficiency in mouse lenses causes nuclear cataract with defective degradation of nuclei and organelles in lens fiber cells, accompanied by activation of the unfolded protein response (upregulation of BiP, CHOP, TRIB3, CHAC1) and increased cell death. Jamc knockout mice (C57BL/6), RNA sequencing, RT-qPCR, Western blot, immunofluorescence, TUNEL staining Investigative ophthalmology & visual science Medium 36048019
2022 Epigenetic silencing of JAM3 by promoter methylation activates Wnt/beta-catenin signaling in esophageal cancer cells; JAM3 restoration suppressed EC cell proliferation, colony formation, migration and invasion by inhibiting Wnt/beta-catenin signaling, and 5-aza-2'-deoxycytidine treatment restored JAM3 expression. Methylation-specific PCR, Western blot, MTT/colony/migration assays, xenograft mouse models, 5-aza treatment Clinical epigenetics Medium 36461092
2025 JAM-C inhibits ocular fibrosis by suppressing the nuclear localization and function of TAZ, which otherwise binds to KLF6 to promote its expression and activate the EMT cascade; AAV-mediated JAM-C augmentation alleviated ocular fibrosis in mouse models. Co-IP, ChIP-qPCR, luciferase reporter assay, RNA sequencing, siRNA knockdown, Jam-c KO mice, AAV overexpression in vivo Journal of advanced research High 40398745
2024 JAM-C mediates ferroptosis resistance in high-adhesion ovarian cancer cells through NRF2-induced upregulation of FSP1 (a lipid peroxidation suppressor); JAM3 knockdown/blockade sensitized cells to ferroptosis inducers RSL3 and erastin, while JAM3 overexpression conferred resistance; inhibition of the NRF2/FSP1 pathway eliminated JAM3-mediated ferroptosis resistance. siRNA knockdown, JAM3 overexpression, ferroptosis inducers (RSL3, erastin), NRF2/FSP1 pathway inhibition, in vitro and in vivo cisplatin resistance assays Free radical biology & medicine Medium 39706500
2025 Pard3 polarity protein and JAM-C cooperate to promote surface recruitment of the DCC receptor, gating Netrin-1-dependent repulsion that drives cerebellar granule neuron exit from the germinal zone; the E3 ubiquitin ligase Siah2 antagonizes this Pard3/JAM-C function by inhibiting DCC surface recruitment. In vivo mouse cerebellar genetics, DCC surface recruitment assays, epistasis between Siah2, Pard3, JamC, and DCC Nature communications Medium 39774925
2025 JAM-C maintains lens cell adhesion and ball-and-socket junction integrity; JAM-C deficiency elevates intracellular Ca2+ in lens cells, activates calpain (evidenced by degradation of IIα spectrin and F-actin), and disrupts FGF/ERK signaling in lens epithelial cells. Jamc knockout mice, calcium imaging, Western blot for calpain substrates (IIα spectrin, F-actin), FGF/ERK pathway analysis, electron microscopy of junctions Experimental eye research Medium 41173413
2021 Soluble JAM-C ectodomain (sJAM-C), which is cleaved and secreted by adipose-derived stromal/stem cells (ADSCs), forms a complex with JAM-B and stimulates ADSC adhesion, proliferation, and expression of mesenchymal stem cell markers. CRISPR/Cas9 deletion confirmed that sJAM-C/JAM-B coupling mediates ADSC adhesion and maintenance. Immunoprecipitation, CRISPR/Cas9 genome editing, culture plate coating with sJAM-C, cell adhesion and proliferation assays, flow cytometry for MSC markers Biomedicines Medium 33801826
2016 JAM-C at homeostatic copy numbers forms a unidirectional vascular barrier for leukocyte TEM; overexpression or gene silencing of JAM-C in endothelium under flow conditions both result in higher rates of monocyte reverse-TEM, and anti-JAM-C blockade in atherosclerotic recipients induced monocyte-derived cell emigration from plaques and reduced plaque size. siRNA and overexpression in human endothelium under flow, aortic arch transplantation model (ApoE-/- into wild-type), JAM-C blockade in vivo PloS one Medium 27442505
2026 JAM3 promotes meningioma development by interacting with Mac-1 (CD11b) on neutrophils (confirmed by Co-IP) to activate AKT phosphorylation, thereby promoting neutrophil migration and neutrophil extracellular trap (NET) formation; JAM3 knockdown in meningioma cells suppressed AKT phosphorylation, reduced NET formation, and inhibited tumor growth in xenograft models. Co-IP confirming JAM3/Mac-1 interaction, siRNA knockdown, AKT activator rescue (SC79), neutrophil migration and NET assays, xenograft tumor model, DNase I NET abolition Cellular signalling Medium 41500374
2023 JAM-C deletion in mice results in decreased lens epithelial cell (LEC) quantity and proliferation, downregulation of the transcription factor FOXE3, disorganization of lens fibers, and altered distribution of gap junction proteins Cx46 and Cx50 and reduced gamma-crystallin in fiber cells. Jamc knockout mice, BrdU incorporation assay, TUNEL staining, immunofluorescence, Western blot, histological analysis across developmental stages Investigative ophthalmology & visual science Medium 38095908
2025 JAM3 promotes laryngeal squamous cell carcinoma oncogenesis by inhibiting the Hippo pathway; JAM3 overexpression activated Hippo signaling suppressing proliferation, migration and invasion, whereas JAM3 knockdown enhanced these behaviors by inhibiting the Hippo pathway, both in vitro and in vivo. Western blot, immunofluorescence, Cell Counting Kit-8, colony formation, Transwell assays, 5-Aza-2'-deoxycytidine treatment, in vivo experiments Oncology reports Medium 39749700
2025 In serous ovarian carcinoma cells, JAM3 overexpression suppresses proliferation, migration, and invasion and promotes apoptosis by inhibiting the PI3K/AKT signaling pathway; JAM3 knockdown produced opposite effects, confirmed by AKT inhibitor (MK2206) rescue experiments. RNA sequencing, Western blot, CCK8, flow cytometry, scratch-wound, Transwell assays, AKT inhibitor rescue, immunohistochemistry Epigenomics Medium 40711818

Source papers

Stage 0 corpus · 86 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo. Nature immunology 476 21706006
2003 The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity. Journal of cell science 204 12953056
2001 Cloning of human junctional adhesion molecule 3 (JAM3) and its identification as the JAM2 counter-receptor. The Journal of biological chemistry 172 11590146
2002 JAM2 interacts with alpha4beta1. Facilitation by JAM3. The Journal of biological chemistry 140 12070135
2002 Vascular endothelial-junctional adhesion molecule (VE-JAM)/JAM 2 interacts with T, NK, and dendritic cells through JAM 3. Journal of immunology (Baltimore, Md. : 1950) 118 11823489
2007 Platelets recruit human dendritic cells via Mac-1/JAM-C interaction and modulate dendritic cell function in vitro. Arteriosclerosis, thrombosis, and vascular biology 115 17379836
2004 JAM-C is a component of desmosomes and a ligand for CD11b/CD18-mediated neutrophil transepithelial migration. Molecular biology of the cell 111 15194813
2005 Dual interaction of JAM-C with JAM-B and alpha(M)beta2 integrin: function in junctional complexes and leukocyte adhesion. Molecular biology of the cell 98 16093349
2010 A homozygous mutation in the tight-junction protein JAM3 causes hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. American journal of human genetics 85 21109224
2011 Jamb and jamc are essential for vertebrate myocyte fusion. PLoS biology 80 22180726
2006 Coxsackievirus and adenovirus receptor (CAR) is expressed in male germ cells and forms a complex with the differentiation factor JAM-C in mouse testis. Experimental cell research 78 16410001
2006 JAM-C regulates tight junctions and integrin-mediated cell adhesion and migration. The Journal of biological chemistry 75 17099249
2005 The role of junctional adhesion molecule-C (JAM-C) in oxidized LDL-mediated leukocyte recruitment. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 75 16195363
2016 Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury. Scientific reports 68 26841848
2022 Exosomal hsa_circ_0004658 derived from RBPJ overexpressed-macrophages inhibits hepatocellular carcinoma progression via miR-499b-5p/JAM3. Cell death & disease 61 35013102
2018 JAM3 maintains leukemia-initiating cell self-renewal through LRP5/AKT/β-catenin/CCND1 signaling. The Journal of clinical investigation 57 29584620
2019 JAM3 functions as a novel tumor suppressor and is inactivated by DNA methylation in colorectal cancer. Cancer management and research 41 30988641
2009 JAM-C induces endothelial cell permeability through its association and regulation of {beta}3 integrins. Arteriosclerosis, thrombosis, and vascular biology 41 19461049
2008 Expression, localization, and function of junctional adhesion molecule-C (JAM-C) in human retinal pigment epithelium. Investigative ophthalmology & visual science 41 19060272
2002 Narrowing the critical region within 11q24-qter for hypoplastic left heart and identification of a candidate gene, JAM3, expressed during cardiogenesis. Genomics 40 11944976
2013 Delineation of the clinical, molecular and cellular aspects of novel JAM3 mutations underlying the autosomal recessive hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Human mutation 38 23255084
2006 The role of junctional adhesion molecule C (JAM-C) in acute pancreatitis. The Journal of pathology 36 16767690
2008 Genetic deletion of JAM-C reveals a role in myeloid progenitor generation. Blood 35 19109565
2014 Function of Jam-B/Jam-C interaction in homing and mobilization of human and mouse hematopoietic stem and progenitor cells. Stem cells (Dayton, Ohio) 34 24357068
2012 Junctional adhesion molecule (JAM)-C deficient C57BL/6 mice develop a severe hydrocephalus. PloS one 34 23029139
2012 The Junctional Adhesion Molecule-B regulates JAM-C-dependent melanoma cell metastasis. FEBS letters 34 23068611
2015 JAM3 methylation status as a biomarker for diagnosis of preneoplastic and neoplastic lesions of the cervix. Oncotarget 33 26517242
2013 Two bHLH-type transcription factors, JA-ASSOCIATED MYC2-LIKE2 and JAM3, are transcriptional repressors and affect male fertility. Plant signaling & behavior 32 24056034
2017 Genetic, structural, and chemical insights into the dual function of GRASP55 in germ cell Golgi remodeling and JAM-C polarized localization during spermatogenesis. PLoS genetics 31 28617811
2012 Homing of human B cells to lymphoid organs and B-cell lymphoma engraftment are controlled by cell adhesion molecule JAM-C. Cancer research 27 23221386
2020 Exosomal miR-146a-5p from Treponema pallidum-stimulated macrophages reduces endothelial cells permeability and monocyte transendothelial migration by targeting JAM-C. Experimental cell research 22 31926946
2014 JAM-C promotes lymphangiogenesis and nodal metastasis in non-small cell lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 24584816
2018 Junctional adhesion molecules JAM-B and JAM-C promote autoimmune-mediated liver fibrosis in mice. Journal of autoimmunity 21 29753567
2018 Jam3 promotes migration and suppresses apoptosis of renal carcinoma cell lines. International journal of molecular medicine 21 30226554
2007 Junctional adhesion molecule C (JAM-C) distinguishes CD27+ germinal center B lymphocytes from non-germinal center cells and constitutes a new diagnostic tool for B-cell malignancies. Leukemia 21 17429428
2016 Divergent JAM-C Expression Accelerates Monocyte-Derived Cell Exit from Atherosclerotic Plaques. PloS one 20 27442505
2012 JAM-C is an apical surface marker for neural stem cells. Stem cells and development 19 22114908
2009 Deletion of JAM-C, a candidate gene for heart defects in Jacobsen syndrome, results in a normal cardiac phenotype in mice. American journal of medical genetics. Part A 19 19533782
2022 Epigenetic silencing of JAM3 promotes esophageal cancer development by activating Wnt signaling. Clinical epigenetics 18 36461092
2016 Murine junctional adhesion molecules JAM-B and JAM-C mediate endothelial and stellate cell interactions during hepatic fibrosis. Cell adhesion & migration 18 27111582
2010 Targeted JAM-C deletion in germ cells by Spo11-controlled Cre recombinase. Journal of cell science 18 21147852
2011 Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 22090315
2023 Surfaceome Profiling of Cell Lines and Patient-Derived Xenografts Confirm FGFR4, NCAM1, CD276, and Highlight AGRL2, JAM3, and L1CAM as Surface Targets for Rhabdomyosarcoma. International journal of molecular sciences 15 36768928
2018 Junctional adhesion molecule C (JAM-C) dimerization aids cancer cell migration and metastasis. Biochimica et biophysica acta. Molecular cell research 15 29378216
2018 Genetic Mutations in jamb, jamc, and myomaker Revealed Different Roles on Myoblast Fusion and Muscle Growth. Marine biotechnology (New York, N.Y.) 15 30467785
2019 Dynamic trafficking and turnover of JAM-C is essential for endothelial cell migration. PLoS biology 14 31790392
2020 Intrauterine growth restriction compromises cerebellar development by affecting radial migration of granule cells via the JamC/Pard3a molecular pathway. Experimental neurology 13 33259808
2011 Cutting edge: JAM-C controls homeostatic chemokine secretion in lymph node fibroblastic reticular cells expressing thrombomodulin. Journal of immunology (Baltimore, Md. : 1950) 13 21685324
2018 Lipopolysaccharide Mediates the Destruction of Intercellular Tight Junction among Renal Tubular Epithelial Cells via RhoT1/SMAD-4/JAM-3 Pathway. International journal of medical sciences 12 29725250
2016 Anti-JAM-C therapy eliminates tumor engraftment in a xenograft model of mantle cell lymphoma. Journal of leukocyte biology 12 27256571
2009 Adaptive immune response in JAM-C-deficient mice: normal initiation but reduced IgG memory. Journal of immunology (Baltimore, Md. : 1950) 12 19342649
2024 Triage performance of PAX1m/JAM3m in opportunistic cervical cancer screening of non‒16/18 human papillomavirus-positive women: a multicenter prospective study in China. Clinical epigenetics 11 39152491
2021 A novel homozygous variant in JAM3 gene causing hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts (HDBSCC) with neonatal onset. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 11 34292449
2021 Immunoglobulin superfamily receptor Junctional adhesion molecule 3 (Jam3) requirement for melanophore survival and patterning during formation of zebrafish stripes. Developmental biology 10 33933422
2017 JAM-C maintains VEGR2 expression to promote retinal pigment epithelium cell survival under oxidative stress. Thrombosis and haemostasis 9 28203682
2024 Cervical cancer screening: efficacy of PAX1 and JAM3 methylation assay in the triage of atypical squamous cell of undetermined significance (ASC-US). BMC cancer 8 39528979
2024 Evaluating PAX1/JAM3 methylation for triage in HPV 16/18-infected women. Clinical epigenetics 8 39726021
2009 Evidence for cross-reactivity of JAM-C antibodies: implications for cellular localization studies. Biology of the cell 8 19143587
2024 JAM3 promotes cervical cancer metastasis by activating the HIF-1α/VEGFA pathway. BMC women's health 7 38760803
2024 High-adhesion ovarian cancer cell resistance to ferroptosis: The activation of NRF2/FSP1 pathway by junctional adhesion molecule JAM3. Free radical biology & medicine 7 39706500
2022 ADAM10 facilitates rapid neural stem cell cycling and proper positioning within the subventricular zone niche via JAMC/RAP1Gap signaling. Neural regeneration research 7 35535899
2022 Deficiency of Jamc Leads to Congenital Nuclear Cataract and Activates the Unfolded Protein Response in Mouse Lenses. Investigative ophthalmology & visual science 7 36048019
2022 Case report: Prenatal diagnosis of fetal intracranial hemorrhage due to compound mutations in the JAM3 gene. Frontiers in genetics 7 36339007
2024 Assessment of PAX1 and JAM3 methylation triage efficacy across HPV genotypes and age groups in high-risk HPV-positive women in China. Frontiers in oncology 6 39659794
2023 JAM-C Is Important for Lens Epithelial Cell Proliferation and Lens Fiber Maturation in Murine Lens Development. Investigative ophthalmology & visual science 6 38095908
2024 [A multicenter study on the accuracy of PAX1/JAM3 dual genes methylation testing for screening cervical cancer]. Zhonghua yi xue za zhi 5 38782754
2022 miR-127-5p Targets JAM3 to Regulate Ferroptosis, Proliferation, and Metastasis in Malignant Meningioma Cells. Disease markers 5 35818586
2025 Epigenetic silencing of JAM3 promotes laryngeal squamous cell carcinoma development by inhibiting the Hippo pathway. Oncology reports 4 39749700
2015 Loss of JAM-C leads to impaired esophageal innervations and megaesophagus in mice. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus 4 26123848
2025 Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit. Nature communications 3 39774925
2023 High-grade cervical lesions diagnosed by JAM3/PAX1 methylation in high-risk human papillomavirus-infected patients. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 3 38448375
2021 Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells. Biomedicines 2 33801826
2025 JAM-C prevents ocular fibrosis by suppressing the TAZ/KLF6 pathway. Journal of advanced research 1 40398745
2024 Antagonistic action of Siah2 and Pard3/JamC to promote germinal zone exit of differentiated cerebellar granule neurons by modulating Ntn1 signaling via Dcc. Research square 1 39399669
2024 The performance of JAM3/PAX1 methylation in the diagnosis of high-grade squamous intraepithelial lesions for women with high-risk HPV infection. BMC cancer 1 39696066
2011 Jamb and jamc muscle in on myoblast fusion. PLoS biology 1 22180727
2026 JAM3 orchestrates Mac-1-dependent AKT phosphorylation to facilitate neutrophil extracellular trap-driven meningioma pathogenesis. Cellular signalling 0 41500374
2026 Utility of PAX1/JAM3 methylation analysis for triage of high-risk HPV-positive individuals. Laboratory medicine 0 41686686
2026 Effectiveness analysis and clinical application potential exploration of combined detection of PAX1/JAM3 gene methylation in early diagnosis of cervical precancerous lesions. Clinical epigenetics 0 41845480
2026 PAX1/JAM3 methylation-a novel biomarker for early detection and accurate management of cervical adenocarcinoma. American journal of cancer research 0 42163865
2025 The role of PAX1 and JAM3 methylation in predicting the pathological upgrading of cervical intraepithelial neoplasia before conization. Scientific reports 0 40399320
2025 Epigenetic silencing of JAM3 promoted progression in serous ovarian carcinoma through PI3K/AKT pathway. Epigenomics 0 40711818
2025 PALB2 mutations increase oncogenic properties of breast epithelial cells by enhancing JAM3 and PARVB expression. Biochemical and biophysical research communications 0 40730089
2025 Pharmacological and toxicological profiling of JAMC-4/108: targeted induction of apoptosis in human colorectal cancer cells. The Journal of pharmacology and experimental therapeutics 0 41124967
2025 Role of JAM-C in lens cell adhesion, calcium homeostasis, and cataract pathogenesis. Experimental eye research 0 41173413
2024 Junctional Adhesion Molecule (JAM)-C recruitment of Pard3 and drebrin to cell contacts initiates neuron-glia recognition and layer-specific cell sorting in developing cerebella. bioRxiv : the preprint server for biology 0 38585827

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