Affinage

CEACAM1

Cell adhesion molecule CEACAM1 · UniProt P13688

Length
526 aa
Mass
57.6 kDa
Annotated
2026-06-09
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEACAM1 is a transmembrane cell adhesion molecule that functions principally as an inhibitory immunoreceptor, regulating immune cell signaling, hepatic insulin metabolism, epithelial morphogenesis, and host responses to pathogens (PMID:17081782, PMID:12128284). Its inhibitory output is encoded by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the long cytoplasmic-domain isoform; phosphorylation of the ITIM tyrosine (Y459/Y488) recruits the phosphatases SHP-1 and SHP-2, and mutation of this tyrosine abolishes inhibitory signaling (PMID:11493628, PMID:17081782). Through this ITIM/SHP-1 module CEACAM1 dampens TCR-CD3 signaling and T cell proliferation and cytokine production (PMID:17081782), inhibits NK cell NKG2D-mediated cytolysis via SHP-1-dependent dephosphorylation of Vav1 (PMID:23696226), and negatively regulates platelet collagen responses through the GPVI/FcR-γ receptor (PMID:19008452). Trans-homophilic engagement of CEACAM1 induces cis-dimerization transmitted allosterically through the N-terminal Ig domain, and the monomer/dimer equilibrium of CEACAM1-L sets the balance of SHP-2 versus c-Src recruitment, with the short isoform CEACAM1-S antagonizing long-isoform homodimerization (PMID:19948503). Beyond inhibition, CEACAM1 provides positive and pro-survival signals: it recruits Lck into the TCR immunological synapse to sustain antiviral CD8+ T cell responses (PMID:29967450), promotes B cell survival via the BTK/Syk/NF-κB axis (PMID:25692415), and supports monocyte and granulocyte survival through PI3K/Akt and SHP-1-dependent pathways (PMID:17071610, PMID:15909305). In the liver CEACAM1 is a substrate of the insulin receptor whose phosphorylation drives receptor-mediated insulin endocytosis and clearance; loss of this function causes insulin resistance, and hepatic overexpression protects against diet-induced hyperinsulinemia (PMID:12128284, PMID:25972571). As an EGFR substrate, phosphorylated CEACAM1 sequesters Shc to uncouple EGFR from Ras/MAPK signaling (PMID:15467833). The short isoform CEACAM1-4S binds annexin II and downregulates β1-integrin to drive lumen formation and central-cell apoptosis during epithelial morphogenesis (PMID:14522961, PMID:12522268, PMID:15339048), while HIF-1α/Ptbp1-controlled alternative splicing toward CEACAM1-S protects hepatocytes by repressing the ASK1/p-p38 death pathway in ischemia-reperfusion injury (PMID:37531413, PMID:32027621). CEACAM1 is exploited as a receptor by multiple pathogens, including Neisseria, Helicobacter pylori, Fusobacterium nucleatum, and Streptococcus pyogenes, all binding its N-terminal Ig domain to subvert epithelial integrity and immune responses (PMID:18836450, PMID:30321907, PMID:34336716, PMID:37080973). A structurally defined cis/trans heterodimer with TIM-3 has been reported as required for TIM-3-mediated T cell inhibition (PMID:25363763), although a subsequent study found no detectable CEACAM1-TIM-3 interaction and concluded CEACAM1 inhibition operates independently of TIM-3 (PMID:32222966).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 Medium

    Establishing CEACAM1's binding partners on innate immune cells, the protein was identified as a major granule-stored galectin-3 receptor on neutrophils, an early clue to its extracellular ligand repertoire.

    Evidence galectin-3-Sepharose affinity chromatography from neutrophil granules with immunoblotting

    PMID:10553088

    Open questions at the time
    • functional consequence of galectin-3 binding not defined
    • single lab affinity capture without binding kinetics
  2. 2001 High

    To define the molecular basis of CEACAM1 inhibitory signaling, the cytoplasmic Y459 motif was shown to be a functional ITIM requiring both SHP-1 and SHP-2 to suppress calcium influx.

    Evidence FcγRIIB-BGPa chimera in SHP-1/SHP-2-null DT40 B cells with Y-to-F mutagenesis and calcium assays

    PMID:11493628

    Open questions at the time
    • studied in a chimeric receptor context, not native CEACAM1
    • relative contributions of SHP-1 vs SHP-2 in physiological cells unresolved
  3. 2002 Medium

    Defining a metabolic role, CEACAM1 was identified as an insulin receptor substrate whose phosphorylation drives hepatic insulin clearance, linking the receptor to systemic insulin sensitivity.

    Evidence L-SACC1 dominant-negative S503A transgenic mice with insulin clearance and metabolic phenotyping

    PMID:12128284

    Open questions at the time
    • primarily a review summarizing prior transfection data
    • structural basis of insulin receptor docking not resolved
  4. 2003 High

    To explain epithelial morphogenetic functions, CEACAM1-4S was shown to bind annexin II directly and to restore lumen formation through intrinsic-pathway apoptosis of central acinar cells.

    Evidence GST pull-down, reciprocal co-IP, SPR (KD ~30 nM), and 3D Matrigel culture with Bax/cytochrome c readouts

    PMID:12522268 PMID:14522961

    Open questions at the time
    • how cytoplasmic annexin II binding triggers apoptosis mechanistically unclear
    • isoform-specific signaling downstream of CEACAM1-4S not fully mapped
  5. 2004 High

    Broadening the substrate concept, CEACAM1 was identified as an EGFR substrate that sequesters Shc to dampen Ras/MAPK proliferation, and as a Tyr-488-dependent promoter of melanoma invasion via integrin β3.

    Evidence co-IP with Shc and integrin β3, EGF stimulation, invasion assays, Tyr-488 mutagenesis, transgenic mice

    PMID:15339048 PMID:15467833 PMID:15509546

    Open questions at the time
    • context-dependence of growth-suppressive vs invasion-promoting roles unresolved
    • structural detail of Shc/integrin docking unknown
  6. 2006 High

    Reciprocal genetic approaches established CEACAM1 as a bona fide negative regulator of T cells, acting through long-isoform ITIMs and SHP-1 to restrain TCR-CD3 signaling, and as a PI3K/Akt-dependent survival factor in monocytes.

    Evidence CEACAM1 overexpression and conditional T cell deletion in mice; antibody/soluble-CEACAM1 treatment of monocytes with apoptosis and inhibitor assays

    PMID:17071610 PMID:17081782

    Open questions at the time
    • how the same receptor switches between inhibitory and survival outputs unresolved
    • monocyte survival mechanism is Medium-confidence and from a single lab
  7. 2008 High

    Linking CEACAM1 to host defense and hemostasis, the receptor was shown to negatively regulate TLR2-driven inflammation upon bacterial engagement and to inhibit platelet GPVI/collagen signaling, both via ITIM/SHP-1.

    Evidence bacterial infection of primary epithelial cells with pathway readouts; Ceacam1-/- platelet aggregation, adhesion, and in vivo thrombosis assays

    PMID:18836450 PMID:19008452

    Open questions at the time
    • how pathogen binding couples to ITIM phosphorylation mechanistically unclear
    • platelet ITIM kinase upstream of phosphorylation not identified
  8. 2009 High

    Resolving how trans engagement signals across the membrane, trans-homophilic binding was shown to induce cis-dimerization of CEACAM1-L allosterically, with the monomer/dimer equilibrium setting the SHP-2 vs c-Src balance.

    Evidence FRET, cross-linking, co-clustering and co-IP with CFP/YFP-tagged isoforms in epithelial monolayers

    PMID:19948503

    Open questions at the time
    • physiological triggers shifting the equilibrium in vivo not defined
    • SHP-1 binding not observed, leaving its in vivo role open
  9. 2013 High

    Defining a tumor-immune evasion mechanism, NK-cell CEACAM1 was shown to inhibit NKG2D cytolysis via trans-homophilic interaction, NKG2D association, SHP-1 recruitment, and Vav1 dephosphorylation, complementing earlier evidence that tumor CEACAM1 retains NKG2D ligands intracellularly.

    Evidence NK cytolysis assays, reciprocal NKG2D-CEACAM1 co-IP, SHP-1 recruitment, Vav1 phosphorylation blotting; CEACAM1 silencing with surface-ligand flow cytometry

    PMID:22143889 PMID:23696226

    Open questions at the time
    • mechanism of NKG2D ligand intracellular retention unresolved
    • relative importance of homophilic vs receptor-cis mechanisms in vivo unclear
  10. 2014 High

    A structurally defined CEACAM1-TIM-3 cis/trans heterodimer was reported as required for TIM-3-mediated T cell inhibition, proposing a co-receptor model for T cell tolerance.

    Evidence X-ray crystallography, co-IP, biophysical binding, and adoptive-transfer colitis with CEACAM1-deficient T cell reconstitution

    PMID:25363763

    Open questions at the time
    • the interaction was later not reproduced (see 2020 entry)
    • structural interface conditions vs cellular physiology not reconciled
  11. 2015 High

    Extending CEACAM1's survival role to humoral immunity and metabolism, intrinsic CEACAM1 signaling was shown to sustain B cell survival via BTK/Syk/NF-κB for antiviral antibody responses, and hepatic overexpression to protect insulin clearance.

    Evidence Ceacam1-/- mice with VSV infection and B cell survival assays; liver-specific CEACAM1 transgenic mice on high-fat diet

    PMID:25692415 PMID:25972571

    Open questions at the time
    • how CEACAM1 couples to BTK/Syk activation mechanistically unclear
    • link between hepatic insulin clearance and fatty-acid oxidation incompletely defined
  12. 2018 Medium

    Defining antiviral and pathogen-cooperative roles, CEACAM1 was shown to be induced via IRF3 at an ISRE to suppress viral replication through SHP-2/mTOR, while also being required for H. pylori T4SS-dependent CagA delivery.

    Evidence IRF3 ChIP at CEACAM1 ISRE, SHP-2/mTOR functional assays, decidua organ culture; CEACAM1/CEACAM5 reconstitution in AZ-521 cells with CagA translocation assays

    PMID:27264178 PMID:30321907

    Open questions at the time
    • how SHP-2 connects to mTOR inhibition mechanistically unresolved
    • both single-lab studies awaiting independent confirmation
  13. 2018 High

    Revising the inhibitory paradigm, CEACAM1 was found to act positively in CD8+ T cells by recruiting Lck into the immunological synapse to sustain antiviral responses and prevent exhaustion.

    Evidence LCMV infection of Ceacam1-/- mice, synapse imaging, Lck recruitment assays, anti-CEACAM1 antibody validation in human cells

    PMID:29967450

    Open questions at the time
    • molecular determinants of Lck recruitment by CEACAM1 not defined
    • reconciliation of positive CD8 role with ITIM-based inhibition unresolved
  14. 2020 Medium

    Directly challenging the 2014 model, a binding and reporter study found no detectable cis or trans CEACAM1-TIM-3 interaction and concluded CEACAM1 inhibition functions independently of TIM-3.

    Evidence T cell reporter platform with extensive cell-based and soluble-protein binding assays and co-expression analysis

    PMID:32222966

    Open questions at the time
    • negative result directly contradicts the structural study
    • single lab; conditions distinguishing the two outcomes not established
  15. 2023 High

    Defining isoform-selective cytoprotection, HIF-1α/Ptbp1-driven splicing toward CEACAM1-S was shown to repress ASK1/p-p38-mediated hepatocyte death, while neutrophil CEACAM1-L modulates NETosis via S1PR2/S1PR3 in liver ischemia-reperfusion injury.

    Evidence HIF-1α ChIP, luciferase, adenoviral CEACAM1-S reconstitution and morpholino isoform switching in IRI models; isoform-specific CC1-L ablation in mouse OLT with S1PR pathway and NET assays; CC1-KO OLT ASK1/p38 analysis

    PMID:32027621 PMID:36719377 PMID:37531413

    Open questions at the time
    • how distinct cytoplasmic domains specify opposing cell-fate outcomes unresolved
    • translation of isoform-switching strategy to human therapy untested
  16. 2023 High

    Cementing CEACAM1 as a convergent bacterial target, S. pyogenes R28 and F. nucleatum CbpF were shown to bind its N-terminal Ig domain to subvert epithelial repair and T cell function.

    Evidence high-resolution structural analysis of R28-CEACAM1 interface with adhesion/wound-repair/immune assays; defined F. nucleatum adhesin mutants with T cell inhibition and antibody blocking

    PMID:34336716 PMID:37080973

    Open questions at the time
    • whether diverse pathogens engage overlapping or distinct N-domain epitopes unresolved
    • downstream signaling triggered by bacterial vs homophilic binding not compared

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CEACAM1 switches between inhibitory (ITIM/SHP) and activating/pro-survival (Lck, BTK/Syk, PI3K/Akt) outputs in the same cell, and whether the disputed TIM-3 partnership operates physiologically, remain unresolved.
  • no unifying model reconciling inhibitory and activating signaling
  • CEACAM1-TIM-3 interaction unresolved between contradicting studies
  • upstream kinases controlling ITIM phosphorylation in each cell type not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3 GO:0098631 cell adhesion mediator activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 3 GO:0031410 cytoplasmic vesicle 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1430728 Metabolism 2 R-HSA-109582 Hemostasis 1
Partners
ANNEXIN IIINTEGRIN BETA3NKG2DPAXILLINSHCSHP-1SHP-2TIM-3

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 CEACAM1 forms a cis heterodimer with TIM-3 via their membrane-distal IgV-like N-terminal domains, facilitating TIM-3 maturation and cell surface expression; CEACAM1 also binds TIM-3 in trans through the same domains. Both cis and trans interactions are required for TIM-3-mediated T cell inhibition. X-ray crystallography and biochemical/biophysical studies established the structural basis of this interaction. X-ray crystallography, biochemical co-immunoprecipitation, biophysical binding assays, mouse adoptive transfer colitis model, CEACAM1-deficient T cell reconstitution experiments Nature High 25363763
2006 CEACAM1 isoforms containing the long cytoplasmic domain inhibit T cell functions (proliferation, allogeneic reactivity, cytokine production) via immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the cytoplasmic domain and recruitment of the phosphatase SHP-1. Conditional deletion of CEACAM1 in T cells increased TCR-CD3 complex signaling, confirming inhibitory function. CEACAM1 overexpression and conditional T cell-specific deletion in mice, in vitro proliferation and cytokine assays, in vivo delayed-type hypersensitivity and IBD models, ITIM mutant analysis, SHP-1 dependency assays Immunity High 17081782
2001 The cytoplasmic domain tyrosine motif of CEACAM1 (BGPa) functions as an ITIM: substitution of Y459 with phenylalanine abolished inhibitory signaling. CEACAM1-mediated inhibition of calcium influx required both SHP-1 and SHP-2, shown using SHP-1/SHP-2-deficient DT40 B cells and a FcγRIIB-BGPa chimeric receptor. FcγRIIB-BGPa chimeric receptor expression in DT40 B cells, tyrosine-to-phenylalanine mutagenesis, calcium influx assay, SHP-1/SHP-2 mutant cell lines Journal of leukocyte biology High 11493628
2008 Bacterial engagement of CEACAM1 by M. catarrhalis UspA1 or N. meningitidis Opa proteins triggers ITIM tyrosine phosphorylation and SHP-1 recruitment, which negatively regulates TLR2-dependent PI3K-Akt activation and NF-κB-dependent inflammatory responses in primary pulmonary epithelial cells. Infection of primary pulmonary epithelial cells with bacterial pathogens, phosphorylation assays, SHP-1 recruitment assays, PI3K/Akt and NF-κB pathway readouts Nature immunology High 18836450
2009 Trans-homophilic CEACAM1 binding induces cis-dimerization of CEACAM1-L via an allosteric mechanism transmitted through the N-terminal Ig domain. The monomer/dimer equilibrium of CEACAM1-L determines the balance of SHP-2 versus c-Src binding; CEACAM1-S coexpression reduces CEACAM1-L homodimerization. SHP-1 does not bind under physiological conditions. CFP/YFP-tagged CEACAM1 isoform expression, FRET, cross-linking, co-clustering, co-immunoprecipitation, phosphotyrosine-induced recruitment assays in epithelial cell monolayers The Journal of cell biology High 19948503
2013 CEACAM1 on IL-2-activated NK cells inhibits NKG2D-mediated cytolysis through trans-homophilic CEACAM1 interactions with tumor cells. Co-engagement of NKG2D and CEACAM1 leads to biochemical association between these receptors, recruitment of SHP-1, dephosphorylation of the guanine nucleotide exchange factor Vav1, and blockade of downstream cytolytic signaling. NK cell activation assays, cytolysis assays, co-immunoprecipitation of NKG2D and CEACAM1, SHP-1 recruitment assays, Vav1 phosphorylation western blotting European journal of immunology High 23696226
2011 Tumor cell-associated CEACAM1 causes intracellular retention of NKG2D ligands (MICA, ULBP2 and others) in mouse and human tumor cells, reducing their cell surface expression and decreasing NK cell-mediated cytolysis. CEACAM1 silencing restored surface NKG2D ligand levels and increased NK-mediated rejection in vitro and in vivo. CEACAM1 silencing in tumor cells, flow cytometry for NKG2D ligand surface expression, NK cell cytolysis assays in vitro, tumor rejection assays in vivo The Journal of experimental medicine High 22143889
2002 CEACAM1 is a substrate of the insulin receptor in liver; CEACAM1 phosphorylation promotes receptor-mediated insulin endocytosis and degradation to regulate insulin clearance. A phosphorylation-defective S503A CEACAM1 mutant expressed as a dominant negative in liver (L-SACC1 transgenic mice) impaired insulin clearance and caused insulin resistance. Transgenic mouse model (L-SACC1) expressing dominant-negative S503A CEACAM1 mutant, insulin clearance assays, metabolic phenotyping Trends in endocrinology and metabolism Medium 12128284
2004 CEACAM1 is a substrate of the EGF receptor (EGFR). Upon EGFR-mediated phosphorylation, CEACAM1 binds and sequesters Shc, uncoupling EGFR signaling from the Ras/MAPK pathway and reducing EGF-dependent cell proliferation. Transfected COS-7 and MCF-7 cells, EGF stimulation assays, co-immunoprecipitation of CEACAM1 with Shc, L-SACC1 transgenic mouse model, EGFR signaling pathway analysis The Journal of clinical investigation High 15467833
2000 CEACAM1 cell surface expression on primary endothelial cells is transcriptionally induced by Neisseria gonorrhoeae infection via NF-κB (p50/p65 heterodimer) activation. LPS from bacteria triggers TLR4-dependent NF-κB activation, upregulating CEACAM1 splice variants (CEACAM1-3L and CEACAM1-4L), which in turn increases Opa52-dependent neisserial binding. Gonococcal infection of HUVECs, NF-κB activation and nuclear translocation assays, NF-κB inhibitor experiments, RT-PCR for CEACAM1 splice variant expression, bacterial binding assays The Journal of biological chemistry Medium 11306560
2008 CEACAM1 is expressed on platelet surfaces and in intracellular pools, and negatively regulates platelet signaling through the GPVI/FcR-γ-chain collagen receptor. CEACAM1-null platelets show enhanced collagen-induced aggregation, adhesion, and granule secretion. CEACAM1's inhibitory function depends on its ITIM motifs that recruit SHP-1. Ceacam1-/- mouse platelets, platelet aggregation assays, collagen adhesion assays, granule secretion assays, intravital microscopy of mesenteric arterioles, pulmonary thromboembolism model, GPVI depletion experiments Blood High 19008452
2006 CEACAM1-long isoform engagement activates a PI3K-dependent Akt pathway in human monocytes, upregulating Bcl-2 and preventing caspase-3 activation. This confers survival signals to primary monocytes, distinct from ERK pathway signaling. PI3K inhibitor LY294002 blocked CEACAM1-dependent survival. CEACAM1-specific antibody and soluble CEACAM1 treatment of peripheral blood mononuclear cells/monocytes, apoptosis assays (annexin V, caspase-3), PI3K inhibitor experiments, Bcl-2 western blotting, ERK and Akt phosphorylation assays The Journal of biological chemistry Medium 17071610
2005 CEACAM1 engagement on granulocytes delays spontaneous and Fas ligand-induced apoptosis. This anti-apoptotic effect requires CEACAM1-L tyrosine phosphorylation, SHP-1 association, and involves ERK1/2 and caspase-3 activation pathways. CEACAM1-specific antibody, Fab fragments, and soluble CEACAM1-Fc treatment of rat granulocytes; DNA fragmentation assays, annexin V staining, SHP-1 co-immunoprecipitation, ERK1/2 and caspase-3 activation assays European journal of immunology Medium 15909305
2003 CEACAM1-4S (short cytoplasmic isoform) directly associates with annexin II via its cytoplasmic domain (KD ~30 nM), confirmed by GST pull-down, reciprocal co-immunoprecipitation, surface plasmon resonance with oriented peptides, and co-localization in mammary epithelial cells in Matrigel. CEACAM1 also co-localizes with annexin II/p11 at plasma membrane and in secretory vesicles. GST pull-down assay, reciprocal co-immunoprecipitation, surface plasmon resonance with oriented CEACAM1-4S cytoplasmic domain peptides, confocal laser microscopy in 3D Matrigel culture The Journal of biological chemistry High 14522961
2003 CEACAM1-4S expression in MCF7 mammary carcinoma cells restores lumen formation in 3D Matrigel culture via apoptosis of central cells. Apoptosis involves Bax translocation to mitochondria and cytochrome c release into cytoplasm (intrinsic pathway), and is partially inhibited by caspase inhibitors. CEACAM1-4S localizes initially between cells and later exclusively apically in mature acini. 3D Matrigel culture of MCF7 cells stably transfected with CEACAM1-4S, apoptosis assays (nuclear condensation, membrane blebbing, caspase activation, DNA laddering), Bax translocation and cytochrome c release assays, caspase inhibitor treatment, immunofluorescence localization Proceedings of the National Academy of Sciences of the United States of America High 12522268
2002 Homotypic CD66a (CEACAM1) interactions between melanoma cells and NK cells inhibit NK cell cytotoxicity via a class I MHC-independent mechanism. 721.221 cells expressing CD66a were protected from lysis by YTS cells and NK cells expressing CD66a; the inhibitory effect correlated with CD66a expression levels. NK cell cytotoxicity assays, redirected lysis experiments, transfection of 721.221 cells with CD66a, expression level correlation analysis Journal of immunology Medium 11884449
2004 CEACAM1 enhances melanoma cell invasion and migration, dependent on Tyr-488 within the full-length cytoplasmic CEACAM1 domain. CEACAM1 co-localizes and interacts with integrin β3 via the cytoplasmic domain. RGD peptides blocking integrin αvβ3 abolished CEACAM1-enhanced invasion, and integrin β3 expression induces CEACAM1 upregulation. Stable CEACAM1 transfection of melanocytic/melanoma cells, in vitro invasion and migration assays (Matrigel), anti-CEACAM1 antibody inhibition, RGD peptide blocking, Tyr-488 mutant analysis, co-immunoprecipitation of CEACAM1 with integrin β3 The American journal of pathology Medium 15509546
1999 CD66a (CEACAM1) and CD66b are the major galectin-3 receptors on human neutrophils, stored in intracellular gelatinase and specific granules. Galectin-3-Sepharose affinity chromatography from neutrophil granules isolated CD66a (160 kDa) and CD66b (100 kDa) as the primary binding proteins. Galectin-3-Sepharose affinity chromatography from neutrophil granule preparations, SDS-PAGE, immunoblotting, HL-60 cell differentiation model, subcellular fractionation Journal of immunology Medium 10553088
2000 CEACAM1 cytoplasmic domain associates with paxillin in a tyrosine phosphorylation-dependent manner (requiring Tyr-488). CEACAM1-paxillin complexes co-immunoprecipitated from granulocytes, HT29 colon cells, and HUVECs, with co-localization at the plasma membrane, linking CEACAM1 to the actin cytoskeleton. Phosphorylated cytoplasmic domain pull-down from granulocyte extracts, co-immunoprecipitation from multiple cell types, confocal microscopy co-localization, Tyr-488 mutant analysis Experimental cell research Medium 11035932
2018 CEACAM1 is induced by HCMV and influenza virus via their respective innate DNA/RNA sensors (IFI16 and RIG-I), mediated by IRF3 binding to an ISRE element in the human CEACAM1 promoter. Upon induction, CEACAM1 suppresses viral replication through an SHP-2-dependent process that inhibits mTOR-mediated protein biosynthesis. Virus infection assays (HCMV, influenza), innate sensor knockdown, IRF3 chromatin immunoprecipitation at CEACAM1 ISRE, SHP-2-dependent assays, mTOR activity assays, ex vivo human decidua organ culture Cell reports Medium 27264178
2018 CEACAM1 or CEACAM5 expression in AZ-521 cells is necessary and sufficient to restore H. pylori type IV secretion system (T4SS)-dependent CagA translocation and phosphorylation. This defines an integrin-β1- and CEACAM1- or CEACAM5-dependent T4SS delivery pathway for CagA, independent of VacA. Transfection of CEACAM1 or CEACAM5 into AZ-521 cells, H. pylori infection, CagA translocation and phosphorylation assays, vinculin and cortactin dephosphorylation as functional readouts Cellular microbiology Medium 30321907
2008 CEA induces CEACAM1-mediated apoptosis in HT29 colon cancer cells dependent on CEACAM1 cell surface abundance. Apoptosis triggers dual cleavage of CEACAM1-4L (at intracellular and extracellular sites) and activates caspases including caspase-1 and -3, as well as non-caspase proteases. CEA treatment of HT29/Jurkat/HEK293 cells, caspase activity assays, CEACAM1 cleavage detection, cell death assays Oncogene Medium 18278069
2015 CEACAM1 intrinsic signaling promotes B cell survival via the BTK/Syk/NF-κB axis. CEACAM1 deficiency in Ceacam1-/- mice limits survival of proliferating B cells and prevents generation of protective antiviral neutralizing antibody responses during VSV infection. Ceacam1-/- mice, VSV infection model, B cell survival assays, BTK/Syk/NF-κB pathway analysis, antibody neutralization assays Nature communications High 25692415
2018 CEACAM1 is essential for recruiting lymphocyte-specific protein kinase (Lck) into the T cell receptor complex to form an efficient immunological synapse. Absence of CEACAM1 on virus-specific CD8+ T cells limits antiviral CD8+ T cell responses; anti-CEACAM1 antibody stabilizes Lck in the immunological synapse and prevents CD8+ T cell exhaustion in LCMV infection. LCMV infection of Ceacam1-/- mice, immunological synapse analysis, Lck recruitment assays, anti-CEACAM1 antibody treatment, CD8+ T cell proliferation and exhaustion assays in mouse and human cells Nature communications High 29967450
2010 CEACAM1 is tyrosine-phosphorylated in endothelial cells upon VEGF treatment in a SHP-1- and Src-dependent manner. The long cytoplasmic domain of CEACAM1 is required for this phosphorylation and for VEGF-dependent nitric oxide (NO) production. CEACAM1 deficiency causes increased basal Akt and eNOS activation and defective VEGF-mediated vascular permeability. Ceacam1-/- mice, primary murine lung endothelial cells, VEGF stimulation, CEACAM1 phosphorylation assays, SHP-1/Src inhibitor experiments, eNOS/Akt phosphorylation assays, in vivo vascular permeability assays Journal of cell science Medium 21081647
2002 CEACAM1 clustering in PC12 cells induces rapid transient CEACAM1 tyrosine dephosphorylation, reduced SHP-2 association, binding to the actin cytoskeleton, and activation of ERK1/2 (but not JNK or p38) MAPK signaling downstream. Antibody-induced CEACAM1 clustering on PC12 cell surface, tyrosine phosphorylation assays, SHP-2 co-immunoprecipitation, detergent fractionation for cytoskeletal association, ERK1/2/JNK/p38 activation assays Biological chemistry Medium 12108545
2023 HIF-1α directly binds the polypyrimidine tract binding protein 1 (Ptbp1) promoter to transcriptionally regulate Ptbp1, which promotes alternative splicing of Ceacam1 toward the short cytoplasmic isoform (Ceacam1-S) during hypoxia/IRI. Ceacam1-S protects hepatocytes by repressing the ASK1/p-p38 cell death pathway. Established by ChIP and luciferase assays. Chromatin immunoprecipitation (ChIP) of HIF-1α at Ptbp1 promoter, luciferase reporter assays, adenoviral Ceacam1-S transfection into Ceacam1-deficient hepatocytes, morpholino-mediated isoform switching, warm IRI mouse model, human liver biopsy correlations Science translational medicine High 37531413
2023 Neutrophil CEACAM1-long (CC1-L) isoform determines susceptibility to NET formation by regulating the S1P-S1PR2/S1PR3 signaling axis and autophagy signaling. Ablation of CC1-L in recipient neutrophils aggravated hepatic ischemia-reperfusion injury in mouse OLT by promoting NETosis. Mouse OLT model with isoform-specific CC1-L ablation, S1PR2/S1PR3 pathway analysis, autophagy signaling assays, NET formation assays, human OLT patient cohort analysis The Journal of clinical investigation Medium 36719377
2021 F. nucleatum CbpF (trimeric autotransporter adhesin) binds and activates CEACAM1 to inhibit CD4+ T cell function. Other fusobacterial trimeric autotransporter adhesins (fvcB, fvcC, fvcD) are not involved. Anti-CEACAM1 antibodies directed against the N-terminal domain block CbpF-CEACAM1 interaction. F. nucleatum deletion mutants lacking fvcA (CbpF)/fvcB/fvcC/fvcD, CEACAM1 binding assays, T cell functional inhibition assays, antibody blocking experiments Frontiers in cellular and infection microbiology Medium 34336716
2023 S. pyogenes R28 protein specifically targets human CEACAM1 via an IgI3-like fold domain that binds the N-terminal domain of CEACAM1. This interaction mediates bacterial adhesion to cervical cells, suppresses epithelial wound repair, and subverts innate immune responses. High-resolution structural analysis established the binding interface. High-resolution structural analysis of R28-CEACAM1 N-terminal domain interaction, bacterial adhesion assays to cervical cells, epithelial wound repair assays, innate immune response functional assays Nature communications High 37080973
2020 In liver transplantation (OLT), CEACAM1 deficiency in donor liver augments ischemia-reperfusion injury by enhancing ROS expression and HMGB1 translocation during cold storage via ASK1/p-p38 pathway upregulation. Adjunctive ASK1 inhibition alleviates IRI in CC1-KO livers by suppressing p-p38, ROS, and HMGB1. CC1-KO→WT mouse OLT model, ASK1/p38 pathway analysis, ROS and HMGB1 measurement, bone marrow-derived macrophage activation assays from hepatic flush, ASK1 siRNA in hepatocyte cultures, human donor liver biopsy correlations The Journal of clinical investigation Medium 32027621
2015 Forced liver-specific CEACAM1 overexpression in mice prevents diet-induced hyperinsulinemia and insulin resistance by protecting hepatic insulin clearance. This is partly mediated by increased hepatic β-fatty acid oxidation and energy expenditure. Liver-specific inducible CEACAM1 transgenic mice on high-fat diet, insulin clearance assays, metabolic phenotyping, β-fatty acid oxidation measurements Diabetes Medium 25972571
2014 CEACAM1-Long (but not CEACAM1-Short or truncation mutants) intracellularly promotes Sox-2 expression in melanoma cells to enhance cell proliferation. This effect is not blocked by anti-CEACAM1 antibodies, indicating it is not mediated by homophilic intercellular interactions but by intracellular CEACAM1-L signaling. CEACAM1 knockdown and selective isoform/truncation mutant overexpression in melanoma cells, Sox-2 expression analysis, proliferation assays in vitro and xenograft in vivo, anti-CEACAM1 antibody blocking experiments, CEACAM1 promoter SNP analysis Neoplasia Medium 24931667
2020 TIM-3 and CEACAM1 do not interact in cis or in trans, as shown by extensive binding studies and a T cell reporter platform. CEACAM1-mediated inhibition is confirmed but functions independently of TIM-3; TIM-3 cytoplasmic sequences can independently promote inhibitory signaling. T cell reporter platform, extensive cell-based and soluble protein binding assays for TIM-3/CEACAM1 interaction, flow cytometric co-expression analysis European journal of immunology Medium 32222966
2004 CEACAM1-4S directly associates with and downregulates β1-integrin expression in mammary epithelial cells during 3D morphogenesis. Immuno-electron microscopy reveals CEACAM1-coated vesicles within lumena, and CEACAM1 is detected in breast milk lipid fractions. 3D Matrigel culture, co-immunoprecipitation of CEACAM1 with β1-integrin, immuno-electron microscopy, breast milk lipid fractionation, immunohistochemistry Journal of molecular histology Medium 15339048

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature 586 25363763
2006 CEACAM1: contact-dependent control of immunity. Nature reviews. Immunology 432 16724098
2003 CEACAM1-4S, a cell-cell adhesion molecule, mediates apoptosis and reverts mammary carcinoma cells to a normal morphogenic phenotype in a 3D culture. Proceedings of the National Academy of Sciences of the United States of America 149 12522268
2002 CD66a interactions between human melanoma and NK cells: a novel class I MHC-independent inhibitory mechanism of cytotoxicity. Journal of immunology (Baltimore, Md. : 1950) 145 11884449
2019 Fusobacterium nucleatum supresses anti-tumor immunity by activating CEACAM1. Oncoimmunology 140 31069151
1998 Biliary glycoprotein (CD66a), a cell adhesion molecule of the immunoglobulin superfamily, on human lymphocytes: structure, expression and involvement in T cell activation. European journal of immunology 123 9842909
1996 CD66a, CD66b, CD66c, and CD66d each independently stimulate neutrophils. Journal of leukocyte biology 120 8699114
2006 SHP1 phosphatase-dependent T cell inhibition by CEACAM1 adhesion molecule isoforms. Immunity 117 17081782
2017 CEACAM1 as a multi-purpose target for cancer immunotherapy. Oncoimmunology 108 28811966
2002 Regulation of insulin action by CEACAM1. Trends in endocrinology and metabolism: TEM 106 12128284
2004 CEACAM1 enhances invasion and migration of melanocytic and melanoma cells. The American journal of pathology 104 15509546
2008 CEACAM1 inhibits Toll-like receptor 2-triggered antibacterial responses of human pulmonary epithelial cells. Nature immunology 102 18836450
2019 CEACAM1 structure and function in immunity and its therapeutic implications. Seminars in immunology 98 31604530
1999 Identification of CD66a and CD66b as the major galectin-3 receptor candidates in human neutrophils. Journal of immunology (Baltimore, Md. : 1950) 92 10553088
1997 Differential expression of CD66a (BGP), a cell adhesion molecule of the carcinoembryonic antigen family, in benign, premalignant, and malignant lesions of the human mammary gland. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 92 9212821
1997 Expression of CD66a (human C-CAM) and other members of the carcinoembryonic antigen gene family of adhesion molecules in human colorectal adenomas. Cancer research 81 9192807
1999 Regulation of human intestinal intraepithelial lymphocyte cytolytic function by biliary glycoprotein (CD66a). Journal of immunology (Baltimore, Md. : 1950) 79 10415036
1998 Dysregulated expression of CD66a (BGP, C-CAM), an adhesion molecule of the CEA family, in endometrial cancer. The American journal of pathology 78 9626043
2005 CEACAM1 (CD66a) mediates delay of spontaneous and Fas ligand-induced apoptosis in granulocytes. European journal of immunology 75 15909305
1999 Tumor-suppressive activity of CD66a in prostate cancer. Cancer gene therapy 74 10419049
2016 Co-expression of TIM-3 and CEACAM1 promotes T cell exhaustion in colorectal cancer patients. International immunopharmacology 68 28038383
2001 Pathogenic Neisseria trigger expression of their carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1; previously CD66a) receptor on primary endothelial cells by activating the immediate early response transcription factor, nuclear factor-kappaB. The Journal of biological chemistry 66 11306560
2001 Biliary glycoprotein (BGPa, CD66a, CEACAM1) mediates inhibitory signals. Journal of leukocyte biology 66 11493628
2008 CEACAM1 negatively regulates platelet-collagen interactions and thrombus growth in vitro and in vivo. Blood 65 19008452
2005 Neisseria gonorrhoeae kills carcinoembryonic antigen-related cellular adhesion molecule 1 (CD66a)-expressing human B cells and inhibits antibody production. Infection and immunity 65 15972507
2011 CEACAM1 dampens antitumor immunity by down-regulating NKG2D ligand expression on tumor cells. The Journal of experimental medicine 61 22143889
2009 Homophilic adhesion and CEACAM1-S regulate dimerization of CEACAM1-L and recruitment of SHP-2 and c-Src. The Journal of cell biology 59 19948503
1998 Expression of biliary glycoprotein (CD66a) in normal and malignant breast epithelial cells. Anticancer research 58 9858884
2004 CEACAM1 modulates epidermal growth factor receptor--mediated cell proliferation. The Journal of clinical investigation 57 15467833
2003 CEACAM1 is a potent regulator of B cell receptor complex-induced activation. Journal of leukocyte biology 56 12832451
2010 Systemic dysregulation of CEACAM1 in melanoma patients. Cancer immunology, immunotherapy : CII 54 19633846
2021 Fusobacterium nucleatum CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activation. Frontiers in cellular and infection microbiology 53 34336716
2020 Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury. The Journal of clinical investigation 53 32027621
2009 CEACAM1+ myeloid cells control angiogenesis in inflammation. Blood 53 19273835
2006 CEACAM1 (CD66a) promotes human monocyte survival via a phosphatidylinositol 3-kinase- and AKT-dependent pathway. The Journal of biological chemistry 53 17071610
2015 Forced Hepatic Overexpression of CEACAM1 Curtails Diet-Induced Insulin Resistance. Diabetes 52 25972571
1990 Properties of BGP1, a poly(dG)-binding protein from chicken erythrocytes. Nucleic acids research 52 2402439
2018 CEACAM1 in Liver Injury, Metabolic and Immune Regulation. International journal of molecular sciences 50 30314283
2010 CEACAM1: a key regulator of vascular permeability. Journal of cell science 49 21081647
2003 CEACAM1, a cell-cell adhesion molecule, directly associates with annexin II in a three-dimensional model of mammary morphogenesis. The Journal of biological chemistry 49 14522961
2013 CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function and signaling. European journal of immunology 48 23696226
2011 The CEACAM1 expression is decreased in the liver of severely obese patients with or without diabetes. Diagnostic pathology 47 21569294
2023 Neutrophil CEACAM1 determines susceptibility to NETosis by regulating the S1PR2/S1PR3 axis in liver transplantation. The Journal of clinical investigation 46 36719377
2018 CEACAM1 promotes CD8+ T cell responses and improves control of a chronic viral infection. Nature communications 46 29967450
2000 The adhesion molecule CEACAM1 (CD66a, C-CAM, BGP) is specifically expressed by the extravillous intermediate trophoblast. The American journal of pathology 46 10751340
2000 Locally inducible CD66a (CEACAM1) as an amplifier of the human intestinal T cell response. European journal of immunology 45 11009093
2015 CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production. Nature communications 44 25692415
2006 Role of CEACAM1 as a regulator of T cells. Annals of the New York Academy of Sciences 44 17057197
2004 The tumour suppressor gene CEACAM1 is completely but reversibly downregulated in renal cell carcinoma. The Journal of pathology 43 15476270
1995 Increased synovial expression of the adhesion molecules CD66a, CD66b, and CD31 in rheumatoid and osteoarthritis. Clinical immunology and immunopathology 39 7614736
2021 T cell-mediated elimination of cancer cells by blocking CEACAM6-CEACAM1 interaction. Oncoimmunology 36 35141051
2013 CEACAM1 loss links inflammation to insulin resistance in obesity and non-alcoholic steatohepatitis (NASH). Seminars in immunopathology 36 24258517
2012 The expression and modulation of CEACAM1 and tumor cell transformation. Annali dell'Istituto superiore di sanita 36 22751559
2001 Differences in tissue-specific and embryonic expression of mouse Ceacam1 and Ceacam2 genes. The Biochemical journal 36 11284729
2019 Size Matters: The Functional Role of the CEACAM1 Isoform Signature and Its Impact for NK Cell-Mediated Killing in Melanoma. Cancers 35 30871206
2018 Expression of CEACAM1 or CEACAM5 in AZ-521 cells restores the type IV secretion deficiency for translocation of CagA by Helicobacter pylori. Cellular microbiology 35 30321907
2010 Generation of human CEACAM1 transgenic mice and binding of Neisseria Opa protein to their neutrophils. PloS one 35 20404914
2008 The CEACAM1-mediated apoptosis pathway is activated by CEA and triggers dual cleavage of CEACAM1. Oncogene 34 18278069
1998 Purified, soluble recombinant mouse hepatitis virus receptor, Bgp1(b), and Bgp2 murine coronavirus receptors differ in mouse hepatitis virus binding and neutralizing activities. Journal of virology 34 9696818
2014 CEACAM1 promotes melanoma cell growth through Sox-2. Neoplasia (New York, N.Y.) 33 24931667
2022 TIM3/CEACAM1 pathway involves in myeloid-derived suppressor cells induced CD8+ T cells exhaustion and bone marrow inflammatory microenvironment in myelodysplastic syndrome. Immunology 32 35470423
2018 On the Dual Role of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 (CEACAM1) in Human Malignancies. Journal of immunology research 32 30406153
2016 The role of CEA-related cell adhesion molecule-1 (CEACAM1) in vascular homeostasis. Histochemistry and cell biology 32 27695943
2006 The expression of CD66a and possible roles in colorectal adenoma and adenocarcinoma. International journal of colorectal disease 32 17143599
2018 Endothelial barrier function is differentially regulated by CEACAM1-mediated signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 31 29746166
1997 Dysregulation of carcinoembryonic antigen group members CGM2, CD66a (biliary glycoprotein), and nonspecific cross-reacting antigen in colorectal carcinomas. Comparative analysis by northern blot and in situ hybridization. The American journal of pathology 31 9250164
2008 CEACAM1 and the regulation of mucosal inflammation. Mucosal immunology 30 19079227
2016 SOX9 indirectly regulates CEACAM1 expression and immune resistance in melanoma cells. Oncotarget 29 26885752
2015 Roles of CEACAM1 in cell communication and signaling of lung cancer and other diseases. Cancer metastasis reviews 29 26081722
2000 Cell adhesion molecule CEACAM1 associates with paxillin in granulocytes and epithelial and endothelial cells. Experimental cell research 28 11035932
2020 TIM-3 and CEACAM1 do not interact in cis and in trans. European journal of immunology 27 32222966
2015 CEACAM1-3S Drives Melanoma Cells into NK Cell-Mediated Cytolysis and Enhances Patient Survival. Cancer research 26 25744717
2022 A Selective β-Catenin-Metadherin/CEACAM1-CCL3 Axis Mediates Metastatic Heterogeneity upon Tumor-Macrophage Interaction. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 25 35403834
2023 Alternative splicing of CEACAM1 by hypoxia-inducible factor-1α enhances tolerance to hepatic ischemia in mice and humans. Science translational medicine 24 37531413
2018 CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells. Scientific reports 24 30089785
2014 Expression of carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1) and its correlation with angiogenesis in gastric cancer. Pathology, research and practice 22 24846314
2018 Characterizing the Tumor Suppressor Role of CEACAM1 in Multiple Myeloma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 21 29486474
2015 Down-regulation of CEACAM1 in breast cancer. Acta biochimica et biophysica Sinica 21 26341981
2012 CEACAM1 in malignant melanoma: a diagnostic and therapeutic target. Current topics in medicinal chemistry 21 22196267
1995 CD49f (alpha 6 integrin) and CD66a (BGP) are specifically induced by retinoids during human monocytic differentiation. Leukemia 21 8609714
2016 CEACAM1-Mediated Inhibition of Virus Production. Cell reports 20 27264178
2010 Regulation of CEACAM1 transcription in human breast epithelial cells. BMC molecular biology 20 21050451
2004 Cell-cell adhesion molecule CEACAM1 is expressed in normal breast and milk and associates with beta1 integrin in a 3D model of morphogenesis. Journal of molecular histology 19 15339048
2015 Hepatic CEACAM1 Over-Expression Protects Against Diet-Induced Fibrosis and Inflammation in White Adipose Tissue. Frontiers in endocrinology 18 26284027
2010 Genetic alterations and expression pattern of CEACAM1 in colorectal adenomas and cancers. Pathology oncology research : POR 18 20524097
2004 Establishment and phenotypic characterization of human U937 cells with inducible P210 BCR/ABL expression reveals upregulation of CEACAM1 (CD66a). Leukemia 17 14712293
2023 Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis. Nature communications 16 37080973
2017 CEACAM1 is associated with recurrence after hepatectomy for colorectal liver metastasis. The Journal of surgical research 16 29180203
2009 Expression of newly identified secretory CEACAM1(a) isoforms in the intestinal epithelium. Biochemical and biophysical research communications 16 19358828
2002 Secreted CEACAM1 splice variants in rat cell lines and in vivo in rat serum. Biochemical and biophysical research communications 16 11922629
2023 T Cell CEACAM1-TIM-3 Crosstalk Alleviates Liver Transplant Injury in Mice and Humans. Gastroenterology 15 37479191
2018 Assessing the Impact of Targeting CEACAM1 in Head and Neck Squamous Cell Carcinoma. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 15 29436278
2016 CEACAM1 is overexpressed in oral tumors and related to tumorigenesis. Medical molecular morphology 15 27464654
2013 Role of CEACAM1 and CEACAM20 in an in vitro model of prostate morphogenesis. PloS one 15 23358633
2004 Retinoic acid treated HL60 cells express CEACAM1 (CD66a) and phagocytose Neisseria gonorrhoeae. FEMS immunology and medical microbiology 15 15364113
2002 Clustering-induced signaling of CEACAM1 in PC12 cells. Biological chemistry 15 12108545
2020 CEACAM1 regulates CD8+ T cell immunity and protects from severe pathology during Citrobacter rodentium induced colitis. Gut microbes 14 32521208
2017 Inhibition of cell invasion and migration by CEACAM1-4S in breast cancer. Oncology letters 14 29085477
2009 CEACAM1 distribution and it's effects on angiogenesis and lymphangiogenesis in oral carcinoma. Oral oncology 14 19442569
2008 Differential expression of the carcinoembryonic antigen-related cell adhesion molecules panCD66, CD66a, CD66c and of sialyl-Lewis x (CD15s) on blast cells of acute leukemias. International journal of hematology 14 18299959

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