{"gene":"CEACAM20","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":2015,"finding":"CEACAM20 is a substrate of the receptor-type protein tyrosine phosphatase SAP-1 (PTPRH); SAP-1 ablation leads to greatly increased tyrosine phosphorylation of CEACAM20 in intestinal epithelium, and SAP-1 and CEACAM20 form a complex through interaction of their ectodomains.","method":"Phosphotyrosine analysis in SAP-1-deficient mice, co-immunoprecipitation/complex formation assay via ectodomain interaction","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (in vivo phosphorylation in KO model, complex formation, downstream signaling readouts) in a single rigorous study","pmids":["26195794"],"is_preprint":false},{"year":2015,"finding":"Tyrosine phosphorylation of CEACAM20 by c-Src promotes its association with spleen tyrosine kinase (Syk), leading to activation of NF-κB and production of IL-8 in cultured intestinal epithelial cells.","method":"Forced expression of c-Src in cultured cells, co-immunoprecipitation of CEACAM20 with Syk, NF-κB reporter assay, IL-8 ELISA","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 — reciprocal co-IP plus functional cytokine/NF-κB readouts in same study","pmids":["26195794"],"is_preprint":false},{"year":2013,"finding":"CEACAM20 contains an ITAM (immunoreceptor tyrosine-based activation motif) in its cytoplasmic region; c-Src phosphorylates CEACAM20 on Tyr522, Tyr559, and Tyr570 (the latter two within the ITAM), and mutation of Tyr559/Tyr570 to phenylalanine abolishes CEACAM20-mediated phagocytic activity.","method":"Site-directed mutagenesis of ITAM tyrosines, pervanadate treatment and forced c-Src expression, phagocytosis assay with anti-Myc-coated microbeads","journal":"The Kobe journal of medical sciences","confidence":"Medium","confidence_rationale":"Tier 1-2 — mutagenesis plus functional phagocytosis assay, single lab","pmids":["28659570"],"is_preprint":false},{"year":2013,"finding":"CEACAM20-mediated phagocytic activity requires sequential activation of Src family kinases, Syk, PI3K, and PLCγ, as well as actin polymerization, placing CEACAM20 upstream of this signaling cascade.","method":"Pharmacological inhibition of SFKs, Syk, PI3K, PLCγ (kinase inhibitors), and actin polymerization (Cytochalasin D) in phagocytosis assay","journal":"The Kobe journal of medical sciences","confidence":"Medium","confidence_rationale":"Tier 2 — multiple inhibitors with defined functional readout, single lab","pmids":["28659570"],"is_preprint":false},{"year":2013,"finding":"CEACAM20 localizes to the apical/luminal surface of prostate acini and is required for tubule formation in a 3D Matrigel prostate morphogenesis model; antisense oligonucleotide inhibition of CEACAM20 completely inhibited tubule formation and stunted acinar growth.","method":"3D Matrigel organoid culture, confocal microscopy localization, antisense oligonucleotide knockdown with morphogenesis readout","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization plus loss-of-function with defined morphogenetic phenotype, single lab","pmids":["23358633"],"is_preprint":false},{"year":2015,"finding":"CEACAM20 is co-localized with CEACAM1 at the apical surface of intestinal epithelial cells; expression of CEACAM20 (but not CEACAM1) in intestinal organoids is specifically upregulated by butyrate, a short-chain fatty acid produced by gut bacterial fermentation, linking commensal Gram-positive bacteria to CEACAM20 regulation.","method":"Immunofluorescence/confocal microscopy localization, intestinal organoid culture with cytokine/butyrate treatment, RT-PCR and protein expression analysis in germ-free and antibiotic-treated mice","journal":"Genes to cells : devoted to molecular & cellular mechanisms","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization and functional regulation established by multiple experimental conditions, single lab","pmids":["25908210"],"is_preprint":false},{"year":2005,"finding":"CEACAM20 is an evolutionarily conserved member of the CEA family with orthologs in mouse, rat, and human at syntenic genomic locations; gene-specific RT-PCR revealed a very distinct tissue expression pattern, suggesting diversified function within the CEA family.","method":"Genome-wide sequence analysis, RT-PCR across 31 tissues","journal":"Genomics","confidence":"Low","confidence_rationale":"Tier 4 — identification and expression profiling only, no direct mechanistic experiment","pmids":["16139472"],"is_preprint":false}],"current_model":"CEACAM20 is an ITAM-containing transmembrane protein of the CEA family that localizes to the apical/microvillus surface of intestinal epithelial and prostate cells, where it is phosphorylated on cytoplasmic tyrosines (Tyr559/Tyr570 within the ITAM) by c-Src, recruits and activates Syk, and signals through PI3K and PLCγ to promote phagocytosis and NF-κB-driven IL-8 production; its phosphorylation is negatively regulated by the receptor-type phosphatase SAP-1 (PTPRH) via direct ectodomain interaction, and it plays a structural role in prostate lumen/tubule morphogenesis."},"narrative":{"teleology":[{"year":2005,"claim":"Identification of CEACAM20 as an evolutionarily conserved CEA family member with a restricted tissue expression pattern established it as a distinct gene warranting functional investigation.","evidence":"Comparative genomics and RT-PCR across 31 tissues in mouse, rat, and human","pmids":["16139472"],"confidence":"Low","gaps":["No protein-level characterization or mechanistic data","Expression profiling alone does not define function","No loss-of-function or gain-of-function experiments"]},{"year":2013,"claim":"Demonstrating that CEACAM20 contains a functional ITAM phosphorylated by c-Src and that its ITAM tyrosines are essential for phagocytosis via Src→Syk→PI3K→PLCγ signaling defined the core signaling cascade downstream of CEACAM20.","evidence":"Site-directed mutagenesis of ITAM tyrosines, pharmacological kinase/actin inhibitor panel, and phagocytosis assay with anti-Myc-coated microbeads in cultured cells","pmids":["28659570"],"confidence":"Medium","gaps":["Phagocytic function shown only with antibody-coated beads, not physiological ligands","Single laboratory study; independent replication absent","In vivo relevance of CEACAM20-mediated phagocytosis not tested"]},{"year":2013,"claim":"Showing that CEACAM20 localizes to the apical surface of prostate acini and is required for tubule morphogenesis revealed a structural/morphogenetic role beyond innate immune signaling.","evidence":"3D Matrigel organoid culture of prostate epithelial cells, confocal microscopy, antisense oligonucleotide knockdown","pmids":["23358633"],"confidence":"Medium","gaps":["Knockdown achieved by antisense oligonucleotide only; genetic knockout not performed","Mechanism linking CEACAM20 to tubulogenesis (signaling vs. adhesion) unresolved","In vivo prostate phenotype in CEACAM20-deficient animals not examined"]},{"year":2015,"claim":"Identifying SAP-1 (PTPRH) as a phosphatase that dephosphorylates CEACAM20 through ectodomain interaction, and showing that loss of SAP-1 hyperactivates CEACAM20→Syk→NF-κB→IL-8 signaling, established the negative regulatory mechanism controlling CEACAM20 activity in intestinal epithelium.","evidence":"Phosphotyrosine analysis in SAP-1-knockout mouse intestine, co-immunoprecipitation of ectodomain complex, NF-κB reporter assay, IL-8 ELISA in cultured cells","pmids":["26195794"],"confidence":"High","gaps":["Whether SAP-1 directly dephosphorylates CEACAM20 ITAM tyrosines or acts indirectly through Src regulation not fully resolved","Physiological ligand or bacterial trigger for CEACAM20 activation in vivo unknown"]},{"year":2015,"claim":"Showing that butyrate selectively upregulates CEACAM20 in intestinal organoids and that CEACAM20 expression depends on commensal microbiota linked its signaling function to host–microbe communication.","evidence":"Intestinal organoid culture with butyrate/cytokine treatment, germ-free and antibiotic-treated mouse models, RT-PCR and immunofluorescence","pmids":["25908210"],"confidence":"Medium","gaps":["Transcriptional mechanism by which butyrate induces CEACAM20 not identified","Whether butyrate-induced CEACAM20 is functionally active (phosphorylated, signaling) not tested","Contribution to intestinal homeostasis vs. inflammation in vivo unclear"]},{"year":null,"claim":"The physiological ligand(s) that activate CEACAM20 at the epithelial surface, the in vivo consequence of CEACAM20 deletion on intestinal immunity and prostate morphogenesis, and the structural basis for the SAP-1–CEACAM20 ectodomain interaction remain unknown.","evidence":"","pmids":[],"confidence":"High","gaps":["No CEACAM20-knockout mouse phenotype reported","No endogenous activating ligand identified","No structural data for CEACAM20 or the SAP-1–CEACAM20 complex"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[1,2,3]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[4,5]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[1,2,3]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,1,3]}],"complexes":[],"partners":["PTPRH","SYK","SRC"],"other_free_text":[]},"mechanistic_narrative":"CEACAM20 is an ITAM-bearing transmembrane glycoprotein of the CEA family that functions as a signaling receptor at apical epithelial surfaces to drive phagocytosis and pro-inflammatory cytokine production. c-Src phosphorylates its cytoplasmic ITAM tyrosines (Tyr559/Tyr570), enabling recruitment and activation of Syk and downstream signaling through PI3K and PLCγ to promote actin-dependent phagocytosis, as well as NF-κB activation and IL-8 secretion in intestinal epithelial cells [PMID:28659570, PMID:26195794]. CEACAM20 phosphorylation is negatively regulated by the receptor-type phosphatase SAP-1 (PTPRH), which engages CEACAM20 through an ectodomain-mediated complex [PMID:26195794]. In prostate epithelium, CEACAM20 localizes to the apical/luminal surface and is required for tubule morphogenesis in 3D organoid models, and its intestinal expression is selectively upregulated by the microbial metabolite butyrate [PMID:23358633, PMID:25908210]."},"prefetch_data":{"uniprot":{"accession":"Q6UY09","full_name":"Cell adhesion molecule CEACAM20","aliases":["Carcinoembryonic antigen-related cell adhesion molecule 20","CEA cell adhesion molecule 20"],"length_aa":596,"mass_kda":65.8,"function":"Together with the tyrosine-protein kinase SYK, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response","subcellular_location":"Cell projection, microvillus membrane; Apical cell membrane","url":"https://www.uniprot.org/uniprotkb/Q6UY09/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CEACAM20","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":74,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CEACAM20","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"intestine","ntpm":35.6}],"url":"https://www.proteinatlas.org/search/CEACAM20"},"hgnc":{"alias_symbol":["UNQ9366"],"prev_symbol":[]},"alphafold":{"accession":"Q6UY09","domains":[{"cath_id":"2.60.40.10","chopping":"72-158","consensus_level":"high","plddt":94.0444,"start":72,"end":158},{"cath_id":"2.60.40.10","chopping":"165-251","consensus_level":"high","plddt":92.6617,"start":165,"end":251},{"cath_id":"2.60.40.10","chopping":"258-341","consensus_level":"high","plddt":95.0535,"start":258,"end":341},{"cath_id":"2.60.40.10","chopping":"346-437","consensus_level":"high","plddt":90.1355,"start":346,"end":437}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6UY09","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6UY09-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6UY09-F1-predicted_aligned_error_v6.png","plddt_mean":74.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CEACAM20","jax_strain_url":"https://www.jax.org/strain/search?query=CEACAM20"},"sequence":{"accession":"Q6UY09","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6UY09.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6UY09/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6UY09"}},"corpus_meta":[{"pmid":"16139472","id":"PMC_16139472","title":"Identification of a novel group of evolutionarily conserved members within the rapidly diverging murine Cea family.","date":"2005","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/16139472","citation_count":81,"is_preprint":false},{"pmid":"32488569","id":"PMC_32488569","title":"The old CEACAMs find their new role in tumor immunotherapy.","date":"2020","source":"Investigational new drugs","url":"https://pubmed.ncbi.nlm.nih.gov/32488569","citation_count":37,"is_preprint":false},{"pmid":"26195794","id":"PMC_26195794","title":"Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epithelium.","date":"2015","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/26195794","citation_count":28,"is_preprint":false},{"pmid":"33037855","id":"PMC_33037855","title":"Characterization of hepatitis B virus DNA integration patterns in intrahepatic cholangiocarcinoma.","date":"2020","source":"Hepatology research : the official journal of the Japan Society of Hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/33037855","citation_count":17,"is_preprint":false},{"pmid":"25908210","id":"PMC_25908210","title":"Regulation by gut commensal bacteria of carcinoembryonic antigen-related cell adhesion molecule expression in the intestinal epithelium.","date":"2015","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/25908210","citation_count":16,"is_preprint":false},{"pmid":"23358633","id":"PMC_23358633","title":"Role of CEACAM1 and CEACAM20 in an in vitro model of prostate morphogenesis.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23358633","citation_count":15,"is_preprint":false},{"pmid":"28659570","id":"PMC_28659570","title":"Tyrosine Phosphorylation of Carcinoembryonic Antigen-related Cell Adhesion Molecule 20 and Its Functional Role.","date":"2013","source":"The Kobe journal of medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/28659570","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4860,"output_tokens":1780,"usd":0.02064},"stage2":{"model":"claude-opus-4-6","input_tokens":5057,"output_tokens":1801,"usd":0.105465},"total_usd":0.126105,"stage1_batch_id":"msgbatch_011kfMfE81o6CTcyhVUqumuW","stage2_batch_id":"msgbatch_01DTputS6WNkH745x1nVSoBo","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"CEACAM20 is a substrate of the receptor-type protein tyrosine phosphatase SAP-1 (PTPRH); SAP-1 ablation leads to greatly increased tyrosine phosphorylation of CEACAM20 in intestinal epithelium, and SAP-1 and CEACAM20 form a complex through interaction of their ectodomains.\",\n      \"method\": \"Phosphotyrosine analysis in SAP-1-deficient mice, co-immunoprecipitation/complex formation assay via ectodomain interaction\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (in vivo phosphorylation in KO model, complex formation, downstream signaling readouts) in a single rigorous study\",\n      \"pmids\": [\"26195794\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Tyrosine phosphorylation of CEACAM20 by c-Src promotes its association with spleen tyrosine kinase (Syk), leading to activation of NF-κB and production of IL-8 in cultured intestinal epithelial cells.\",\n      \"method\": \"Forced expression of c-Src in cultured cells, co-immunoprecipitation of CEACAM20 with Syk, NF-κB reporter assay, IL-8 ELISA\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal co-IP plus functional cytokine/NF-κB readouts in same study\",\n      \"pmids\": [\"26195794\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CEACAM20 contains an ITAM (immunoreceptor tyrosine-based activation motif) in its cytoplasmic region; c-Src phosphorylates CEACAM20 on Tyr522, Tyr559, and Tyr570 (the latter two within the ITAM), and mutation of Tyr559/Tyr570 to phenylalanine abolishes CEACAM20-mediated phagocytic activity.\",\n      \"method\": \"Site-directed mutagenesis of ITAM tyrosines, pervanadate treatment and forced c-Src expression, phagocytosis assay with anti-Myc-coated microbeads\",\n      \"journal\": \"The Kobe journal of medical sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 — mutagenesis plus functional phagocytosis assay, single lab\",\n      \"pmids\": [\"28659570\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CEACAM20-mediated phagocytic activity requires sequential activation of Src family kinases, Syk, PI3K, and PLCγ, as well as actin polymerization, placing CEACAM20 upstream of this signaling cascade.\",\n      \"method\": \"Pharmacological inhibition of SFKs, Syk, PI3K, PLCγ (kinase inhibitors), and actin polymerization (Cytochalasin D) in phagocytosis assay\",\n      \"journal\": \"The Kobe journal of medical sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple inhibitors with defined functional readout, single lab\",\n      \"pmids\": [\"28659570\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CEACAM20 localizes to the apical/luminal surface of prostate acini and is required for tubule formation in a 3D Matrigel prostate morphogenesis model; antisense oligonucleotide inhibition of CEACAM20 completely inhibited tubule formation and stunted acinar growth.\",\n      \"method\": \"3D Matrigel organoid culture, confocal microscopy localization, antisense oligonucleotide knockdown with morphogenesis readout\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization plus loss-of-function with defined morphogenetic phenotype, single lab\",\n      \"pmids\": [\"23358633\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"CEACAM20 is co-localized with CEACAM1 at the apical surface of intestinal epithelial cells; expression of CEACAM20 (but not CEACAM1) in intestinal organoids is specifically upregulated by butyrate, a short-chain fatty acid produced by gut bacterial fermentation, linking commensal Gram-positive bacteria to CEACAM20 regulation.\",\n      \"method\": \"Immunofluorescence/confocal microscopy localization, intestinal organoid culture with cytokine/butyrate treatment, RT-PCR and protein expression analysis in germ-free and antibiotic-treated mice\",\n      \"journal\": \"Genes to cells : devoted to molecular & cellular mechanisms\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization and functional regulation established by multiple experimental conditions, single lab\",\n      \"pmids\": [\"25908210\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"CEACAM20 is an evolutionarily conserved member of the CEA family with orthologs in mouse, rat, and human at syntenic genomic locations; gene-specific RT-PCR revealed a very distinct tissue expression pattern, suggesting diversified function within the CEA family.\",\n      \"method\": \"Genome-wide sequence analysis, RT-PCR across 31 tissues\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 — identification and expression profiling only, no direct mechanistic experiment\",\n      \"pmids\": [\"16139472\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CEACAM20 is an ITAM-containing transmembrane protein of the CEA family that localizes to the apical/microvillus surface of intestinal epithelial and prostate cells, where it is phosphorylated on cytoplasmic tyrosines (Tyr559/Tyr570 within the ITAM) by c-Src, recruits and activates Syk, and signals through PI3K and PLCγ to promote phagocytosis and NF-κB-driven IL-8 production; its phosphorylation is negatively regulated by the receptor-type phosphatase SAP-1 (PTPRH) via direct ectodomain interaction, and it plays a structural role in prostate lumen/tubule morphogenesis.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CEACAM20 is an ITAM-bearing transmembrane glycoprotein of the CEA family that functions as a signaling receptor at apical epithelial surfaces to drive phagocytosis and pro-inflammatory cytokine production. c-Src phosphorylates its cytoplasmic ITAM tyrosines (Tyr559/Tyr570), enabling recruitment and activation of Syk and downstream signaling through PI3K and PLCγ to promote actin-dependent phagocytosis, as well as NF-κB activation and IL-8 secretion in intestinal epithelial cells [PMID:28659570, PMID:26195794]. CEACAM20 phosphorylation is negatively regulated by the receptor-type phosphatase SAP-1 (PTPRH), which engages CEACAM20 through an ectodomain-mediated complex [PMID:26195794]. In prostate epithelium, CEACAM20 localizes to the apical/luminal surface and is required for tubule morphogenesis in 3D organoid models, and its intestinal expression is selectively upregulated by the microbial metabolite butyrate [PMID:23358633, PMID:25908210].\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Identification of CEACAM20 as an evolutionarily conserved CEA family member with a restricted tissue expression pattern established it as a distinct gene warranting functional investigation.\",\n      \"evidence\": \"Comparative genomics and RT-PCR across 31 tissues in mouse, rat, and human\",\n      \"pmids\": [\"16139472\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No protein-level characterization or mechanistic data\",\n        \"Expression profiling alone does not define function\",\n        \"No loss-of-function or gain-of-function experiments\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Demonstrating that CEACAM20 contains a functional ITAM phosphorylated by c-Src and that its ITAM tyrosines are essential for phagocytosis via Src→Syk→PI3K→PLCγ signaling defined the core signaling cascade downstream of CEACAM20.\",\n      \"evidence\": \"Site-directed mutagenesis of ITAM tyrosines, pharmacological kinase/actin inhibitor panel, and phagocytosis assay with anti-Myc-coated microbeads in cultured cells\",\n      \"pmids\": [\"28659570\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Phagocytic function shown only with antibody-coated beads, not physiological ligands\",\n        \"Single laboratory study; independent replication absent\",\n        \"In vivo relevance of CEACAM20-mediated phagocytosis not tested\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Showing that CEACAM20 localizes to the apical surface of prostate acini and is required for tubule morphogenesis revealed a structural/morphogenetic role beyond innate immune signaling.\",\n      \"evidence\": \"3D Matrigel organoid culture of prostate epithelial cells, confocal microscopy, antisense oligonucleotide knockdown\",\n      \"pmids\": [\"23358633\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Knockdown achieved by antisense oligonucleotide only; genetic knockout not performed\",\n        \"Mechanism linking CEACAM20 to tubulogenesis (signaling vs. adhesion) unresolved\",\n        \"In vivo prostate phenotype in CEACAM20-deficient animals not examined\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Identifying SAP-1 (PTPRH) as a phosphatase that dephosphorylates CEACAM20 through ectodomain interaction, and showing that loss of SAP-1 hyperactivates CEACAM20→Syk→NF-κB→IL-8 signaling, established the negative regulatory mechanism controlling CEACAM20 activity in intestinal epithelium.\",\n      \"evidence\": \"Phosphotyrosine analysis in SAP-1-knockout mouse intestine, co-immunoprecipitation of ectodomain complex, NF-κB reporter assay, IL-8 ELISA in cultured cells\",\n      \"pmids\": [\"26195794\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether SAP-1 directly dephosphorylates CEACAM20 ITAM tyrosines or acts indirectly through Src regulation not fully resolved\",\n        \"Physiological ligand or bacterial trigger for CEACAM20 activation in vivo unknown\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Showing that butyrate selectively upregulates CEACAM20 in intestinal organoids and that CEACAM20 expression depends on commensal microbiota linked its signaling function to host–microbe communication.\",\n      \"evidence\": \"Intestinal organoid culture with butyrate/cytokine treatment, germ-free and antibiotic-treated mouse models, RT-PCR and immunofluorescence\",\n      \"pmids\": [\"25908210\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Transcriptional mechanism by which butyrate induces CEACAM20 not identified\",\n        \"Whether butyrate-induced CEACAM20 is functionally active (phosphorylated, signaling) not tested\",\n        \"Contribution to intestinal homeostasis vs. inflammation in vivo unclear\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological ligand(s) that activate CEACAM20 at the epithelial surface, the in vivo consequence of CEACAM20 deletion on intestinal immunity and prostate morphogenesis, and the structural basis for the SAP-1–CEACAM20 ectodomain interaction remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No CEACAM20-knockout mouse phenotype reported\",\n        \"No endogenous activating ligand identified\",\n        \"No structural data for CEACAM20 or the SAP-1–CEACAM20 complex\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [1, 2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [4, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [1, 2, 3]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 1, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PTPRH\", \"SYK\", \"SRC\"],\n    \"other_free_text\": []\n  }\n}\n```"}