{"gene":"CEACAM20","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2015,"finding":"CEACAM20 is a substrate of the receptor-type protein tyrosine phosphatase SAP-1 (PTPRH): tyrosine phosphorylation of CEACAM20 is greatly increased in SAP-1-deficient intestinal epithelium, and SAP-1 and CEACAM20 form a complex through interaction of their ectodomains.","method":"Phosphotyrosine immunoblotting in SAP-1 KO mice, co-immunoprecipitation of ectodomain complex","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal biochemical evidence (phosphorylation in KO tissue + ectodomain Co-IP) combined with functional cellular readout, published in peer-reviewed journal","pmids":["26195794"],"is_preprint":false},{"year":2015,"finding":"Tyrosine phosphorylation of CEACAM20 by c-Src kinase leads to association of CEACAM20 with spleen tyrosine kinase (Syk), which promotes IL-8 production through NF-κB activation in intestinal epithelial cells.","method":"c-Src forced expression, co-immunoprecipitation of CEACAM20–Syk complex, NF-κB reporter assay, IL-8 ELISA in cultured cells","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP, reporter assay, cytokine measurement) in a single rigorous study with clear pathway placement","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 ITAM tyrosines Tyr559/Tyr570 are required for CEACAM20-mediated phagocytic activity.","method":"Pervanadate treatment and c-Src forced expression followed by phosphotyrosine immunoblotting; site-directed mutagenesis (Y559F/Y570F) with phagocytosis bead assay","journal":"The Kobe journal of medical sciences","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — mutagenesis identifies critical residues and links phosphorylation to function, but single lab, single publication","pmids":["28659570"],"is_preprint":false},{"year":2013,"finding":"CEACAM20-mediated phagocytosis requires sequential activation of Src family kinases (SFKs), Syk, PI3K, and PLCγ, as well as actin polymerization, placing CEACAM20 upstream of this signaling cascade.","method":"Pharmacological inhibition of SFKs (PP2), Syk (piceatannol), PI3K (wortmannin), PLCγ (U73122), and actin polymerization (Cytochalasin D) in bead phagocytosis assay","journal":"The Kobe journal of medical sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis established by multiple inhibitor treatments in a defined functional assay, single lab","pmids":["28659570"],"is_preprint":false},{"year":2013,"finding":"CEACAM20 is localized to acinar luminal structures in prostate organoids grown on Matrigel, and antisense oligonucleotide-mediated inhibition of CEACAM20 completely inhibits tubule formation and stunts acinar growth, demonstrating a required role in prostate epithelial morphogenesis.","method":"Confocal microscopy of prostate organoids on Matrigel; antisense oligonucleotide knockdown with quantitative morphometric readout","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — direct localization by imaging plus loss-of-function with defined structural phenotype, single lab","pmids":["23358633"],"is_preprint":false},{"year":2015,"finding":"CEACAM20 protein expression in intestinal epithelial cells is regulated by gut commensal Gram-positive bacteria; it is reduced in germ-free and antibiotic-treated mice. Butyrate (a short-chain fatty acid from bacterial fermentation) specifically increases CEACAM20 expression in intestinal organoids, whereas TNF-α does not, distinguishing its regulatory inputs from those of CEACAM1.","method":"Western blot and RT-PCR in germ-free mice and antibiotic-treated mice; intestinal organoid exposure to IFN-γ, TNF-α, and butyrate","journal":"Genes to cells : devoted to molecular & cellular mechanisms","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple in vivo and ex vivo conditions tested, single lab","pmids":["25908210"],"is_preprint":false},{"year":2005,"finding":"CEACAM20 was identified as a novel CEA-family member with orthologs in mouse, rat, and human at syntenic genomic locations; tissue-specific RT-PCR revealed a distinct expression pattern, suggesting a diverged function within the CEA family.","method":"Genome-wide bioinformatic analysis and tissue-panel RT-PCR","journal":"Genomics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/expression identification only, no direct functional experiment on CEACAM20 protein mechanism","pmids":["16139472"],"is_preprint":false}],"current_model":"CEACAM20 is an ITAM-containing transmembrane Ig-superfamily protein localized to intestinal and prostate epithelial microvilli/lumina, where c-Src phosphorylates its ITAM tyrosines (Tyr559/Tyr570) to recruit Syk and activate a SFK→Syk→PI3K→PLCγ→NF-κB signaling cascade that drives IL-8 production and phagocytosis; this activity is held in check by the phosphatase SAP-1 (PTPRH), which dephosphorylates CEACAM20 after forming an ectodomain complex with it, thereby protecting against intestinal inflammation, while CEACAM20 is also required for prostate tubulogenesis in organoid models."},"narrative":{"mechanistic_narrative":"CEACAM20 is an ITAM-containing transmembrane immunoglobulin-superfamily protein of epithelial tissues that couples extracellular cues to intracellular tyrosine-kinase signaling and innate effector functions [PMID:28659570, PMID:26195794]. Its cytoplasmic ITAM is phosphorylated by c-Src on Tyr559 and Tyr570, and these residues are required for CEACAM20-mediated phagocytosis [PMID:28659570]; phosphorylation recruits the spleen tyrosine kinase Syk and drives a sequential SFK→Syk→PI3K→PLCγ cascade that, together with actin polymerization, supports both phagocytic engulfment and NF-κB-dependent IL-8 production in intestinal epithelial cells [PMID:26195794, PMID:28659570]. This signaling output is restrained by the receptor-type tyrosine phosphatase SAP-1 (PTPRH), which forms an ectodomain complex with CEACAM20 and dephosphorylates it, since CEACAM20 phosphorylation is markedly elevated in SAP-1-deficient intestinal epithelium [PMID:26195794]. CEACAM20 expression itself is shaped by the gut environment, being induced by commensal-derived butyrate and reduced in germ-free or antibiotic-treated animals [PMID:25908210]. Beyond the intestine, CEACAM20 localizes to acinar luminal structures and is required for tubule formation in prostate organoids [PMID:23358633].","teleology":[{"year":2005,"claim":"Establishing that CEACAM20 exists as a conserved CEA-family gene with a distinct expression pattern framed the question of what diverged function it serves.","evidence":"Genome-wide bioinformatic analysis and tissue-panel RT-PCR across mouse, rat, and human","pmids":["16139472"],"confidence":"Low","gaps":["Computational/expression identification only, no functional or biochemical assay","No protein-level localization or interaction data","Diverged function inferred but not tested"]},{"year":2013,"claim":"Identifying the cytoplasmic ITAM and the c-Src-phosphorylated tyrosines, and showing Tyr559/Tyr570 are required for phagocytosis, defined CEACAM20 as a signaling receptor with a functional readout.","evidence":"Pervanadate/c-Src forced expression with phosphotyrosine immunoblotting and Y559F/Y570F mutagenesis in a bead phagocytosis assay","pmids":["28659570"],"confidence":"Medium","gaps":["Single lab, single publication","No physiological ligand for the ectodomain identified","Kinase responsible in vivo not established beyond forced c-Src expression"]},{"year":2013,"claim":"Pharmacological epistasis placed CEACAM20 upstream of an SFK→Syk→PI3K→PLCγ and actin cascade, ordering the downstream effector pathway.","evidence":"Inhibitor panel (PP2, piceatannol, wortmannin, U73122, Cytochalasin D) in phagocytosis assay","pmids":["28659570"],"confidence":"Medium","gaps":["Inhibitor specificity not orthogonally validated","Direct binding of each kinase to CEACAM20 not all demonstrated","Performed in a single functional context"]},{"year":2013,"claim":"Localization to acinar lumina and loss-of-function in organoids established a morphogenetic role for CEACAM20 outside the intestine.","evidence":"Confocal imaging and antisense oligonucleotide knockdown with morphometric readout in prostate organoids on Matrigel","pmids":["23358633"],"confidence":"Medium","gaps":["Mechanistic link between signaling cascade and tubulogenesis untested","Antisense knockdown not validated by independent loss-of-function method","In vivo prostate relevance not shown"]},{"year":2015,"claim":"Demonstrating Syk recruitment and NF-κB-driven IL-8 production connected CEACAM20 phosphorylation to a pro-inflammatory transcriptional output in epithelium.","evidence":"c-Src forced expression, CEACAM20–Syk co-immunoprecipitation, NF-κB reporter assay, and IL-8 ELISA in cultured cells","pmids":["26195794"],"confidence":"High","gaps":["Trigger that initiates c-Src phosphorylation in vivo not defined","Direct vs indirect Syk–CEACAM20 binding not fully resolved","Connection to the phagocytosis cascade not unified in one system"]},{"year":2015,"claim":"Identifying SAP-1 (PTPRH) as the phosphatase that forms an ectodomain complex with and dephosphorylates CEACAM20 supplied the off-switch restraining the cascade.","evidence":"Phosphotyrosine immunoblotting in SAP-1 KO mice and ectodomain co-immunoprecipitation","pmids":["26195794"],"confidence":"High","gaps":["Structural basis of the ectodomain interaction unknown","Whether SAP-1 loss drives intestinal inflammation via CEACAM20 specifically not isolated","Kinetics of the kinase/phosphatase balance not quantified"]},{"year":2015,"claim":"Showing that commensal Gram-positive bacteria and butyrate, but not TNF-α, regulate CEACAM20 levels placed its expression under microbiota control distinct from CEACAM1.","evidence":"Western blot/RT-PCR in germ-free and antibiotic-treated mice; cytokine and butyrate exposure of intestinal organoids","pmids":["25908210"],"confidence":"Medium","gaps":["Transcriptional mechanism of butyrate induction not defined","Functional consequence of altered expression on signaling output not measured","Single lab"]},{"year":null,"claim":"The physiological ligand engaging the CEACAM20 ectodomain and the upstream trigger that initiates c-Src phosphorylation in vivo remain unidentified.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No extracellular ligand defined","Unifying model linking phagocytosis, IL-8/NF-κB, and prostate tubulogenesis absent","No structural model of CEACAM20 or its complexes"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[1,2,3]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,2]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,4]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1,2,3]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[1,3]}],"complexes":[],"partners":["PTPRH","SRC","SYK"],"other_free_text":[]}},"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":82,"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":39,"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":5621,"output_tokens":1859,"usd":0.022374,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8735,"output_tokens":2699,"usd":0.055575,"stage2_stop_reason":"end_turn"},"total_usd":0.077949,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","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): tyrosine phosphorylation of CEACAM20 is greatly increased in SAP-1-deficient intestinal epithelium, and SAP-1 and CEACAM20 form a complex through interaction of their ectodomains.\",\n      \"method\": \"Phosphotyrosine immunoblotting in SAP-1 KO mice, co-immunoprecipitation of ectodomain complex\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal biochemical evidence (phosphorylation in KO tissue + ectodomain Co-IP) combined with functional cellular readout, published in peer-reviewed journal\",\n      \"pmids\": [\"26195794\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Tyrosine phosphorylation of CEACAM20 by c-Src kinase leads to association of CEACAM20 with spleen tyrosine kinase (Syk), which promotes IL-8 production through NF-κB activation in intestinal epithelial cells.\",\n      \"method\": \"c-Src forced expression, co-immunoprecipitation of CEACAM20–Syk complex, NF-κB reporter assay, IL-8 ELISA in cultured cells\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP, reporter assay, cytokine measurement) in a single rigorous study with clear pathway placement\",\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 ITAM tyrosines Tyr559/Tyr570 are required for CEACAM20-mediated phagocytic activity.\",\n      \"method\": \"Pervanadate treatment and c-Src forced expression followed by phosphotyrosine immunoblotting; site-directed mutagenesis (Y559F/Y570F) with phagocytosis bead assay\",\n      \"journal\": \"The Kobe journal of medical sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — mutagenesis identifies critical residues and links phosphorylation to function, but single lab, single publication\",\n      \"pmids\": [\"28659570\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CEACAM20-mediated phagocytosis requires sequential activation of Src family kinases (SFKs), Syk, PI3K, and PLCγ, as well as actin polymerization, placing CEACAM20 upstream of this signaling cascade.\",\n      \"method\": \"Pharmacological inhibition of SFKs (PP2), Syk (piceatannol), PI3K (wortmannin), PLCγ (U73122), and actin polymerization (Cytochalasin D) in bead phagocytosis assay\",\n      \"journal\": \"The Kobe journal of medical sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis established by multiple inhibitor treatments in a defined functional assay, single lab\",\n      \"pmids\": [\"28659570\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CEACAM20 is localized to acinar luminal structures in prostate organoids grown on Matrigel, and antisense oligonucleotide-mediated inhibition of CEACAM20 completely inhibits tubule formation and stunts acinar growth, demonstrating a required role in prostate epithelial morphogenesis.\",\n      \"method\": \"Confocal microscopy of prostate organoids on Matrigel; antisense oligonucleotide knockdown with quantitative morphometric readout\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — direct localization by imaging plus loss-of-function with defined structural phenotype, single lab\",\n      \"pmids\": [\"23358633\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"CEACAM20 protein expression in intestinal epithelial cells is regulated by gut commensal Gram-positive bacteria; it is reduced in germ-free and antibiotic-treated mice. Butyrate (a short-chain fatty acid from bacterial fermentation) specifically increases CEACAM20 expression in intestinal organoids, whereas TNF-α does not, distinguishing its regulatory inputs from those of CEACAM1.\",\n      \"method\": \"Western blot and RT-PCR in germ-free mice and antibiotic-treated mice; intestinal organoid exposure to IFN-γ, TNF-α, and butyrate\",\n      \"journal\": \"Genes to cells : devoted to molecular & cellular mechanisms\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple in vivo and ex vivo conditions tested, single lab\",\n      \"pmids\": [\"25908210\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"CEACAM20 was identified as a novel CEA-family member with orthologs in mouse, rat, and human at syntenic genomic locations; tissue-specific RT-PCR revealed a distinct expression pattern, suggesting a diverged function within the CEA family.\",\n      \"method\": \"Genome-wide bioinformatic analysis and tissue-panel RT-PCR\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/expression identification only, no direct functional experiment on CEACAM20 protein mechanism\",\n      \"pmids\": [\"16139472\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CEACAM20 is an ITAM-containing transmembrane Ig-superfamily protein localized to intestinal and prostate epithelial microvilli/lumina, where c-Src phosphorylates its ITAM tyrosines (Tyr559/Tyr570) to recruit Syk and activate a SFK→Syk→PI3K→PLCγ→NF-κB signaling cascade that drives IL-8 production and phagocytosis; this activity is held in check by the phosphatase SAP-1 (PTPRH), which dephosphorylates CEACAM20 after forming an ectodomain complex with it, thereby protecting against intestinal inflammation, while CEACAM20 is also required for prostate tubulogenesis in organoid models.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CEACAM20 is an ITAM-containing transmembrane immunoglobulin-superfamily protein of epithelial tissues that couples extracellular cues to intracellular tyrosine-kinase signaling and innate effector functions [#2, #1]. Its cytoplasmic ITAM is phosphorylated by c-Src on Tyr559 and Tyr570, and these residues are required for CEACAM20-mediated phagocytosis [#2]; phosphorylation recruits the spleen tyrosine kinase Syk and drives a sequential SFK\\u2192Syk\\u2192PI3K\\u2192PLC\\u03b3 cascade that, together with actin polymerization, supports both phagocytic engulfment and NF-\\u03baB-dependent IL-8 production in intestinal epithelial cells [#1, #3]. This signaling output is restrained by the receptor-type tyrosine phosphatase SAP-1 (PTPRH), which forms an ectodomain complex with CEACAM20 and dephosphorylates it, since CEACAM20 phosphorylation is markedly elevated in SAP-1-deficient intestinal epithelium [#0]. CEACAM20 expression itself is shaped by the gut environment, being induced by commensal-derived butyrate and reduced in germ-free or antibiotic-treated animals [#5]. Beyond the intestine, CEACAM20 localizes to acinar luminal structures and is required for tubule formation in prostate organoids [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Establishing that CEACAM20 exists as a conserved CEA-family gene with a distinct expression pattern framed the question of what diverged function it serves.\",\n      \"evidence\": \"Genome-wide bioinformatic analysis and tissue-panel RT-PCR across mouse, rat, and human\",\n      \"pmids\": [\"16139472\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Computational/expression identification only, no functional or biochemical assay\", \"No protein-level localization or interaction data\", \"Diverged function inferred but not tested\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Identifying the cytoplasmic ITAM and the c-Src-phosphorylated tyrosines, and showing Tyr559/Tyr570 are required for phagocytosis, defined CEACAM20 as a signaling receptor with a functional readout.\",\n      \"evidence\": \"Pervanadate/c-Src forced expression with phosphotyrosine immunoblotting and Y559F/Y570F mutagenesis in a bead phagocytosis assay\",\n      \"pmids\": [\"28659570\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, single publication\", \"No physiological ligand for the ectodomain identified\", \"Kinase responsible in vivo not established beyond forced c-Src expression\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Pharmacological epistasis placed CEACAM20 upstream of an SFK\\u2192Syk\\u2192PI3K\\u2192PLC\\u03b3 and actin cascade, ordering the downstream effector pathway.\",\n      \"evidence\": \"Inhibitor panel (PP2, piceatannol, wortmannin, U73122, Cytochalasin D) in phagocytosis assay\",\n      \"pmids\": [\"28659570\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Inhibitor specificity not orthogonally validated\", \"Direct binding of each kinase to CEACAM20 not all demonstrated\", \"Performed in a single functional context\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Localization to acinar lumina and loss-of-function in organoids established a morphogenetic role for CEACAM20 outside the intestine.\",\n      \"evidence\": \"Confocal imaging and antisense oligonucleotide knockdown with morphometric readout in prostate organoids on Matrigel\",\n      \"pmids\": [\"23358633\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link between signaling cascade and tubulogenesis untested\", \"Antisense knockdown not validated by independent loss-of-function method\", \"In vivo prostate relevance not shown\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Demonstrating Syk recruitment and NF-\\u03baB-driven IL-8 production connected CEACAM20 phosphorylation to a pro-inflammatory transcriptional output in epithelium.\",\n      \"evidence\": \"c-Src forced expression, CEACAM20\\u2013Syk co-immunoprecipitation, NF-\\u03baB reporter assay, and IL-8 ELISA in cultured cells\",\n      \"pmids\": [\"26195794\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Trigger that initiates c-Src phosphorylation in vivo not defined\", \"Direct vs indirect Syk\\u2013CEACAM20 binding not fully resolved\", \"Connection to the phagocytosis cascade not unified in one system\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Identifying SAP-1 (PTPRH) as the phosphatase that forms an ectodomain complex with and dephosphorylates CEACAM20 supplied the off-switch restraining the cascade.\",\n      \"evidence\": \"Phosphotyrosine immunoblotting in SAP-1 KO mice and ectodomain co-immunoprecipitation\",\n      \"pmids\": [\"26195794\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the ectodomain interaction unknown\", \"Whether SAP-1 loss drives intestinal inflammation via CEACAM20 specifically not isolated\", \"Kinetics of the kinase/phosphatase balance not quantified\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Showing that commensal Gram-positive bacteria and butyrate, but not TNF-\\u03b1, regulate CEACAM20 levels placed its expression under microbiota control distinct from CEACAM1.\",\n      \"evidence\": \"Western blot/RT-PCR in germ-free and antibiotic-treated mice; cytokine and butyrate exposure of intestinal organoids\",\n      \"pmids\": [\"25908210\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Transcriptional mechanism of butyrate induction not defined\", \"Functional consequence of altered expression on signaling output not measured\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological ligand engaging the CEACAM20 ectodomain and the upstream trigger that initiates c-Src phosphorylation in vivo remain unidentified.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No extracellular ligand defined\", \"Unifying model linking phagocytosis, IL-8/NF-\\u03baB, and prostate tubulogenesis absent\", \"No structural model of CEACAM20 or its complexes\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [1, 2, 3]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1, 2, 3]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PTPRH\", \"SRC\", \"SYK\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":4,"faith_total":5,"faith_pct":80.0}}