{"gene":"COLEC11","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":2010,"finding":"CL-11 (CL-K1) circulates in plasma and physically associates with MASP-1 and/or MASP-3, demonstrated by co-purification and ELISA. CL-11 forms disulfide-linked oligomers (~100 and 200 kDa). It exhibits Ca2+-dependent lectin activity with preference for L-fucose and D-mannose, and binds intact bacteria, fungi, and viruses, including decreasing influenza A virus infectivity.","method":"Gel permeation chromatography, co-purification, ELISA, Western blot, mass spectrometry, in vitro binding assays","journal":"Journal of immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (co-purification, ELISA, binding assays, MS) in a single rigorous characterization study; replicated in subsequent papers","pmids":["20956340"],"is_preprint":false},{"year":2006,"finding":"CL-K1 is a secreted protein with Ca2+-dependent sugar-binding activity showing preference for fucose and weakly mannose, but not N-acetyl-galactosamine, N-acetyl-glucosamine, or maltose. It recognizes specific bacterial saccharides.","method":"cDNA cloning, immunostaining of CL-K1 cDNA-expressing CHO cells, sugar-binding assays","journal":"Microbiology and immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding assays and cell expression system in founding characterization study, single lab","pmids":["17179669"],"is_preprint":false},{"year":2011,"finding":"Loss-of-function mutations in COLEC11 cause 3MC syndrome. CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney and vertebral bodies. In zebrafish, morpholino knockdown of COLEC11 produces pigmentary defects and severe craniofacial abnormalities. CL-K1 serves as a guidance cue for neural crest cell migration.","method":"Human genetic sequencing (11 families), in situ hybridization/immunostaining in murine embryos, zebrafish morpholino knockdown, neural crest cell migration assay","journal":"Nature genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — human genetic data combined with zebrafish loss-of-function and neural crest migration functional assay, replicated across multiple families and orthogonal systems","pmids":["21258343"],"is_preprint":false},{"year":2013,"finding":"CL-11 binds DNA in a calcium-independent manner via a binding site distinct from its carbohydrate-recognition domain. Binding is sensitive to ionic strength and pH, and oligomericity is required for binding activity. CL-11 also binds apoptotic cells presenting extracellular DNA. The dissociation constant for double-stranded DNA is KD = 9–20 nM (surface plasmon resonance). In vitro, CL-11 binding to DNA-coated surfaces leads to C4b deposition via MASP-2, indicating lectin pathway complement activation.","method":"Binding assays, competition studies, surface plasmon resonance, in vitro C4b deposition assay","journal":"Molecular immunology","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — SPR quantitative binding, competition/mutagenesis-like domain separation, functional complement activation assay; single lab but multiple orthogonal methods","pmids":["23954398"],"is_preprint":false},{"year":2012,"finding":"CL-11 is a serum protein, whereas its paralog CL-L1 is restricted to the cytosol. CL-11 CRD binds most avidly to L-fucose and D-mannose; CL-L1 shows different specificity. CL-11 binds E. coli, Candida albicans, and influenza A virus. CL-11 is found in circulation in complexes with MASP-1/3.","method":"Structural characterization, specificity analysis of CRD, binding assays, co-immunoprecipitation/co-purification","journal":"Immunobiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — review/characterization paper consolidating prior experimental findings with some new structural comparisons; single lab","pmids":["22475410"],"is_preprint":false},{"year":2018,"finding":"CL-K1 and CL-L1 have widespread, nearly identical tissue distribution with high expression in epithelial cells of endo-/exocrine secretory tissues and mucosa. Local synthesis at peripheral sites is responsible for the peripheral localization and likely the formation of CL-LK heteromeric complexes. Both proteins co-localize, consistent with heteromeric complex formation in peripheral tissues.","method":"Immunohistochemistry with monoclonal antibodies, mRNA in situ localization across human tissues","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — systematic IHC with mRNA validation across tissues, single lab, localization without direct functional consequence established","pmids":["30108587"],"is_preprint":false},{"year":2018,"finding":"CL-11 circulates in heterocomplexes with CL-10 (collectin-10) as two major complexes of ~400 and >600 kDa. CL-11 can bind zymosan independently of calcium via a site separate from its carbohydrate-binding region. CL-11/MASP-2 complexes trigger C4b deposition on zymosan, demonstrating lectin pathway activation.","method":"Size exclusion chromatography, ELISA, in vitro C4b deposition assay, calcium-independent binding assays","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional complement activation assay and biochemical characterization of complexes, single lab, multiple methods","pmids":["30323815"],"is_preprint":false},{"year":2007,"finding":"CL-K1 localizes to proximal tubules of kidney, gastrointestinal mucosa, bronchial glands, hepatocytes around central veins (consistent with hepatic synthesis and secretion into blood), vascular smooth muscle, intestinal Paneth cells, mesangial cells of kidney, pancreatic islet D cells, and neurons.","method":"Immunohistochemistry and real-time PCR in murine tissues","journal":"The journal of histochemistry and cytochemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — systematic IHC across multiple murine tissues; single lab, no direct functional consequence established","pmids":["18040075"],"is_preprint":false}],"current_model":"COLEC11 (CL-K1) is a secreted, oligomeric C-type lectin collectin that circulates in plasma as heteromeric complexes with CL-L1 (CL-LK) and associates with MASP-1/3; it binds microbial surfaces via Ca2+-dependent recognition of L-fucose and D-mannose and binds DNA/apoptotic cells via a separate, Ca2+-independent site, in both cases activating the lectin complement pathway through MASP-2-dependent C4b deposition; during embryogenesis, CL-K1 acts as a guidance cue for neural crest cell migration, and loss-of-function mutations in COLEC11 cause the developmental disorder 3MC syndrome."},"narrative":{"mechanistic_narrative":"COLEC11 (CL-K1/CL-11) is a secreted, oligomeric C-type lectin collectin that functions as a recognition molecule of the lectin complement pathway and as a developmental guidance cue [PMID:20956340, PMID:21258343]. It circulates in plasma as disulfide-linked oligomers in association with MASP-1/3, and recognizes microbial surfaces—bacteria, fungi, and viruses including influenza A—through Ca2+-dependent binding of L-fucose and D-mannose [PMID:20956340, PMID:22475410]. In parallel, it engages DNA and apoptotic cells presenting extracellular DNA through a high-affinity, Ca2+-independent site distinct from its carbohydrate-recognition domain, with oligomerization required for binding [PMID:23954398]. Upon engaging either microbial carbohydrate or DNA ligands, CL-11 drives MASP-2-dependent C4b deposition, activating the lectin pathway [PMID:23954398, PMID:30323815]. It circulates and acts in heteromeric complexes with the paralogous collectin CL-10/CL-L1, whose co-expression at peripheral epithelial and secretory tissues supports local heterocomplex assembly [PMID:30108587, PMID:30323815]. Beyond innate immunity, CL-K1 serves as a guidance cue for neural crest cell migration during embryogenesis, and loss-of-function mutations in COLEC11 cause the developmental disorder 3MC syndrome [PMID:21258343].","teleology":[{"year":2006,"claim":"Establishing that CL-K1 is a secreted protein with defined Ca2+-dependent sugar specificity answered the basic question of what class of molecule it is and what it recognizes.","evidence":"cDNA cloning, CHO cell expression, and sugar-binding assays","pmids":["17179669"],"confidence":"Medium","gaps":["No physiological ligand or downstream pathway identified","Single lab, founding characterization","No oligomeric or complex partner defined"]},{"year":2007,"claim":"Mapping CL-K1 tissue distribution addressed where the protein is produced and likely acts, implicating hepatic synthesis with secretion into blood and broad epithelial expression.","evidence":"Immunohistochemistry and real-time PCR across murine tissues","pmids":["18040075"],"confidence":"Medium","gaps":["Localization without direct functional consequence","Does not establish secretion mechanism or circulating form"]},{"year":2010,"claim":"Demonstrating physical association with MASP-1/3 and oligomerization placed CL-11 within the lectin complement pathway and connected its carbohydrate recognition to an effector module.","evidence":"Co-purification, ELISA, mass spectrometry, and in vitro microbial binding assays","pmids":["20956340"],"confidence":"High","gaps":["Did not demonstrate direct C4b deposition/complement activation","MASP-1 vs MASP-3 functional roles not resolved"]},{"year":2011,"claim":"Identifying COLEC11 loss-of-function as the cause of 3MC syndrome and a neural crest guidance role established a developmental function distinct from immunity.","evidence":"Human genetic sequencing across 11 families, murine embryo expression, zebrafish morpholino knockdown, and neural crest migration assay","pmids":["21258343"],"confidence":"High","gaps":["Molecular receptor/signaling for neural crest guidance not defined","Relationship between immune and developmental functions unresolved"]},{"year":2012,"claim":"Distinguishing CL-11 (serum) from its cytosolic paralog CL-L1 and detailing CRD specificity clarified which collectin operates extracellularly in circulation.","evidence":"Structural/specificity characterization, binding assays, and co-purification","pmids":["22475410"],"confidence":"Medium","gaps":["Consolidation paper, limited new primary data","Heterocomplex stoichiometry not defined"]},{"year":2013,"claim":"Showing high-affinity, Ca2+-independent DNA binding via a site separate from the CRD, coupled to MASP-2-driven C4b deposition, revealed a second ligand class linking CL-11 to apoptotic-cell handling and complement activation.","evidence":"Surface plasmon resonance, competition/domain-separation binding studies, apoptotic cell binding, and in vitro C4b deposition assay","pmids":["23954398"],"confidence":"High","gaps":["DNA-binding site not mapped at residue level","In vivo relevance of DNA-triggered complement activation not established"]},{"year":2018,"claim":"Defining CL-11/CL-10 heterocomplexes and their tissue co-expression established the physiological circulating and local assembly state of the protein and confirmed MASP-2-dependent activation on microbial surfaces.","evidence":"Size exclusion chromatography, ELISA, IHC/mRNA localization, and in vitro C4b deposition on zymosan","pmids":["30323815","30108587"],"confidence":"Medium","gaps":["Functional difference between homo- and heterocomplexes not quantified","Single lab biochemistry"]},{"year":null,"claim":"How CL-K1 transduces neural crest guidance and whether this developmental role intersects with its complement-activating function remains unresolved.","evidence":"No direct mechanistic study in the available corpus links the guidance cue activity to a receptor or signaling pathway","pmids":[],"confidence":"Low","gaps":["No neural crest receptor identified","No structural model of ligand discrimination","Mechanistic basis of 3MC pathology unexplained"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[3]},{"term_id":"GO:0001618","term_label":"virus receptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005576","term_label":"extracellular region","supporting_discovery_ids":[0,4,7]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[0,3,6]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[2]}],"complexes":["CL-LK (CL-K1/CL-L1 heterocomplex)","CL-K1/MASP-1/3 complex","CL-11/CL-10 heterocomplex"],"partners":["MASP1","MASP3","MASP2","COLEC10","COLEC9"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BWP8","full_name":"Collectin-11","aliases":["Collectin kidney protein 1","CL-K1"],"length_aa":271,"mass_kda":28.7,"function":"Lectin that plays a role in innate immunity, apoptosis and embryogenesis (PubMed:21258343, PubMed:23954398, PubMed:25912189). Calcium-dependent lectin that binds self and non-self glycoproteins presenting high mannose oligosaccharides with at least one terminal alpha-1,2-linked mannose epitope (PubMed:25912189). Primarily recognizes the terminal disaccharide of the glycan (PubMed:25912189). Also recognizes a subset of fucosylated glycans and lipopolysaccharides (PubMed:17179669, PubMed:25912189). Plays a role in innate immunity through its ability to bind non-self sugars presented by microorganisms and to activate the complement through the recruitment of MAPS1 (PubMed:20956340, PubMed:25912189). Also plays a role in apoptosis through its ability to bind in a calcium-independent manner the DNA present at the surface of apoptotic cells and to activate the complement in response to this binding (Probable). Finally, plays a role in development, probably serving as a guidance cue during the migration of neural crest cells and other cell types during embryogenesis (PubMed:21258343, PubMed:28301481)","subcellular_location":"Secreted","url":"https://www.uniprot.org/uniprotkb/Q9BWP8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/COLEC11","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/COLEC11","total_profiled":1310},"omim":[{"mim_id":"612502","title":"COLLECTIN 11; COLEC11","url":"https://www.omim.org/entry/612502"},{"mim_id":"605102","title":"MANNAN-BINDING LECTIN SERINE PROTEASE 2; MASP2","url":"https://www.omim.org/entry/605102"},{"mim_id":"600521","title":"MANNAN-BINDING LECTIN SERINE PROTEASE 1; MASP1","url":"https://www.omim.org/entry/600521"},{"mim_id":"265050","title":"3MC SYNDROME 2; 3MC2","url":"https://www.omim.org/entry/265050"},{"mim_id":"257920","title":"3MC SYNDROME 1; 3MC1","url":"https://www.omim.org/entry/257920"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"gallbladder","ntpm":50.7},{"tissue":"liver","ntpm":108.9},{"tissue":"ovary","ntpm":50.7}],"url":"https://www.proteinatlas.org/search/COLEC11"},"hgnc":{"alias_symbol":["MGC3279","CL-K1","CL-11"],"prev_symbol":[]},"alphafold":{"accession":"Q9BWP8","domains":[{"cath_id":"3.10.100.10","chopping":"152-268","consensus_level":"high","plddt":97.1356,"start":152,"end":268}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BWP8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BWP8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BWP8-F1-predicted_aligned_error_v6.png","plddt_mean":78.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=COLEC11","jax_strain_url":"https://www.jax.org/strain/search?query=COLEC11"},"sequence":{"accession":"Q9BWP8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BWP8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BWP8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BWP8"}},"corpus_meta":[{"pmid":"21258343","id":"PMC_21258343","title":"Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome.","date":"2011","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/21258343","citation_count":197,"is_preprint":false},{"pmid":"20956340","id":"PMC_20956340","title":"Collectin 11 (CL-11, CL-K1) is a MASP-1/3-associated plasma collectin with microbial-binding activity.","date":"2010","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/20956340","citation_count":170,"is_preprint":false},{"pmid":"17179669","id":"PMC_17179669","title":"Identification and characterization of a novel human collectin CL-K1.","date":"2006","source":"Microbiology and immunology","url":"https://pubmed.ncbi.nlm.nih.gov/17179669","citation_count":122,"is_preprint":false},{"pmid":"22475410","id":"PMC_22475410","title":"Structure and function of collectin liver 1 (CL-L1) and collectin 11 (CL-11, CL-K1).","date":"2012","source":"Immunobiology","url":"https://pubmed.ncbi.nlm.nih.gov/22475410","citation_count":79,"is_preprint":false},{"pmid":"27377710","id":"PMC_27377710","title":"The collectins CL-L1, CL-K1 and CL-P1, and their roles in complement and innate immunity.","date":"2016","source":"Immunobiology","url":"https://pubmed.ncbi.nlm.nih.gov/27377710","citation_count":71,"is_preprint":false},{"pmid":"23954398","id":"PMC_23954398","title":"Characterization of the interaction between collectin 11 (CL-11, CL-K1) and nucleic acids.","date":"2013","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/23954398","citation_count":53,"is_preprint":false},{"pmid":"22301270","id":"PMC_22301270","title":"An enzyme-linked immunosorbent assay (ELISA) for quantification of human collectin 11 (CL-11, CL-K1).","date":"2011","source":"Journal of immunological methods","url":"https://pubmed.ncbi.nlm.nih.gov/22301270","citation_count":50,"is_preprint":false},{"pmid":"30108587","id":"PMC_30108587","title":"CL-L1 and CL-K1 Exhibit Widespread Tissue Distribution With High and Co-Localized Expression in Secretory Epithelia and Mucosa.","date":"2018","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/30108587","citation_count":29,"is_preprint":false},{"pmid":"18040075","id":"PMC_18040075","title":"Immunolocalization of a novel collectin CL-K1 in murine tissues.","date":"2007","source":"The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society","url":"https://pubmed.ncbi.nlm.nih.gov/18040075","citation_count":29,"is_preprint":false},{"pmid":"25710878","id":"PMC_25710878","title":"Genetic variation of COLEC10 and COLEC11 and association with serum levels of collectin liver 1 (CL-L1) and collectin kidney 1 (CL-K1).","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25710878","citation_count":28,"is_preprint":false},{"pmid":"32751929","id":"PMC_32751929","title":"Association of Polymorphisms of MASP1/3, COLEC10, and COLEC11 Genes with 3MC Syndrome.","date":"2020","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32751929","citation_count":25,"is_preprint":false},{"pmid":"30323815","id":"PMC_30323815","title":"Development of a Quantitative Assay for the Characterization of Human Collectin-11 (CL-11, CL-K1).","date":"2018","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/30323815","citation_count":17,"is_preprint":false},{"pmid":"25807310","id":"PMC_25807310","title":"Lectin complement protein Collectin 11 (CL-K1) and susceptibility to urinary schistosomiasis.","date":"2015","source":"PLoS neglected tropical diseases","url":"https://pubmed.ncbi.nlm.nih.gov/25807310","citation_count":14,"is_preprint":false},{"pmid":"30995222","id":"PMC_30995222","title":"Human collectin-11 (COLEC11) and its synergic genetic interaction with MASP2 are associated with the pathophysiology of Chagas Disease.","date":"2019","source":"PLoS neglected tropical diseases","url":"https://pubmed.ncbi.nlm.nih.gov/30995222","citation_count":11,"is_preprint":false},{"pmid":"36669601","id":"PMC_36669601","title":"The collectin subfamily member 11 (Ca-Colec11) from Qihe crucian carp (Carassius auratus) agglutinates and inhibits Aeromonas hydrophila and Staphylococcus aureus.","date":"2023","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/36669601","citation_count":8,"is_preprint":false},{"pmid":"38180157","id":"PMC_38180157","title":"CL-K1 Promotes Complement Activation and Regulates Opsonophagocytosis of Macrophages with CD93 Interaction in a Primitive Vertebrate.","date":"2024","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/38180157","citation_count":6,"is_preprint":false},{"pmid":"41578380","id":"PMC_41578380","title":"COLEC10 and COLEC11 are new serum biomarkers of chronic liver disease.","date":"2026","source":"European journal of medical research","url":"https://pubmed.ncbi.nlm.nih.gov/41578380","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11236,"output_tokens":2114,"usd":0.032709,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9067,"output_tokens":2509,"usd":0.05403,"stage2_stop_reason":"end_turn"},"total_usd":0.086739,"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\": 2010,\n      \"finding\": \"CL-11 (CL-K1) circulates in plasma and physically associates with MASP-1 and/or MASP-3, demonstrated by co-purification and ELISA. CL-11 forms disulfide-linked oligomers (~100 and 200 kDa). It exhibits Ca2+-dependent lectin activity with preference for L-fucose and D-mannose, and binds intact bacteria, fungi, and viruses, including decreasing influenza A virus infectivity.\",\n      \"method\": \"Gel permeation chromatography, co-purification, ELISA, Western blot, mass spectrometry, in vitro binding assays\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (co-purification, ELISA, binding assays, MS) in a single rigorous characterization study; replicated in subsequent papers\",\n      \"pmids\": [\"20956340\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"CL-K1 is a secreted protein with Ca2+-dependent sugar-binding activity showing preference for fucose and weakly mannose, but not N-acetyl-galactosamine, N-acetyl-glucosamine, or maltose. It recognizes specific bacterial saccharides.\",\n      \"method\": \"cDNA cloning, immunostaining of CL-K1 cDNA-expressing CHO cells, sugar-binding assays\",\n      \"journal\": \"Microbiology and immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding assays and cell expression system in founding characterization study, single lab\",\n      \"pmids\": [\"17179669\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Loss-of-function mutations in COLEC11 cause 3MC syndrome. CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney and vertebral bodies. In zebrafish, morpholino knockdown of COLEC11 produces pigmentary defects and severe craniofacial abnormalities. CL-K1 serves as a guidance cue for neural crest cell migration.\",\n      \"method\": \"Human genetic sequencing (11 families), in situ hybridization/immunostaining in murine embryos, zebrafish morpholino knockdown, neural crest cell migration assay\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — human genetic data combined with zebrafish loss-of-function and neural crest migration functional assay, replicated across multiple families and orthogonal systems\",\n      \"pmids\": [\"21258343\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CL-11 binds DNA in a calcium-independent manner via a binding site distinct from its carbohydrate-recognition domain. Binding is sensitive to ionic strength and pH, and oligomericity is required for binding activity. CL-11 also binds apoptotic cells presenting extracellular DNA. The dissociation constant for double-stranded DNA is KD = 9–20 nM (surface plasmon resonance). In vitro, CL-11 binding to DNA-coated surfaces leads to C4b deposition via MASP-2, indicating lectin pathway complement activation.\",\n      \"method\": \"Binding assays, competition studies, surface plasmon resonance, in vitro C4b deposition assay\",\n      \"journal\": \"Molecular immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — SPR quantitative binding, competition/mutagenesis-like domain separation, functional complement activation assay; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"23954398\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CL-11 is a serum protein, whereas its paralog CL-L1 is restricted to the cytosol. CL-11 CRD binds most avidly to L-fucose and D-mannose; CL-L1 shows different specificity. CL-11 binds E. coli, Candida albicans, and influenza A virus. CL-11 is found in circulation in complexes with MASP-1/3.\",\n      \"method\": \"Structural characterization, specificity analysis of CRD, binding assays, co-immunoprecipitation/co-purification\",\n      \"journal\": \"Immunobiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — review/characterization paper consolidating prior experimental findings with some new structural comparisons; single lab\",\n      \"pmids\": [\"22475410\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CL-K1 and CL-L1 have widespread, nearly identical tissue distribution with high expression in epithelial cells of endo-/exocrine secretory tissues and mucosa. Local synthesis at peripheral sites is responsible for the peripheral localization and likely the formation of CL-LK heteromeric complexes. Both proteins co-localize, consistent with heteromeric complex formation in peripheral tissues.\",\n      \"method\": \"Immunohistochemistry with monoclonal antibodies, mRNA in situ localization across human tissues\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — systematic IHC with mRNA validation across tissues, single lab, localization without direct functional consequence established\",\n      \"pmids\": [\"30108587\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CL-11 circulates in heterocomplexes with CL-10 (collectin-10) as two major complexes of ~400 and >600 kDa. CL-11 can bind zymosan independently of calcium via a site separate from its carbohydrate-binding region. CL-11/MASP-2 complexes trigger C4b deposition on zymosan, demonstrating lectin pathway activation.\",\n      \"method\": \"Size exclusion chromatography, ELISA, in vitro C4b deposition assay, calcium-independent binding assays\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional complement activation assay and biochemical characterization of complexes, single lab, multiple methods\",\n      \"pmids\": [\"30323815\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"CL-K1 localizes to proximal tubules of kidney, gastrointestinal mucosa, bronchial glands, hepatocytes around central veins (consistent with hepatic synthesis and secretion into blood), vascular smooth muscle, intestinal Paneth cells, mesangial cells of kidney, pancreatic islet D cells, and neurons.\",\n      \"method\": \"Immunohistochemistry and real-time PCR in murine tissues\",\n      \"journal\": \"The journal of histochemistry and cytochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — systematic IHC across multiple murine tissues; single lab, no direct functional consequence established\",\n      \"pmids\": [\"18040075\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"COLEC11 (CL-K1) is a secreted, oligomeric C-type lectin collectin that circulates in plasma as heteromeric complexes with CL-L1 (CL-LK) and associates with MASP-1/3; it binds microbial surfaces via Ca2+-dependent recognition of L-fucose and D-mannose and binds DNA/apoptotic cells via a separate, Ca2+-independent site, in both cases activating the lectin complement pathway through MASP-2-dependent C4b deposition; during embryogenesis, CL-K1 acts as a guidance cue for neural crest cell migration, and loss-of-function mutations in COLEC11 cause the developmental disorder 3MC syndrome.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"COLEC11 (CL-K1/CL-11) is a secreted, oligomeric C-type lectin collectin that functions as a recognition molecule of the lectin complement pathway and as a developmental guidance cue [#0, #2]. It circulates in plasma as disulfide-linked oligomers in association with MASP-1/3, and recognizes microbial surfaces—bacteria, fungi, and viruses including influenza A—through Ca2+-dependent binding of L-fucose and D-mannose [#0, #4]. In parallel, it engages DNA and apoptotic cells presenting extracellular DNA through a high-affinity, Ca2+-independent site distinct from its carbohydrate-recognition domain, with oligomerization required for binding [#3]. Upon engaging either microbial carbohydrate or DNA ligands, CL-11 drives MASP-2-dependent C4b deposition, activating the lectin pathway [#3, #6]. It circulates and acts in heteromeric complexes with the paralogous collectin CL-10/CL-L1, whose co-expression at peripheral epithelial and secretory tissues supports local heterocomplex assembly [#5, #6]. Beyond innate immunity, CL-K1 serves as a guidance cue for neural crest cell migration during embryogenesis, and loss-of-function mutations in COLEC11 cause the developmental disorder 3MC syndrome [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing that CL-K1 is a secreted protein with defined Ca2+-dependent sugar specificity answered the basic question of what class of molecule it is and what it recognizes.\",\n      \"evidence\": \"cDNA cloning, CHO cell expression, and sugar-binding assays\",\n      \"pmids\": [\"17179669\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No physiological ligand or downstream pathway identified\", \"Single lab, founding characterization\", \"No oligomeric or complex partner defined\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Mapping CL-K1 tissue distribution addressed where the protein is produced and likely acts, implicating hepatic synthesis with secretion into blood and broad epithelial expression.\",\n      \"evidence\": \"Immunohistochemistry and real-time PCR across murine tissues\",\n      \"pmids\": [\"18040075\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Localization without direct functional consequence\", \"Does not establish secretion mechanism or circulating form\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Demonstrating physical association with MASP-1/3 and oligomerization placed CL-11 within the lectin complement pathway and connected its carbohydrate recognition to an effector module.\",\n      \"evidence\": \"Co-purification, ELISA, mass spectrometry, and in vitro microbial binding assays\",\n      \"pmids\": [\"20956340\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not demonstrate direct C4b deposition/complement activation\", \"MASP-1 vs MASP-3 functional roles not resolved\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Identifying COLEC11 loss-of-function as the cause of 3MC syndrome and a neural crest guidance role established a developmental function distinct from immunity.\",\n      \"evidence\": \"Human genetic sequencing across 11 families, murine embryo expression, zebrafish morpholino knockdown, and neural crest migration assay\",\n      \"pmids\": [\"21258343\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular receptor/signaling for neural crest guidance not defined\", \"Relationship between immune and developmental functions unresolved\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Distinguishing CL-11 (serum) from its cytosolic paralog CL-L1 and detailing CRD specificity clarified which collectin operates extracellularly in circulation.\",\n      \"evidence\": \"Structural/specificity characterization, binding assays, and co-purification\",\n      \"pmids\": [\"22475410\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Consolidation paper, limited new primary data\", \"Heterocomplex stoichiometry not defined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Showing high-affinity, Ca2+-independent DNA binding via a site separate from the CRD, coupled to MASP-2-driven C4b deposition, revealed a second ligand class linking CL-11 to apoptotic-cell handling and complement activation.\",\n      \"evidence\": \"Surface plasmon resonance, competition/domain-separation binding studies, apoptotic cell binding, and in vitro C4b deposition assay\",\n      \"pmids\": [\"23954398\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"DNA-binding site not mapped at residue level\", \"In vivo relevance of DNA-triggered complement activation not established\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Defining CL-11/CL-10 heterocomplexes and their tissue co-expression established the physiological circulating and local assembly state of the protein and confirmed MASP-2-dependent activation on microbial surfaces.\",\n      \"evidence\": \"Size exclusion chromatography, ELISA, IHC/mRNA localization, and in vitro C4b deposition on zymosan\",\n      \"pmids\": [\"30323815\", \"30108587\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional difference between homo- and heterocomplexes not quantified\", \"Single lab biochemistry\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CL-K1 transduces neural crest guidance and whether this developmental role intersects with its complement-activating function remains unresolved.\",\n      \"evidence\": \"No direct mechanistic study in the available corpus links the guidance cue activity to a receptor or signaling pathway\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No neural crest receptor identified\", \"No structural model of ligand discrimination\", \"Mechanistic basis of 3MC pathology unexplained\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0030246\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0001618\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [0, 4, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [0, 3, 6]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"CL-LK (CL-K1/CL-L1 heterocomplex)\", \"CL-K1/MASP-1/3 complex\", \"CL-11/CL-10 heterocomplex\"],\n    \"partners\": [\"MASP1\", \"MASP3\", \"MASP2\", \"COLEC10\", \"COLEC9\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}