{"gene":"COLEC11","run_date":"2026-04-28T17:28:53","timeline":{"discoveries":[{"year":2010,"finding":"CL-11 (COLEC11) forms disulfide-linked oligomers and associates with MASP-1 and/or MASP-3 in plasma, demonstrated by co-purification, ELISA, and gel permeation chromatography. CL-11 shows Ca2+-dependent lectin activity with preference for L-fucose and D-mannose, binds intact bacteria, fungi, and viruses, reduces influenza A virus infectivity, and forms complexes with DNA.","method":"Co-purification, ELISA, gel permeation chromatography, Western blotting, mass spectrometry, in vitro binding and infectivity assays","journal":"Journal of immunology","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal biochemical methods in a single study, replicated by subsequent work","pmids":["20956340"],"is_preprint":false},{"year":2006,"finding":"CL-K1 (COLEC11) is a secreted protein with Ca2+-dependent sugar-binding activity for L-fucose and weakly D-mannose, identified by cloning, immunostaining of transfected CHO cells, and immunoblotting of blood.","method":"RT-PCR, immunostaining of CL-K1 cDNA-expressing CHO cells, immunoblotting, sugar-binding ELISA","journal":"Microbiology and immunology","confidence":"Medium","confidence_rationale":"Tier 2 — direct functional assays with recombinant protein; single lab","pmids":["17179669"],"is_preprint":false},{"year":2011,"finding":"Mutations in COLEC11 cause 3MC syndrome. CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney, and vertebral bodies. Zebrafish morphants for COLEC11 develop pigmentary defects and severe craniofacial abnormalities. CL-K1 serves as a guidance cue for neural crest cell migration.","method":"Human genetics (mutation identification), in situ hybridization/immunostaining in mouse embryos, zebrafish morpholino knockdown with phenotypic readout, neural crest cell migration assay","journal":"Nature genetics","confidence":"High","confidence_rationale":"Tier 2 — genetic and functional evidence across multiple species; 196 citations indicating broad replication and acceptance","pmids":["21258343"],"is_preprint":false},{"year":2013,"finding":"CL-11 binds DNA from various origins in a calcium-independent manner, distinct from its carbohydrate-binding site. CL-11 binds apoptotic cells presenting extracellular DNA. Surface plasmon resonance measured KD = 9-20 nM for dsDNA oligonucleotides. CL-11 bound to DNA-coated surfaces leads to C4b deposition via MASP-2, linking CL-11-DNA interaction to complement activation.","method":"ELISA competition assays, surface plasmon resonance, in vitro C4b deposition assay, flow cytometry (apoptotic cell binding)","journal":"Molecular immunology","confidence":"High","confidence_rationale":"Tier 1-2 — SPR quantification plus functional complement assay, multiple orthogonal methods in single study","pmids":["23954398"],"is_preprint":false},{"year":2014,"finding":"MAP-1 forms heterocomplexes with MASP-1 and MASP-3 in a calcium-dependent manner, and MASP-1 and MASP-3 also form heterocomplexes with each other; these complexes, which include collectin-11 as a recognition molecule, exist in normal human serum/plasma.","method":"ELISA, size-exclusion chromatography, immunoblotting using recombinant proteins and serum/plasma","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal ELISA and chromatography in serum; single lab","pmids":["24683193"],"is_preprint":false},{"year":2018,"finding":"CL-L1 and CL-K1 exhibit widespread, nearly identical tissue distribution with high expression in epithelial cells of endo-/exocrine secretory tissues and mucosa, consistent with local synthesis forming peripheral CL-LK heterocomplexes, as confirmed by correspondence between mRNA and protein localization.","method":"Immunohistochemistry with monoclonal antibodies, mRNA localization by in situ methods across human tissues","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2 — direct protein localization with functional context; single lab but comprehensive tissue coverage","pmids":["30108587"],"is_preprint":false},{"year":2018,"finding":"CL-11 engages with L-fucose exposed at the surface of proximal tubular epithelial cells under ischaemic stress, triggering local complement activation as a tissue-based pattern recognition molecule.","method":"In vitro binding assays, complement activation assays with renal epithelial cells under ischaemic conditions","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2-3 — mechanistic hypothesis with supporting in vitro evidence; single lab","pmids":["30237800"],"is_preprint":false},{"year":2018,"finding":"CL-11 binds zymosan independently of calcium via a site separate from its carbohydrate-binding region. CL-11/MASP-2 complexes trigger C4b deposition on zymosan. Native CL-11 circulates as CL-10/11 heterocomplexes of ~400 and >600 kDa.","method":"ELISA with blocking antibodies, size exclusion chromatography, C4b deposition assay, immunoprecipitation","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2 — multiple functional assays identifying distinct binding site; single lab","pmids":["30323815"],"is_preprint":false},{"year":2023,"finding":"Soluble CL-11 inhibits T cell proliferation via its collagen-like domain binding to T cells; this suppression is abrogated by the RGD peptide blocking CL-11 collagen-like domain binding. RPE cells bind and secrete CL-11 under stress, contributing to immunosuppression via CD28 downregulation on T cells.","method":"Co-culture of RPE cells with T cells, proliferation assays, RGD peptide blocking, flow cytometry for CD28","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2 — functional co-culture assays with specific blocking peptide; single lab","pmids":["37443840"],"is_preprint":false},{"year":2024,"finding":"CL-11 circulates as two alternatively spliced isoforms (A and D) differing in collagen-like region length. Both associate with CL-10, but CL-11D does so less efficiently. CL-10/11 heterocomplexes consist of trimeric subunits and are more stable than homotrimers. Native CL-11 associates with MASP-1 and MASP-3 but not necessarily MASP-2 in CL-10/11 heterocomplexes. CL-11D has reduced ligand binding and is hypothesized to have lower complement activation potential.","method":"Recombinant protein production, immunoprecipitation, mass spectrometry, size exclusion chromatography, functional binding assays","journal":"FASEB journal","confidence":"High","confidence_rationale":"Tier 1-2 — recombinant isoform reconstitution, mass spectrometry of native serum complexes, multiple orthogonal methods","pmids":["38466278"],"is_preprint":false},{"year":2025,"finding":"CL-11 deletion combined with deficiency of complement components MASP-2, CFB, or C3 causes vertebral bone loss and spinal curvature in mice. Ex vivo osteoclast differentiation is impaired in double-knockout mice but restored by CL-11 supplementation. CL-11 and C5b-9 (membrane attack complex) co-localize to osteoclasts and their precursors from embryonic stages, identifying CL-11 as a regulator of osteoclastogenesis in concert with complement.","method":"Double-knockout mouse models, ex vivo osteoclast differentiation assay, CL-11 supplementation rescue, immunolocalization of CL-11 and C5b-9 in bone tissue","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 — genetic epistasis via double-KO mice with rescue experiment; preprint, not yet peer-reviewed","pmids":["bio_10.1101_2025.05.08.652605"],"is_preprint":true}],"current_model":"COLEC11 (CL-K1/CL-11) is a secreted collectin that forms disulfide-linked oligomers and circulates in plasma as heterocomplexes with CL-L1 (CL-10) in two alternatively spliced isoforms; it binds L-fucose and D-mannose via its Ca2+-dependent carbohydrate recognition domain, binds DNA and apoptotic cells via a separate site, associates with MASP-1/MASP-3 to activate the lectin complement pathway (generating C4b deposition), serves as a guidance cue for neural crest cell migration during embryogenesis, and acts in concert with complement components to regulate osteoclastogenesis and bone maintenance, while its collagen-like domain can also suppress T cell proliferation independently of complement."},"narrative":{"teleology":[{"year":2006,"claim":"Identification of COLEC11 as a secreted collectin with Ca²⁺-dependent sugar-binding activity established it as a new member of the collectin family capable of recognizing L-fucose and D-mannose.","evidence":"Cloning, recombinant expression in CHO cells, sugar-binding ELISA, and detection in human blood","pmids":["17179669"],"confidence":"Medium","gaps":["Single lab; ligand specificity not fully characterized","No in vivo functional data","Oligomeric state and serum partners unknown"]},{"year":2010,"claim":"Demonstration that CL-11 forms disulfide-linked oligomers, associates with MASP-1/MASP-3, binds intact pathogens, reduces influenza infectivity, and complexes with DNA revealed it as a functional innate immune recognition molecule capable of engaging both microbial and self ligands.","evidence":"Co-purification, ELISA, gel permeation chromatography, mass spectrometry, in vitro pathogen-binding and viral infectivity assays","pmids":["20956340"],"confidence":"High","gaps":["Complement activation downstream of MASP association not yet demonstrated","DNA-binding site relationship to CRD not resolved","In vivo relevance of antiviral activity not tested"]},{"year":2011,"claim":"Discovery that COLEC11 mutations cause 3MC syndrome and that CL-K1 acts as a neural crest cell migration guidance cue resolved the gene's developmental role and established a direct genotype–phenotype link to craniofacial malformation.","evidence":"Human genetic studies identifying causative mutations, mouse embryo expression mapping, zebrafish morpholino knockdown with craniofacial and pigmentary phenotypes, neural crest migration assay","pmids":["21258343"],"confidence":"High","gaps":["Receptor on neural crest cells mediating CL-K1 guidance not identified","Whether complement activation is required for developmental function is unknown","Molecular mechanism of migration guidance not dissected"]},{"year":2013,"claim":"Showing that CL-11 binds DNA with nanomolar affinity via a Ca²⁺-independent site distinct from the CRD, engages apoptotic cells, and triggers MASP-2-dependent C4b deposition established CL-11 as a dual-site recognition molecule linking self-DNA sensing to lectin pathway complement activation.","evidence":"Surface plasmon resonance (KD 9–20 nM), ELISA competition, C4b deposition assay, flow cytometry on apoptotic cells","pmids":["23954398"],"confidence":"High","gaps":["Physiological relevance of DNA-triggered complement activation in vivo not tested","Whether CL-11-DNA binding contributes to autoimmune pathology unknown"]},{"year":2014,"claim":"Characterization of MAP-1/MASP-1/MASP-3 heterocomplexes with CL-11 in normal human plasma defined the native serine protease partners of the CL-11 recognition complex.","evidence":"Reciprocal ELISA, size-exclusion chromatography, immunoblotting with recombinant and serum-derived proteins","pmids":["24683193"],"confidence":"Medium","gaps":["Single lab study","Functional consequence of MAP-1 inclusion in the complex not determined","Stoichiometry of native complexes not resolved"]},{"year":2018,"claim":"Three studies collectively established that CL-11 circulates as CL-10/CL-11 heterocomplexes of ~400 and >600 kDa, is co-expressed with CL-L1 in epithelial and secretory tissues, binds zymosan via a calcium-independent site, and recognizes L-fucose on ischaemic renal tubular cells to trigger local complement activation.","evidence":"Immunohistochemistry across human tissues, size exclusion chromatography, ELISA with blocking antibodies, C4b deposition assay, binding assays on ischaemic renal epithelial cells","pmids":["30108587","30237800","30323815"],"confidence":"Medium","gaps":["In vivo ischaemia-reperfusion studies with CL-11 knockout not yet performed at this stage","Structural basis of calcium-independent zymosan binding unknown","Relative contribution of CL-10/11 heterocomplexes versus CL-11 homotrimers to complement activation in vivo unclear"]},{"year":2023,"claim":"Discovery that CL-11's collagen-like domain suppresses T cell proliferation by downregulating CD28, blocked by RGD peptide, revealed a complement-independent immunoregulatory function mediated through integrin engagement.","evidence":"RPE/T cell co-culture, proliferation assays, RGD peptide competition, flow cytometry for CD28","pmids":["37443840"],"confidence":"Medium","gaps":["Specific integrin receptor on T cells not identified","In vivo immunosuppressive relevance not demonstrated","Whether this function operates outside the ocular microenvironment is unknown"]},{"year":2024,"claim":"Resolution of two alternatively spliced CL-11 isoforms (A and D) differing in collagen-like domain length, with isoform D showing reduced CL-10 association and ligand binding, clarified the molecular heterogeneity of circulating CL-10/11 complexes.","evidence":"Recombinant isoform production, immunoprecipitation, mass spectrometry of native serum complexes, size exclusion chromatography, functional binding assays","pmids":["38466278"],"confidence":"High","gaps":["Functional consequence of isoform ratio differences in disease not tested","Crystal structure of CL-10/11 heterocomplex not available","Whether isoform D has distinct developmental or immunoregulatory roles is unknown"]},{"year":2025,"claim":"Genetic epistasis experiments showing that CL-11 deletion combined with complement deficiency causes vertebral bone loss, rescued by CL-11 supplementation, established CL-11 as a regulator of osteoclastogenesis acting in concert with the complement cascade.","evidence":"(preprint) Double-knockout mice (CL-11 with MASP-2, CFB, or C3), ex vivo osteoclast differentiation with rescue, immunolocalization of CL-11 and C5b-9 in bone","pmids":["bio_10.1101_2025.05.08.652605"],"confidence":"Medium","gaps":["Preprint, not yet peer-reviewed","Direct molecular mechanism by which CL-11 promotes osteoclast differentiation not defined","Whether the bone phenotype relates to 3MC syndrome skeletal features unknown"]},{"year":null,"claim":"The receptor on neural crest cells that mediates CL-K1 guidance signaling, the structural basis of the CL-10/CL-11 heterocomplex, and the relative physiological contributions of the two splice isoforms and complement-dependent versus complement-independent functions of CL-11 remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["Neural crest receptor for CL-K1 unidentified","No high-resolution structure of CL-10/11 complex","In vivo functional partitioning between isoforms A and D not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[0,1,6]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[0,3]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[3,7,10]}],"localization":[{"term_id":"GO:0005576","term_label":"extracellular region","supporting_discovery_ids":[0,1,5,9]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[0,3,7]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[2]}],"complexes":["CL-10/CL-11 (CL-LK) heterocomplex","CL-11/MASP-1/MASP-3 complex"],"partners":["COLEC10","MASP1","MASP2","MAP1"],"other_free_text":[]},"mechanistic_narrative":"COLEC11 (CL-K1/CL-11) is a secreted collectin that functions as a soluble pattern recognition molecule in innate immunity, complement activation, embryonic development, and bone homeostasis. It forms disulfide-linked oligomers that circulate predominantly as heterocomplexes with CL-L1 (CL-10) in two alternatively spliced isoforms, associates with MASP-1 and MASP-3, and activates the lectin complement pathway via MASP-2-dependent C4b deposition upon binding L-fucose, D-mannose, DNA, or zymosan through both Ca²⁺-dependent and Ca²⁺-independent recognition sites [PMID:20956340, PMID:23954398, PMID:30323815, PMID:38466278]. Loss-of-function mutations in COLEC11 cause 3MC syndrome, a developmental disorder with craniofacial abnormalities, reflecting CL-K1's role as a guidance cue for neural crest cell migration during embryogenesis [PMID:21258343]. CL-11 additionally suppresses T cell proliferation through its collagen-like domain via an integrin-dependent mechanism involving CD28 downregulation, and cooperates with complement components to regulate osteoclastogenesis and vertebral bone maintenance [PMID:37443840, PMID:bio_10.1101_2025.05.08.652605]."},"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":196,"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":70,"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":48,"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":28,"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":"30237800","id":"PMC_30237800","title":"Collectin-11 (CL-11) Is a Major Sentinel at Epithelial Surfaces and Key Pattern Recognition Molecule in Complement-Mediated Ischaemic Injury.","date":"2018","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/30237800","citation_count":22,"is_preprint":false},{"pmid":"24683193","id":"PMC_24683193","title":"Heterocomplex formation between MBL/ficolin/CL-11-associated serine protease-1 and -3 and MBL/ficolin/CL-11-associated protein-1.","date":"2014","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/24683193","citation_count":17,"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":16,"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":"36265742","id":"PMC_36265742","title":"Identification and functional characterization of CL-11 in black rockfish (Sebastes schlegelii).","date":"2022","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/36265742","citation_count":5,"is_preprint":false},{"pmid":"35063609","id":"PMC_35063609","title":"Inhibition of CL-11 reduces pulmonary inflammation in a mouse model of Klebsiella pneumoniae lung infection.","date":"2022","source":"Microbial pathogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/35063609","citation_count":5,"is_preprint":false},{"pmid":"37443840","id":"PMC_37443840","title":"Soluble Collectin 11 (CL-11) Acts as an Immunosuppressive Molecule Potentially Used by Stem Cell-Derived Retinal Epithelial Cells to Modulate T Cell Response.","date":"2023","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/37443840","citation_count":4,"is_preprint":false},{"pmid":"38466278","id":"PMC_38466278","title":"CL-11 circulates in serum as functionally distinct isoforms.","date":"2024","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/38466278","citation_count":1,"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},{"pmid":"40562260","id":"PMC_40562260","title":"Molecular characterization of CL-11 in large yellow croaker (Larimichthys crocea) and its role in antibacterial defense.","date":"2025","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/40562260","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.05.08.652605","title":"Collectin-11 regulates osteoclastogenesis and bone maintenance via a complement-dependent mechanism","date":"2025-05-13","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.08.652605","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":14337,"output_tokens":2715,"usd":0.041868},"stage2":{"model":"claude-opus-4-6","input_tokens":6040,"output_tokens":2693,"usd":0.146287},"total_usd":0.188155,"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\": 2010,\n      \"finding\": \"CL-11 (COLEC11) forms disulfide-linked oligomers and associates with MASP-1 and/or MASP-3 in plasma, demonstrated by co-purification, ELISA, and gel permeation chromatography. CL-11 shows Ca2+-dependent lectin activity with preference for L-fucose and D-mannose, binds intact bacteria, fungi, and viruses, reduces influenza A virus infectivity, and forms complexes with DNA.\",\n      \"method\": \"Co-purification, ELISA, gel permeation chromatography, Western blotting, mass spectrometry, in vitro binding and infectivity assays\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal biochemical methods in a single study, replicated by subsequent work\",\n      \"pmids\": [\"20956340\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"CL-K1 (COLEC11) is a secreted protein with Ca2+-dependent sugar-binding activity for L-fucose and weakly D-mannose, identified by cloning, immunostaining of transfected CHO cells, and immunoblotting of blood.\",\n      \"method\": \"RT-PCR, immunostaining of CL-K1 cDNA-expressing CHO cells, immunoblotting, sugar-binding ELISA\",\n      \"journal\": \"Microbiology and immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct functional assays with recombinant protein; single lab\",\n      \"pmids\": [\"17179669\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Mutations in COLEC11 cause 3MC syndrome. CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney, and vertebral bodies. Zebrafish morphants for COLEC11 develop pigmentary defects and severe craniofacial abnormalities. CL-K1 serves as a guidance cue for neural crest cell migration.\",\n      \"method\": \"Human genetics (mutation identification), in situ hybridization/immunostaining in mouse embryos, zebrafish morpholino knockdown with phenotypic readout, neural crest cell migration assay\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic and functional evidence across multiple species; 196 citations indicating broad replication and acceptance\",\n      \"pmids\": [\"21258343\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CL-11 binds DNA from various origins in a calcium-independent manner, distinct from its carbohydrate-binding site. CL-11 binds apoptotic cells presenting extracellular DNA. Surface plasmon resonance measured KD = 9-20 nM for dsDNA oligonucleotides. CL-11 bound to DNA-coated surfaces leads to C4b deposition via MASP-2, linking CL-11-DNA interaction to complement activation.\",\n      \"method\": \"ELISA competition assays, surface plasmon resonance, in vitro C4b deposition assay, flow cytometry (apoptotic cell binding)\",\n      \"journal\": \"Molecular immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — SPR quantification plus functional complement assay, multiple orthogonal methods in single study\",\n      \"pmids\": [\"23954398\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"MAP-1 forms heterocomplexes with MASP-1 and MASP-3 in a calcium-dependent manner, and MASP-1 and MASP-3 also form heterocomplexes with each other; these complexes, which include collectin-11 as a recognition molecule, exist in normal human serum/plasma.\",\n      \"method\": \"ELISA, size-exclusion chromatography, immunoblotting using recombinant proteins and serum/plasma\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal ELISA and chromatography in serum; single lab\",\n      \"pmids\": [\"24683193\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CL-L1 and CL-K1 exhibit widespread, nearly identical tissue distribution with high expression in epithelial cells of endo-/exocrine secretory tissues and mucosa, consistent with local synthesis forming peripheral CL-LK heterocomplexes, as confirmed by correspondence between mRNA and protein localization.\",\n      \"method\": \"Immunohistochemistry with monoclonal antibodies, mRNA localization by in situ methods across human tissues\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct protein localization with functional context; single lab but comprehensive tissue coverage\",\n      \"pmids\": [\"30108587\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CL-11 engages with L-fucose exposed at the surface of proximal tubular epithelial cells under ischaemic stress, triggering local complement activation as a tissue-based pattern recognition molecule.\",\n      \"method\": \"In vitro binding assays, complement activation assays with renal epithelial cells under ischaemic conditions\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — mechanistic hypothesis with supporting in vitro evidence; single lab\",\n      \"pmids\": [\"30237800\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CL-11 binds zymosan independently of calcium via a site separate from its carbohydrate-binding region. CL-11/MASP-2 complexes trigger C4b deposition on zymosan. Native CL-11 circulates as CL-10/11 heterocomplexes of ~400 and >600 kDa.\",\n      \"method\": \"ELISA with blocking antibodies, size exclusion chromatography, C4b deposition assay, immunoprecipitation\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple functional assays identifying distinct binding site; single lab\",\n      \"pmids\": [\"30323815\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Soluble CL-11 inhibits T cell proliferation via its collagen-like domain binding to T cells; this suppression is abrogated by the RGD peptide blocking CL-11 collagen-like domain binding. RPE cells bind and secrete CL-11 under stress, contributing to immunosuppression via CD28 downregulation on T cells.\",\n      \"method\": \"Co-culture of RPE cells with T cells, proliferation assays, RGD peptide blocking, flow cytometry for CD28\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — functional co-culture assays with specific blocking peptide; single lab\",\n      \"pmids\": [\"37443840\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CL-11 circulates as two alternatively spliced isoforms (A and D) differing in collagen-like region length. Both associate with CL-10, but CL-11D does so less efficiently. CL-10/11 heterocomplexes consist of trimeric subunits and are more stable than homotrimers. Native CL-11 associates with MASP-1 and MASP-3 but not necessarily MASP-2 in CL-10/11 heterocomplexes. CL-11D has reduced ligand binding and is hypothesized to have lower complement activation potential.\",\n      \"method\": \"Recombinant protein production, immunoprecipitation, mass spectrometry, size exclusion chromatography, functional binding assays\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — recombinant isoform reconstitution, mass spectrometry of native serum complexes, multiple orthogonal methods\",\n      \"pmids\": [\"38466278\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CL-11 deletion combined with deficiency of complement components MASP-2, CFB, or C3 causes vertebral bone loss and spinal curvature in mice. Ex vivo osteoclast differentiation is impaired in double-knockout mice but restored by CL-11 supplementation. CL-11 and C5b-9 (membrane attack complex) co-localize to osteoclasts and their precursors from embryonic stages, identifying CL-11 as a regulator of osteoclastogenesis in concert with complement.\",\n      \"method\": \"Double-knockout mouse models, ex vivo osteoclast differentiation assay, CL-11 supplementation rescue, immunolocalization of CL-11 and C5b-9 in bone tissue\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis via double-KO mice with rescue experiment; preprint, not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.05.08.652605\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"COLEC11 (CL-K1/CL-11) is a secreted collectin that forms disulfide-linked oligomers and circulates in plasma as heterocomplexes with CL-L1 (CL-10) in two alternatively spliced isoforms; it binds L-fucose and D-mannose via its Ca2+-dependent carbohydrate recognition domain, binds DNA and apoptotic cells via a separate site, associates with MASP-1/MASP-3 to activate the lectin complement pathway (generating C4b deposition), serves as a guidance cue for neural crest cell migration during embryogenesis, and acts in concert with complement components to regulate osteoclastogenesis and bone maintenance, while its collagen-like domain can also suppress T cell proliferation independently of complement.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"COLEC11 (CL-K1/CL-11) is a secreted collectin that functions as a soluble pattern recognition molecule in innate immunity, complement activation, embryonic development, and bone homeostasis. It forms disulfide-linked oligomers that circulate predominantly as heterocomplexes with CL-L1 (CL-10) in two alternatively spliced isoforms, associates with MASP-1 and MASP-3, and activates the lectin complement pathway via MASP-2-dependent C4b deposition upon binding L-fucose, D-mannose, DNA, or zymosan through both Ca²⁺-dependent and Ca²⁺-independent recognition sites [PMID:20956340, PMID:23954398, PMID:30323815, PMID:38466278]. Loss-of-function mutations in COLEC11 cause 3MC syndrome, a developmental disorder with craniofacial abnormalities, reflecting CL-K1's role as a guidance cue for neural crest cell migration during embryogenesis [PMID:21258343]. CL-11 additionally suppresses T cell proliferation through its collagen-like domain via an integrin-dependent mechanism involving CD28 downregulation, and cooperates with complement components to regulate osteoclastogenesis and vertebral bone maintenance [PMID:37443840, PMID:bio_10.1101_2025.05.08.652605].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Identification of COLEC11 as a secreted collectin with Ca²⁺-dependent sugar-binding activity established it as a new member of the collectin family capable of recognizing L-fucose and D-mannose.\",\n      \"evidence\": \"Cloning, recombinant expression in CHO cells, sugar-binding ELISA, and detection in human blood\",\n      \"pmids\": [\"17179669\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab; ligand specificity not fully characterized\", \"No in vivo functional data\", \"Oligomeric state and serum partners unknown\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Demonstration that CL-11 forms disulfide-linked oligomers, associates with MASP-1/MASP-3, binds intact pathogens, reduces influenza infectivity, and complexes with DNA revealed it as a functional innate immune recognition molecule capable of engaging both microbial and self ligands.\",\n      \"evidence\": \"Co-purification, ELISA, gel permeation chromatography, mass spectrometry, in vitro pathogen-binding and viral infectivity assays\",\n      \"pmids\": [\"20956340\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Complement activation downstream of MASP association not yet demonstrated\", \"DNA-binding site relationship to CRD not resolved\", \"In vivo relevance of antiviral activity not tested\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Discovery that COLEC11 mutations cause 3MC syndrome and that CL-K1 acts as a neural crest cell migration guidance cue resolved the gene's developmental role and established a direct genotype–phenotype link to craniofacial malformation.\",\n      \"evidence\": \"Human genetic studies identifying causative mutations, mouse embryo expression mapping, zebrafish morpholino knockdown with craniofacial and pigmentary phenotypes, neural crest migration assay\",\n      \"pmids\": [\"21258343\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Receptor on neural crest cells mediating CL-K1 guidance not identified\", \"Whether complement activation is required for developmental function is unknown\", \"Molecular mechanism of migration guidance not dissected\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Showing that CL-11 binds DNA with nanomolar affinity via a Ca²⁺-independent site distinct from the CRD, engages apoptotic cells, and triggers MASP-2-dependent C4b deposition established CL-11 as a dual-site recognition molecule linking self-DNA sensing to lectin pathway complement activation.\",\n      \"evidence\": \"Surface plasmon resonance (KD 9–20 nM), ELISA competition, C4b deposition assay, flow cytometry on apoptotic cells\",\n      \"pmids\": [\"23954398\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological relevance of DNA-triggered complement activation in vivo not tested\", \"Whether CL-11-DNA binding contributes to autoimmune pathology unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Characterization of MAP-1/MASP-1/MASP-3 heterocomplexes with CL-11 in normal human plasma defined the native serine protease partners of the CL-11 recognition complex.\",\n      \"evidence\": \"Reciprocal ELISA, size-exclusion chromatography, immunoblotting with recombinant and serum-derived proteins\",\n      \"pmids\": [\"24683193\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab study\", \"Functional consequence of MAP-1 inclusion in the complex not determined\", \"Stoichiometry of native complexes not resolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Three studies collectively established that CL-11 circulates as CL-10/CL-11 heterocomplexes of ~400 and >600 kDa, is co-expressed with CL-L1 in epithelial and secretory tissues, binds zymosan via a calcium-independent site, and recognizes L-fucose on ischaemic renal tubular cells to trigger local complement activation.\",\n      \"evidence\": \"Immunohistochemistry across human tissues, size exclusion chromatography, ELISA with blocking antibodies, C4b deposition assay, binding assays on ischaemic renal epithelial cells\",\n      \"pmids\": [\"30108587\", \"30237800\", \"30323815\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"In vivo ischaemia-reperfusion studies with CL-11 knockout not yet performed at this stage\", \"Structural basis of calcium-independent zymosan binding unknown\", \"Relative contribution of CL-10/11 heterocomplexes versus CL-11 homotrimers to complement activation in vivo unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Discovery that CL-11's collagen-like domain suppresses T cell proliferation by downregulating CD28, blocked by RGD peptide, revealed a complement-independent immunoregulatory function mediated through integrin engagement.\",\n      \"evidence\": \"RPE/T cell co-culture, proliferation assays, RGD peptide competition, flow cytometry for CD28\",\n      \"pmids\": [\"37443840\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific integrin receptor on T cells not identified\", \"In vivo immunosuppressive relevance not demonstrated\", \"Whether this function operates outside the ocular microenvironment is unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Resolution of two alternatively spliced CL-11 isoforms (A and D) differing in collagen-like domain length, with isoform D showing reduced CL-10 association and ligand binding, clarified the molecular heterogeneity of circulating CL-10/11 complexes.\",\n      \"evidence\": \"Recombinant isoform production, immunoprecipitation, mass spectrometry of native serum complexes, size exclusion chromatography, functional binding assays\",\n      \"pmids\": [\"38466278\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of isoform ratio differences in disease not tested\", \"Crystal structure of CL-10/11 heterocomplex not available\", \"Whether isoform D has distinct developmental or immunoregulatory roles is unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Genetic epistasis experiments showing that CL-11 deletion combined with complement deficiency causes vertebral bone loss, rescued by CL-11 supplementation, established CL-11 as a regulator of osteoclastogenesis acting in concert with the complement cascade.\",\n      \"evidence\": \"(preprint) Double-knockout mice (CL-11 with MASP-2, CFB, or C3), ex vivo osteoclast differentiation with rescue, immunolocalization of CL-11 and C5b-9 in bone\",\n      \"pmids\": [\"bio_10.1101_2025.05.08.652605\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, not yet peer-reviewed\", \"Direct molecular mechanism by which CL-11 promotes osteoclast differentiation not defined\", \"Whether the bone phenotype relates to 3MC syndrome skeletal features unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The receptor on neural crest cells that mediates CL-K1 guidance signaling, the structural basis of the CL-10/CL-11 heterocomplex, and the relative physiological contributions of the two splice isoforms and complement-dependent versus complement-independent functions of CL-11 remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Neural crest receptor for CL-K1 unidentified\", \"No high-resolution structure of CL-10/11 complex\", \"In vivo functional partitioning between isoforms A and D not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [0, 1, 6]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [3, 7, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [0, 1, 5, 9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [0, 3, 7]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"CL-10/CL-11 (CL-LK) heterocomplex\",\n      \"CL-11/MASP-1/MASP-3 complex\"\n    ],\n    \"partners\": [\n      \"COLEC10\",\n      \"MASP1\",\n      \"MASP2\",\n      \"MAP1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}