Affinage

COLEC12

Collectin-12 · UniProt Q5KU26

Length
742 aa
Mass
81.5 kDa
Annotated
2026-06-09
30 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COLEC12 (CL-P1/SRCL) is a type II transmembrane scavenger receptor collectin expressed on vascular endothelial cells, placental trophoblasts, and tissue macrophages that links innate pattern recognition to ligand clearance and complement regulation (PMID:11564734, PMID:18423602). It recognizes ligands through spatially distinct domains: a positively charged collagen-like domain (residues R496/K499/K502) and a coiled-coil region engage microbes and oxidized LDL, while a Ca2+-dependent C-type carbohydrate recognition domain (CRD) binds sugar antigens (PMID:25199873). Through these domains it binds and phagocytoses bacteria, yeast, and OxLDL but not acetylated LDL, with uptake blocked by polyanionic competitors (PMID:11564734), and is the dominant non-opsonic fungal recognition receptor for zymosan in endothelial cells (PMID:19073604). Its CRD specifically recognizes GalNAc and the carcinoma-associated Tn antigen and mediates internalization of GalNAc-conjugated particles (PMID:12761161), and binds Lewis x structures on CEACAM glycoproteins (PMID:20034698). Ligand endocytosis proceeds through a cytoplasmic tyrosine-based YXXΦ motif that recruits the AP-2 μ2 subunit, coupling the receptor to clathrin- and dynamin-2-dependent uptake (PMID:25109811). Beyond clearance, COLEC12 binds the pentraxins CRP, SAP, and PTX3 to drive classical and alternative complement activation while these same ligands recruit complement factor H and C4-binding protein to the cell surface, restraining terminal complement complex formation on host cells (PMID:26922829, PMID:27864148). The receptor is induced by hypoxia/reoxygenation and ischemia/reperfusion in vascular tissue (PMID:21723916), binds fibrillar Aβ in the context of Alzheimer pathology (PMID:16868960), and functions as an extracellular guidance cue confining cranial neural crest cell migration during embryogenesis (PMID:36692868), with an ortholog requirement for vasculogenesis in zebrafish (PMID:22001438).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 High

    Established COLEC12's foundational identity as an endothelial scavenger receptor, answering what class of receptor it is and what it recognizes.

    Evidence Transfection of CHO cells with binding and phagocytosis assays against bacteria, yeast, and OxLDL, plus cDNA cloning and flow cytometry

    PMID:11162630 PMID:11564734

    Open questions at the time
    • Domain responsible for each ligand class not yet dissected
    • Internalization machinery unknown
    • Physiological versus overexpression behavior not distinguished
  2. 2003 Medium

    Resolved that the CRD confers Ca2+-dependent sugar specificity, showing COLEC12 recognizes GalNAc and the tumor-associated Tn antigen and internalizes glycan-bearing particles.

    Evidence Secreted CRD-alkaline phosphatase fusion affinity binding, free-sugar inhibition, and confocal imaging of particle uptake in transfectants

    PMID:12761161

    Open questions at the time
    • Endogenous glycoprotein ligands not identified in this study
    • In vivo significance of Tn recognition unaddressed
  3. 2006 Medium

    Extended ligand repertoire to fibrillar Aβ, raising COLEC12 as a candidate amyloid clearance receptor in brain.

    Evidence CHO-K1 transfection with Aβ binding assay plus immunohistochemistry in APP/PS1 mice and human AD brain

    PMID:16868960

    Open questions at the time
    • Direct demonstration of Aβ degradation/clearance not shown
    • Causal contribution to AD pathology untested
  4. 2008 High

    Defined COLEC12 as the dominant endothelial fungal recognition receptor and clarified that endogenous protein is largely cytosolic under steady state.

    Evidence siRNA epistasis against multiple scavenger receptors and pharmacological inhibitors in primary HUVECs; IHC across human tissues

    PMID:18423602 PMID:19073604

    Open questions at the time
    • Trigger for surface translocation of cytosolic pool unknown
    • Mechanism distinguishing CL-P1 from other receptors not biochemically resolved
  5. 2010 Medium

    Identified Lewis x on CEACAM glycoproteins as physiological glycan ligands, connecting COLEC12 recognition to specific fucosylated cell-surface partners.

    Evidence Recombinant glycan-binding receptor assay with mass spectrometry glycan characterization

    PMID:20034698

    Open questions at the time
    • Functional consequence of CEACAM recognition not established
    • Single-lab binding study without in vivo validation
  6. 2011 Medium

    Showed COLEC12 is stress-inducible in the vasculature and that its ortholog is required for vasculogenesis, linking the receptor to vascular development and injury responses.

    Evidence Hypoxia/reoxygenation and rat ischemia/reperfusion induction models; zebrafish morpholino knockdown with mRNA rescue

    PMID:21723916 PMID:22001438

    Open questions at the time
    • Transcriptional regulators driving induction not identified
    • Molecular placement within the VEGF pathway not defined
  7. 2014 High

    Dissected the domain architecture of ligand binding and the endocytic mechanism, the key advance separating recognition from internalization.

    Evidence Systematic deletion and point mutagenesis of binding domains; yeast two-hybrid, YXXΦ motif mutation, and siRNA against clathrin/AP-2/dynamin-2

    PMID:25109811 PMID:25199873

    Open questions at the time
    • Structural basis of charge-dependent collagen-domain binding not solved
    • Whether different ligands traffic to distinct compartments unknown
  8. 2016 Medium

    Established COLEC12 as a pentraxin receptor that both activates and restrains complement on cell surfaces, defining its role at the innate-humoral interface.

    Evidence ELISA binding and cell-based C3/TCC deposition assays with CRP/SAP/PTX3 and depletion of CFH, C4BP, and CFI

    PMID:26922829 PMID:27864148

    Open questions at the time
    • In vivo relevance of host-protective complement regulation untested
    • Single-lab cell-based assays without animal model
  9. 2018 Medium

    Linked COLEC12 pathogen recognition to downstream adaptive immune conditioning, showing it senses fucosylated H. pylori to prime dendritic cell IL-23 production.

    Evidence Trans-well co-culture of infected gastric stromal cells with dendritic cells using COLEC12 knockdown, antibody blocking, and a fucosyltransferase-null H. pylori strain

    PMID:29491476

    Open questions at the time
    • Direct COLEC12-glycan binding to H. pylori not biochemically isolated here
    • PGE2-EP2/4 coupling mechanism downstream of receptor not detailed
  10. 2020 Low

    Placed COLEC12 upstream of TLR4 in suppressing tumor inflammation and apoptosis in osteosarcoma.

    Evidence Dual lentiviral knockdown of COLEC12 and TLR4 in Saos-2 cells and xenografts with expression and tumor-growth readouts

    PMID:32822099

    Open questions at the time
    • No biochemical demonstration of direct COLEC12-TLR4 interaction
    • Mechanism of inflammatory suppression not resolved
    • Single-lab finding
  11. 2023 Medium

    Revealed a developmental morphogenetic role distinct from immune scavenging, showing extracellular COLEC12 confines cranial neural crest migration trajectories.

    Evidence In vitro protein stripe assay and gain/loss-of-function in chick embryo with 3D confocal imaging

    PMID:36692868

    Open questions at the time
    • Receptor or signaling partner on neural crest cells unidentified
    • Relationship to scavenger/endocytic function unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the cytosolic versus surface distribution is regulated and whether the immune-scavenger and developmental-guidance functions share a common molecular mechanism remain unresolved.
  • No structural model of ligand engagement
  • Trigger for endogenous surface trafficking unknown
  • Knockout phenotype in mammals not described in this corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 3 GO:0038024 cargo receptor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 2 GO:0005576 extracellular region 1 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 2 R-HSA-5653656 Vesicle-mediated transport 1
Partners
AP2M1C4BPCEACAM1CFHCRPPTX3TLR4

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CL-P1 (COLEC12) is a type II membrane glycoprotein expressed on vascular endothelial cells that functions as a scavenger receptor, capable of binding and phagocytosing bacteria (E. coli, S. aureus), yeast (S. cerevisiae), and oxidized LDL (OxLDL), but not acetylated LDL. Binding is inhibited by polyanionic ligands (polyinosinic acid, dextran sulfate) but not polycationic ligands. Immunoblotting, flow cytometry, transfection of CHO cells, binding/phagocytosis assays with bacteria, yeast, and OxLDL The Journal of biological chemistry High 11564734
2001 Human SRCL (COLEC12) type I contains a C-type lectin/carbohydrate recognition domain (CRD) and a collagen-like domain, is localized to the plasma membrane forming clusters, and binds E. coli and S. aureus. Type II isoform lacking the CRD also binds bacteria. cDNA cloning from human placenta library, expression in CHO-K1 cells, flow cytometry, ligand-binding assay Biochemical and biophysical research communications Medium 11162630
2003 The C-type lectin domain (CRD) of SRCL/CL-P1 (COLEC12) specifically binds GalNAc in a Ca2+-dependent manner and recognizes the carcinoma-associated Tn antigen. Cells expressing SRCL internalized GalNAc-conjugated particles but not mannose-conjugated particles. Expression of secreted CRD-alkaline phosphatase fusion in 293/EBNA-1 cells, affinity binding to GalNAc-conjugated gel, inhibition assays with free sugars, confocal microscopy of particle uptake in SRCL-transfected cells Journal of biochemistry Medium 12761161
2008 CL-P1 (COLEC12) predominantly mediates non-opsonic phagocytosis of zymosan by vascular endothelial cells. Uptake was inhibited by cytochalasin D, wortmannin, poly(I), and dextran sulfate. siRNA knockdown of CL-P1 (but not other scavenger receptors) blocked zymosan ingestion in HUVECs, establishing CL-P1 as the dominant fungal recognition receptor in these cells. Stable CHO/CL-P1 transfectants, siRNA knockdown of CL-P1 and other scavenger receptors (LOX-1, Stabilin-2, MARCO) in primary HUVECs, real-time RT-PCR, inhibitor studies The Journal of biological chemistry High 19073604
2008 CL-P1 (COLEC12) protein in HUVECs localizes predominantly to the cytosol rather than the plasma membrane under steady-state conditions in normal tissues, despite mRNA expression. Main expression in vivo is in cytotrophoblasts and syncytiotrophoblasts of placenta, and alveolar macrophages. Immunohistochemistry of cryo- and formalin-fixed human tissue sections using characterized monoclonal antibodies, real-time RT-PCR Molecular immunology Medium 18423602
2006 SRCL (COLEC12) expressed in astrocytes and microglia binds fibrillar Aβ(1-42) in vitro, and is induced in Aβ-positive astrocytes and vascular/perivascular cells in AD mouse models and human AD brain, with SRCL/Aβ double-positive particles accumulating in intracellular compartments, suggesting a role in Aβ clearance. CHO-K1 transfection with SRCL isoforms, fibrillar Aβ(1-42) binding assay, immunohistochemistry in Tg-APP/PS1 mice and human AD brain tissue Journal of neuroscience research Medium 16868960
2014 CL-P1 (COLEC12) mainly utilizes its collagen-like domain (positively charged residues R496, K499, K502) to bind microbes and OxLDL, while the CRD mediates sugar ligand binding, and the coiled-coil domain additionally contributes to OxLDL binding. Deletion mutants and point mutations at the three charged residues revealed domain-specific ligand binding. Construction of seven CL-P1 deletion mutants and amino acid point mutants, binding assays with sugar ligands, microbes, and OxLDL in transfected cells Biochimica et biophysica acta High 25199873
2014 CL-P1 (COLEC12) mediates endocytosis of OxLDL via the tyrosine-based YXXΦ motif in its cytoplasmic domain by associating with the μ2 subunit of the AP-2 adaptor complex. Endocytosis is dependent on clathrin, dynamin-2, and AP-2. Tyrphostin A23 and YXXΦ motif mutation inhibited OxLDL internalization. Yeast two-hybrid screen of placental cDNA library with CL-P1 cytoplasmic domain, tyrphostin A23 inhibitor assay, site-directed mutagenesis of YXXΦ motif, siRNA knockdown of clathrin, AP-2, and dynamin-2 in CL-P1 transfectant cells Biochimica et biophysica acta High 25109811
2011 Zebrafish CL-P1 (ortholog of COLEC12) is essential for vasculogenesis: morpholino knockdown caused severe morphological abnormalities (short body, defects in dorsal aorta) at 48 hpf, rescued by co-injection of synthetic zCL-P1 or zVEGF mRNA, placing zCL-P1 in a VEGF-related vasculogenic pathway. Morpholino antisense oligonucleotide knockdown in zebrafish embryos, rescue by synthetic mRNA injection, 3D confocal microscopy Biochimica et biophysica acta Medium 22001438
2016 CL-P1 (COLEC12) binds CRP in a charge-dependent manner and facilitates classical complement pathway activation via C1q and an amplification pathway via properdin. CRP also recruits complement factor H (CFH) to CL-P1-expressing cell surfaces, inhibiting terminal complement complex (TCC) formation under normal serum conditions. ELISA binding assays, CHO/ldlA7 cells expressing CL-P1, C3 deposition and TCC formation assays on HEK293/CL-P1 cells, CFH depletion experiments Biochimica et biophysica acta Medium 26922829
2016 CL-P1 (COLEC12) also binds serum amyloid P component (SAP) and pentraxin 3 (PTX3), activating both classical and alternative complement pathways via factor B. CRP and PTX3 recruit CFH whereas SAP recruits C4-binding protein to CL-P1-expressing cell surfaces, preventing TCC formation. Soluble complement receptor 1 inhibited PTX-induced TCC formation. ELISA, CL-P1-expressing CHO/ldlA7 and HEK293 cells, C3 and TCC deposition assays, complement factor depletion (CFH, C4BP, CFI) Biochimica et biophysica acta. General subjects Medium 27864148
2011 CL-P1 (COLEC12) expression is induced by hypoxia/reoxygenation in HUVECs at the mRNA and protein level (onset at 72 h, sustained to 120 h after reoxygenation), with a distinct kinetic profile from LOX-1. In rat carotid artery, ischemia/reperfusion also induced CL-P1 mRNA peaking at 72 h and protein at 7 days. In vitro hypoxia/reoxygenation of HUVECs, RT-PCR and Western blot; in vivo rat carotid artery ischemia/reperfusion model Biochimica et biophysica acta Medium 21723916
2018 COLEC12 acts as a receptor in gastric stromal cells for H. pylori recognition, mediating PGE2-dependent priming of dendritic cells (DCs) to produce IL-23. Anti-COLEC12 antibodies, COLEC12 knockdown, or use of an alpha3-fucosyltransferase-null H. pylori strain (futB/HP0651) inhibited this priming effect, linking COLEC12-mediated Hp recognition to downstream adaptive immune conditioning via the PGE2-EP2/4 axis. Trans-well co-culture of H. pylori-infected gastric stromal cells (GSCs) with monocyte-derived DCs, ELISA for cytokines and PGE2, COLEC12 knockdown, anti-COLEC12 antibody blocking, futB-null H. pylori strain, flow cytometry, immunohistochemistry Scientific reports Medium 29491476
2010 SRCL (COLEC12) binds Lewis x (Lex) structures on CEACAM1 and CEA glycoproteins. Fucosyltransferase IX is responsible for attaching terminal fucose creating Lex on these glycoproteins, and macrophage subpopulations expressing SRCL can interact with Lex-carrying CEACAMs. Recombinant glycan-binding receptor assay, mass spectrometry with enzymatic digestion for glycan characterization, binding assay with SRCL European journal of cell biology Medium 20034698
2020 COLEC12 knockdown in osteosarcoma cells and tumors increased inflammation (elevated MPO, TLR4, NF-κB, C3, and inflammatory cytokines) and enhanced apoptosis, while TLR4 knockdown suppressed the inflammatory increase caused by COLEC12 knockdown, placing TLR4 downstream of COLEC12 in this signaling axis. COLEC12 knockdown and TLR4 knockdown lentivirus in Saos-2 cells and in vivo xenograft model, Western blot, RT-PCR, tumor growth assays Journal of clinical laboratory analysis Low 32822099
2023 Colec12 (COLEC12) protein stripes in the extracellular environment confine cranial neural crest cell (NCC) trajectories in vitro and in vivo (chick). Gain-of-function enhanced confinement; loss-of-function diverted cell trajectories. Colec12 influenced NCC cell morphology and dynamic migratory characteristics during collective migration. In vitro protein stripe assay with Colec12 and Trail, gain- and loss-of-function in chick embryo, three-dimensional confocal microscopy Developmental dynamics : an official publication of the American Association of Anatomists Medium 36692868

Source papers

Stage 0 corpus · 30 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The membrane-type collectin CL-P1 is a scavenger receptor on vascular endothelial cells. The Journal of biological chemistry 173 11564734
2001 Molecular cloning and functional characterization of a human scavenger receptor with C-type lectin (SRCL), a novel member of a scavenger receptor family. Biochemical and biophysical research communications 90 11162630
2016 The collectins CL-L1, CL-K1 and CL-P1, and their roles in complement and innate immunity. Immunobiology 71 27377710
2008 Scavenger receptor collectin placenta 1 (CL-P1) predominantly mediates zymosan phagocytosis by human vascular endothelial cells. The Journal of biological chemistry 52 19073604
2006 Possible role of scavenger receptor SRCL in the clearance of amyloid-beta in Alzheimer's disease. Journal of neuroscience research 40 16868960
2018 Stromal C-type lectin receptor COLEC12 integrates H. pylori, PGE2-EP2/4 axis and innate immunity in gastric diseases. Scientific reports 31 29491476
2008 Expression and tissue localization of collectin placenta 1 (CL-P1, SRCL) in human tissues. Molecular immunology 29 18423602
2001 Molecular cloning of a mouse scavenger receptor with C-type lectin (SRCL)(1), a novel member of the scavenger receptor family. Biochimica et biophysica acta 26 11718900
2020 COLEC12 regulates apoptosis of osteosarcoma through Toll-like receptor 4-activated inflammation. Journal of clinical laboratory analysis 24 32822099
2017 Detection of susceptibility loci on APOA5 and COLEC12 associated with metabolic syndrome using a genome-wide association study in a Taiwanese population. Oncotarget 24 29212154
2003 SRCL/CL-P1 recognizes GalNAc and a carcinoma-associated antigen, Tn antigen. Journal of biochemistry 23 12761161
2016 Three pentraxins C-reactive protein, serum amyloid p component and pentraxin 3 mediate complement activation using Collectin CL-P1. Biochimica et biophysica acta. General subjects 19 27864148
2019 HnRNPL inhibits the osteogenic differentiation of PDLCs stimulated by SrCl2 through repressing Setd2. Journal of cellular and molecular medicine 18 30746871
2016 Collectin CL-P1 utilizes C-reactive protein for complement activation. Biochimica et biophysica acta 18 26922829
2011 Molecular cloning and functional analysis of scavenger receptor zebrafish CL-P1. Biochimica et biophysica acta 18 22001438
2018 Identification of three class A scavenger receptors from rainbow trout (Oncorhynchus mykiss): SCARA3, SCARA4, and SCARA5. Fish & shellfish immunology 15 29471060
2014 Scavenger receptor CL-P1 mainly utilizes a collagen-like domain to uptake microbes and modified LDL. Biochimica et biophysica acta 15 25199873
2010 DC-SIGN and SRCL bind glycans of carcinoembryonic antigen (CEA) and CEA-related cell adhesion molecule 1 (CEACAM1): recombinant human glycan-binding receptors as analytical tools. European journal of cell biology 13 20034698
2011 The induction of human CL-P1 expression in hypoxia/reoxygenation culture condition and rat CL-P1 after ischemic/reperfusion treatment. Biochimica et biophysica acta 8 21723916
2001 Biochemical responses in cultured cells following exposure to (89)SrCl(2): potential relevance to the mechanism of action in pain palliation. European journal of cancer (Oxford, England : 1990) 7 11720844
2023 Colec12 and Trail signaling confine cranial neural crest cell trajectories and promote collective cell migration. Developmental dynamics : an official publication of the American Association of Anatomists 6 36692868
2014 Scavenger receptor CL-P1 mediates endocytosis by associating with AP-2μ2. Biochimica et biophysica acta 6 25109811
2024 Dysregulated AEBP1 and COLEC12 Genes in Late-Onset Alzheimer's Disease: Insights from Brain Cortex and Peripheral Blood Analysis. Journal of molecular neuroscience : MN 5 38568322
2021 Characterization and the potential immune role of class A scavenger receptor member 4 (SCARA4) in bacterial infection in turbot (Scophthalmus maximus L.). Fish & shellfish immunology 5 34965442
2025 Mathematical modeling predicts novel mechanisms of stream confinement from Trail/Colec12/Dan in the collective migration of cranial neural crest cells. Developmental dynamics : an official publication of the American Association of Anatomists 1 41201178
2022 Radiochemical quality control of the radiopharmaceutical, 89SrCl2 produced in FBTR. Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine 1 36493679
2019 Mean Activity Coefficients of KCl in KCl + SrCl2 + H2O Ternary System at 288.15 K Determined by EMF Method. The journal of physical chemistry. A 1 31790230
2018 Preparation and investigation of novel SrCl2/DCMC-modified (via DOPA) decellularized arteries with excellent physicochemical properties and cytocompatibility for vascular scaffolds. RSC advances 1 35546814
2026 Identification and expression analysis of scavenger receptor SCARA4 in Nibea albiflora. Fish & shellfish immunology 0 41747916
2025 Bioinformatic identification of COLEC12 as a diagnostic biomarker and risk factor in pediatric FSGS. Frontiers in pediatrics 0 40236664

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