CLEC-60 is a secreted C-type lectin domain-containing protein with a von Willebrand factor type A (VWA) domain that functions as an antimicrobial effector molecule in C. elegans innate immunity. It is strongly upregulated (8.3-fold) in intestinal epithelial cells during Staphylococcus aureus infection and is part of the host defense response to Gram-positive bacterial pathogens. CLEC-60 is expressed in the intestine and is induced by multiple pathogens including S. aureus, P. aeruginosa, and M. nematophilum. Overexpression of the clec-60,61 gene cluster confers enhanced survival during S. aureus infection, demonstrating a protective role in antibacterial defense. The protein contains a signal peptide suggesting it is secreted, consistent with a role as an antimicrobial effector that may directly interact with or agglutinate pathogen surface molecules via its C-type lectin domain.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0050830 defense response to Gram-positive bacterium | IGI PMID:20617181 Distinct pathogenesis and host responses during infection of... | ACCEPT | Summary: This annotation is well-supported by experimental evidence from PMID:20617181. The study demonstrates that clec-60 is strongly induced (8.3-fold) during S. aureus (Gram-positive) infection in C. elegans intestinal epithelial cells. The IGI evidence is based on the observation that overexpression of the clec-60,61 gene cluster (with clec-61/Q23565 as the With/From gene) confers increased survival during S. aureus infection (LT50 = 54.2 h vs 47.3 h for controls, p = 0.019). This demonstrates a functional protective role in defense against Gram-positive bacteria. Reason: The annotation accurately reflects the experimentally demonstrated function of CLEC-60 in defense against Gram-positive bacteria. The evidence from PMID:20617181 shows both transcriptional induction during S. aureus infection and functional protection via overexpression studies. The C-type lectin domain is consistent with carbohydrate-binding activity that could recognize pathogen-associated molecular patterns on bacterial surfaces. This represents a core function for this antimicrobial effector protein. Supporting Evidence: PMID:20617181 C-type lectin, von Willebrand factor, type A8.3AntimicrobialIntestine3 PMID:20617181 clec-60,61/CTL overexpression is protective during S. aureus infection. PMID:20617181 Transgenic animals carrying clec-60,61 cluster extrachromosomal arrays survived longer (LT50 = 54.2 h; N = 79; p = 0.019) during S. aureus infection than control animals bearing arrays composed of coinjection marker and clec-60::GFP promoter fusion (LT50 = 47.3 h; N = 95). PMID:20617181 M. nematophilum (UP)8.3C-type lectin file:worm/clec-60/clec-60-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0030246 carbohydrate binding | IEA GO_REF:0000002 | NEW | Summary: CLEC-60 contains a C-type lectin-like domain (CDD: cd00037, InterPro: IPR001304, SMART: SM00034) as identified by domain prediction algorithms. C-type lectin domains are characterized by their calcium-dependent carbohydrate-binding activity. The domain architecture supports the predicted carbohydrate binding function, which would be consistent with recognition of pathogen surface carbohydrates as part of its antimicrobial function. Reason: While not explicitly present in the GOA file, the carbohydrate binding activity is strongly supported by the domain composition of CLEC-60. The UniProt record shows C-type lectin domain annotations from multiple sources (CDD, Gene3D, InterPro, PANTHER, SMART, SUPFAM). This molecular function is mechanistically linked to its biological role in pathogen recognition and defense. C-type lectins typically bind carbohydrates in a calcium-dependent manner and can recognize pathogen-associated molecular patterns such as bacterial cell wall components. Supporting Evidence: UniProt:Q23564 CDD; cd00037; CLECT; 1 |
| GO:0140367 antibacterial innate immune response | IMP PMID:20617181 Distinct pathogenesis and host responses during infection of... | NEW | Summary: CLEC-60 functions as an effector of the innate immune response to bacterial infection. The protein is transcriptionally induced during infection by multiple bacterial pathogens and overexpression confers protection against S. aureus killing. This represents a broader characterization of its innate immune function. Reason: The evidence from PMID:20617181 demonstrates that CLEC-60 is part of the C. elegans innate immune response to bacterial infection. The study shows: (1) transcriptional induction during S. aureus and M. nematophilum infection, (2) expression in intestinal epithelial cells which represent the host's first line of defense, (3) protective effect of overexpression on host survival, and (4) the protein contains a signal peptide consistent with secretion as an antimicrobial effector. GO:0140367 (antibacterial innate immune response) appropriately captures this broader immune function. Supporting Evidence: PMID:20617181 S. aureus activates a strong transcriptional response in C. elegans intestinal epithelial cells, which aids host survival during infection and shares elements with human innate responses. PMID:20617181 C-type lectin, von Willebrand factor, type A8.3AntimicrobialIntestine3 |
| GO:0005576 extracellular region | IEA GO_REF:0000002 | NEW | Summary: CLEC-60 contains a signal peptide (residues 1-17) as predicted by SignalP, indicating secretion to the extracellular space. This is consistent with its proposed role as a secreted antimicrobial effector molecule. Reason: The UniProt record shows a predicted signal peptide at residues 1-17, strongly suggesting that CLEC-60 is a secreted protein. This cellular component annotation is important for understanding its function as an extracellular antimicrobial effector that would encounter pathogens in the intestinal lumen. Supporting Evidence: UniProt:Q23564 Signal {ECO:0000256|SAM:SignalP} |
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Download this section (compressed HTML)Q: What is the specific carbohydrate ligand recognized by CLEC-60? Does it bind peptidoglycan or lipoteichoic acid components of Gram-positive bacterial cell walls? Understanding the molecular target would provide insight into the mechanism of pathogen recognition and potential specificity for Gram-positive vs Gram-negative bacteria.
Q: Is CLEC-60 directly bactericidal/bacteriostatic, or does it function primarily through agglutination/opsonization of bacteria? The mechanism of antimicrobial action is not established. C-type lectins can function through various mechanisms including direct killing, agglutination, or recruitment of other immune effectors.
Q: What is the functional relationship between CLEC-60 and the closely related CLEC-61 and CLEC-62 proteins in the same gene cluster? The genes appear to be co-regulated and overexpression of the cluster confers protection. Understanding their individual vs collective contributions would clarify functional redundancy.
Experiment: Single-gene RNAi knockdown of clec-60 alone (vs the cluster) to determine whether it is individually required for defense against S. aureus infection. If clec-60 is required, RNAi should result in increased susceptibility to S. aureus killing compared to control animals.
Hypothesis: clec-60 knockdown will increase susceptibility to S. aureus infection
Experiment: Recombinant CLEC-60 protein binding assays with purified Gram-positive bacterial cell wall components (peptidoglycan, lipoteichoic acid) vs Gram-negative components (LPS). This would reveal ligand specificity and whether the protein preferentially recognizes Gram-positive bacterial surfaces.
Hypothesis: CLEC-60 preferentially binds Gram-positive bacterial cell wall components
Experiment: In vitro antimicrobial activity assays with purified recombinant CLEC-60 against S. aureus and other bacteria. This would determine whether CLEC-60 has direct bactericidal/bacteriostatic activity or functions through other mechanisms.
Hypothesis: CLEC-60 has direct antimicrobial activity against S. aureus
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