TEP10 is a thioester-containing protein (TEP) in Anopheles gambiae, a member of the expanded TEP family (19+ paralogs) in this malaria vector mosquito. TEPs are arthropod complement-like opsonins with C3/alpha-2-macroglobulin-like domain architecture including a thioester-containing domain (TED) with conserved GCGEQ motif. While TEP10 specifically remains poorly characterized with no direct experimental studies, family-based inference suggests it functions as a secreted hemolymph opsonin that covalently binds pathogens via its thioester bond, potentially contributing to immune responses including phagocytosis and melanization. TEP10 may interact with LRIM1/APL1C-type stabilizing complexes similar to the well-characterized TEP1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002376 immune system process | IEA GO_REF:0000043 | ACCEPT | Summary: TEP10 is annotated to immune system process based on UniProtKB keyword mapping. This is appropriate as TEP family proteins are key components of arthropod innate immunity. The well-characterized TEP1, TEP3, and TEP4 paralogs function as complement-like opsonins in mosquito immune responses against bacteria and Plasmodium parasites. While TEP10 specifically lacks direct experimental characterization, domain architecture and family membership support involvement in immune processes. Reason: TEP family membership and conserved domain architecture strongly support immune function. The deep research states TEPs are "arthropod complement-like factors" that promote "phagocytosis, lysis, or melanization". The broad term "immune system process" is appropriately conservative for a poorly characterized paralog. Supporting Evidence: file:ANOGA/TEP10/TEP10-deep-research-falcon.md Thioester-containing proteins (TEPs) are arthropod complement-like factors with a conserved intramolecular thioester |
| GO:0004866 endopeptidase inhibitor activity | IEA GO_REF:0000002 | REMOVE | Summary: This annotation derives from InterPro2GO mapping of the alpha-2-macroglobulin (A2M) domain (IPR001599) and MG2 domain (IPR002890). While vertebrate A2M proteins can inhibit proteases by trapping them, ARTHROPOD TEPs have functionally diverged and do NOT function as protease inhibitors. Instead, insect TEPs are complement C3-like opsonins that use their thioester bond for COVALENT attachment to pathogen surfaces rather than protease trapping. The InterPro2GO mapping is misleading for this evolutionary context. Reason: The annotation represents an inappropriate transfer of vertebrate A2M function to an arthropod TEP. The deep research confirms insect TEPs function as "complement C3-like opsonins" rather than protease inhibitors. The UniProt function annotation explicitly states TEP10 "Binds covalently through a thioester bond to the pathogen surface resulting in pathogen clearance" - this is opsonin function, not protease inhibition. There is no evidence that arthropod TEPs inhibit endopeptidases; their A2M-like domains have been repurposed for immune opsonization. Supporting Evidence: file:ANOGA/TEP10/TEP10-deep-research-falcon.md AgTEP1 is the best-characterized member and is a complement C3-like opsonin file:ANOGA/TEP10/TEP10-deep-research-falcon.md act as opsonins that covalently tag microbes or parasites to promote phagocytosis, lysis, or melanization |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: TEP10 is annotated to extracellular region based on InterPro domain analysis (alpha-macroglobulin receptor-binding domain) and UniProt subcellular location data. TEP family proteins are secreted into the hemolymph where they function as opsonins. UniProt explicitly states TEP10 is "Secreted" based on ARBA annotation. Reason: TEP family proteins are established hemolymph (extracellular) factors. The UniProt entry states "SUBCELLULAR LOCATION: Secreted" and the keyword "Secreted" is present. The deep research confirms TEPs are "hemolymph factors produced primarily by the fat body/hemocytes" that "operate systemically". Signal peptide prediction and domain architecture support secretion. Supporting Evidence: file:ANOGA/TEP10/TEP10-deep-research-falcon.md TEPs are hemolymph factors produced primarily by the fat body/hemocytes; they operate systemically |
| GO:0005615 extracellular space | IEA GO_REF:0000120 | ACCEPT | Summary: TEP10 is annotated to extracellular space, consistent with its secreted nature and function as a hemolymph opsonin. This term is more specific than extracellular region and accurately captures hemolymph localization. Reason: Hemolymph is equivalent to extracellular space in insects. The term is appropriate and consistent with TEP family biology. TEPs circulate in hemolymph where they encounter and opsonize pathogens. Supporting Evidence: file:ANOGA/TEP10/TEP10-deep-research-falcon.md TEP10 is likely secreted into the hemolymph (produced by fat body/hemocytes) and may act systemically |
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Download this section (compressed HTML)Q: Does TEP10 possess a functional thioester bond capable of covalent pathogen binding, or has it lost this activity like some other TEP family paralogs?
Q: Does TEP10 interact with the LRIM1/APL1C stabilizing complex, and if so, which APL1 paralog does it preferentially bind?
Q: What is the expression pattern of TEP10 - is it constitutively expressed or induced upon infection, and in which tissues?
Experiment: Express recombinant TEP10 and test for covalent binding to bacterial or Plasmodium ookinete surfaces using immunofluorescence microscopy. Compare to TEP1 as positive control. Use mass spectrometry to confirm thioester bond formation with pathogen surface molecules.
Hypothesis: TEP10 possesses opsonin activity and can bind to pathogen surfaces
Experiment: Perform RNAi knockdown of TEP10 in Anopheles gambiae and challenge with Plasmodium berghei. Quantify oocyst numbers in midguts compared to GFP dsRNA controls. Assess melanization phenotypes.
Hypothesis: TEP10 contributes to mosquito immune defense against Plasmodium
Experiment: Measure TEP10 mRNA levels by qRT-PCR in naive mosquitoes versus those challenged with bacteria (E. coli, S. aureus) or Plasmodium infection at various timepoints.
Hypothesis: TEP10 expression is induced upon immune challenge
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