TEP1 (Thioester-containing protein 1) is a secreted complement-like protein that plays a central role in the innate immune response of the African malaria mosquito Anopheles gambiae. The ~165 kDa glycoprotein contains a conserved thioester motif (GCGEQ) that enables covalent attachment to pathogen surfaces, functioning as an opsonin to mark pathogens for destruction. TEP1 is expressed primarily in the fat body and secreted into the hemolymph, where it circulates in complex with LRIM1/APL1C leucine-rich repeat proteins that stabilize the active cleaved form (TEP1cut). Upon pathogen challenge, TEP1 binds to microbial surfaces (including Plasmodium ookinetes, bacteria, and fungal hyphae), triggering either direct lysis or recruitment of the phenoloxidase cascade leading to melanization. TEP1 is a key determinant of vectorial capacity, with allelic variants (TEP1*R vs TEP1*S) conferring differential resistance to malaria parasites.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002376 immune system process | IEA GO_REF:0000043 | ACCEPT | Summary: This IEA annotation is derived from the UniProt keyword "Immunity" (KW-0391) through automated mapping. While TEP1 is unquestionably an immune protein, this term is very high-level. The existing experimental annotations provide much more precise terms (antibacterial innate immune response, antifungal innate immune response, defense response to symbiont). Reason: Although GO:0002376 "immune system process" is a very general term, it is technically correct for TEP1 which functions in innate immunity. The more specific IMP/IDA annotations already capture the specific immune functions. Retaining this broad IEA annotation is acceptable. Supporting Evidence: PMID:15006349 complement-like protein TEP1 from the mosquito Anopheles gambiae binds to and mediates killing of midgut stages of the rodent malaria parasite Plasmodium berghei file:ANOGA/TEP1/TEP1-deep-research-falcon.md AgTEP1 is a complement-like thioester protein that acts as a central opsonin in the mosquito hemolymph |
| GO:0004866 endopeptidase inhibitor activity | IEA GO_REF:0000002 | REMOVE | Summary: This annotation is derived from InterPro domain mapping (IPR001599 and IPR002890) which correspond to the alpha-2-macroglobulin family. While alpha-2-macroglobulin proteins in vertebrates function as protease inhibitors, TEP1 functions differently as a complement-like opsonin. There is no experimental evidence that TEP1 acts as an endopeptidase inhibitor in mosquitoes. Reason: TEP1 is a thioester-containing protein that functions as an opsonin in the insect complement-like pathway, not as a protease inhibitor. While it shares structural domains with alpha-2-macroglobulin proteins, its functional mechanism is different. No experimental evidence supports endopeptidase inhibitor activity. This appears to be an over-annotation based on domain homology. Supporting Evidence: PMID:15006349 complement-like protein TEP1 from the mosquito Anopheles gambiae binds to and mediates killing of midgut stages of the rodent malaria parasite Plasmodium berghei file:ANOGA/TEP1/TEP1-deep-research-falcon.md TEP1 opsonizes Plasmodium ookinetes via thioester-mediated binding, leading to parasite lysis or triggering melanization |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: This IEA annotation is derived from combined automated methods based on InterPro domains and UniProt subcellular location annotations. It is supported by experimental evidence from multiple studies. Reason: The annotation is correct. TEP1 is synthesized primarily in the fat body and secreted into the hemolymph (extracellular region). This is validated by experimental IDA evidence. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md TEP1 is produced mainly by the fat body, secreted into the hemolymph |
| GO:0005615 extracellular space | IEA GO_REF:0000120 | ACCEPT | Summary: This IEA annotation is based on InterPro domain mapping and ARBA rule mapping. TEP1 circulates in the hemolymph (extracellular space of insects). Reason: The annotation is correct and is independently confirmed by IDA evidence from multiple publications showing TEP1 in the hemolymph/extracellular space. Supporting Evidence: PMID:19286136 RNAi silencing of the LRR-encoding genes results in deposition of TEP1 on Anopheles tissues, thereby depleting TEP1 from circulation in the hemolymph and impeding its binding to Plasmodium |
| GO:0005615 extracellular space | IDA PMID:25012124 A serine protease homolog negatively regulates TEP1 consumpt... | ACCEPT | Summary: This annotation is based on direct assays from Yassine et al. (2014) showing TEP1 localization in mosquito hemolymph during systemic bacterial infections. Reason: The paper demonstrates TEP1 presence in hemolymph (extracellular space) through western blot analysis. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md TEP1 is produced mainly by the fat body, secreted into the hemolymph |
| GO:0048023 positive regulation of melanin biosynthetic process | IMP PMID:25012124 A serine protease homolog negatively regulates TEP1 consumpt... | ACCEPT | Summary: This annotation captures TEP1's role in promoting melanization as part of the mosquito immune response. TEP1 knockdown affects phenoloxidase activity. Reason: TEP1 is required for activation of the melanization cascade. TEP1 knockdown reduces phenoloxidase activity and prevents melanization of pathogens. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md TEP1 opsonizes Plasmodium ookinetes via thioester-mediated binding, leading to parasite lysis or triggering melanization |
| GO:0140367 antibacterial innate immune response | IMP PMID:25012124 A serine protease homolog negatively regulates TEP1 consumpt... | ACCEPT | Summary: This annotation reflects TEP1's essential role in defense against bacterial infection. TEP1 silencing increases bacterial proliferation and reduces mosquito survival following E. coli infection. Reason: This is a core function of TEP1. The protein binds to bacterial surfaces and promotes their clearance through phagocytosis and melanization. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md In knockdown mosquitos infected with bacterium E.coli, survival is reduced, bacteria proliferation is increased |
| GO:0140546 defense response to symbiont | IMP PMID:25012124 A serine protease homolog negatively regulates TEP1 consumpt... | ACCEPT | Summary: This annotation captures TEP1's broader role in defense against organisms living in symbiotic (including parasitic) relationship with the mosquito. Reason: TEP1 mediates defense against multiple pathogens including Plasmodium parasites and bacteria. The term "defense response to symbiont" appropriately captures this broad anti-pathogen function. Supporting Evidence: PMID:15006349 complement-like protein TEP1 from the mosquito Anopheles gambiae binds to and mediates killing of midgut stages of the rodent malaria parasite Plasmodium berghei |
| GO:0005615 extracellular space | IDA PMID:15006349 Complement-like protein TEP1 is a determinant of vectorial c... | ACCEPT | Summary: Blandin et al. (2004) demonstrated TEP1 localization in the hemolymph (extracellular space) in their foundational paper on TEP1. Reason: This is the original Cell paper establishing TEP1 as a circulating hemolymph protein. Supporting Evidence: PMID:15006349 complement-like protein TEP1 from the mosquito Anopheles gambiae binds to and mediates killing of midgut stages of the rodent malaria parasite Plasmodium berghei |
| GO:0140546 defense response to symbiont | IDA PMID:15006349 Complement-like protein TEP1 is a determinant of vectorial c... | ACCEPT | Summary: This annotation from the foundational Blandin et al. (2004) Cell paper documents TEP1's role in killing Plasmodium berghei ookinetes. Reason: The paper directly demonstrates TEP1 binding to and killing Plasmodium parasites. This is a core immune function and the foundational discovery. Supporting Evidence: PMID:15006349 The dsRNA knockdown of TEP1 in adults completely abolishes melanotic refractoriness in a genetically selected refractory strain |
| GO:0005515 protein binding | IPI PMID:19286136 Two mosquito LRR proteins function as complement control fac... | MODIFY | Summary: This annotation documents TEP1 interaction with LRIM1 and APL1C based on Fraiture et al. (2009). The LRIM1/APL1C heterodimer stabilizes circulating TEP1cut in the hemolymph. Reason: While TEP1 does bind to LRIM1 and APL1C proteins, "protein binding" is too vague and uninformative. The interaction has a specific functional consequence. No better term exists currently so this can be retained with the interactors documented. Proposed replacements: protein binding Supporting Evidence: PMID:19286136 LRIM1 and APL1 not only stabilize circulating TEP1, they also stabilize each other prior to their interaction with TEP1 |
| GO:0005515 protein binding | IPI PMID:24039584 The CLIP-domain serine protease homolog SPCLIP1 regulates co... | MODIFY | Summary: This annotation documents TEP1 interaction with SPCLIP1 based on Povelones et al. (2013). SPCLIP1 is required for TEP1 accumulation on microbial surfaces. Reason: "Protein binding" is uninformative. The TEP1-SPCLIP1 interaction is functionally important for the complement-like pathway. The annotation can be retained with interactor documentation. Proposed replacements: protein binding Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md The CLIP-domain homolog SPCLIP1 regulates recruitment/accumulation of TEP1 on microbial/plasmodial surfaces |
| GO:0005576 extracellular region | IDA PMID:23166497 The mosquito melanization response is implicated in defense ... | ACCEPT | Summary: Yassine et al. (2012) demonstrated TEP1 localization to the extracellular space during fungal infection studies with Beauveria bassiana. Reason: The study provides direct evidence of TEP1 in the extracellular environment where it binds to fungal hyphae. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md TEP1 is produced mainly by the fat body, secreted into the hemolymph |
| GO:0005576 extracellular region | IDA PMID:24039584 The CLIP-domain serine protease homolog SPCLIP1 regulates co... | ACCEPT | Summary: Povelones et al. (2013) demonstrated TEP1 localization in the hemolymph and on microbial surfaces through western blot and immunolocalization. Reason: The study provides clear evidence of TEP1 in the extracellular compartment. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md TEP1 is produced mainly by the fat body, secreted into the hemolymph |
| GO:0005615 extracellular space | IDA PMID:19286136 Two mosquito LRR proteins function as complement control fac... | ACCEPT | Summary: Fraiture et al. (2009) demonstrated circulating TEP1 in the hemolymph and its stabilization by the LRIM1/APL1C complex. Reason: This study provides key evidence that TEP1 circulates in the hemolymph as part of a complex with LRIM1/APL1C. Supporting Evidence: PMID:19286136 RNAi silencing of the LRR-encoding genes results in deposition of TEP1 on Anopheles tissues, thereby depleting TEP1 from circulation in the hemolymph and impeding its binding to Plasmodium |
| GO:0048023 positive regulation of melanin biosynthetic process | IMP PMID:23166497 The mosquito melanization response is implicated in defense ... | ACCEPT | Summary: Yassine et al. (2012) demonstrated that TEP1 is required for melanization of fungal hyphae during B. bassiana infection. Reason: This is a core function of TEP1 - promoting melanization as an immune effector mechanism. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md TEP1 opsonizes Plasmodium ookinetes via thioester-mediated binding, leading to parasite lysis or triggering melanization |
| GO:0048023 positive regulation of melanin biosynthetic process | IMP PMID:24039584 The CLIP-domain serine protease homolog SPCLIP1 regulates co... | ACCEPT | Summary: Povelones et al. (2013) showed that TEP1 is upstream of the melanization pathway. Reason: TEP1 is essential for triggering the melanization cascade through the CLIP-domain serine protease pathway. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md TEP1 opsonizes Plasmodium ookinetes via thioester-mediated binding, leading to parasite lysis or triggering melanization |
| GO:0048023 positive regulation of melanin biosynthetic process | IMP PMID:30690067 Complement-like proteins TEP1, TEP3 and TEP4 are positive re... | ACCEPT | Summary: Yan and Hillyer (2019) showed that TEP1 knockdown reduces melanin deposition at periostial regions during bacterial infection. Reason: This study extends the role of TEP1 in melanization to the periostial regions of the heart. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md TEP1 opsonizes Plasmodium ookinetes via thioester-mediated binding, leading to parasite lysis or triggering melanization |
| GO:0061760 antifungal innate immune response | IMP PMID:23166497 The mosquito melanization response is implicated in defense ... | ACCEPT | Summary: Yassine et al. (2012) demonstrated TEP1's role in defense against the entomopathogenic fungus Beauveria bassiana. Reason: This is a well-documented immune function of TEP1. Knockdown experiments clearly demonstrate increased susceptibility to fungal infection. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md AgTEP1 is a complement-like thioester protein that acts as a central opsonin in the mosquito hemolymph |
| GO:0098743 cell aggregation | IMP PMID:30690067 Complement-like proteins TEP1, TEP3 and TEP4 are positive re... | KEEP AS NON CORE | Summary: Yan and Hillyer (2019) showed that TEP1 knockdown reduces hemocyte aggregation at periostial regions during bacterial infection. Reason: While TEP1 does influence hemocyte aggregation at periostial regions, this appears to be an indirect consequence of its primary immune function rather than a core molecular function. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md AgTEP1 is a complement-like thioester protein that acts as a central opsonin in the mosquito hemolymph |
| GO:0140367 antibacterial innate immune response | IMP PMID:24039584 The CLIP-domain serine protease homolog SPCLIP1 regulates co... | ACCEPT | Summary: Povelones et al. (2013) demonstrated TEP1's role in antibacterial defense. Reason: TEP1 directly binds to bacteria and is required for their clearance through the complement-like pathway. This is a core immune function. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md AgTEP1 is a complement-like thioester protein that acts as a central opsonin in the mosquito hemolymph |
| GO:0140367 antibacterial innate immune response | IMP PMID:30690067 Complement-like proteins TEP1, TEP3 and TEP4 are positive re... | ACCEPT | Summary: Yan and Hillyer (2019) showed that TEP1 knockdown results in slower bacterial clearance. Reason: This study provides additional evidence for TEP1's antibacterial function. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md AgTEP1 is a complement-like thioester protein that acts as a central opsonin in the mosquito hemolymph |
| GO:0140546 defense response to symbiont | IMP PMID:24039584 The CLIP-domain serine protease homolog SPCLIP1 regulates co... | ACCEPT | Summary: Povelones et al. (2013) demonstrated TEP1's role in defense against Plasmodium berghei parasites. Reason: Defense against Plasmodium parasites is a core function of TEP1, as established by multiple studies. Supporting Evidence: file:ANOGA/TEP1/TEP1-deep-research-falcon.md TEP1 opsonizes Plasmodium ookinetes via thioester-mediated binding, leading to parasite lysis or triggering melanization |
| GO:0008228 opsonization | IDA PMID:15006349 Complement-like protein TEP1 is a determinant of vectorial c... | NEW | Summary: TEP1 functions as an opsonin, binding covalently to pathogen surfaces via its thioester bond to mark them for destruction. Reason: Opsonization is the primary biological process of TEP1. The protein binds to pathogen surfaces (ookinetes, bacteria, fungal hyphae) and marks them for clearance. Supporting Evidence: PMID:15006349 complement-like protein TEP1 from the mosquito Anopheles gambiae binds to and mediates killing of midgut stages of the rodent malaria parasite Plasmodium berghei |
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Download this section (compressed HTML)Q: What is the identity of the protease that cleaves full-length TEP1-F to generate the active TEP1cut form?
Q: Does TEP1 have any function beyond immunity, such as in development or reproduction?
Q: What are the precise molecular determinants that distinguish TEP1*R and TEP1*S allele function?
Experiment: Structural characterization of the TEP1-LRIM1-APL1C complex to understand the complement-like convertase mechanism.
Hypothesis: The TEP1-LRIM1-APL1C complex resembles vertebrate complement convertase in its structural organization.
Experiment: Investigation of TEP1 role in defense against human malaria parasites (P. falciparum) rather than rodent models.
Hypothesis: TEP1 shows similar anti-parasitic activity against human malaria parasites.
Experiment: Characterization of TEP1 potential role in male fertility and sperm quality control as suggested by UniProt annotation.
Hypothesis: TEP1 recognizes and eliminates defective sperm cells during spermatogenesis.
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