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
|
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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template_variables:
organism: ANOGA
gene_id: TEP10
gene_symbol: TEP10
uniprot_accession: Q7PSK0
protein_description: 'RecName: Full=TEP1-F {ECO:0000256|ARBA:ARBA00078071};'
gene_info: Name=TEP10 {ECO:0000313|EMBL:EAA05464.3}; ORFNames=AgaP_AGAP010819 {ECO:0000313|EMBL:EAA05464.3};
organism_full: Anopheles gambiae (African malaria mosquito).
protein_family: Not specified in UniProt
protein_domains: A-macroglobulin_rcpt-bd. (IPR009048); A-macroglobulin_rcpt-bd_sf.
(IPR036595); A2M/Complement_sys. (IPR050473); A2M_N_BRD. (IPR011625); Alpha-macroglobulin_TED.
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BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.
DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'TEP10' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information
Please provide a comprehensive research report on the gene TEP10 (gene ID: TEP10, UniProt: Q7PSK0) in ANOGA.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.
BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.
DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'TEP10' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information
Please provide a comprehensive research report on the gene TEP10 (gene ID: TEP10, UniProt: Q7PSK0) in ANOGA.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Research plan status
We verified identity and domains for the target (Q7PSK0; AGAP010819; annotated as TEP10/TEP1‑F) in Anopheles gambiae, searched recent and foundational literature, gathered evidence, and created a concise artifact summarizing identity, gaps, and cautious inferences. Below is a comprehensive research report with citations to the evidence gathered.
- Identity: UniProt Q7PSK0 corresponds to an Anopheles gambiae TEP-family protein annotated as TEP10 / AGAP010819 (annotation shows a TEP-family/TEP1‑like naming variant); primary literature for this exact paralog was not found (li2025comparativeimmunologicalroles pages 11-12, li2025comparativeimmunologicalroles pages 5-6)
- Literature gap / ambiguity: No direct functional or expression studies specifically for TEP10 (AGAP010819/Q7PSK0) were retrieved; multiple sources state most AgTEP paralogs beyond TEP1/3/4 remain poorly characterized (li2025comparativeimmunologicalroles pages 5-6, qin2025thioestercontainingproteintep15 pages 1-2)
- Domain architecture (family evidence): AgTEPs typically have C3/A2M-like domain architecture (multiple MG domains, CUB domain, TED with conserved thioester motif GCGEQ), consistent with the UniProt/IPR domain annotations for Q7PSK0 (rono2017variationinthe pages 36-39, aoun2010analysisofthioestercontaining pages 1-2)
- Cautious functional inference: By homology, TEP10 is likely a secreted, hemolymph-localized thioester-containing opsonin that could mediate covalent pathogen tagging (opsonization), contribute to melanization or phagocytosis, and—if structurally compatible—interact with LRIM1/APL1C-type stabilizers as seen for TEP1/TEP3 (li2025comparativeimmunologicalroles pages 11-12, yan2019complementlikeproteinstep1 pages 29-38, li2025comparativeimmunologicalroles pages 3-5)
- Limits and recommendation: These functional assignments are inferential; empirical validation (expression/localization, proteolytic activation, thioester reactivity, LRIM1/APL1C binding and loss-of-function phenotypes) is required to confirm roles for TEP10 (li2025comparativeimmunologicalroles pages 2-3, aoun2010analysisofthioestercontaining pages 1-2)
Blockquote: A concise, cited summary verifying Q7PSK0/TEP10 identity, noting scarce paralog-specific literature, and providing cautious family-based functional inferences with explicit limits and recommended validation steps.
Comprehensive research report: TEP10 (AGAP010819; UniProt Q7PSK0) in Anopheles gambiae
1) Key concepts and definitions with current understanding
- Thioester‑containing proteins (TEPs) are arthropod complement‑like factors with a conserved intramolecular thioester (e.g., GCGEQ motif) embedded in a C3/A2M‑like scaffold of macroglobulin (MG) domains, a CUB domain, and a thioester‑containing domain (TED). They are typically secreted into the hemolymph and act as opsonins that covalently tag microbes or parasites to promote phagocytosis, lysis, or melanization (family‑level concept established primarily from AgTEP1) (rono2017variationinthe pages 36-39, aoun2010analysisofthioestercontaining pages 1-2, li2025comparativeimmunologicalroles pages 2-3).
- In Anopheles gambiae, the TEP family is expanded (≥19 paralogs). AgTEP1 is the best‑characterized member and is a complement C3‑like opsonin; other paralogs such as TEP3 and TEP4 have demonstrated immune roles, while many others remain poorly characterized (li2025comparativeimmunologicalroles pages 5-6, li2025comparativeimmunologicalroles pages 11-12, li2025comparativeimmunologicalroles pages 2-3).
- Activation and stabilization: For AgTEP1, proteolytic cleavage generates a disulfide‑linked “cut” form with exposed thioester reactivity; the LRIM1/APL1C heterodimer binds and stabilizes the cleaved TEP, directs deposition onto pathogens, and prevents off‑target damage. Related LRIM/APL1 complexes can carry other TEPs (e.g., TEP3) (li2025comparativeimmunologicalroles pages 3-5, li2025comparativeimmunologicalroles pages 5-6, rono2017variationinthe pages 36-39).
- Localization and anatomical context: TEPs are hemolymph factors produced primarily by the fat body/hemocytes; they operate systemically and influence hemocyte aggregation at periostial regions of the heart, a hub of immune activity in mosquitoes (demonstrated for TEP1/3/4) (yan2019complementlikeproteinstep1 pages 29-38).
- Naming/identity of target: UniProt Q7PSK0 maps to An. gambiae AGAP010819, annotated as TEP10, with a naming note referencing “TEP1‑F,” indicating historical/annotation ambiguity within the TEP family. Domain annotations match the C3/A2M‑like TEP architecture (A2M_N, TED, A‑macroglobulin receptor‑binding) (li2025comparativeimmunologicalroles pages 11-12, rono2017variationinthe pages 36-39).
2) Recent developments and latest research (prioritize 2023–2024)
- Family/system updates: Recent studies continue to emphasize TEP1 as a central opsonin and report expression changes of TEP family members in various contexts, including insecticide resistance and salivary gland infections; however, TEP10‑specific data remain absent in the 2023–2024 literature retrieved here (li2025comparativeimmunologicalroles pages 5-6, li2025comparativeimmunologicalroles pages 15-16). For example, 2024 transcriptomics in field mosquitoes noted TEP family gene overexpression associated with resistance phenotypes and highlighted the immunological importance of TEPs broadly, though mechanistic assignments are focused on TEP1/3/4 (li2025comparativeimmunologicalroles pages 15-16).
- Periostial immunity: Foundational but still relevant, TEP1/3/4 were shown to promote periostial hemocyte aggregation and regulate melanin deposition at the heart ostia after infection, highlighting a coordinated complement‑like and cellular response interface (yan2019complementlikeproteinstep1 pages 29-38).
- Structural/interaction paradigms (ongoing relevance): Mechanistic studies detailing LRIM1/APL1C complex formation with TEP1, and the capacity to carry other TEPs (e.g., TEP3), continue to serve as the primary model for how mosquito complement‑like opsonins are stabilized and targeted (li2025comparativeimmunologicalroles pages 3-5, rono2017variationinthe pages 36-39).
- Gap for TEP10: No primary studies from 2023–2024 specifically addressing AGAP010819/TEP10 function, expression, or localization were identified in the retrieved evidence set; reviews emphasize that many AgTEP paralogs remain to be characterized (li2025comparativeimmunologicalroles pages 5-6, li2025comparativeimmunologicalroles pages 2-3).
3) Current applications and real‑world implementations
- Vector competence and transmission‑blocking: AgTEP1 is integral to mosquito resistance to Plasmodium; population studies and functional assays link TEP1 allelic variation to parasite outcomes. These paradigms inform genetic/vector‑control strategies that seek to leverage or enhance endogenous complement‑like immunity, but such applications are built on TEP1/3/4 evidence and cannot yet be extended specifically to TEP10 without data (rono2017variationinthe pages 36-39, li2025comparativeimmunologicalroles pages 5-6, li2025comparativeimmunologicalroles pages 11-12).
- Systems immunology and surveillance: Transcriptomic and proteomic screens increasingly include TEPs as biomarkers of immune activation or insecticide exposure in field mosquitoes, underscoring their broader relevance to resistance management; however, paralog‑specific functional roles remain unresolved for many TEPs including TEP10 (li2025comparativeimmunologicalroles pages 15-16, li2025comparativeimmunologicalroles pages 5-6).
4) Expert opinions and analysis from authoritative sources
- Reviews synthesizing Anopheles TEP biology agree that AgTEP1 is a C3‑like opsonin stabilized by LRIM1/APL1C and that multiple TEP paralogs exist with diverse and incompletely defined roles; most paralogs (AgTEP2–19) are still poorly characterized (li2025comparativeimmunologicalroles pages 5-6, li2025comparativeimmunologicalroles pages 11-12, li2025comparativeimmunologicalroles pages 2-3).
- Foundational mechanistic work on LRIM1/APL1C–TEP1 interaction and TEP1 structural allelic differences underpins the model for complement‑like effector action and allele‑specific vector competence, serving as the framework for inferring, but not asserting, similar features in other AgTEPs (li2025comparativeimmunologicalroles pages 3-5, rono2017variationinthe pages 36-39).
5) Relevant statistics and data from recent studies
- Periostial aggregation roles: RNAi knockdown studies showed that TEP1, TEP3, and TEP4 positively regulate periostial hemocyte aggregation and melanin deposition at the heart’s ostia after infection; TEP1 also reduces systemic bacterial loads, supporting a broad antibacterial role (statistics reported via two‑way ANOVA in the study) (yan2019complementlikeproteinstep1 pages 29-38).
- Structural/activation insights: Structural and biochemical studies establish that TEP1 exists as a ~165 kDa precursor cleaved into disulfide‑linked chains; the cleaved form binds pathogens via an exposed thioester and requires LRIM1/APL1C for stabilization and pathogen targeting (rono2017variationinthe pages 36-39, li2025comparativeimmunologicalroles pages 3-5).
- Knowledge gap quantified: Reviews state explicitly that the “biological functions of other AgTEP members (AgTEP2–19) remain largely unexplored,” highlighting a major annotation deficit relevant to TEP10 (li2025comparativeimmunologicalroles pages 5-6).
Functional annotation for TEP10 (Q7PSK0; AGAP010819) with confidence statements
- Verified identity and domains: Q7PSK0 encodes an An. gambiae thioester‑containing protein annotated as TEP10; domain signatures align with C3/A2M‑like TEPs (A2M_N, TED, A‑macroglobulin receptor‑binding), consistent with a secreted complement‑like opsonin (li2025comparativeimmunologicalroles pages 11-12, rono2017variationinthe pages 36-39).
- Localization (inferred): By family analogy, TEP10 is likely secreted into the hemolymph (produced by fat body/hemocytes) and may act systemically; specific cellular or tissue localization data for TEP10 were not retrieved (rono2017variationinthe pages 36-39, aoun2010analysisofthioestercontaining pages 1-2, li2025comparativeimmunologicalroles pages 5-6).
- Biochemical mechanism (inferred): Likely possesses a reactive thioester enabling covalent attachment to pathogen surfaces following proteolytic activation. Potential to be stabilized/carried by LRIM1/APL1C‑like complexes if compatible, as shown for TEP1 and some other TEPs (li2025comparativeimmunologicalroles pages 3-5, li2025comparativeimmunologicalroles pages 5-6). These remain hypotheses absent TEP10‑specific assays.
- Pathways (inferred): May participate in the mosquito complement‑like pathway that culminates in opsonization, phagocytosis, and/or melanization; TEP family members TEP1/3/4 influence periostial immune cell aggregation and melanotic encapsulation, suggesting a possible role sphere for other TEPs, but TEP10’s precise role is unknown (yan2019complementlikeproteinstep1 pages 29-38, li2025comparativeimmunologicalroles pages 5-6, li2025comparativeimmunologicalroles pages 11-12).
Ambiguity and precautions
- The gene symbol “TEP10” is not well represented in current literature for An. gambiae; no direct TEP10 experimental studies were found in the retrieved set. Therefore, any functional statements beyond domain‑based inference must be treated as hypotheses pending empirical validation (li2025comparativeimmunologicalroles pages 5-6, li2025comparativeimmunologicalroles pages 2-3).
Evidence‑based next steps
- Experimental: Determine TEP10 expression (qPCR/RNA‑seq across tissues and infection states), secretion to hemolymph (western blot/shotgun proteomics), proteolytic processing and thioester reactivity (mass spectrometry/chemical capture), LRIM1/APL1C binding (co‑IP/SEC‑MALS), pathogen binding (immunofluorescence on bacteria/ookinetes), and functional impact (RNAi/CRISPR knockouts with bacterial and Plasmodium challenges) (li2025comparativeimmunologicalroles pages 11-12, li2025comparativeimmunologicalroles pages 5-6, yan2019complementlikeproteinstep1 pages 29-38).
- Comparative/phylogenetic: Place TEP10 within AgTEP clades to anticipate interaction partners and mechanisms (C3‑like vs A2M‑like), leveraging the established architecture for TEP1 and other family members (li2025comparativeimmunologicalroles pages 5-6, li2025comparativeimmunologicalroles pages 2-3).
Source details and URLs (where available)
- Yan Y, Hillyer JF. Complement‑like proteins TEP1, TEP3 and TEP4 are positive regulators of periostial hemocyte aggregation in Anopheles gambiae. Insect Biochem Mol Biol. 2019-04. https://doi.org/10.1016/j.ibmb.2019.01.007 (yan2019complementlikeproteinstep1 pages 29-38)
- Povelones M, Upton LM, Sala KA, Christophides GK. Structure‑function of LRIM1/APL1C and interaction with TEP1; complex can carry other TEPs. PLoS Pathog. 2011-04. https://doi.org/10.1371/journal.ppat.1002023 (li2025comparativeimmunologicalroles pages 3-5)
- Le BV, Williams M, Logarajah S, Baxter RHG. Structural analysis of TEP1 susceptible and resistant alleles; activation and stabilization paradigms. PLoS Pathog. 2012-10. https://doi.org/10.1371/journal.ppat.1002958 (rono2017variationinthe pages 36-39)
- Bou Aoun R et al. Analysis of insect TEPs; Anopheles TEP1 as hemolymph opsonin and family conservation. J Innate Immun. 2010-11. https://doi.org/10.1159/000321554 (aoun2010analysisofthioestercontaining pages 1-2)
- Comparative immunological roles of TEP1 in An. gambiae and Biomphalaria glabrata (review summarizing AgTEP family, emphasizing limited characterization of many paralogs). Frontiers Immunol. 2025-10. https://doi.org/10.3389/fimmu.2025.1629262 (li2025comparativeimmunologicalroles pages 5-6, li2025comparativeimmunologicalroles pages 11-12, li2025comparativeimmunologicalroles pages 2-3)
Conclusion
- Identity verified: Q7PSK0 encodes an An. gambiae TEP family protein annotated as TEP10 with C3/A2M‑like domains. However, TEP10‑specific literature is currently limited; most functional insights derive from better‑studied paralogs (TEP1/3/4). We provide a cautious, domain‑ and family‑based functional annotation and explicit recommendations for experiments to resolve TEP10’s role in the mosquito complement‑like pathway (li2025comparativeimmunologicalroles pages 11-12, yan2019complementlikeproteinstep1 pages 29-38, li2025comparativeimmunologicalroles pages 3-5, rono2017variationinthe pages 36-39).
References
(li2025comparativeimmunologicalroles pages 11-12): Hongyu Li, Yilu Feng, Yuncheng Qian, Wenjie Jiang, Yunhuan Zhu, Jialu Xu, Xianwei Li, Xinyi Fei, Ruke Wang, Yuqing Shao, Lailing Du, Xiaofen Zhang, and Keda Chen. Comparative immunological roles of tep1 in anopheles gambiae and biomphalaria glabrata: implications for malaria and schistosomiasis control. Frontiers in Immunology, Oct 2025. URL: https://doi.org/10.3389/fimmu.2025.1629262, doi:10.3389/fimmu.2025.1629262. This article has 1 citations and is from a peer-reviewed journal.
(li2025comparativeimmunologicalroles pages 5-6): Hongyu Li, Yilu Feng, Yuncheng Qian, Wenjie Jiang, Yunhuan Zhu, Jialu Xu, Xianwei Li, Xinyi Fei, Ruke Wang, Yuqing Shao, Lailing Du, Xiaofen Zhang, and Keda Chen. Comparative immunological roles of tep1 in anopheles gambiae and biomphalaria glabrata: implications for malaria and schistosomiasis control. Frontiers in Immunology, Oct 2025. URL: https://doi.org/10.3389/fimmu.2025.1629262, doi:10.3389/fimmu.2025.1629262. This article has 1 citations and is from a peer-reviewed journal.
(qin2025thioestercontainingproteintep15 pages 1-2): Xin Qin, Jianyong Li, Feng Zhu, and Jian Zhang. Thioester-containing protein tep15 promotes malaria parasite development in mosquitoes through negative regulation of melanization. Parasites & Vectors, Apr 2025. URL: https://doi.org/10.1186/s13071-025-06772-5, doi:10.1186/s13071-025-06772-5. This article has 2 citations and is from a peer-reviewed journal.
(rono2017variationinthe pages 36-39): Evans Kiplangat Rono. Variation in the anopheles gambiae tep1 gene shapes local population structures of malaria mosquitoes. ArXiv, Nov 2017. URL: https://doi.org/10.18452/18573, doi:10.18452/18573. This article has 9 citations.
(aoun2010analysisofthioestercontaining pages 1-2): Richard Bou Aoun, Charles Hetru, Laurent Troxler, Daniel Doucet, Dominique Ferrandon, and Nicolas Matt. Analysis of thioester-containing proteins during the innate immune response of drosophila melanogaster. Journal of Innate Immunity, 3:52-64, Nov 2010. URL: https://doi.org/10.1159/000321554, doi:10.1159/000321554. This article has 126 citations and is from a peer-reviewed journal.
(yan2019complementlikeproteinstep1 pages 29-38): Yan Yan and Julián F. Hillyer. Complement-like proteins tep1, tep3 and tep4 are positive regulators of periostial hemocyte aggregation in the mosquito anopheles gambiae. Insect Biochemistry and Molecular Biology, 107:1-9, Apr 2019. URL: https://doi.org/10.1016/j.ibmb.2019.01.007, doi:10.1016/j.ibmb.2019.01.007. This article has 32 citations and is from a peer-reviewed journal.
(li2025comparativeimmunologicalroles pages 3-5): Hongyu Li, Yilu Feng, Yuncheng Qian, Wenjie Jiang, Yunhuan Zhu, Jialu Xu, Xianwei Li, Xinyi Fei, Ruke Wang, Yuqing Shao, Lailing Du, Xiaofen Zhang, and Keda Chen. Comparative immunological roles of tep1 in anopheles gambiae and biomphalaria glabrata: implications for malaria and schistosomiasis control. Frontiers in Immunology, Oct 2025. URL: https://doi.org/10.3389/fimmu.2025.1629262, doi:10.3389/fimmu.2025.1629262. This article has 1 citations and is from a peer-reviewed journal.
(li2025comparativeimmunologicalroles pages 2-3): Hongyu Li, Yilu Feng, Yuncheng Qian, Wenjie Jiang, Yunhuan Zhu, Jialu Xu, Xianwei Li, Xinyi Fei, Ruke Wang, Yuqing Shao, Lailing Du, Xiaofen Zhang, and Keda Chen. Comparative immunological roles of tep1 in anopheles gambiae and biomphalaria glabrata: implications for malaria and schistosomiasis control. Frontiers in Immunology, Oct 2025. URL: https://doi.org/10.3389/fimmu.2025.1629262, doi:10.3389/fimmu.2025.1629262. This article has 1 citations and is from a peer-reviewed journal.
(li2025comparativeimmunologicalroles pages 15-16): Hongyu Li, Yilu Feng, Yuncheng Qian, Wenjie Jiang, Yunhuan Zhu, Jialu Xu, Xianwei Li, Xinyi Fei, Ruke Wang, Yuqing Shao, Lailing Du, Xiaofen Zhang, and Keda Chen. Comparative immunological roles of tep1 in anopheles gambiae and biomphalaria glabrata: implications for malaria and schistosomiasis control. Frontiers in Immunology, Oct 2025. URL: https://doi.org/10.3389/fimmu.2025.1629262, doi:10.3389/fimmu.2025.1629262. This article has 1 citations and is from a peer-reviewed journal.
id: Q7PSK0
gene_symbol: TEP10
product_type: PROTEIN
status: DRAFT
taxon:
id: NCBITaxon:7165
label: Anopheles gambiae
description: >-
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.
existing_annotations:
- term:
id: GO:0002376
label: immune system process
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
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.
action: ACCEPT
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.
additional_reference_ids:
- file:ANOGA/TEP10/TEP10-deep-research-falcon.md
supported_by:
- reference_id: file:ANOGA/TEP10/TEP10-deep-research-falcon.md
supporting_text: "Thioester-containing proteins (TEPs) are arthropod complement-like factors with a conserved intramolecular thioester"
- term:
id: GO:0004866
label: endopeptidase inhibitor activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
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.
action: REMOVE
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.
additional_reference_ids:
- file:ANOGA/TEP10/TEP10-deep-research-falcon.md
supported_by:
- reference_id: file:ANOGA/TEP10/TEP10-deep-research-falcon.md
supporting_text: "AgTEP1 is the best-characterized member and is a complement C3-like opsonin"
- reference_id: file:ANOGA/TEP10/TEP10-deep-research-falcon.md
supporting_text: "act as opsonins that covalently tag microbes or parasites to promote phagocytosis, lysis, or melanization"
- term:
id: GO:0005576
label: extracellular region
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
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.
action: ACCEPT
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.
additional_reference_ids:
- file:ANOGA/TEP10/TEP10-deep-research-falcon.md
supported_by:
- reference_id: file:ANOGA/TEP10/TEP10-deep-research-falcon.md
supporting_text: "TEPs are hemolymph factors produced primarily by the fat body/hemocytes; they operate systemically"
- term:
id: GO:0005615
label: extracellular space
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
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.
action: ACCEPT
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.
additional_reference_ids:
- file:ANOGA/TEP10/TEP10-deep-research-falcon.md
supported_by:
- reference_id: file:ANOGA/TEP10/TEP10-deep-research-falcon.md
supporting_text: "TEP10 is likely secreted into the hemolymph (produced by fat body/hemocytes) and may act systemically"
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO terms
findings:
- statement: >-
InterPro2GO mapping from A2M domain (IPR001599) incorrectly assigns endopeptidase
inhibitor activity to arthropod TEPs which have diverged to opsonin function
supporting_text: "[This is a curator assessment based on comparison of domain-function mapping with TEP family biology]"
- id: GO_REF:0000043
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
findings:
- statement: Keyword "Immunity" appropriately maps to immune system process
supporting_text: "[Standard keyword mapping is appropriate for this gene]"
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings:
- statement: Subcellular location annotations are appropriate based on secretion signals and domain architecture
supporting_text: "[Automated localization predictions are consistent with TEP family biology]"
- id: file:ANOGA/TEP10/TEP10-deep-research-falcon.md
title: Deep research summary for TEP10 gene function
findings:
- statement: >-
TEP10 lacks direct experimental characterization but can be functionally
inferred from TEP family biology as a complement-like opsonin
supporting_text: "No direct functional or expression studies specifically for TEP10 (AGAP010819/Q7PSK0) were retrieved"
- statement: >-
TEPs are complement C3-like opsonins, not protease inhibitors
supporting_text: "Thioester-containing proteins (TEPs) are arthropod complement-like factors...They are typically secreted into the hemolymph and act as opsonins that covalently tag microbes or parasites"
- statement: >-
Many TEP paralogs including TEP10 remain poorly characterized
supporting_text: "biological functions of other AgTEP members (AgTEP2-19) remain largely unexplored"
core_functions:
- description: >-
TEP10 is predicted to function as a secreted complement-like opsonin in the mosquito
hemolymph. Based on conserved TEP family features including the thioester-containing
domain (TED) with GCGEQ motif, TEP10 likely binds covalently to pathogen surfaces
via its reactive thioester, marking them for phagocytosis and/or melanotic encapsulation.
This function has not been directly demonstrated for TEP10 but is well-established
for paralogous TEP1, TEP3, and TEP4. NOTE: A specific molecular function term is not
assigned because opsonization (GO:0008228) is a biological process, and no appropriate
MF term exists for thioester-mediated pathogen binding activity.
molecular_function:
id: GO:0005515
label: protein binding
directly_involved_in:
- id: GO:0002376
label: immune system process
- id: GO:0008228
label: opsonization
locations:
- id: GO:0005615
label: extracellular space
supported_by:
- reference_id: file:ANOGA/TEP10/TEP10-deep-research-falcon.md
supporting_text: "TEP10 is likely a secreted, hemolymph-localized thioester-containing opsonin that could mediate covalent pathogen tagging (opsonization)"
suggested_questions:
- question: >-
Does TEP10 possess a functional thioester bond capable of covalent pathogen binding,
or has it lost this activity like some other TEP family paralogs?
- question: >-
Does TEP10 interact with the LRIM1/APL1C stabilizing complex, and if so,
which APL1 paralog does it preferentially bind?
- question: >-
What is the expression pattern of TEP10 - is it constitutively expressed or
induced upon infection, and in which tissues?
suggested_experiments:
- hypothesis: TEP10 possesses opsonin activity and can bind to pathogen surfaces
description: >-
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 contributes to mosquito immune defense against Plasmodium
description: >-
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 expression is induced upon immune challenge
description: >-
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.