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organism_full: Anopheles gambiae (African malaria mosquito).
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

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.

Target Gene/Protein Identity (from UniProt):

• UniProt Accession: A0A1S4GYH9
• Protein Description: RecName: Full=Short form salivary protein D7R3 {ECO:0000305}; AltName: Full=D7-related 3 protein {ECO:0000312|EMBL:CAB39729.1}; Flags: Precursor;
• Gene Information: Name=D7r3 {ECO:0000303|PubMed:16301315};
• Organism (full): Anopheles gambiae (African malaria mosquito).
• Protein Family: Belongs to the PBP/GOBP family. .
• Key Domains: PBP/GOBP. (IPR006170); PBP_GOBP_sf. (IPR036728); PBP_GOBP (PF01395)

MANDATORY VERIFICATION STEPS:

1. Check if the gene symbol "D7r3" matches the protein description above
2. Verify the organism is correct: Anopheles gambiae (African malaria mosquito).
3. Check if protein family/domains align with what you find in literature
4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'D7r3' 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

Research Target:

Please provide a comprehensive research report on the gene D7r3 (gene ID: D7r3, UniProt: A0A1S4GYH9) 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this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.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.

Output

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.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

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.

Target Gene/Protein Identity (from UniProt):

• UniProt Accession: A0A1S4GYH9
• Protein Description: RecName: Full=Short form salivary protein D7R3 {ECO:0000305}; AltName: Full=D7-related 3 protein {ECO:0000312|EMBL:CAB39729.1}; Flags: Precursor;
• Gene Information: Name=D7r3 {ECO:0000303|PubMed:16301315};
• Organism (full): Anopheles gambiae (African malaria mosquito).
• Protein Family: Belongs to the PBP/GOBP family. .
• Key Domains: PBP/GOBP. (IPR006170); PBP_GOBP_sf. (IPR036728); PBP_GOBP (PF01395)

MANDATORY VERIFICATION STEPS:

1. Check if the gene symbol "D7r3" matches the protein description above
2. Verify the organism is correct: Anopheles gambiae (African malaria mosquito).
3. Check if protein family/domains align with what you find in literature
4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'D7r3' 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

Research Target:

Please provide a comprehensive research report on the gene D7r3 (gene ID: D7r3, UniProt: A0A1S4GYH9) 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.

Title: Functional Annotation of Anopheles gambiae D7r3 (UniProt: A0A1S4GYH9)

Executive summary
We verified that D7r3 is a short-form D7 salivary protein from Anopheles gambiae belonging to the odorant/pheromone-binding protein superfamily (PBP/GOBP), secreted by female salivary glands and deployed during blood feeding. Short-form D7s, including D7r3, function primarily as non-enzymatic “kratagonists” that sequester host biogenic amines (notably serotonin, and to varying degrees norepinephrine, histamine, and epinephrine) to suppress vasoconstriction, platelet activation, pain, and inflammation at the bite site. Quantitative binding data indicate D7r3 binds serotonin with subnanomolar-to-low-nanomolar affinity and other biogenic amines with lower affinity. Recent research (2023–2024) highlights translational uses of D7 proteins as exposure biomarkers and expands functional genetics in mosquitoes; transcriptomic data associate overexpression of salivary proteins (including D7 family members) with insecticide resistance in Anopheles arabiensis. (calvo2006functionandevolution pages 1-1, calvo2006functionandevolution pages 4-5, oseno2022characterizationofanopheles pages 1-2, omoke2024wholetranscriptomicanalysis pages 12-14, martinmartin2023aedesaegyptid7 pages 7-9)

1) Key concepts and definitions with current understanding
- Identity and nomenclature verification
- D7r3 is one of five short-form D7 paralogs (D7r1–D7r5) within the D7 gene cluster of An. gambiae; the D7 family contains three long-form and five short-form members within ~20 kb on chromosome 3R. This matches the provided UniProt accession and the short-form annotation. (Arcà et al., 2017; BMC Genomics; https://doi.org/10.1186/s12864-017-3579-8). (arca2017anophelinesalivaryprotein pages 7-9)
- D7 proteins are distantly related to odorant-binding proteins and belong to the PBP/GOBP-related superfamily, consistent with the PBP/GOBP domain model. (Valenzuela et al., 2002; Insect Mol Biol; https://doi.org/10.1046/j.1365-2583.2002.00319.x). (valenzuela2002thed7family pages 3-6)

• Protein form and domains

• Short-form D7s (~17–18 kDa) comprise a single OBP-like domain; long-form D7s possess two OBP-like domains with bifunctional ligand binding (N-terminal domain typically binding eicosanoids; C-terminal domain binding biogenic amines). The short-form classification of D7r3 aligns with a single OBP-like domain. (Arcà et al., 2017; Valenzuela et al., 2002). (arca2017anophelinesalivaryprotein pages 7-9, valenzuela2002thed7family pages 3-6)

• Localization and secretion

• D7s are abundantly and specifically expressed in adult female salivary glands and are secreted into saliva for deployment during blood feeding. Recombinant antigen work for An. gambiae included D7r3 among expressed short forms for human IgG assays, supporting its identity as a secreted salivary antigen. (Calvo et al., 2006; J Biol Chem; https://doi.org/10.1074/jbc.m510359200; Oseno et al., 2022; Parasites & Vectors; https://doi.org/10.1186/s13071-021-05130-5). (calvo2006functionandevolution pages 1-1, oseno2022characterizationofanopheles pages 1-2)

• Primary biochemical function

• Short-form D7s are non-enzymatic scavengers of host biogenic amines (serotonin, histamine, norepinephrine, epinephrine), reducing vasoconstriction, platelet aggregation, pain, and inflammatory signaling at bite sites—thereby facilitating hematophagy. (Calvo et al., 2006; J Biol Chem). (calvo2006functionandevolution pages 1-1, calvo2006functionandevolution pages 5-6)

2) Recent developments and latest research (priority to 2023–2024)
- Functional genetics of D7 proteins (Aedes model)
- CRISPR/Cas9 knockouts of D7 long forms in Aedes aegypti (D7L1/D7L2) increased probing time; phenotypes were rescued in leukotriene-deficient mice, highlighting in vivo leukotriene scavenging. While focused on Aedes, these data reinforce D7s’ conserved anti-inflammatory roles at blood-feeding sites. (mBio, Dec 2023; https://doi.org/10.1128/mbio.02289-23). (martinmartin2023aedesaegyptid7 pages 7-9)

• Exposure biomarkers and sero-epidemiology
• An. gambiae D7 antigens (including D7r3) elicited strong IgG responses in malaria-exposed populations; D7L2 antibody levels correlated with exposure intensity and were reduced among bednet users, demonstrating utility as serological markers of vector contact. (Oseno et al., 2022; https://doi.org/10.1186/s13071-021-05130-5). (oseno2022characterizationofanopheles pages 1-2)

• Systematic review (Aedes spp.) supports the broader concept: anti-saliva (including anti-D7) antibody responses reflect mosquito exposure dynamics and vary with age and epidemiological context. (Frontiers in Tropical Diseases, Nov 2023; https://doi.org/10.3389/fitd.2023.1145340). (etienne2023antibodiestoaedes pages 9-11)

• Insecticide resistance context

• Whole-transcriptome analyses in field An. arabiensis populations (Kenya) showed widespread overexpression of salivary gland proteins, including D7 family members (e.g., D7L1/D7L2), associated with pyrethroid and organophosphate resistance. While species- and paralog-specific effects vary, this links D7-family overexpression to resistance phenotypes in Anopheles. (BMC Genomics, Mar 2024; https://doi.org/10.1186/s12864-024-10182-9). (omoke2024wholetranscriptomicanalysis pages 12-14)

3) Current applications and real-world implementations
- Exposure monitoring and public health surveillance
- D7 antigens (short and long forms) have been used as sero-epidemiological tools to quantify human–vector contact, inform transmission intensity, and evaluate interventions (e.g., bednet use). D7r3 was part of the antigen panel in An. gambiae. (Oseno et al., 2022; https://doi.org/10.1186/s13071-021-05130-5). (oseno2022characterizationofanopheles pages 1-2)
- Broader pooled analyses in Aedes systems underpin anti-saliva IgG as markers of exposure, supporting the translational use-case across mosquito genera. (Etienne et al., 2023; https://doi.org/10.3389/fitd.2023.1145340). (etienne2023antibodiestoaedes pages 9-11)

• Mechanistic underpinnings of saliva-assisted transmission and feeding
• While direct 2023–2024 D7r3-specific data are limited, the Aedes CRISPR study indicates D7 proteins shorten probing time via leukotriene scavenging and can modulate parasite infection outcomes, suggesting D7s (by extension short forms in Anopheles) contribute to both feeding efficiency and pathogen ecology. (mBio, 2023; https://doi.org/10.1128/mbio.02289-23). (martinmartin2023aedesaegyptid7 pages 7-9)

4) Expert opinions and analysis from authoritative sources
- Comprehensive functional framework
- Foundational work in An. gambiae established that short-form D7s—including D7r3—bind biogenic amines with high affinity (serotonin highest), acting as kratagonists to inhibit host hemostatic and inflammatory pathways at the bite site. This consensus view, from J Biol Chem (2006) and evolutionary analyses (BMC Genomics, 2017), remains current for D7r3’s principal function. (https://doi.org/10.1074/jbc.m510359200; https://doi.org/10.1186/s12864-017-3579-8). (calvo2006functionandevolution pages 4-5, arca2017anophelinesalivaryprotein pages 7-9)
- The D7 family’s relationship to OBP/PBP-GOBP proteins and the division into short and long forms—with long forms often binding eicosanoids and short forms specializing in biogenic amines—provides a structural/evolutionary rationale for D7r3’s substrate scope. (Insect Mol Biol, 2002; https://doi.org/10.1046/j.1365-2583.2002.00319.x). (valenzuela2002thed7family pages 3-6)

5) Relevant statistics and data from recent and foundational studies
- Binding specificity and affinity (D7r3; An. gambiae; isothermal titration calorimetry)
- Serotonin (5-HT): Kd ≈ 0.16 (units as reported; subnanomolar–low-nanomolar context); stoichiometry ≈ 0.64–0.71 per protein, consistent with one binding site. (J Biol Chem, 2006; https://doi.org/10.1074/jbc.m510359200). (calvo2006functionandevolution pages 4-5)
- Norepinephrine: Kd ≈ 3.19; Histamine: Kd ≈ 41; Epinephrine: Kd ≈ 312. Relative affinities: 5-HT >> NE > Histamine > Epi. (J Biol Chem, 2006). (calvo2006functionandevolution pages 4-5)
- Functional assays: short-form D7s antagonize smooth-muscle responses to 5-HT/Histamine/NE; D7r1 uniquely showed anticoagulant activity in clotting assays, not shared by other short forms at higher concentrations—implying D7r3 lacks the D7r1-specific anticoagulant effect. (J Biol Chem, 2006). (calvo2006functionandevolution pages 5-6, calvo2006functionandevolution pages 4-5)

• Expression, abundance, and deployment during feeding
• D7 proteins may account for ~5–20% of total salivary protein; salivary glands contain ~1–3 µg total protein and ~50% is secreted during a feed; local sequestration needs estimated at ~0.03–0.3 µg for effective antagonism. (J Biol Chem, 2006). (calvo2006functionandevolution pages 5-6)

• Transcript evidence: D7r1–D7r4 have high EST counts (~70–200), whereas D7r5 is low (~7), indicating D7r3 belongs to the highly expressed subset. (J Biol Chem, 2006). (calvo2006functionandevolution pages 6-7)

• Evolutionary and structural context

• Short D7s likely arose by truncation/duplication from long D7 ancestors; across anophelines, short forms retained/optimized amine binding (5-HT ancestral), with paralog-specific tuning (e.g., NE/Epi binding optimized in the D7r2/3 clade). (J Biol Chem, 2006; BMC Genomics, 2017). (calvo2006functionandevolution pages 6-7, arca2017anophelinesalivaryprotein pages 7-9)

• 2023–2024 field-relevant findings

• An. arabiensis resistance transcriptomics: salivary gland protein overexpression rates of ≈93–97% across comparisons; D7L1/D7L2 among upregulated SGPs associated with pyrethroid and organophosphate resistance—implicating salivary families in resistance-associated expression programs. (BMC Genomics, 2024; https://doi.org/10.1186/s12864-024-10182-9). (omoke2024wholetranscriptomicanalysis pages 12-14)

Pathways and localization
- Site of action: extracellular (host dermis at the bite site), where secreted D7 proteins bind host agonists in the hemostasis and inflammatory pathways. (Calvo et al., 2006; https://doi.org/10.1074/jbc.m510359200). (calvo2006functionandevolution pages 1-1, calvo2006functionandevolution pages 5-6)
- Pathways impacted: vasoconstriction (norepinephrine/epinephrine), platelet activation/aggregation (serotonin, histamine, ADP in long-form D7s in other genera), and inflammation/itch/pain (histamine, leukotrienes notably for long forms). For D7r3, the dominant target class is biogenic amines. (Calvo et al., 2006; Arcà et al., 2017). (calvo2006functionandevolution pages 4-5, arca2017anophelinesalivaryprotein pages 7-9)

Ambiguity and limits of the literature for D7r3
- The D7 family is well-characterized; however, D7r3-specific literature is less extensive than for D7r1 and D7r4 (including structural studies on D7r4). Where D7r3-specific data are limited, we infer function from direct binding measurements for D7r3 (biogenic amines) and from paralog/family context indicating no eicosanoid binding by short forms. We did not find short-form D7r3 eicosanoid binding. (Calvo et al., 2006; Arcà et al., 2017). (calvo2006functionandevolution pages 4-5, arca2017anophelinesalivaryprotein pages 7-9)

Verification against mandatory criteria
- Gene symbol, organism, family/domains: Verified as Anopheles gambiae D7r3, short-form D7 in the PBP/GOBP-related family. (Arcà et al., 2017; Valenzuela et al., 2002). (arca2017anophelinesalivaryprotein pages 7-9, valenzuela2002thed7family pages 3-6)
- Organism correctness: All cited An. gambiae/Anopheles sources are consistent with the target organism. (arca2017anophelinesalivaryprotein pages 7-9, calvo2006functionandevolution pages 1-1)
- Family/domains alignment: D7 family is OBP/PBP-GOBP-related; short form consistent with single OBP-like domain. (valenzuela2002thed7family pages 3-6, arca2017anophelinesalivaryprotein pages 7-9)

Primary functional annotation for D7r3 (concise)
- Molecular function: High-affinity binding to serotonin; moderate-to-low affinity binding to norepinephrine, histamine, and epinephrine; non-enzymatic sequestration of biogenic amines. (Calvo et al., 2006; https://doi.org/10.1074/jbc.m510359200). (calvo2006functionandevolution pages 4-5)
- Biological process: Anti-hemostatic/anti-inflammatory action aiding blood meal acquisition by antagonizing vasoconstriction, platelet aggregation, and inflammatory signaling. (Calvo et al., 2006; Arcà et al., 2017). (calvo2006functionandevolution pages 5-6, arca2017anophelinesalivaryprotein pages 7-9)
- Cellular component: Secreted protein from female salivary glands; acts extracellularly in host skin at the bite site. (Calvo et al., 2006; Oseno et al., 2022). (calvo2006functionandevolution pages 1-1, oseno2022characterizationofanopheles pages 1-2)

URLs and publication dates (selection)
- Calvo et al., 2006 (J Biol Chem), Jan 2006: https://doi.org/10.1074/jbc.m510359200 (binding and function for short forms, including D7r3). (calvo2006functionandevolution pages 4-5)
- Arcà et al., 2017 (BMC Genomics), Feb 2017: https://doi.org/10.1186/s12864-017-3579-8 (evolutionary overview, gene family structure). (arca2017anophelinesalivaryprotein pages 7-9)
- Valenzuela et al., 2002 (Insect Mol Biol), Apr 2002: https://doi.org/10.1046/j.1365-2583.2002.00319.x (D7 family description; OBP/PBP-GOBP relation). (valenzuela2002thed7family pages 3-6)
- Oseno et al., 2022 (Parasites & Vectors), Jan 2022: https://doi.org/10.1186/s13071-021-05130-5 (D7r3 included among An. gambiae D7 antigens; biomarker results). (oseno2022characterizationofanopheles pages 1-2)
- Etienne et al., 2023 (Frontiers in Tropical Diseases), Nov 2023: https://doi.org/10.3389/fitd.2023.1145340 (pooled analysis of anti-saliva antibody responses; Aedes-focused but relevant to D7 biomarker concept). (etienne2023antibodiestoaedes pages 9-11)
- Martin-Martin et al., 2023 (mBio), Dec 2023: https://doi.org/10.1128/mbio.02289-23 (CRISPR functional genetics of D7 long forms; conserved roles). (martinmartin2023aedesaegyptid7 pages 7-9)
- Omoke et al., 2024 (BMC Genomics), Mar 2024: https://doi.org/10.1186/s12864-024-10182-9 (SGP, including D7 family, overexpression in resistant An. arabiensis). (omoke2024wholetranscriptomicanalysis pages 12-14)

Integrated synthesis artifact
| Feature | Summary | Data / Values | Sources |
|---|---|---:|---|
| Identity verification | D7r3 is a short-form D7 salivary protein from Anopheles gambiae; member of the PBP/GOBP (OBP-like) family. | Gene symbol: D7r3; organism: An. gambiae; UniProt (user-supplied): A0A1S4GYH9. | (arca2017anophelinesalivaryprotein pages 7-9, valenzuela2002thed7family pages 3-6, calvo2006functionandevolution pages 1-1) |
| Localization & detection | Secreted, adult female salivary-gland specific; detected in salivary gland and saliva proteomes. | Salivary-gland expression (female-only); present in saliva proteomes and recombinant antigen studies. | (calvo2006functionandevolution pages 1-1, oseno2022characterizationofanopheles pages 1-2, sorsuwan2014identificationofsalivary pages 9-9) |
| Biochemical function & ligand specificity | Scavenges host biogenic amines to antagonize vasoconstriction, platelet activation and pain. Short-form D7r3 binds biogenic amines (serotonin strongest). Eicosanoid binding not reported for D7r3. | Approximate affinities reported (Calvo et al. 2006): Kd ≈ 0.16 (serotonin), 3.19 (norepinephrine), 41 (histamine), 312 (epinephrine); stoichiometry ~0.6–0.7 per protein. | (calvo2006functionandevolution pages 4-5, calvo2006functionandevolution pages 2-3, calvo2006functionandevolution pages 5-6) |
| Structural notes | D7 family related to odorant/pheromone-binding proteins (PBP/GOBP); short vs long distinction driven by presence/absence of N-terminal domain. | Short D7s: ~144–148 aa (~17 kDa), single OBP-like domain; long D7s: two OBP-like domains (bifunctional ligand pockets). | (valenzuela2002thed7family pages 3-6, arca2017anophelinesalivaryprotein pages 7-9, calvo2006functionandevolution pages 1-1) |
| Quantitative/statistical highlights | Abundance estimates, expression evidence and resistance-associated upregulation. | D7 proteins estimated to comprise ~5–20% of total salivary protein; local sequestration requirement ~0.03–0.3 µg; salivary gland total ~1–3 µg (≈ half secreted per feed); EST counts for D7r1–r4 ≈70–200 vs ~7 for D7r5; insecticide-resistant Anopheles arabiensis shows widespread SGP upregulation (SGP upregulation ≈96–97% in some Res–Sus comparisons). | (calvo2006functionandevolution pages 5-6, calvo2006functionandevolution pages 4-5, calvo2006functionandevolution pages 6-7, omoke2024wholetranscriptomicanalysis pages 12-14) |
| Applications & recent developments (2022–2024) | D7s as exposure biomarkers, immunological assays, functional genetics and links to resistance; vaccine/antigen interest. | D7 antigens (short and long forms) elicit human IgG and D7L2 correlates with exposure and bednet use (Oseno 2022); pooled analyses of anti-saliva antibodies support transient exposure signals (Etienne 2023); CRISPR KO of D7 long proteins in Aedes reveals effects on probing time and parasite infection (Martin-Martin 2023); transcriptomics shows D7-family upregulation in insecticide-resistant mosquitoes (Omoke 2024). | (oseno2022characterizationofanopheles pages 1-2, etienne2023antibodiestoaedes pages 9-11, martinmartin2023aedesaegyptid7 pages 7-9, omoke2024wholetranscriptomicanalysis pages 12-14) |

Table: Concise verification and synthesis table summarizing identity, localization, biochemical activity (with approximate Kd values), structural features, quantitative findings, and 2022–2024 applications/research developments for Anopheles gambiae D7r3. Sources cite key extracted evidence (pqac-...).

Conclusions
D7r3 of Anopheles gambiae is a secreted short-form D7 salivary protein in the PBP/GOBP-related family that primarily binds biogenic amines—most strongly serotonin—with quantitative affinities supporting a potent kratagonist role at the blood-feeding site. Its biochemical specificity and salivary deployment position it as an anti-hemostatic/anti-inflammatory effector promoting blood meal acquisition. While D7r3-specific literature is limited relative to some paralogs, direct binding data exist, and family-level evidence provides a coherent mechanism and pathway context. Contemporary applications leverage D7 proteins (including D7r3 as an antigen) as exposure biomarkers, and recent field transcriptomics link salivary protein upregulation (including D7s) to insecticide resistance, underscoring the epidemiological and vector-control relevance of this protein family. (calvo2006functionandevolution pages 4-5, calvo2006functionandevolution pages 1-1, oseno2022characterizationofanopheles pages 1-2, omoke2024wholetranscriptomicanalysis pages 12-14, martinmartin2023aedesaegyptid7 pages 7-9)

References

1. (calvo2006functionandevolution pages 1-1): Eric Calvo, Ben J. Mans, John F. Andersen, and José M.C. Ribeiro. Function and evolution of a mosquito salivary protein family*. Journal of Biological Chemistry, 281:1935-1942, Jan 2006. URL: https://doi.org/10.1074/jbc.m510359200, doi:10.1074/jbc.m510359200. This article has 292 citations and is from a domain leading peer-reviewed journal.

2. (calvo2006functionandevolution pages 4-5): Eric Calvo, Ben J. Mans, John F. Andersen, and José M.C. Ribeiro. Function and evolution of a mosquito salivary protein family*. Journal of Biological Chemistry, 281:1935-1942, Jan 2006. URL: https://doi.org/10.1074/jbc.m510359200, doi:10.1074/jbc.m510359200. This article has 292 citations and is from a domain leading peer-reviewed journal.

3. (oseno2022characterizationofanopheles pages 1-2): Brenda Oseno, Faith Marura, Rodney Ogwang, Martha Muturi, James Njunge, Irene Nkumama, Robert Mwakesi, Kennedy Mwai, Martin K. Rono, Ramadhan Mwakubambanya, Faith Osier, and James Tuju. Characterization of anopheles gambiae d7 salivary proteins as markers of human–mosquito bite contact. Parasites & Vectors, Jan 2022. URL: https://doi.org/10.1186/s13071-021-05130-5, doi:10.1186/s13071-021-05130-5. This article has 11 citations and is from a peer-reviewed journal.

4. (omoke2024wholetranscriptomicanalysis pages 12-14): Diana Omoke, Lucy Mackenzie Impoinvil, Dieunel Derilus, Stephen Okeyo, Helga Saizonou, Nicola Mulder, Nsa Dada, Audrey Lenhart, Luc Djogbénou, and Eric Ochomo. Whole transcriptomic analysis reveals overexpression of salivary gland and cuticular proteins genes in insecticide-resistant anopheles arabiensis from western kenya. BMC Genomics, Mar 2024. URL: https://doi.org/10.1186/s12864-024-10182-9, doi:10.1186/s12864-024-10182-9. This article has 7 citations and is from a peer-reviewed journal.

5. (martinmartin2023aedesaegyptid7 pages 7-9): Ines Martin-Martin, Bianca Burini Kojin, Azadeh Aryan, Adeline E. Williams, Alvaro Molina-Cruz, Paola Carolina Valenzuela-Leon, Gaurav Shrivastava, Karina Botello, Mahnaz Minai, Zach N. Adelman, and Eric Calvo. aedes aegypti d7 long salivary proteins modulate blood feeding and parasite infection. mBio, Dec 2023. URL: https://doi.org/10.1128/mbio.02289-23, doi:10.1128/mbio.02289-23. This article has 14 citations and is from a domain leading peer-reviewed journal.

6. (arca2017anophelinesalivaryprotein pages 7-9): Bruno Arcà, Fabrizio Lombardo, Claudio J. Struchiner, and José M. C. Ribeiro. Anopheline salivary protein genes and gene families: an evolutionary overview after the whole genome sequence of sixteen anopheles species. BMC Genomics, Feb 2017. URL: https://doi.org/10.1186/s12864-017-3579-8, doi:10.1186/s12864-017-3579-8. This article has 86 citations and is from a peer-reviewed journal.

7. (valenzuela2002thed7family pages 3-6): J. G. Valenzuela, R. Charlab, E. C. Gonzalez, I. K. F. De Miranda‐Santos, O. Marinotti, I. M. B. Francischetti, and J. M. C. Ribeiro. The d7 family of salivary proteins in blood sucking diptera. Insect Molecular Biology, 11:149-155, Apr 2002. URL: https://doi.org/10.1046/j.1365-2583.2002.00319.x, doi:10.1046/j.1365-2583.2002.00319.x. This article has 128 citations and is from a peer-reviewed journal.

8. (calvo2006functionandevolution pages 5-6): Eric Calvo, Ben J. Mans, John F. Andersen, and José M.C. Ribeiro. Function and evolution of a mosquito salivary protein family*. Journal of Biological Chemistry, 281:1935-1942, Jan 2006. URL: https://doi.org/10.1074/jbc.m510359200, doi:10.1074/jbc.m510359200. This article has 292 citations and is from a domain leading peer-reviewed journal.

9. (etienne2023antibodiestoaedes pages 9-11): Veronique Etienne, Adriana Gallagher, Rebecca C. Christofferson, Michael K. McCracken, Derek A.T. Cummings, and Maureen T. Long. Antibodies to aedes spp. salivary proteins: a systematic review and pooled analysis. Frontiers in Tropical Diseases, Nov 2023. URL: https://doi.org/10.3389/fitd.2023.1145340, doi:10.3389/fitd.2023.1145340. This article has 4 citations.

10. (calvo2006functionandevolution pages 6-7): Eric Calvo, Ben J. Mans, John F. Andersen, and José M.C. Ribeiro. Function and evolution of a mosquito salivary protein family*. Journal of Biological Chemistry, 281:1935-1942, Jan 2006. URL: https://doi.org/10.1074/jbc.m510359200, doi:10.1074/jbc.m510359200. This article has 292 citations and is from a domain leading peer-reviewed journal.

11. (sorsuwan2014identificationofsalivary pages 9-9): Sriwatapron Sor-suwan, Narissara Jariyapan, Sittiruk Roytrakul, Atchara Paemanee, Atchara Phumee, Benjarat Phattanawiboon, Nuchpicha Intakhan, Wetpisit Chanmol, Paul A. Bates, Atiporn Saeung, and Wej Choochote. Identification of salivary gland proteins depleted after blood feeding in the malaria vector anopheles campestris-like mosquitoes (diptera: culicidae). PLoS ONE, 9:e90809, Mar 2014. URL: https://doi.org/10.1371/journal.pone.0090809, doi:10.1371/journal.pone.0090809. This article has 14 citations and is from a peer-reviewed journal.

12. (calvo2006functionandevolution pages 2-3): Eric Calvo, Ben J. Mans, John F. Andersen, and José M.C. Ribeiro. Function and evolution of a mosquito salivary protein family*. Journal of Biological Chemistry, 281:1935-1942, Jan 2006. URL: https://doi.org/10.1074/jbc.m510359200, doi:10.1074/jbc.m510359200. This article has 292 citations and is from a domain leading peer-reviewed journal.

Citations

1. arca2017anophelinesalivaryprotein pages 7-9
2. oseno2022characterizationofanopheles pages 1-2
3. etienne2023antibodiestoaedes pages 9-11
4. omoke2024wholetranscriptomicanalysis pages 12-14
5. calvo2006functionandevolution pages 4-5
6. calvo2006functionandevolution pages 5-6
7. calvo2006functionandevolution pages 6-7
8. calvo2006functionandevolution pages 1-1
9. sorsuwan2014identificationofsalivary pages 9-9
10. calvo2006functionandevolution pages 2-3
11. https://doi.org/10.1186/s12864-017-3579-8
12. https://doi.org/10.1046/j.1365-2583.2002.00319.x
13. https://doi.org/10.1074/jbc.m510359200;
14. https://doi.org/10.1186/s13071-021-05130-5
15. https://doi.org/10.1128/mbio.02289-23
16. https://doi.org/10.3389/fitd.2023.1145340
17. https://doi.org/10.1186/s12864-024-10182-9
18. https://doi.org/10.1074/jbc.m510359200
19. https://doi.org/10.1074/jbc.m510359200,
20. https://doi.org/10.1186/s13071-021-05130-5,
21. https://doi.org/10.1186/s12864-024-10182-9,
22. https://doi.org/10.1128/mbio.02289-23,
23. https://doi.org/10.1186/s12864-017-3579-8,
24. https://doi.org/10.1046/j.1365-2583.2002.00319.x,
25. https://doi.org/10.3389/fitd.2023.1145340,
26. https://doi.org/10.1371/journal.pone.0090809,