D7r5 is a member of the short-form D7 salivary protein family in Anopheles gambiae. Critically, unlike other D7 proteins that bind biogenic amines (serotonin, histamine, norepinephrine) to facilitate blood feeding, D7r5 does NOT bind these compounds. The protein is poorly expressed in salivary glands and may be on the evolutionary path to becoming a pseudogene. Its actual function, if any, remains unknown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005615 extracellular space | IBA GO_REF:0000033 | ACCEPT | Summary: The IBA annotation for extracellular space is based on phylogenetic inference from related D7 proteins. UniProt indicates D7r5 is secreted, and the protein has a signal peptide (residues 1-22). While D7r5 is poorly expressed (PMID:16301315), when expressed it would be expected to be secreted like other D7 family members. Reason: The extracellular localization is consistent with the protein having a signal peptide and being a member of the secreted D7 salivary protein family. Even though D7r5 may be functionally divergent or degenerating, its structural features support extracellular localization. Supporting Evidence: PMID:16301315 The D7 salivary family of proteins is abundantly expressed in blood-feeding Diptera |
| GO:0007608 sensory perception of smell | IBA GO_REF:0000033 | REMOVE | Summary: This IBA annotation propagates from odorant-binding protein (OBP) family members in Drosophila that function in olfaction. However, D7 proteins are salivary proteins involved in blood feeding, not olfactory receptors. D7r5 specifically has been shown experimentally to NOT bind biogenic amines (PMID:16301315), and there is no evidence it functions in sensory perception of smell. Reason: This annotation is incorrectly propagated. D7 salivary proteins, while distantly related to the OBP superfamily, have evolved distinct functions in blood feeding (binding biogenic amines to antagonize host hemostatic responses). D7r5 specifically does not even perform this function - it is "The nonbinding D7 protein" that "is poorly expressed in the salivary glands and appears to be on the path to becoming a pseudogene" (PMID:16301315). There is no experimental or logical basis for sensory perception of smell annotation. Supporting Evidence: PMID:16301315 The D7 salivary family of proteins is abundantly expressed in blood-feeding Diptera and is distantly related to the odorant-binding protein superfamily. PMID:16301315 four of these five short D7 proteins and the D7 long form bind serotonin with high affinity, as well as histamine and norepinephrine. The nonbinding D7 protein is poorly expressed in the salivary glands and appears to be on the path to becoming a pseudogene. |
| GO:0005549 odorant binding | IEA GO_REF:0000002 | REMOVE | Summary: This IEA annotation is based on InterPro domain assignment (IPR006170 PBP/GOBP family). While D7r5 belongs to the pheromone/general odorant-binding protein superfamily structurally, experimental evidence directly contradicts any binding function for this protein. PMID:16301315 explicitly tested D7r5 and found it does NOT bind biogenic amines, unlike other D7 proteins. Reason: This is a clear over-annotation based on domain homology that contradicts experimental evidence. The original study (PMID:16301315) specifically tested binding using isothermal microcalorimetry and chromatographic methods, finding that "four of these five short D7 proteins...bind serotonin with high affinity, as well as histamine and norepinephrine. The nonbinding D7 protein [D7r5] is poorly expressed in the salivary glands and appears to be on the path to becoming a pseudogene." Structural similarity to OBPs does not confer odorant binding function - D7r5 has lost or never had functional binding activity. Supporting Evidence: PMID:16301315 four of these five short D7 proteins and the D7 long form bind serotonin with high affinity, as well as histamine and norepinephrine. The nonbinding D7 protein is poorly expressed in the salivary glands and appears to be on the path to becoming a pseudogene. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: This IEA annotation is based on UniProt subcellular location annotation indicating the protein is secreted. D7r5 has a predicted signal peptide and belongs to the secreted D7 salivary protein family. This is a broader term than GO:0005615 (extracellular space) which is already annotated via IBA. Reason: The extracellular region annotation is consistent with structural features (signal peptide) and family membership. While D7r5 is poorly expressed and may be degenerating, when expressed it would be secreted. This broader CC term is appropriately supported by the UniProt secreted annotation. Supporting Evidence: PMID:16301315 The D7 salivary family of proteins is abundantly expressed in blood-feeding Diptera |
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Download this section (compressed HTML)Q: Is D7r5 actually expressed at the protein level in any tissue or developmental stage?
Q: Has D7r5 evolved a novel binding specificity for ligands not yet tested?
Q: Is D7r5 accumulating deleterious mutations consistent with pseudogenization?
Experiment: Test D7r5 binding to a broader panel of ligands beyond biogenic amines using isothermal microcalorimetry
Hypothesis: D7r5 may have evolved to bind a novel class of ligands not yet tested
Experiment: Perform expression profiling across tissues and developmental stages using RT-qPCR or proteomics
Hypothesis: D7r5 may be expressed in tissues other than salivary glands
Experiment: Sequence D7r5 across Anopheles populations to assess selective constraint using dN/dS analysis
Hypothesis: If D7r5 is becoming a pseudogene, it should show relaxed selection (dN/dS approaching 1)
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