Psidin is the auxiliary (non-catalytic) subunit of the NatB N-terminal acetyltransferase complex, orthologous to NAA25/MDM20 in other eukaryotes. The core molecular function of psidin is to scaffold the catalytic subunit NAA20 and position the NatB complex at ribosomes for co-translational N-terminal acetylation of nascent proteins with Met-[Asp/Glu/Asn/Met] N-termini. The gene was originally named "phagocyte signaling-impaired protein" based on Drosophila phenotypic studies showing immune defects (Brennan et al. 2007), but these represent downstream consequences of NatB function in hemocytes rather than the primary molecular role. In Drosophila, psidin also has a separable NatB-independent role in actin regulation via Tropomyosin antagonism, affecting cytoskeleton organization and neuronal axon targeting (Stephan et al. 2012).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Psidin localizes to the cytoplasm as part of the NatB complex, which is ribosome-associated for co-translational activity. This is consistent with the conserved function of NAA25/MDM20 orthologs across eukaryotes. Reason: The cytoplasmic localization is well-supported by phylogenetic inference (IBA) and consistent with the NatB complex function. NatB functions at ribosomes in the cytoplasm for co-translational N-terminal acetylation. Studies in C. elegans show NATC-1::GFP (related NatC subunit) localizes to cytoplasm [PMID:25330323 "NATC-1::GFP was detected in a wide range of cells and tissues in a pattern that suggests cytoplasmic localization"]. The ribosome-proximal localization is conserved [deep research: "NAA25/MDM20 positions NatB on ribosomes for co-translational substrate access"]. Supporting Evidence: GO_REF:0000033 Annotation inferred from phylogenetic analysis |
| GO:0007010 cytoskeleton organization | IBA GO_REF:0000033 | ACCEPT | Summary: In Drosophila, psidin has a NatB-independent role in actin regulation, affecting growth cone lamellipodia and axon targeting by antagonizing Tropomyosin (Tm1). This cytoskeletal function is mechanistically separable from NatB complex activity. Reason: This annotation captures a real, experimentally demonstrated function from Drosophila psidin ortholog studies. Stephan et al. 2012 showed that "Psidin independently regulates growth-cone lamellipodia and axon targeting by antagonizing Tropomyosin and modulating actin dynamics; this role is separable from NatB binding" [deep research citing Stephan 2012]. The IBA annotation is appropriate as this function appears conserved in insects. While this is likely a secondary (non-core NatB) function, it represents a legitimate biological process annotation. Supporting Evidence: GO_REF:0000033 Inferred from Drosophila psidin ortholog |
| GO:0010698 acetyltransferase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: As the auxiliary subunit of NatB, psidin scaffolds and activates the catalytic subunit NAA20 for N-terminal acetyltransferase activity. This is the core molecular function of the protein. Reason: This accurately captures the core molecular function of psidin. The deep research confirms "NatB is composed of a catalytic subunit NAA20 (Nat3) and an auxiliary subunit NAA25 (MDM20/psidin) that together mediate NatB activity" and "psidin encodes the auxiliary subunit of the NatB N-terminal acetyltransferase complex that scaffolds the catalytic subunit NAA20 and positions NatB on ribosomes" [citing Stephan 2012, Guedes 2024]. The term GO:0010698 "acetyltransferase activator activity" precisely describes the non-catalytic role of enabling/activating the acetyltransferase activity of the NAA20 partner. Supporting Evidence: GO_REF:0000033 Phylogenetic inference from conserved NatB complex function |
| GO:0031416 NatB complex | IBA GO_REF:0000033 | ACCEPT | Summary: Psidin is a component of the NatB N-terminal acetyltransferase complex. This is the core identity of the protein as the NAA25/MDM20 ortholog. Reason: This is the primary identity annotation for psidin. The UniProt record explicitly states "Component of the N-terminal acetyltransferase B (NatB) complex" and the deep research confirms "psidin encodes the conserved NatB auxiliary subunit NAA25/MDM20" with the NAA25_NatB_aux_su domain (IPR019183). The GO term definition matches: "A conserved complex that catalyzes the transfer of an acetyl group to the N-terminal residue of a protein acceptor molecule that has a Met-Glu, Met-Asp, Met-Asn, or Met-Met N-terminus." This is a core annotation that should be retained. Supporting Evidence: GO_REF:0000033 Phylogenetic inference from NAA25/MDM20 family membership |
| GO:0002376 immune system process | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: This annotation derives from UniProt keyword mapping based on the protein name "Phagocyte signaling-impaired protein" and associated immunity keywords. However, immune functions are downstream phenotypic consequences in specific cell types (hemocytes), not the primary molecular role of the NatB complex. Reason: This annotation reflects the historical naming based on Drosophila phenotypic studies (Brennan et al. 2007) rather than the core molecular function. The UniProt keywords (KW-0391 Immunity) were assigned based on phenotypic observations, but the deep research clarifies that "psidin is required for hemocyte phagocytic degradation and systemic immune activation" as a downstream consequence of NatB function, not as the primary role. The core function is N-terminal acetyltransferase complex activity. While not entirely incorrect (there are legitimate immune phenotypes in Drosophila), this is too broad and misleading as a function annotation for what is fundamentally a NatB complex subunit. Supporting Evidence: GO_REF:0000043 Inferred from UniProtKB keyword KW-0391 Immunity |
| GO:0005764 lysosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Lysosomal localization was reported in Drosophila hemocytes specifically, where psidin was implicated in phagocytic degradation. This is cell-type specific and secondary to the primary cytoplasmic/ribosomal localization. Reason: The UniProt record states "Lysosome {ECO:0000250|UniProtKB:Q9VDQ7}. Note=Blood cell lysosomes" based on similarity to Drosophila ortholog. The deep research notes "in Drosophila, psidin has also been reported in hemocytes with lysosomal associations during phagocytic degradation, suggesting potential cell-type-specific localizations in insects" [citing Brennan 2007]. This represents a cell-type-specific localization in hemocytes rather than the general localization of the protein. The primary localization is cytoplasmic/ribosome-associated. Keeping as non-core reflects that this is a real but specialized localization. Supporting Evidence: GO_REF:0000044 Inferred from UniProtKB Subcellular Location annotation |
| GO:0045087 innate immune response | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Similar to GO:0002376, this annotation derives from UniProt keyword mapping. Innate immune phenotypes in Drosophila hemocytes are downstream consequences of NatB complex function, not the primary role. Reason: This IEA annotation comes from UniProt keyword KW-0399 (Innate immunity). While Drosophila psidin mutants show innate immunity defects in hemocytes [deep research: "psidin also supports hemocyte phagocytic degradation and systemic immune activation"], this reflects cell-type-specific phenotypic consequences of losing NatB function. The protein is not itself an immune signaling component but rather a general NatB complex subunit whose loss affects multiple cellular processes including, in hemocytes, immune functions. Marking as over-annotated rather than removing because there is genuine experimental basis in Drosophila. Supporting Evidence: GO_REF:0000043 Inferred from UniProtKB keyword KW-0399 Innate immunity |
| GO:0005764 lysosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation based on Drosophila ortholog Q9VDQ7 lysosomal localization in hemocytes. This is a duplicate of the IEA annotation with a different evidence code. Reason: This ISS annotation provides stronger evidence than the IEA for hemocyte lysosomal localization, based on sequence similarity to Drosophila psidin (UniProtKB:Q9VDQ7). The same reasoning applies as for the IEA lysosome annotation - this is cell-type specific (hemocyte blood cells) and secondary to the primary cytoplasmic localization. Keeping as non-core acknowledges the experimental basis while recognizing it is not the general localization. Supporting Evidence: GO_REF:0000024 Manual transfer from Drosophila ortholog UniProtKB:Q9VDQ7 |
| GO:0006911 phagocytosis, engulfment | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: This annotation derives from Drosophila studies where psidin mutants showed defects in phagocytic degradation of bacteria in hemocytes. The phenotype is real but represents a cell-type-specific consequence of NatB function. Reason: The deep research notes "psidin is expressed in hemocytes and was reported as a lysosomal protein required for phagocytic degradation and for activating systemic immune responses" [citing Brennan 2007]. However, this reflects the consequences of losing NatB-mediated N-terminal acetylation in hemocytes, not a direct role in phagocytosis. The protein does not directly participate in phagocytic engulfment machinery. Psidin/NAA25 is a general NatB complex subunit present in all cell types; phagocytosis defects are one manifestation of NatB loss in immune cells. This is over-annotation that conflates phenotype with function. Supporting Evidence: GO_REF:0000024 Manual transfer from Drosophila ortholog based on phagocytosis phenotype |
| GO:0006955 immune response | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Similar to other immune annotations, this derives from Drosophila phenotypic studies showing immune defects in psidin mutants. The protein is not an immune-specific component. Reason: The ISS annotation transfers from Drosophila ortholog studies showing immune phenotypes. The UniProt function states psidin "Has 2 roles in the larval immune response: required both for the phagocytic degradation of internalized bacteria and for the induction of Defensin in the fat body." However, these are phenotypic consequences of losing NatB complex function in specific tissues, not the molecular function. The NatB complex acetylates many proteins globally; immune cells happen to depend on this for proper function. This annotation is misleading because it implies psidin is an immune-specific gene when it is actually a fundamental N-terminal acetyltransferase complex subunit. Supporting Evidence: GO_REF:0000024 Manual transfer from Drosophila ortholog based on immune phenotypes |
| GO:0006474 N-terminal protein amino acid acetylation | IBA GO_REF:0000033 | NEW | Summary: As the auxiliary subunit of NatB, psidin enables co-translational N-terminal acetylation of proteins with Met-[Asp/Glu/Asn/Met] N-termini. This biological process annotation is missing from the current GOA file but should be a core annotation. Reason: This is a core biological process that should be annotated. The deep research clearly establishes that "NatB catalyzes co-translational N-terminal acetylation (Nt-acetylation) of nascent polypeptides, in particular N-termini beginning with Met-Asp or Met-Glu" and psidin is the essential auxiliary subunit. GO:0006474 "N-terminal protein amino acid acetylation" is the appropriate biological process term. This annotation would be more informative than the phenotypic immune annotations currently present. Proposed replacements: N-terminal protein amino acid acetylation Supporting Evidence: GO_REF:0000033 Conserved NatB complex function across eukaryotes |
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Download this section (compressed HTML)Q: Has psidin function been directly studied in Anopheles gambiae, or are all functional inferences from Drosophila ortholog studies? Current annotations rely heavily on Drosophila studies. Direct experimental evidence in mosquito would strengthen annotations.
Q: Is the NatB-independent actin regulatory function of Drosophila psidin conserved in Anopheles psidin? Stephan et al. 2012 showed Drosophila psidin has separable NatB-dependent and NatB-independent functions. Conservation in mosquitoes is unknown.
Experiment: RNAi knockdown of psidin in Anopheles cells or larvae to assess effects on N-terminal acetylation and immune phenotypes. This would validate ortholog-based functional annotations directly in Anopheles.
Hypothesis: Psidin knockdown will impair N-terminal acetylation and cause immune defects similar to Drosophila
Experiment: Co-immunoprecipitation of psidin with NAA20 ortholog in Anopheles to confirm NatB complex formation. This would directly demonstrate NatB complex assembly in mosquito.
Hypothesis: Psidin physically interacts with NAA20 in Anopheles as part of the NatB complex
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