| Feature | Evidence in human LST2 (Battaglioni 2024) | Evidence in *C. elegans* lst-2 (Sundaram 2013) | Evidence in *Drosophila* Q9VB70/CG6051 (direct vs inferred) | Annotation confidence |
|---|---|---|---|---|
| Family/domain identity (LST2/lst-2 family; FYVE-type zinc finger) | Human LST2/ZFYVE28 is explicitly described as a FYVE-domain protein; the 2024 PNAS study includes cross-species analysis and domain architecture for LST2 family proteins (pqac-00000005, pqac-00000007) | *C. elegans* LST-2 is described as a zinc finger/FYVE domain-containing protein in RTK/Ras signaling review material (pqac-00000000, pqac-00000008) | Direct: Q9VB70 is explicitly listed as the *Drosophila* homolog in the 2024 PNAS alignment; this matches the UniProt assignment of CG6051/Q9VB70 to the lst-2 family with FYVE_LST2/FYVE-related domains (pqac-00000005) | High — direct cross-species homolog listing plus concordant family/domain annotation (pqac-00000005, pqac-00000008) |
| FYVE-mediated membrane/endosomal association | Human LST2 contains a FYVE domain; the isolated FYVE domain colocalizes with early endosomes, consistent with PI3P-dependent membrane targeting (pqac-00000006, pqac-00000007) | Review identifies lst-2 as FYVE-domain protein, but no direct localization data are provided in the retrieved excerpt (pqac-00000000, pqac-00000008) | Inferred: because Q9VB70 is an LST2-family FYVE protein, endosomal/PI3P-associated localization is plausible, but no direct fly localization experiment was retrieved (pqac-00000005) | Medium — strong family logic, but no direct fly localization data in retrieved sources (pqac-00000005, pqac-00000006) |
| TOS motif / RAPTOR binding | Human LST2 has a canonical TOS motif that binds RAPTOR/mTORC1; F401A reduces RAPTOR interaction by ~9-fold, and binding is sub-micromolar (pqac-00000006, pqac-00000010) | No TOS motif or RAPTOR-binding evidence in the retrieved worm review excerpt (pqac-00000000, pqac-00000008) | Weakly inferred/possibly absent: the PNAS study notes the TOS motif is conserved in vertebrates, implying it may not be conserved in fly Q9VB70 (pqac-00000005) | Low — human mechanism is strong, but transfer to fly is uncertain and may not be conserved (pqac-00000005, pqac-00000006) |
| mTORC1 phosphorylation as regulatory PTM | Human LST2 is phosphorylated by mTORC1 at S670, which promotes stabilization and changes distribution (pqac-00000005, pqac-00000006, pqac-00000007, pqac-00000009) | No phosphorylation/PTM evidence in the retrieved worm review excerpt (pqac-00000000, pqac-00000008) | Inferred only at family level: because Q9VB70 is in the homolog alignment, phosphorylation-dependent regulation is conceivable, but no direct fly phosphosite or kinase evidence was retrieved (pqac-00000005) | Low — no direct fly PTM evidence and key motif conservation appears vertebrate-biased (pqac-00000005, pqac-00000009) |
| Monoubiquitination-dependent stabilization | In human cells, S670 phosphorylation promotes monoubiquitination at K87 and stabilizes LST2 (pqac-00000007) | No analogous ubiquitination evidence in retrieved worm excerpt (pqac-00000000, pqac-00000008) | Inferred only from human mechanism; no direct evidence for ubiquitination/stability control of Q9VB70 in fly was retrieved (pqac-00000005, pqac-00000007) | Low — purely transferred hypothesis without direct fly support (pqac-00000005, pqac-00000007) |
| Subcellular localization pattern | Full-length human LST2 shows broad reticular distribution; isolated FYVE domain localizes to early endosomes; K87 and S670 status influence endosomal vs reticular distribution, with quantification using Manders’ coefficients (pqac-00000006, pqac-00000007, pqac-00000009) | No explicit localization data in retrieved worm excerpt beyond FYVE-domain annotation (pqac-00000008) | No direct localization data for Q9VB70/CG6051 were retrieved; endosomal localization remains a domain-based inference (pqac-00000005) | Medium-low — human localization is detailed, but fly evidence is absent (pqac-00000005, pqac-00000009) |
| Negative regulation of EGFR / RTK trafficking-signaling | Human LST2 negatively regulates EGFR; loss of LST2 enhances EGFR signaling, and LST2 affects other RTKs as well (FGFR, IGF1R, insulin receptor, VEGFR2) (pqac-00000006, pqac-00000007, pqac-00000009) | Worm lst-2 genetically modulates RTK/Ras signaling; phenotype is WT alone but Muv in combination with *gap-1*, supporting a modulatory role in EGFR/Ras pathway output (pqac-00000000, pqac-00000008) | Inferred: Q9VB70 is a homolog in the same family, so RTK/EGFR pathway modulation is a plausible primary annotation, but no direct *Drosophila* EGFR assay was retrieved (pqac-00000005) | Medium — conserved pathway theme across human and worm, but still lacking direct fly functional validation (pqac-00000005, pqac-00000008) |
| Role in endosomal signaling/trafficking | Human data support a trafficking-linked mechanism: FYVE-dependent endosome association, altered receptor stability/recycling, and feedback control of signaling (pqac-00000006, pqac-00000007, pqac-00000009) | Worm evidence is genetic rather than cell biological; endosomal role is not directly shown in retrieved excerpt, though FYVE domain is consistent with membrane signaling roles (pqac-00000000, pqac-00000008) | Inferred for fly from family/domain architecture and homolog assignment; no direct trafficking assay for Q9VB70/CG6051 was retrieved (pqac-00000005) | Medium-low — coherent mechanistic transfer, but direct fly evidence is absent (pqac-00000005, pqac-00000006) |
| RTK–mTORC1 negative-feedback pathway placement | Human LST2 forms part of a negative-feedback loop where mTORC1 phosphorylates/stabilizes LST2 to inhibit upstream EGFR signaling (pqac-00000005, pqac-00000009, pqac-00000010) | Worm lst-2 is placed in EGFR/Ras pathway genetics, but no mTORC1 link appears in the retrieved review excerpt (pqac-00000000, pqac-00000008) | Inferred only at broad pathway level: fly Q9VB70 likely participates in RTK signaling control, but specific mTORC1 feedback involvement is untested in retrieved fly literature (pqac-00000005) | Low-medium — pathway role may be partly conserved, but key upstream regulatory mechanism is not established in fly (pqac-00000005, pqac-00000009) |
| Germline phenotype / spliceosome association | No human evidence in retrieved sources for spliceosome or fly germline phenotypes (pqac-00000007) | No worm evidence in retrieved sources for spliceosome or germline phenotypes (pqac-00000008) | Direct but ambiguous: a 2016 fly RNAi screen lists CG6051 among spliceosome-complex genes required for germline stem cell self-renewal/early differentiation, but the figure appears to label CG6015, so assignment to Q9VB70 is uncertain (pqac-00000001, pqac-00000003, pqac-00000004) | Low — direct fly mention exists, but gene-identity ambiguity prevents confident transfer to Q9VB70 (pqac-00000001, pqac-00000004) |


*Table: This table maps mechanistic features from mammalian LST2 and C. elegans lst-2 onto Drosophila CG6051/Q9VB70, separating direct evidence from inference. It is useful for functional annotation because it highlights which claims are strongly supported versus provisional due to limited fly-specific data.*