Tango5 (Q9W2S1) notes

2026-10-21 — Full re-review, independent of the ProtNLM2 predictions

Scope: Q9W2S1 is the 530-residue product of Drosophila Tango5/vmp1 (FBgn0052675).
It is the UniProt entry GO Central uses for the PAINT IBAs on this gene. The benchmark
entry Q7KVQ7 (reviewed in genes/DROME/Tango5/) is identical to residues 103-530 of
Q9W2S1 (file:DROME/Tango5/Tango5-bioinformatics/RESULTS.md). No ProtNLM2 output was
opened or used for this review.

Deep research

just deep-research-falcon DROME Tango5__Q9W2S1 --fallback perplexity-lite failed:
falcon returned "Failed to authenticate", and the perplexity fallback returned HTTP 401
(insufficient quota). No deep-research file was produced for this folder. The falcon report
written for the same gene under the Q7KVQ7 accession
(genes/DROME/Tango5/Tango5-deep-research-falcon.md) was read as background only. Every
claim below is checked against the cached primary papers.

Evolutionary placement

• PANTHER family PTHR10281 is heterogeneous. It joins the VMP1 subfamilies with
  cytochrome-b5-domain MAPR proteins (PGRMC1/2, neudesin, neuferricin)
  (interpro/panther/panther.obo). Assertions at the root node PTN000031541 (membrane,
  endomembrane system) therefore cover both kinds of protein and say little.
• Q9W2S1, Q7KVQ7 and human VMP1 (Q96GC9) are all in PTHR10281:SF1 "VACUOLE MEMBRANE PROTEIN 1"
  (file:DROME/Tango5/Tango5-bioinformatics/RESULTS.md). Their global identity is about 55%.
• PAINT nodes (interpro/panther/PTHR10281/PTHR10281-paint.tsv):
• PTN000031590 (eukaryotic VMP1 clade, which includes Arabidopsis KMS1/KMS2):
  ER (seeded by plant, fly, human and Dicty members), phospholipid scramblase activity
  (seeded by human VMP1 only), and endomembrane system organization.
• PTN000031591: autophagosome assembly (human VMP1, Dicty Vmp1) and Golgi organization
  (fly Tango5, Dicty Vmp1).
• The fly protein-secretion IMP was not propagated to any node. I treat that as a
  deliberate decision.
• UniProt features on Q9W2S1: four Phobius TM helices (171-188, 208-233, 348-364,
  470-491), Pfam KMS1_N (122-219) and VMP1_C (470-501), and a disordered N-terminus
  (1-132). The ARBA-derived CC lines (catalytic activity, subcellular location, "VMP1
  family") are not used as support.

What is established in Drosophila (experimental)

• ER localization. Endogenous GFP-Vmp1 co-localizes with Sec61beta and SERCA in larval
  intestine PMID:34019822.
  The Bard et al. 2006 screen also reported ER localization (IDA; abstract only).
• Essential gene. Lethality is rescued by a duplication PMID:34019822.
• Required for autophagy. With vmp1 loss, Atg8a puncta fail to accumulate and Ref2p
  accumulates PMID:34019822.
• Genetically upstream of Vps13D and Marf in mitochondrial clearance and in limiting
  mitochondria-ER contact PMID:34019822. These are downstream phenotypes and are not
  annotated as process participation.
• S2 RNAi screen: depletion inhibits constitutive secretion and makes Golgi membranes fuse
  with the ER [PMID:16452979, abstract only; details from FlyBase curation of the full text].

What is inferred (not tested in fly)

• Phospholipid scramblase activity. This rests on reconstituted human VMP1 [PMID:33929485;
  PMID:33850023] and on the PTN000031590 IBD. The fly protein has not been assayed.
• A mechanistic role in phagophore expansion, as the ER-leaflet scramblase partnered with
  ATG2 PMID:33850023. Fly data establish only that the gene is required.

Decisions

• Scramblase IBA: ACCEPT, as the core MF (inferred). ND: MODIFY to scramblase.
• ER rows (IBA, IDA, IEA): MODIFY to ER membrane (GO:0005789).
• Vacuolar membrane (ARBA SubCell): MARK_AS_OVER_ANNOTATED.
• Plasma membrane phospholipid scrambling (IEA from the scramblase MF): wrong membrane. The
  fly protein is in the ER. MODIFY to the location-neutral phospholipid translocation
  (GO:0045332).
• Membrane and endomembrane system (root-node IBAs): TOO_GENERAL, beside ER membrane.
• Autophagosome assembly IBA: ACCEPT. It is supported by fly requirement data plus the
  family mechanism.
• Golgi organization (IBA, IMP), endomembrane system organization (IBA) and protein
  secretion (IMP): KEEP_AS_NON_CORE. These are likely consequences of ER membrane
  homeostasis.