hbt (Q9VK03): evidence and ProtNLM claim review

Headbutt is a 451-residue Rost-family protein with six predicted transmembrane helices. It is an integral membrane protein with an unresolved molecular activity and biological role for this isoform.

Exact input: Q9VK03, 451 residues. The accession was fetched explicitly with the gene-directory alias; no canonical-sequence substitution is made.

Raw emitted predictions: hbt-predictions-source.json. Source features: hbt-uniprot.txt, with an exact extraction in hbt-sequence-evidence.json.

Sequence and domain evidence

These are sequence/domain observations or explicitly named feature predictions, not measurements of biological function. ARBA assertions and ProtNLM-derived UniProt names are not counted as validation.

DR   InterPro; IPR049352; Rost.
FT   TRANSMEM        40..63
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        75..98
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        123..145
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        157..177
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        184..205
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        228..250
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"

ProtNLM claims

The snapshot emits names and location/keyword statements, with no GO or EC prediction for this target. Each actual statement is assessed below; no GO term has been substituted for it. Categories follow the function-prediction rubric, with nonspecific “uncharacterized” names marked UNC because they contain no testable function. CNN records an independently supported existing annotation; it does not assert a particular training-set composition.

Literature evidence

No target-specific primary finding is used to establish a molecular activity here. The current assessment is bounded by exact-record architecture and the explicitly identified curated inferences.

Annotation decisions

• GO:0003674 molecular_function (ND): ACCEPT. Six membrane-spanning segments and a Rost-family domain do not establish a transporter substrate or catalytic activity.
• GO:0008150 biological_process (ND): ACCEPT. The exact Headbutt isoform lacks a sufficiently grounded physiological function in the retrieved evidence.
• GO:0016020 membrane (ISS): ACCEPT. The six Phobius transmembrane segments between residues 40 and 250 independently support the existing ISS membrane annotation. The membrane identity and transport activity are unresolved.

Research provenance

Genuine external literature research is requested through the repository Falcon wrapper, with perplexity-lite configured as fallback. Provider output is retained separately as hbt-deep-research-<provider>.md; its source leads are checked against the underlying publications and exact sequence record.

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

ProtNLM2 output was not consulted for this section.

Identity: Q9VK03 is an isoform, not the canonical product

• hbt (FBgn0264308, CG43778) has four unreviewed UniProt products: A0A6H2EJZ8 (isoform E, 1003 aa;
  UniProt gene-centric canonical), M9PFU0 (isoform A, 963 aa), Q9VK01 (isoform C, 663 aa) and Q9VK03
  (isoform D, 451 aa, benchmark). No Swiss-Prot entry exists.
• Q9VK03 residues 1-451 are identical to isoform E 513-963 (and isoform A 513-963): an N-terminally
  truncated product lacking E's first 512 residues (predicted coiled coils, disordered low-complexity
  segment) and E's last 40 residues. It keeps the complete Rost (PF21534) region and all six
  predicted helices (D 40-250 = E 552-762) [file:DROME/hbt/hbt-bioinformatics/RESULTS.md].
• Current QuickGO: the IMP to GO:0051931 regulation of sensory perception (PMID:32761438) and an IBA
  to membrane (PTN001387085, with FB:FBgn0011705) sit on A0A6H2EJZ8 only. Q9VK03, Q9VK01 and M9PFU0
  still carry the 2012 ND MF/BP rows and the membrane ISS.

Literature

• The falcon deep-research report built its "primary study" on Tanaka et al. 2014 (PMID:24671768).
  That paper is about Mabiki (Mabi), a caspase-independent cell death regulator; its cached full text
  never mentions hbt, headbutt or CG43778. The cell-death/pattern-repair framing in the deep research
  is therefore a mis-citation and was not used.
• The real hbt paper is Zhang, Li, Liu & Zhang 2020, Neurosci Bull (PMID:32761438, PMC7475148), a
  Letter. The publisher blocks XML download, so the cache is abstract-only; I read the PMC HTML. Key
  verbatim excerpts:
• "Among all these hits, a previously uncharacterized gene, CG43778, was of particular interest
  because its mutant had the most severe touch defect among all the genes tested and its
  molecular/cellular function had not yet been studied (Fig. 2 B). We named this gene headbutt (hbt)."
• "The back-crossed homozygous knockout of HBT and the trans-heterozygotes of MIMIC and knockout
  showed a touch response defect as severe as the MIMIC line (Fig. 2 D)"
• "HBT is required for larval TO mechanosensation. hbt mutant larval chordotonal neurons in the TO
  show a significantly reduced Ca 2+ response"
• "In the DO, HBT proteins wrap the dendrites of es cells"; "In the TO, HBT proteins wrap glial cells
  of chordotonal neurons"; GFP knock-in at the C-terminus; prospero-positive sheath cells.
• "we identified the novel gene headbutt (hbt) that functions in the cells surrounding the DO and TO
  to regulate the neuronal mechanosensitivity"
  These cannot be quoted in the YAML (cache abstract-only); the review quotes the title and records
  the findings as statements.
• Family: Rolling stone (O44252, PTHR12242:SF46) is a membrane-fraction-enriched protein required for
  myoblast fusion PMID:9230076.
  hbt is SF49, a different subfamily: the myoblast-fusion role is not transferred.
• Parsons et al. 2016 PMID:27018888. This is an HHpred-level hint at a Thr/His
  hydrolase mechanism. My pairwise SW of Q9VK03 vs human AIG1 was not significant (22% over 182 aa,
  score 43), so I make no inference about residues or activity.

Decisions

• GO:0003674 ND: ACCEPT. No activity is known.
• GO:0008150 ND: MODIFY -> GO:0051931 regulation of sensory perception. Superseded by the 2020 IMP that
  FlyBase put on the canonical isoform; the knockout removes all isoforms and D carries the conserved
  core. Regulation (not sensory perception of touch itself) fits expression in sheath/glial cells
  rather than in the neurons.
• GO:0016020 membrane ISS (from rost): ACCEPT. Family-level property, six TM helices, PAINT agrees.
• Core function: membrane protein of sensory sheath cells/glia regulating larval touch sensitivity; MF
  unknown (knowledge gap).

Relatives and family

• Relative to review next: same gene canonical product, hbt isoform E A0A6H2EJZ8
  (folder would be genes/DROME/hbt__A0A6H2EJZ8, since genes/DROME/hbt is keyed to Q9VK03). No review
  exists. Rost (O44252) has no review in the repo either.
• interpro/panther/PTHR12242/PTHR12242-review.yaml: agrees hbt is SF49 and rost SF46. Two issues: the
  SF49 subfamily description is a verbatim copy of the family coherence text rather than a description
  of SF49, and its only representative member is the truncated isoform D (Q9VK03) rather than the
  canonical A0A6H2EJZ8. It does not mention the Zhang 2020 mechanosensation result or the
  AIG1/ADTRP-like observation of PMID:27018888.
• Modules: none found for hbt or Rost-family proteins (rost appears in no module; the myoblast-fusion
  modules such as modules/dmel_irm_myoblast_adhesion.yaml do not include it and are unrelated to hbt).