A0A8C5FPT8 (Gadus morhua tbc1d14) notes

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

No ProtNLM2 files or prediction-evidence folders were consulted.

Identity and gene model

• All ten cod UniProt entries named tbc1d14 are transcripts of one Ensembl gene,
  ENSGMOG00000018292 on chromosome 17 [file:GADMO/A0A8C5FPT8/A0A8C5FPT8-bioinformatics/RESULTS-rereview.md].
  None is reviewed in UniProt, so no reviewed canonical cod entry exists.
• A0A8C5FPT8 (709 aa) is an alternative gene model. It shares 97% identity with the sister model
  A0A8C5FCB4 (750 aa) but has a non-conserved N-terminus (MHFFLTRNYLL...). It also has a
  non-conserved 48-residue C-terminal tail (TDRDGRTDGRG...FYGGLAT) in place of the conserved
  ...QKDQERSSPVLRR end that matches human TBC1D14. The TBC domain (388-596), the TRAPP-binding
  segment and the arginine- and glutamine-finger residues (R457/Q493, equivalent to human
  R472/Q508) are all present.

Orthology vs PANTHER placement

• PANTHER (via UniProt) places tetrapod TBC1D14 in PTHR47219:SF21. Teleost and coelacanth tbc1d14,
  including this protein, are placed in SF15 ("TBC1 DOMAIN FAMILY MEMBER 12 ISOFORM X1").
• A MAFFT and NJ panel puts the cod tbc1d14 models in the TBC1D14 clade: 60-66% identity to
  TBC1D14 orthologs, 54-58% to TBC1D12 orthologs, and 51% to the separate cod TBC1D12-like gene
  LOC115530985. The SF15 placement therefore looks like an HMM mis-assignment. The consequence is
  that cod receives the TreeGrafter GAP and small GTPase binding terms from PTN009208344 (a
  RABGAP1-seeded lineage), but not the TBC1D14-clade PAINT terms (PTN000538677 recycling endosome
  and autophagosome; PTN008586039 regulation of autophagosome assembly).
• Disagreement with interpro/panther/PTHR47219/PTHR47219-review.yaml: that review records the cod
  target as TBC1D12-like and calls paralog identity unresolved. The re-review tree resolves it
  as TBC1D14.

Literature (human ortholog)

• PMID:22613832
• PMID:22613832
• PMID:22613832 Golgi complex.
• PMID:26711178
• PMID:26711178

Changes from the previous review

• GTPase activator activity: changed from UNDECIDED to MARK_AS_OVER_ANNOTATED. The ortholog
  shows no GAP activity across 47 Rabs, and the term reaches cod through a mis-placed subfamily.
• Enzyme binding: changed from MARK_AS_OVER_ANNOTATED to MODIFY, with replacements small GTPase
  binding and protein kinase binding (ULK1).
• Cytoplasmic vesicle: changed from ACCEPT to MODIFY, with replacement recycling endosome.
• Added NEW GO:2000785 regulation of autophagosome assembly. It is supported by the TBC1D14-clade
  PAINT node and by ortholog mechanism, not by phenotype alone.
• Vacuole is still over-annotated. Vesicle-mediated transport and small GTPase binding are
  still accepted.
• Core function location changed to recycling endosome. The description was rewritten.