TBC1D14 (human, Q9P2M4) notes

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

Context: reviewed as the experimentally characterised ortholog of the Atlantic cod model
GADMO/A0A8C5FPT8. No ProtNLM2 files were opened or used.

Deep research: just deep-research-falcon human TBC1D14 --fallback perplexity-lite failed
(Edison API 403 "Failed to authenticate"; perplexity-lite fallback timed out at 600 s). No
deep-research file exists. The review uses the cached full-text papers below.

Evolutionary placement

• PANTHER PTHR47219:SF21 (TBC1 DOMAIN FAMILY MEMBER 14) [file:human/TBC1D14/TBC1D14-uniprot.txt].
• PAINT (interpro/panther/PTHR47219/PTHR47219-paint.tsv): GTPase activator activity is on the
  family-root node PTN000537561, which TBC1D14 does not seed. The TBC1D14-clade nodes
  PTN000538677 (autophagosome, recycling endosome; taxon:33213) and PTN008586039 (regulation of
  autophagosome assembly; taxon:33154) are seeded only by Q9P2M4. The curator gave these nodes no
  GAP term.
• Cod tbc1d14 models fall in the vertebrate TBC1D14 clade, separate from TBC1D12
  (genes/GADMO/A0A8C5FPT8/A0A8C5FPT8-bioinformatics/RESULTS-rereview.md). Fish tbc1d14 is assigned
  PANTHER SF15 (TBC1D12-like), which that tree does not support.
• Catalytic arginine R472 (IxxDxxR motif IKLDISR, 466-472) and glutamine Q508 (YxQ) are retained.

Key findings

• No GAP activity: PMID:22613832.
• Binds active Rab11; Rab11 needed for its RE tubules PMID:22613832.
• Binds ULK1 (Y2H, co-IP; residues 224-330 of the TBC domain) PMID:22613832.
• Depletion increases starvation-induced autophagy PMID:22613832.
• Rab11-TRAPPIII bridge, RAB1 activation, ATG9 RE-to-Golgi traffic, ULK1-independent [PMID:26711178 "These data support a model where TBC1D14 acts as a bridge between a TRAPP complex and activated RAB11."; "However, TBC1D14 depletion resulted in a significant reduction in RAB1B bound to GFP"].
• Shiga toxin block on overexpression independent of catalytic residue PMID:17562788.

Decisions

• GTPase activator activity IBA: MARK_AS_OVER_ANNOTATED (target-specific negative biochemistry; root-node propagation).
• Protein binding: ULK1 -> protein kinase binding; RAB11B -> small GTPase binding; NXF1 (HuRI) REMOVE.
• Autophagosome (IDA, IBA): KEEP_AS_NON_CORE (partial LC3 colocalization only).
• Endosome IEA -> recycling endosome.
• NEW: molecular adaptor activity (IDA, PMID:26711178).
• Transfer guidance: established in human cells (no in vivo/animal data): Rab11 binding, TRAPPIII
  adaptor role, RE-to-Golgi transport, regulation of starvation-induced autophagosome formation,
  RE/Golgi localization. GAP activity is not established and should not be transferred.