RAB3IP curation notes

2026-10-03 — initial review (primary cilium life cycle module, stage 2 ciliary vesicle/membrane)

Human RAB3IP (Rabin8) = UniProt Q96QF0. 68 GOA annotations seeded; all reviewed.

Deep research status

First falcon run (600 s timeout; perplexity fallback unavailable) did not complete; re-run with --timeout 2400
(outcome at end of file). Review based on cached primary literature.

Biology

• Rab8-specific GEF [PMID:12221131 "stimulated nucleotide exchange on Rab8 but not on Rab3A and Rab5"; PMID:20937701
  "Sec2 domain proteins Rabin3/Rabin8 and Rabin3-like/GRAB are specific GEFs for Rab8A and Rab8B and have no activity
  toward Rab10"].
• Rab11 effector; Rab11-GTP stimulates GEF activity [PMID:20308558 "Rab11, in its GTP-bound form, interacts with Rabin8
  and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8"; PMID:26258637 "the
  C-terminal domain of Rabin8 adopts a previously undescribed fold that interacts with Rab11 at an unusual
  effector-binding site"].
• Preciliary trafficking to the centrosome [PMID:21273506 "Rab8-dependent ciliary assembly is initiated by the
  relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome"; "the transport protein
  particle (TRAPP) II complex associates with the Rabin8 NH(2)-terminal domain"; PMID:31467083 "We find that C7orf43
  directly binds to Rabin8 and that C7orf43 knockdown diminishes Rabin8 preciliary centrosome accumulation"].
• NDR2 phosphorylation switch [PMID:23435566 "NDR2 phosphorylates Rabin8 at Ser-272 and defects in this phosphorylation
  impair preciliary membrane assembly and ciliogenesis"; "Rabin8 binds to and colocalizes with GTP-bound Rab11 and
  phosphatidylserine (PS) on pericentrosomal vesicles"].
• BBSome contact PMID:17574030.
• GEF activity determines Rab8 membrane targeting PMID:23382462.
• Timing relative to ciliary vesicle (CV) formation PMID:25686250.
• Non-ciliary: cortical actin, lamellipodia, polarized traffic PMID:12221131.
• Nuclear only on SSX2 co-expression [PMID:12007189 "the RAB3IP protein is normally localized in the cytoplasm";
  "coexpression of both RAB3IP and SSX2 led to colocalization of both proteins in the nucleus"].

Key decisions

• GEF activity (6 rows): ACCEPT, core MF (GO:0017112 Rab GEF was merged into GO:0005085; verified via OLS).
• Protein binding: RAB8A and RAB3A rows MODIFY -> GO:0031267 small GTPase binding; others REMOVE (TRAPPII subunits,
  TRAPPC14, SSX2, RAB3IL1, DCDC5, HuRI and SARS-CoV-2 hits).
• GO:1905349 ciliary transition zone assembly (Reactome TAS R-HSA-5620912): MARK_AS_OVER_ANNOTATED. This row is the
  mechanical replacement for obsoleted GO:0097711 (see projects/CILIARY_BASAL_BODY_DOCKING_OBSOLETION.md; Reactome has
  revised the entry). RAB3IP activates RAB8A for ciliary membrane growth; TZ assembly is executed by TZ proteins.
• Protein targeting to membrane (IDA): ACCEPT (GEF catalysis targets Rab8).
• Nucleus/nucleoplasm (incl. HPA IDA): KEEP_AS_NON_CORE.

HPA cilium atlas vs module role

• HPA: Centrosome (Supported); main location "Nucleoplasm". GOA HPA rows: nucleoplasm, centrosome and cytosol IDA
  (GO_REF:0000052).
• Module role: RAB8 GEF in ciliary vesicle formation / ciliary membrane supply (stage 2). The centrosome call fits the
  literature (Rabin8 accumulates at the mother centriole on Rab11/TRAPPII vesicles). No ciliary-compartment call is
  expected for a cytosolic GEF.
• Nuance against the module wording: Lu et al. 2015 show that ciliary vesicle formation from distal appendage vesicles
  is EHD1/EHD3-dependent and that Rab8 is activated only after the CV forms. RAB3IP therefore belongs to the
  "ciliary membrane supply/extension" part of stage 2 rather than CV formation per se. core_functions state this
  explicitly (GEF activity; cilium assembly; centrosome/vesicle). No NEW GO:1905556 (ciliary vesicle assembly)
  annotation is proposed.

Deep research outcome

The re-run just deep-research-falcon human RAB3IP --timeout 2400 succeeded and produced
RAB3IP-deep-research-falcon.md (2026-10-03). I read it after drafting the review. Its summary agrees with the
cached primary literature used here and changes none of the curation decisions. Annotation-level supporting quotes come
from the cached publications. The first core function also cites one sentence from the deep-research file.