Regulation of Synaptic Vesicle Docking — Obsoletion & MF Refactor

IN_PROGRESS OBSOLETIONFLAGSHIP

Species: mouse, worm

Genes: Camk2a

Regulation of Synaptic Vesicle Docking — Obsoletion & MF Refactor

Bottom line: Before a synaptic vesicle fuses, it docks at the active
zone, held there by specific binding proteins. GO has retired the whole
vesicle-docking process subtree and now represents docking as a
molecular function, GO:0160321 vesicle docking activity. This page
tracks one piece of that change: GO:0099148 regulation of synaptic
vesicle docking, flagged by SynGO (go-annotation#6415), whose
experimental annotations sit on three genes: mouse Camk2a, mouse
Septin5 and worm tom-1. We listed those rows and argued that most
should not become the new MF, because a kinase such as CaMKIIα
regulates docking without doing it. The obsoletion has now landed:
OLS shows GO:0099148 obsolete and GO:0160321 minted. The one affected
review is fixed in #3237 (merged): mouse Camk2a's GO:0099148 entries,
from PMID:17660813, move from ACCEPT to MODIFY → GO:0048172 regulation of
short-term neuronal synaptic plasticity, not the docking MF, because
the paper shows αCaMKII regulates the number of docked vesicles without
docking them. Septin5 and tom-1 still have no review here.

This is the regulation branch of the docking refactor. The parent
tracker VESICLE_DOCKING_OBSOLETION
covers the docking terms themselves (#6379), and
VESICLE_TETHERING_OBSOLETION covers
the earlier tethering step (#6375).

Overview

GO has retired the vesicle-docking biological-process hierarchy and replaced
it with a molecular function term:

The upstream ontology ticket scopes the obsoletion broadly across the whole
GO:0048278 vesicle docking BP subtree and its regulation terms. This project
tracks the annotation-review issue for one of those terms,
GO:0099148 regulation of synaptic vesicle docking (BP), flagged by the
SynGO group.

The rationale (per the ontology editors' checklist) is explicit: "the reason
for obsoletion is that this term represents a molecular function." The
docking step is the binding activity of a specific adaptor/tether protein, so
the curators are moving the representation from a BP process to an MF binding
activity.

This project differs from the other obsoletion trackers in this repo because
one directly affected gene — mouse Camk2a — already has a review here
(genes/mouse/Camk2a/), so this is both a refresh-existing-review and a
queue-new-genes tracker.

Upstream tickets

Upstream obsoletion outcome

The upstream obsoletion retired GO:0048278 vesicle docking, its descendants,
and the associated regulation terms. All are now obsolete; the literal docking
terms carry consider pointers to both GO:0160321 vesicle docking activity
and GO:7770062 vesicle membrane tethering activity, while the regulation
terms, including GO:0099148 regulation of synaptic vesicle docking, carry
consider: GO:0160321:

Obsoleted term ID
vesicle docking GO:0048278
synaptic vesicle docking GO:0016081
Golgi vesicle docking GO:0048211
phagosome-lysosome docking GO:0090384
vesicle docking involved in exocytosis GO:0006904
dense core granule docking GO:0061790
regulation of vesicle docking GO:0106020
positive regulation of vesicle docking GO:0106022
negative regulation of vesicle docking GO:0106021
regulation of synaptic vesicle docking (focus of #6415) GO:0099148

Focus term consider replacement: GO:0160321 vesicle docking activity (MF).

Affected annotations to GO:0099148 (verified via QuickGO, 2026-05-16)

Experimental / curated rows (the SynGO "8 annotations"):

Group Gene Species UniProt Reference Evidence In repo?
SynGO Camk2a M. musculus P11798 PMID:17660813 IMP + IDA (×2) YES — genes/mouse/Camk2a, fixed in #3237
RGD Camk2a R. norvegicus P11275 GO_REF:0000121 ISO no
SynGO Septin5 M. musculus Q9Z2Q6 PMID:20624595 IMP + IDA no
RGD Septin5 R. norvegicus Q9JJM9 GO_REF:0000121 ISO no
SynGO tom-1 C. elegans A0A0K3ATN9 PMID:16895441 IMP (×2) + IDA (×2) no

Plus ~60 IEA orthology rows (GO_REF:0000107, Ensembl / EnsemblMetazoa) on
CAMK2A orthologs across many species — these are electronic and will follow
the obsoletion automatically; no manual action needed.

No InterPro2GO / UniProt-Keyword / UniRule mappings to GO:0099148 were listed
in the upstream issue.

Impact on this repo

Mouse Camk2a is already reviewed here and is directly affected.
genes/mouse/Camk2a/Camk2a-ai-review.yaml carries two GO:0099148 rows
(IMP and IDA, both PMID:17660813), each formerly action: ACCEPT. Both are
now MODIFY → GO:0048172 regulation of short-term neuronal synaptic
plasticity, fixed in #3237 (merged), which also replaced the supporting text
with the abstract's sentences on docked-vesicle number and short-term
presynaptic plasticity.

The refresh is not a mechanical relabel. CaMKIIα is a Ser/Thr kinase that
regulates presynaptic vesicle docking; it is not itself a vesicle-docking
adaptor/tether, so transferring a regulation of synaptic vesicle docking BP
annotation onto the new vesicle docking activity MF is biologically
questionable for this gene. The correct outcome was MODIFY toward a
retained regulatory BP rather than a literal docking-activity MF — exactly the
curator-judgment question this repo exists to evaluate.

Septin5 and tom-1 are not in the repo. The human Septin5 ortholog is
SEPTIN5 / UniProt Q99719 (not yet reviewed; genes/human/ has no SEPT/
SEPTIN entry).

Scope

Candidate genes for initial review

Verify each with just fetch-gene <organism> <gene> and confirm UniProt
accessions before starting.

Tier 1 — refresh required (already in repo)

Tier 2 — direct SynGO experimental annotations, not yet in repo

Proposed approach

  1. Record the upstream outcome. GO:0099148 is obsolete and GO:0160321
    vesicle docking activity is live, so this page no longer depends on a
    placeholder MF term.
  2. Camk2a: done. #3237 regenerated mouse Camk2a, moved the GO:0099148
    entries to GO:0048172, and corrected the PMID:17660813 support.
  3. Queue Septin5 (mouse, with human SEPTIN5 follow-up) as a clean
    new review — the strongest candidate for a legitimate transfer to the new
    docking MF.
  4. Then tom-1 (C. elegans) to cover the invertebrate negative-regulator
    case.
  5. Cross-reference the parallel docking/tethering obsoletions already
    tracked here — CILIARY_BASAL_BODY_DOCKING_OBSOLETION
    and the ER-PM / mito-ER tether trackers — since the new
    membrane-membrane-adaptor MF family is the common destination.

Priority

Medium. Higher than the purely queueing obsoletion trackers because an
existing repo review (Camk2a) did go stale when the obsoletion landed, and
the BP→MF refactor made the correct reannotation non-obvious. Camk2a is fixed
now; Septin5 and tom-1 are the remaining direct experimental cases.

Status