Regulation of Synaptic Vesicle Docking — Obsoletion & MF Refactor

Overview

A GO obsoletion proposal will retire the vesicle-docking biological-process
hierarchy and replace it with a new molecular function term:

GO:0160321 vesicle docking activity (proposed MF; placeholder ID — not
yet minted, see "Replacement-term status" below), defined as "the binding
activity of a protein that directly mediates the stable attachment of a
transport vesicle to a target membrane, bringing the two membranes into
close apposition", proposed parent GO:0140177 membrane-membrane adaptor
activity.

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

Annotation tracker: geneontology/go-annotation#6415
Ontology ticket: geneontology/go-ontology#31880
— "New term request and Obsoletion request: GO:0048278 vesicle docking,
descendants and regulation terms"
Annotation review spreadsheet (SynGO; not machine-accessible):
https://docs.google.com/spreadsheets/d/1oP8qDeDVhVD_43GcnN2_IQgWO4vPxVGAYPY-o_zWq1o

Obsoletion plan (per upstream)

The full upstream proposal retires GO:0048278 vesicle docking plus its
descendants and the associated regulation terms, all redirected to the new MF
GO:0160321 vesicle docking activity:

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

Replacement (consider term): 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`, both rows currently `ACCEPT`
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 currently action: ACCEPT. Once the
obsoletion is applied these become annotations to an obsolete term and the
review must be refreshed.

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 likely correct outcome is MODIFY toward a
retained regulatory BP (or the synaptic-vesicle-cycle process) rather than a
literal docking-activity MF — exactly the curator-judgment question this repo
exists to evaluate. The existing supporting_text on those rows ("Kinase
activity is not required for αCaMKII-dependent presynaptic plasticity at
CA3-CA1 synapses") is also only tangential to docking and should be revisited
against PMID:17660813.

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

Organisms: mouse (Camk2a, Septin5), C. elegans (tom-1); rat ISO
rows mirror the mouse annotations; human SEPTIN5 (Q99719) is the natural
cross-organism follow-up.
GO branch: a BP→MF refactor, not a within-branch terminological
swap. A regulation of … BP annotation does not map 1:1 onto a binding-
activity MF, so each affected gene needs an individual reannotation decision.
Type of fix: structural ontology change. The substantive curation
question per gene is whether the protein performs docking (→ new MF) or
merely regulates/modulates it (→ keep a regulatory BP, MODIFY).

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)

Camk2a (mouse, UniProt P11798) — genes/mouse/Camk2a/. Two
GO:0099148 rows currently ACCEPT; must be re-evaluated once the term is
obsoleted. Highest priority because an existing review goes stale on
obsoletion. Expect MODIFY (regulatory kinase, not a docking adaptor),
not a clean transfer to the new MF.

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

Septin5 / SEPTIN5 (mouse UniProt Q9Z2Q6; human ortholog
Q99719) — presynaptic septin / CDCrel-1, syntaxin-1A interactor;
strong SynGO experimental annotation from PMID:20624595. A genuine
structural component of the docking/SNARE machinery, so this one may
legitimately move to the new docking-activity MF — a good contrast case
against Camk2a.
tom-1 (C. elegans, UniProt A0A0K3ATN9) — tomosyn ortholog; classic
negative regulator of synaptic-vesicle priming/docking
(PMID:16895441). Tests the "regulator, not effector" reannotation
pattern in an invertebrate model.

Proposed approach

Wait for the obsoletion to land. As of 2026-05-16, GO:0099148 is still
active in OLS (is_obsolete: false) and the replacement GO:0160321 is
not yet resolvable via OLS or the GO API (placeholder, like the
GO:7770065 placeholder in #423).
The ontology ticket #31880 is open.
Refresh Camk2a first once the obsoletion is applied: regenerate GOA
(just fetch-gene mouse Camk2a), then re-review the two GO:0099148 rows —
expect MODIFY away from a literal docking-activity MF toward a retained
regulatory BP, with corrected supporting_text. Re-validate
(just validate mouse Camk2a).
Then 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.
Then tom-1 (C. elegans) to cover the invertebrate negative-regulator
case.
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) goes stale the moment the obsoletion is
applied, and the BP→MF refactor makes the correct reannotation non-obvious.
Nothing is broken until the obsoletion lands, so no immediate action is
required.

Status

2026-05-16 — Project file created. Tracking upstream
go-annotation#6415
(last active 2026-05-15) and
go-ontology#31880
(open). Obsoletion not yet applied; GO:0099148 still active and
GO:0160321 not yet minted. Affected experimental annotations: Camk2a
(mouse, in repo — needs refresh), Septin5 (mouse, not in repo), tom-1
(C. elegans, not in repo). No gene reviews started or refreshed yet.