unc-11 — AP180 clathrin assembly protein (Q9XZI6) — curation notes

Identity and architecture

unc-11 (C32E8.10) is the sole C. elegans homologue of the neuronal clathrin assembly protein AP180 (PICALM/SNAP91 family), rescued by cosmid C32E8 PMID:10397769 PMID:10397769. The genome contains no second AP180 homologue PMID:10397769.
Multiple isoforms (a–h) share a conserved N-terminal ANTH domain (UniProt DOMAIN 29..161 ENTH-type) carrying the KKK phosphoinositide-binding motif, and diverge in a C-terminal low-complexity assembly domain PMID:10397769 PMID:10397769. The C-terminal region promotes clathrin assembly in vitro (cited as unpublished data) PMID:10397769.

High in the nervous system, enriched at presynaptic sites and also in cell bodies; lower in coelomocytes, uv1 cells and intestine PMID:10397769 PMID:10397769. Axonal transport of UNC-11 is independent of UNC-104 PMID:10397769.
UniProt (curated from the same paper) records clathrin-coated pit, clathrin-coated vesicle and Golgi localisation [file:worm/unc-11/unc-11-uniprot.txt "Note=Colocalized with clathrin in the Golgi area."].

unc-11 null mutants are viable but uncoordinated (coiling, jerky backing) and defective in release of multiple neurotransmitters PMID:10397769.
Synaptobrevin is specifically mislocalised (diffuse, plasma-membrane-like) while other synaptic vesicle proteins are targeted normally PMID:10397769.
Synaptic membrane is still endocytosed, but vesicles are 33% larger in diameter (29.5 nm → 39–40 nm), i.e. AP180 sets vesicle size during clathrin coat assembly PMID:10397769 PMID:10397769 PMID:10397769.
unc-11; snb-1(hypomorph) double mutants arrest at L1, the only developmental-arrest phenotype reported PMID:10397769.
Deep research (file:worm/unc-11/unc-11-deep-research-falcon.md) adds a 2026 study showing the disordered assembly domain forms actin-recruiting condensates and bridges PI(4,5)P2 liposomes to F-actin, with actin coupling setting vesicle size [file:worm/unc-11/unc-11-deep-research-falcon.md "Full-length protein associated with 50-nm liposomes containing 2% PIP₂ and bridged them to F-actin, whereas phosphatidylcholine-only liposomes showed minimal association."], plus a role in sorting ATG-9 at synapses (Xuan et al. 2023).

Ubiquitin overexpression lowers GLR-1 abundance at synapses and this requires unc-11 (abstract only) PMID:12123612.
UNC-11 is required for GLR-1 endocytosis; unc-11 mutations suppress the GLR-1 loss seen in rab-6.2 retromer-pathway mutants PMID:22213799 PMID:22213799.

High-throughput Y2H/pooling interactome studies (PMID:14704431, 19123269, 19447967, 23549480) list EYA-1, ITSN-1, MAGU-1 and SORB-1 as binders; the ITSN-1 (intersectin SH3) and SORB-1 interactions are consistent with NPF/proline-motif accessory-protein contacts of AP180 family proteins, but none defines a distinct GO molecular function.

Core: PI(4,5)P2 binding and clathrin heavy chain binding driving clathrin coat assembly at the presynaptic membrane, SNARE (synaptobrevin) cargo sorting into regenerated synaptic vesicles, and control of vesicle size; GLR-1 receptor endocytosis as a well-supported additional cargo context.
Non-core/downstream: locomotion, Golgi localisation, GLR-1 synaptic abundance regulation.
Over-annotated: post-embryonic development (only synthetic with snb-1); ubiquitin-dependent protein catabolic process (UNC-11 performs the internalisation step, degradation not shown).
Generic protein binding rows removed as uninformative; necroptotic process IGI left UNDECIDED (abstract-only, unc-11 not named).