EHD1 curation notes

Deep research status

• just deep-research-falcon human EHD1 was attempted (unavailable perplexity-lite fallback; then --timeout 2400, killed with exit 137; then retried). See the end of this file for the final outcome. The review was written from cached primary literature.

Key findings (with provenance)

• ATPase, not GTPase PMID:15710626; ATP binding drives oligomerization and endosome association PMID:15710626
• Endocytic recycling PMID:15020713; PMID:17233914
• MICAL-L1 recruits EHD1 to tubular recycling endosomes and links it to RAB8A PMID:19864458
• EHD1 vesiculates, EHD3 stabilizes tubular recycling endosomes PMID:27189942
• Ciliary vesicle assembly PMID:25686250; required for CP110 loss PMID:25686250; ciliary pocket PMID:25686250
• MICAL-L1 recruits EHD1 to basal bodies PMID:31615969
• Acts downstream of myosin-Va delivery PMID:29335527

Pleiotropy: ciliary vs other roles

• Core non-ciliary role: endocytic recycling ATPase on tubular recycling endosomes (ACCEPT).
• Ciliary role: ciliary vesicle assembly + cilium assembly (ACCEPT existing; NEW GO:1905556).
• Tissue-specific rodent-transferred roles (cholesterol homeostasis/storage, LDL clearance, lipid droplet, neuronal projection/NGF response, synapse, myoblast fusion, platelet DTS): KEEP_AS_NON_CORE.

Curation decisions (summary)

• GTP binding IEA: MODIFY -> ATP binding; NEW ATP hydrolysis activity (ISS, PMID:15710626).
• Ciliary membrane IEA: MODIFY -> ciliary pocket membrane.
• Small GTPase binding (RAB8A) IPI: MARK_AS_OVER_ANNOTATED (bridged by MICAL-L1).
• Protein binding x20: REMOVE; identical protein binding and homooligomerization: ACCEPT (dimerization/oligomerization is functionally essential).
• NEW ciliary vesicle assembly (GO:1905556, IMP, PMID:25686250): EHD1 performs the tubulation/fusion step. Comparator check: no gene product in GO currently carries GO:1905556 (QuickGO, all taxa), so there is no contrary convention; the term definition (small vesicles dock to transitional fibres and fuse) matches the EHD1 step exactly.

HPA cilium atlas vs module role

• Module: stage 2_ciliary_vesicle, "ciliary vesicle formation", membrane-shaping ATPase in the EHD1/EHD3 membrane tubulation step; process ciliary vesicle assembly, location ciliary vesicle; MF not asserted.
• HPA v25: Primary cilium (S), Primary cilium transition zone (S); main location plasma membrane. GOA carries HPA rows (GO_REF:0000052) for cilium, ciliary transition zone and plasma membrane (all ACCEPT).
• Assessment: consistent. HPA proximal cilium/transition-zone signal matches the ciliary pocket localization in ciliated cells (the CV-assembly step itself is transient and precedes the cilium). core_functions agree with the module and fill its open MF slot with ATP hydrolysis activity.

Deep research outcome

• Falcon succeeded on the third attempt (--timeout 2400, after an exit-137 kill): EHD1-deep-research-falcon.md. It strongly supports the ATPase core function (PS-stimulated ATP hydrolysis, ~16-fold, Deo et al. 2018; ATP-hydrolysis-dependent fission) and adds: EHD1 delivers HERC2-bearing centriolar satellites to the mother centriole for CP110 ubiquitination/removal (Xie et al. 2023), EHD1-Smoothened ciliary trafficking in mouse, EHD4-dependent recruitment to sorting endosomes, retromer association, and the human EHD1 p.R398W proteinuria/hearing-loss syndrome (2022). These were incorporated into the description; no further annotations were added.