ARL15 notes
Biology
- GTP/GDP binding and GTPase kinetics PMID:37939768; GTP and CNNM binding; CNNM2 crystal structure; inhibits CNNM2 efflux and TRPM7 uptake PMID:37449820.
- Negative regulator of Mg2+ transport via CNNM complex N-glycosylation PMID:34089346.
- Active ARL15 binds the Smad4 MH2 domain and relieves its autoinhibition; positively regulates TGFbeta-family signalling. Smad4 acts as its GAP PMID:35834310.
- Golgi localization:
- Endogenous protein with golgin-245 in HeLa PMID:35834310.
- Palmitoylation-dependent movement between Golgi compartments in adipocytes PMID:34779483.
- Golgi cargo transport PMID:40241309.
- Knockout mice have cleft palate PMID:37773757. Adipocyte role PMID:29242557.
GOA calls
- ACCEPT: GTP binding, GTPase activity.
- REMOVE: ND root-term rows (data now exist); Y2H protein binding (PDE6D, UNC119, MEOX2).
- Non-core: exosome (HDA).
- NEW: Golgi apparatus (IDA); positive regulation of SMAD protein signal transduction (IDA).
- Round 1 (PR #4177): the CNNM/Mg2+ role is now encoded as NEW transporter inhibitor activity (GO:0141110) plus negative regulation of cation transmembrane transport (GO:1904063), both IDA from PMID:37449820. GO has no magnesium-specific regulation term, so one is proposed in proposed_new_terms. No glycosylation term is proposed: ARL15 promotes CNNM N-glycosylation but does not perform it.
- Round 1 also adds: NEW endolysosome (IDA, PMID:35834310); S-acylation paper PMID:41999893 imported; PMID:36711628 recorded as the bioRxiv preprint of PMID:37449820; a PDE6D/UNC119 chaperone question added.
- Round 2 (PR #4177):
- PMID:37449820 disputes ARL15's intrinsic GTPase activity and the Smad4-as-GAP claim (weak GTP binding, Ala at the catalytic Gln position). Recorded as finding_review DISPUTED on the PMID:37939768 kinetics finding.
- GTPase ACCEPT kept, with both sides quoted. The description and core_functions[1] now say the activity is contested.
- The GO:1904063 support now uses the data sentences (CNNM2 efflux, TRPM7 Zn2+), not the model statement.
- The NTR justification explains why GO:0010960 is not a substitute.
- The glycosylation quote was dropped from core_functions[0].
- The GO:1904063 label was confirmed current in QuickGO (2026-10-04).