MFF

Q: Does GO intend GO:0005096 GTPase activator activity to cover a receptor that raises a dynamin-family GTPase's hydrolysis rate by clustering it, rather than by supplying catalytic residues? MFF stimulates DRP1 GTPase activity about 10-fold in vitro. Of the four mammalian outer-membrane DRP1 receptors - MFF, MIEF1 (MID51), MIEF2 (MID49) and FIS1 - none carries the term, and the only self-assembling dynamin-family GTPase that does is DRP1 itself. Both legs come from a QuickGO query over the whole human carrier set, not only the genes reviewed in this repository, returning 2122 positive enables annotations on GO:0005096 across 1772 accessions and 486 distinct gene symbols; the query and the checks run over its result are logged in MFF-notes.md. Of the 35 human symbols with a GO:0005096 row in this corpus, 34 carry a positive enables - ARFGEF1's only row is NOT|enables, by IDA, and ARFGEF1 is correspondingly absent from the query's 486, which is also the control confirming that the enables filter excludes negated rows. The term is conventionally applied to catalytic activators, GAP-domain proteins among them and also the VPS9 RabGEF ALS2, the RGS protein RGS20 and the TBCC protein RP2. This entry makes no claim about how many of the 34 catalyse, because where a positive row has instead sat on a protein that engages a GTPase without catalysing, this project has questioned it five times and settled three of those against the molecular function - DNM1L by IC from its binding to GTP-bound Rab32, REMOVE; ARHGAP11B, whose UniProt RecName is Inactive Rho GTPase-activating protein 11B, carrying a Reactome TAS row against two IDA negations on the same gene, REMOVE; and ARHGAP36 by IBA over a GAP-domain family whose catalysis this member lost, REMOVE. The other two are ArfGAP IEA transfers from InterPro:IPR001164 on which this project judges catalysis reduced but not disproven - AGFG1, MARK_AS_OVER_ANNOTATED on evidence that predicts substantially reduced GAP activity rather than proving its complete absence, and AGFG2, UNDECIDED because the same conserved-site divergence does not refute catalysis. So five rows questioned across IC, TAS, IBA and IEA, three settled against the molecular function. DNM1L is the closest precedent of the five, not because it engages DRP1 - the GTPase it engages in that row is Rab32 - but because it is the only self-assembling dynamin-family GTPase in the carrier set, so a protein of DRP1's own class received GO:0005096 from non-catalytic GTPase binding and this project removed it. That is the convention the question asks GO to confirm, and the stimulation is therefore recorded here under positive regulation of fission and the adaptor activity rather than as a molecular-function assertion.

Q: How does MFF preferentially bind GTP-bound, oligomeric DRP1, and how do DRP1 phosphorylation (Ser616/Ser637) and MFF phosphorylation by AMPK tune receptor affinity in vivo?

Q: What determines the division of labour between MFF and MIEF1/MIEF2 at the same mitochondrial constriction sites?