MTMR9 is a catalytically inactive myotubularin-family protein that binds active myotubularins and regulates their activity, substrate preference and stability. Association with MTMR6 favors phosphatidylinositol-3,5-bisphosphate turnover, whereas association with MTMR8 regulates phosphatidylinositol-3-phosphate and autophagy. Its GRAM and phosphatase-like regions provide a conserved noncatalytic regulatory architecture.
MTMR9 lacks intrinsic phosphatase catalysis but dimerizes with active MTMR6, MTMR7 and MTMR8. Human MTMR6/MTMR9 and MTMR8/MTMR9 studies directly measure altered catalytic rates, substrate preferences, cellular phosphoinositide levels and downstream phenotypes. The 2009 study also finds increased partner abundance consistent with stabilization. The 2012 study distinguishes the MTMR6/R9 anti-apoptotic role from MTMR8/R9 inhibition of autophagy. These are positive reasons to retain regulatory and process participation claims. The molecular-function distinction between generic phosphatase regulation and binding specifically to a protein phosphatase still needs attention because the experimentally studied partners are lipid phosphatases.
From PMID:22647598(https://pubmed.ncbi.nlm.nih.gov/22647598/):
Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity
The exact target is A0A9L0T3C1, not an arbitrary horse record with a matching name. The reproducible paired-sequence analysis records identity, coverage and internal gaps. It supports homology but is not a reciprocal orthology test. Molecular properties are transferred only with the relevant domain, targeting and paralog constraints. The prediction-time sequence is not independently verified.
The following annotation scopes need source-specific follow-up: phosphatidylinositol biosynthetic process, protein binding, protein phosphatase binding. Experimental annotations are not removed merely because a cached abstract omits the gene or a specific assay. High-throughput protein-binding rows require their actual partner or complex context before replacement with an informative molecular function.
Research provenance: external Falcon/Edison was attempted with Perplexity fallback. Some requests returned HTTP 429 and fallback returned insufficient-quota HTTP 401; successful external reports are preserved separately. Primary-source manual synthesis is explicitly labeled manual where no external report was available.
Scope: re-examined all 76 GOA rows, the description and core functions. No ProtNLM2 file or prediction-evidence folder was opened.
Q96QG7 is the canonical reviewed UniProt entry for human MTMR9 (549 aa), not a fragment or alternative gene model. Isoform 2 (Q96QG7-2, VSP_056209) lacks residues 1-85, most of the PH-GRAM domain (4-99). No annotation in GOA is isoform-specific.
MTMR9-bioinformatics/catalytic_motif_rereview.py → RESULTS-rereview.md: the HCX5R loop at 332-340 reads HGTEGTDST in human and mouse MTMR9, where the active partners MTMR6/7/8 have HCSDGWDRT. Both the catalytic Cys (G333) and Arg (S339) are lost [file:human/MTMR9/MTMR9-bioinformatics/RESULTS-rereview.md "MTMR9 lacks both the catalytic cysteine and the catalytic arginine"]. UniProt states the same thing [UniProt CAUTION "lacks the conserved active site cysteine residue at position 333"].
The falcon report attributes ERGIC/Golgi localization and VSVG/WNT3A secretion effects to a 2020 study and a 2024 thesis (knop2024). Neither source is cached and the primary paper was not identified, so no annotation was based on them. This is listed in suggested_questions.
The closest characterised relative by phylogeny is mouse Mtmr9 (Q9Z2D0), the ortholog in the same PANTHER subfamily PTHR10807:SF56 (the catalytic loop is identical). It has experimental data on MTMR7 binding and macropinocytosis/ruffles. The repo has no mouse Mtmr9 review.
No module or GO-CAM in the repo contains MTMR9.
Rows: GO:0005783 EXP (PMID:19038970) and IEA (GO_REF:0000044, SL-0095).