PTPRN2 is a membrane protein of neuroendocrine secretory vesicles that traffics between secretory granules and the plasma membrane. It regulates vesicle accumulation and secretion and has a phosphatase-like intracellular domain. Conventional phosphoprotein activity is impaired, whereas phosphoinositide phosphatase activity and regulation of membrane PI(4,5)P2 have been reported in mammalian cells.
The 1996 cloning report states that recombinant IAR/PTPRN2 has phosphatase activity, but its abstract does not name the substrate. Later human cell work explicitly distinguishes lack of phosphoprotein-substrate activity from phosphoinositide phosphatase activity and tests the effect of a catalytic-domain mutant on migration and metastasis. Vesicle accumulation, insulin/neurotransmitter release, and membrane phosphoinositide regulation are not interchangeable with protein tyrosine dephosphorylation. Conversely, a biological-process annotation can describe regulation through another enzyme: losing intrinsic protein phosphatase activity alone does not refute all participation in protein dephosphorylation. The exact experimental annotation therefore remains unresolved while the inappropriate electronic intrinsic protein-phosphatase terms can be challenged.
From PMID:26620550(https://pubmed.ncbi.nlm.nih.gov/26620550/):
As a transmembrane protein, PTPRN2 shuttles between secretory vesicles and the plasma membrane.
The exact target is A0A9L0T4W6, 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: ficolin-1-rich granule membrane, protein dephosphorylation, signaling receptor complex, transmembrane receptor protein tyrosine phosphatase activity. 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.
Identity. Q92932 is the reviewed, canonical human PTPRN2 entry (PTPR2_HUMAN, 1015 aa, isoform 1 displayed; four splice isoforms). It is not a fragment or alternative gene model: it has the signal peptide (1-21), luminal pro-region and RESP18 domain, transmembrane helix (616-636), cytoplasmic PTP-like domain (745-1005) and the annotated catalytic Cys945. PANTHER PTHR46106:SF5 (RECEPTOR-TYPE TYROSINE-PROTEIN PHOSPHATASE N2), the same subfamily as mouse Ptprn2 (P80560) and rat Ptprn2/phogrin (Q63475); paralog PTPRN is SF1, invertebrate IDA-1/IA-2 SF4. The family review interpro/panther/PTHR46106/PTHR46106-review.yaml places Q92932 in SF5; no disagreement.
Evidence read. Caromile et al. 2010 [PMID:20097759 "phogrin is able to dephosphorylate specific inositol phospholipids, including phosphatidylinositol (PI) 3-phosphate and PI 4,5-diphosphate but not PI 3,4,5-trisphosphate"; "The PIPase activity of phogrin depended on the catalytic site cysteine and correlated with effects on glucose-stimulated insulin secretion"] (rat, SF5 ortholog). Kubosaki et al. 2004 PMID:15220191. Cai et al. 2011 PMID:21732083. Nishimura et al. 2009 PMID:19361477; neurotransmitter release defects are from the Ptprn/Ptprn2 double KO. Doi et al. 2006 PMID:16418280 IA-2beta overexpression inhibits GSIS in MIN6 cells. Human: Sengelaub et al. 2016 PMID:26620550.
Decisions (changed from previous version).
- GO:0004725 (IEA) REMOVE kept; GO:0005001 (TAS, PMID:8798755) and GO:0006470 (TAS) changed UNDECIDED -> REMOVE. These are TAS/IEA author/domain inferences, contradicted by direct assays (no phosphoprotein/pNPP activity; the cloning-paper activity was weak, at pH 4.5, of questioned relevance per UniProt). No receptor/ligand activity exists.
- Plasma membrane (2 TAS rows): ACCEPT -> KEEP_AS_NON_CORE (transient post-exocytosis residence).
- Secretory granule (IBA, IEA) and secretory granule membrane (IEA, ISS): MODIFY -> GO:0032127 dense core granule membrane.
- Synapse (IBA): MODIFY -> GO:0030672 synaptic vesicle membrane (already carried, ACCEPT).
- Neurotransmitter secretion (IEA, ISS from mouse SF5 ortholog): ACCEPT -> KEEP_AS_NON_CORE; decisive data are double-KO, and PAINT did not place this term on the family nodes.
- Insulin secretion in response to glucose (IBA PTN000439772 vertebrate node, IEA, ISS) and regulation of secretion (IBA PTN000439769 family node): ACCEPT.
- Ficolin-1-rich granule membrane (Reactome TAS): UNDECIDED -> MARK_AS_OVER_ANNOTATED (neutrophil granule proteomics; neuroendocrine protein).
- Signaling receptor complex (IDA PMID:23382219): UNDECIDED retained; the cached SNX17/27 PX-FERM paper does not mention PTPRN2, and an NPxY cargo-peptide binding assay would not establish complex membership.
- NEW GO:0052866 phosphatidylinositol phosphate phosphatase activity now ISS from rat phogrin (PMID:20097759, same SF5 subfamily) rather than IMP from the human cancer-cell paper, which shows PI(4,5)P2 effects but cites Caromile for the catalytic dependence.
Relative. Mouse Ptprn2 (P80560), SF5 ortholog with knockout data; no review exists in the repo.
Modules. No module in modules/ mentions PTPRN2 or PTHR46106; no GO-CAM index entry.