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 selected protein sequence has an internal or terminal difference from the characterized human protein, so its precise activity and regulation remain to be established.
Summary: protein tyrosine phosphatase activity: PTPRN2 does not exhibit conventional phosphoprotein-substrate activity because of changes in its PTP domain; the human cell study explicitly distinguishes this from reported phosphoinositide phosphatase activity. The electronic protein-phosphatase activity assignment overgeneralizes the domain.
Reason: PTPRN2 does not exhibit conventional phosphoprotein-substrate activity because of changes in its PTP domain; the human cell study explicitly distinguishes this from reported phosphoinositide phosphatase activity. The electronic protein-phosphatase activity assignment overgeneralizes the domain.
PTPRN2 belongs to the protein tyrosine phosphatase family, but does not exhibit activity against phosphoprotein substrates due to several critical amino acid variations in the PTP domain (Magistrelli et al, 1996).
The downloaded human Q92932 sequence (1015 residues) and selected horse A0A9L0T4W6 sequence (976 residues) share 71.0% identity among 947 paired residues. Paired coverage is 93.3% of human and 97.0% of horse.
GO:0008138 protein tyrosine/serine/threonine phosphatase activity
IEA GO_REF:0000104
REMOVE
Summary: protein tyrosine/serine/threonine phosphatase activity: PTPRN2 does not exhibit conventional phosphoprotein-substrate activity because of changes in its PTP domain; the human cell study explicitly distinguishes this from reported phosphoinositide phosphatase activity. The electronic protein-phosphatase activity assignment overgeneralizes the domain.
Reason: PTPRN2 does not exhibit conventional phosphoprotein-substrate activity because of changes in its PTP domain; the human cell study explicitly distinguishes this from reported phosphoinositide phosphatase activity. The electronic protein-phosphatase activity assignment overgeneralizes the domain.
PTPRN2 belongs to the protein tyrosine phosphatase family, but does not exhibit activity against phosphoprotein substrates due to several critical amino acid variations in the PTP domain (Magistrelli et al, 1996).
The downloaded human Q92932 sequence (1015 residues) and selected horse A0A9L0T4W6 sequence (976 residues) share 71.0% identity among 947 paired residues. Paired coverage is 93.3% of human and 97.0% of horse.
Summary: hydrolase activity: Generic hydrolase activity is not refuted by loss of protein phosphatase activity because phosphoinositide hydrolysis has been reported. The selected horse protein has a divergent/deleted C-terminal part of the phosphatase-like domain, leaving its precise hydrolytic competence unresolved.
Reason: Generic hydrolase activity is not refuted by loss of protein phosphatase activity because phosphoinositide hydrolysis has been reported. The selected horse protein has a divergent/deleted C-terminal part of the phosphatase-like domain, leaving its precise hydrolytic competence unresolved.
The downloaded human Q92932 sequence (1015 residues) and selected horse A0A9L0T4W6 sequence (976 residues) share 71.0% identity among 947 paired residues. Paired coverage is 93.3% of human and 97.0% of horse.
Summary: secretory granule: PTPRN2 is a secretory-vesicle membrane protein that traffics to the plasma membrane and regulates neuroendocrine secretion. Its vesicle role is supported independently of any protein tyrosine phosphatase claim. Transfer to horse is an inference; the paired-sequence report records model-specific gaps and limits.
Reason: PTPRN2 is a secretory-vesicle membrane protein that traffics to the plasma membrane and regulates neuroendocrine secretion. Its vesicle role is supported independently of any protein tyrosine phosphatase claim. Transfer to horse is an inference; the paired-sequence report records model-specific gaps and limits.
As a transmembrane protein, PTPRN2 shuttles between secretory vesicles and the plasma membrane.
file:human/PTPRN2/PTPRN2-uniprot.txt
CC -!- FUNCTION: Plays a role in vesicle-mediated secretory processes. CC Required for normal accumulation of secretory vesicles in hippocampus, CC pituitary and pancreatic islets. Required for the accumulation of CC normal levels of insulin-containing vesicles and preventing their CC degradation. Plays a role in insulin secretion in response to glucose CC stimuli.
The downloaded human Q92932 sequence (1015 residues) and selected horse A0A9L0T4W6 sequence (976 residues) share 71.0% identity among 947 paired residues. Paired coverage is 93.3% of human and 97.0% of horse.
Summary: transport vesicle membrane: PTPRN2 is a secretory-vesicle membrane protein that traffics to the plasma membrane and regulates neuroendocrine secretion. Its vesicle role is supported independently of any protein tyrosine phosphatase claim. Transfer to horse is an inference; the paired-sequence report records model-specific gaps and limits.
Reason: PTPRN2 is a secretory-vesicle membrane protein that traffics to the plasma membrane and regulates neuroendocrine secretion. Its vesicle role is supported independently of any protein tyrosine phosphatase claim. Transfer to horse is an inference; the paired-sequence report records model-specific gaps and limits.
As a transmembrane protein, PTPRN2 shuttles between secretory vesicles and the plasma membrane.
file:human/PTPRN2/PTPRN2-uniprot.txt
CC -!- FUNCTION: Plays a role in vesicle-mediated secretory processes. CC Required for normal accumulation of secretory vesicles in hippocampus, CC pituitary and pancreatic islets. Required for the accumulation of CC normal levels of insulin-containing vesicles and preventing their CC degradation. Plays a role in insulin secretion in response to glucose CC stimuli.
The downloaded human Q92932 sequence (1015 residues) and selected horse A0A9L0T4W6 sequence (976 residues) share 71.0% identity among 947 paired residues. Paired coverage is 93.3% of human and 97.0% of horse.
Summary: synapse: PTPRN2 is a secretory-vesicle membrane protein that traffics to the plasma membrane and regulates neuroendocrine secretion. Its vesicle role is supported independently of any protein tyrosine phosphatase claim. Transfer to horse is an inference; the paired-sequence report records model-specific gaps and limits.
Reason: PTPRN2 is a secretory-vesicle membrane protein that traffics to the plasma membrane and regulates neuroendocrine secretion. Its vesicle role is supported independently of any protein tyrosine phosphatase claim. Transfer to horse is an inference; the paired-sequence report records model-specific gaps and limits.
As a transmembrane protein, PTPRN2 shuttles between secretory vesicles and the plasma membrane.
file:human/PTPRN2/PTPRN2-uniprot.txt
CC -!- FUNCTION: Plays a role in vesicle-mediated secretory processes. CC Required for normal accumulation of secretory vesicles in hippocampus, CC pituitary and pancreatic islets. Required for the accumulation of CC normal levels of insulin-containing vesicles and preventing their CC degradation. Plays a role in insulin secretion in response to glucose CC stimuli.
The downloaded human Q92932 sequence (1015 residues) and selected horse A0A9L0T4W6 sequence (976 residues) share 71.0% identity among 947 paired residues. Paired coverage is 93.3% of human and 97.0% of horse.
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Human PTPRN2 lacks conventional phosphoprotein-substrate activity, while lipid phosphatase activity and possible regulation of active protein phosphatases are distinct mechanisms. The predicted biological process does not require PTPRN2 itself to catalyze protein dephosphorylation. Evidence for that specific regulatory participation in horse is missing, and the selected horse phosphatase-like domain has a divergent C terminus. Thus catalytic inactivity alone does not justify an incorrect-process verdict.
Supporting Evidence:
PMID:26620550: "PTPRN2 belongs to the protein tyrosine phosphatase family, but does not exhibit activity against phosphoprotein substrates due to several critical amino acid variations in the PTP domain (Magistrelli et al, 1996)."
file:HORSE/PTPRN2/PTPRN2-bioinformatics/RESULTS.md: "The selected horse sequence has a divergent C-terminal region, including deletion of human residues 989–1003 within the annotated phosphatase domain. The N-terminal signal sequence and transmembrane segment are retained. Substrate-specific enzymatic activity requires more than the global homology assignment."