PTPRN2
Description
The PTPRN2 (protein tyrosine phosphatase receptor type N2) is a protein-coding gene located on chromosome 7.
Receptor-type tyrosine-protein phosphatase N2 (R-PTP-N2), also known as islet cell autoantigen-related protein (ICAAR) and phogrin, is an enzyme that in humans is encoded by the PTPRN2 gene. PTPRN and PTPRN2 (this gene) are both found to be major autoantigens associated with insulin-dependent diabetes mellitus.
== Function == Due to a close similarity in the gene sequences, the protein encoded by this gene has traditionally been considered a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. However, recent research has shown that the PTPRN2 mouse homolog, known as phogrin, dephosphorylates the lipid phosphatidylinositol rather than tyrosine. Specifically, phogrin was shown to act upon phosphatidylinositol 3-phosphate and Phosphatidylinositol 4,5-diphosphate, whereas it has never been observed acting upon tyrosine. PTPRN2 should, therefore, be more accurately considered a PIPase rather than a PTPase. Phosphorylated forms of phosphatidylinositol (PI) are called phosphoinositides and play important roles in lipid signaling, cell signaling and membrane trafficking. The protein produced by PTPRN2 possesses an extracellular region, a single transmembrane region, and a single intracellular catalytic domain, and thus represents a receptor-type PTP. The catalytic domain of this PTP is most closely related to PTPRN, also known as IA-2.
== Gene == Three alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported.
PTPRN2 plays a crucial role in vesicle-mediated secretory processes, ensuring the proper accumulation of secretory vesicles in various tissues like the hippocampus, pituitary, and pancreatic islets. This protein is essential for maintaining normal levels of insulin-containing vesicles, preventing their degradation, and regulating insulin secretion in response to glucose stimuli. It also contributes to the accumulation of neurotransmitters like norepinephrine, dopamine, and serotonin in the brain. Furthermore, PTPRN2 is involved in the accumulation and secretion of pituitary hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in females. PTPRN2 regulates renin expression and release, potentially interacting with other protein-tyrosine phosphatases. The protein possesses phosphatidylinositol phosphatase (PIPase) activity, which is involved in regulating insulin secretion. PTPRN2 can dephosphorylate phosphatidylinositol 4,5-biphosphate (PI(4,5)P2), phosphatidylinositol 5-phosphate, and phosphatidylinositol 3-phosphate, impacting the level of PI(4,5)P2 in the plasma membrane and the localization of cofilin. This indirect regulation of cofilin influences actin dynamics related to cell migration and metastasis. PTPRN2 exhibits self-association and interacts with various proteins, including PTPRN, CPE, HAP1, AP2A1, AP2A2, AP1G1, AP2M1, and MYO5A.
PTPRN2 is also known as IA-2beta, IAR, ICAAR, PTPRP, R-PTP-N2.
