PTPRN2

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.{{cite journal | vauthors = Caromile LA, Oganesian A, Coats SA, Seifert RA, Bowen-Pope DF | title = The neurosecretory vesicle protein phogrin functions as a phosphatidylinositol phosphatase to regulate insulin secretion | journal = J. Biol. Chem. | volume = 285 | issue = 14 | pages = 10487–96 |date=April 2010 | pmid = 20097759 | pmc = 2856256 | doi = 10.1074/jbc.M109.066563 | doi-access = free }} 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.

Three alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported.

PTPRN2 has been shown to interact with: CKAP5,{{cite journal | vauthors = Nakayama M, Kikuno R, Ohara O | title = Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs | journal = Genome Res. | volume = 12 | issue = 11 | pages = 1773–84 |date=November 2002 | pmid = 12421765 | pmc = 187542 | doi = 10.1101/gr.406902 }} SPTBN4,{{cite journal | vauthors = Berghs S, Aggujaro D, Dirkx R, Maksimova E, Stabach P, Hermel JM, Zhang JP, Philbrick W, Slepnev V, Ort T, Solimena M | title = betaIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous system | journal = J. Cell Biol. | volume = 151 | issue = 5 | pages = 985–1002 |date=November 2000 | pmid = 11086001 | pmc = 2174349 | doi = 10.1083/jcb.151.5.985}} and UBQLN4.{{cite journal | vauthors = Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY | title = A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration | journal = Cell | volume = 125 | issue = 4 | pages = 801–14 |date=May 2006 | pmid = 16713569 | doi = 10.1016/j.cell.2006.03.032 | s2cid = 13709685 | doi-access = free }}

R-PTP-N2 functions as an autoantigen in diabetes mellitus type 1.{{cite journal | vauthors = Lu J, Li Q, Xie H, Chen ZJ, Borovitskaya AE, Maclaren NK, Notkins AL, Lan MS | title = Identification of a second transmembrane protein tyrosine phosphatase, IA-2beta, as an autoantigen in insulin-dependent diabetes mellitus: precursor of the 37-kDa tryptic fragment | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 6 | pages = 2307–11 |date=March 1996 | pmid = 8637868 | pmc = 39791 | doi = 10.1073/pnas.93.6.2307| bibcode = 1996PNAS...93.2307L | doi-access = free }}{{cite journal | vauthors = Pietropaolo M, Hutton JC, Eisenbarth GS | title = Protein tyrosine phosphatase-like proteins: link with IDDM | journal = Diabetes Care | volume = 20 | issue = 2 | pages = 208–14 |date=February 1997 | pmid = 9118776 | doi = 10.2337/diacare.20.2.208 | s2cid = 5392803 }}

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• {{cite journal | vauthors=Lan MS, Lu J, Goto Y, Notkins AL |title=Molecular cloning and identification of a receptor-type protein tyrosine phosphatase, IA-2, from human insulinoma. |journal=DNA Cell Biol. |volume=13 |issue= 5 |pages= 505–14 |year= 1994 |pmid= 8024693 |doi=10.1089/dna.1994.13.505 |url=https://zenodo.org/record/1235259 }}
• {{cite journal |vauthors=Cui L, Yu WP, DeAizpurua HJ, etal |title=Cloning and characterization of islet cell antigen-related protein-tyrosine phosphatase (PTP), a novel receptor-like PTP and autoantigen in insulin-dependent diabetes. |journal=J. Biol. Chem. |volume=271 |issue= 40 |pages= 24817–23 |year= 1996 |pmid= 8798755 |doi=10.1074/jbc.271.40.24817 |doi-access=free }}
• {{cite journal | vauthors=Kawasaki E, Hutton JC, Eisenbarth GS |title=Molecular cloning and characterization of the human transmembrane protein tyrosine phosphatase homologue, phogrin, an autoantigen of type 1 diabetes. |journal=Biochem. Biophys. Res. Commun. |volume=227 |issue= 2 |pages= 440–7 |year= 1996 |pmid= 8878534 |doi= 10.1006/bbrc.1996.1526 }}
• {{cite journal |vauthors=Schmidli RS, Colman PG, Cui L, etal |title=Antibodies to the protein tyrosine phosphatases IAR and IA-2 are associated with progression to insulin-dependent diabetes (IDDM) in first-degree relatives at-risk for IDDM. |journal=Autoimmunity |volume=28 |issue= 1 |pages= 15–23 |year= 1998 |pmid= 9754810 |doi=10.3109/08916939808993841 }}
• {{cite journal |vauthors=van den Maagdenberg AM, Schepens JT, Schepens MT, etal |title=Assignment of Ptprn2, the gene encoding receptor-type protein tyrosine phosphatase IA-2beta, a major autoantigen in insulin-dependent diabetes mellitus, to mouse chromosome region 12F. |journal=Cytogenet. Cell Genet. |volume=82 |issue= 3–4 |pages= 153–5 |year= 1999 |pmid= 9858807 |doi=10.1159/000015090 |s2cid=46872092 }}
• {{cite journal |vauthors=Berghs S, Aggujaro D, Dirkx R, etal |title=betaIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous system. |journal=J. Cell Biol. |volume=151 |issue= 5 |pages= 985–1002 |year= 2001 |pmid= 11086001 |doi=10.1083/jcb.151.5.985 | pmc=2174349 }}
• {{cite journal |vauthors=Kubosaki A, Gross S, Miura J, etal |title=Targeted disruption of the IA-2beta gene causes glucose intolerance and impairs insulin secretion but does not prevent the development of diabetes in NOD mice. |journal=Diabetes |volume=53 |issue= 7 |pages= 1684–91 |year= 2004 |pmid= 15220191 |doi=10.2337/diabetes.53.7.1684 |doi-access=free }}
• {{cite journal |vauthors=Lim J, Hao T, Shaw C, etal |title=A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. |journal=Cell |volume=125 |issue= 4 |pages= 801–14 |year= 2006 |pmid= 16713569 |doi= 10.1016/j.cell.2006.03.032 |s2cid=13709685 |doi-access=free }}

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{{Protein tyrosine phosphatases}}

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