PTPRN2

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.^[5][6][7] PTPRN and PTPRN2 (this gene) are both found to be major autoantigens associated with insulin-dependent diabetes mellitus.^[7]

PTPRN2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2QEP, 4HTI, 4HTJ
Identifiers
Aliases	PTPRN2, IA-2beta, IAR, ICAAR, PTPRP, R-PTP-N2, protein tyrosine phosphatase, receptor type N2, protein tyrosine phosphatase receptor type N2
External IDs	OMIM: 601698; MGI: 107418; HomoloGene: 2134; GeneCards: PTPRN2; OMA:PTPRN2 - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q36.3 Start 157,539,056 bp[1] End 158,587,823 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12 F2|12 62.65 cM Start 116,449,340 bp[2] End 117,240,469 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in lateral nuclear group of thalamus middle temporal gyrus external globus pallidus Brodmann area 23 entorhinal cortex orbitofrontal cortex frontal pole superior frontal gyrus Brodmann area 46 postcentral gyrus Top expressed in dentate gyrus of hippocampal formation granule cell superior frontal gyrus primary visual cortex primordial pancreas neural layer of retina cerebellar cortex endocrine pancreas islet of Langerhans zygote morula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phosphoprotein phosphatase activity phosphatase activity protein tyrosine phosphatase activity transmembrane receptor protein tyrosine phosphatase activity hydrolase activity Cellular component cytoplasm integral component of membrane endoplasmic reticulum lumen secretory granule membrane membrane receptor complex transport vesicle membrane synapse integral component of plasma membrane synaptic vesicle membrane secretory granule cell junction terminal bouton cytoplasmic vesicle plasma membrane ficolin-1-rich granule membrane integral component of synaptic vesicle membrane Biological process protein dephosphorylation negative regulation of GTPase activity dephosphorylation insulin secretion involved in cellular response to glucose stimulus peptidyl-tyrosine dephosphorylation neurotransmitter secretion lipid metabolism neutrophil degranulation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5799 19276 Ensembl ENSG00000155093 ENSG00000282185 ENSMUSG00000056553 UniProt Q92932 P80560 RefSeq (mRNA) NM_001308267 NM_001308268 NM_002847 NM_130842 NM_130843 NM_011215 RefSeq (protein) NP_001295196 NP_001295197 NP_002838 NP_570857 NP_570858 NP_035345 Location (UCSC) Chr 7: 157.54 – 158.59 Mb Chr 12: 116.45 – 117.24 Mb PubMed search [3] [4]
Wikidata
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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.^[8] 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.^[7]

Gene

Three alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported.^[7]

Interactions

PTPRN2 has been shown to interact with: CKAP5,^[9] SPTBN4,^[10] and UBQLN4.^[11]

Clinical significance

R-PTP-N2 functions as an autoantigen in diabetes mellitus type 1.^[12][13]