Protein: Receptor-type tyrosine-protein phosphatase N2 (R-PTP-N2) (EC 3.1.3.-) (EC 3.1.3.48) (PTP NE-6) (PTPNE6) (Phogrin) [Cleaved into: IA-2beta60] (Q63475)
Organism: Rattus norvegicus (Rat)
Function: Plays a role in vesicle-mediated secretory processes. Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets. Required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation. Plays a role in insulin secretion in response to glucose stimuli. Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain. In females, but not in males, required for normal accumulation and secretion of pituitary hormones, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Required to maintain normal levels of renin expression and renin release. May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization (By similarity). Has phosphatidylinositol phosphatase activity; the PIPase activity is involved in its ability to regulate insulin secretion. Can dephosphorylate phosphatidylinositol 4,5-biphosphate, phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate. Regulates PI(4,5)P2 level in the plasma membrane and localization of cofilin at the plasma membrane and thus is indirectly involved in regulation of actin dynamics related to cell migration and metastasis; upon hydrolyzation of PI(4,5)P2 cofilin is released from the plasma membrane and acts in the cytoplasm in severing F-actin filaments (By similarity).
Subcellular location: Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000269|PubMed:14597614}; Single-pass type I membrane protein {ECO:0000269|PubMed:14597614}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000250|UniProtKB:P80560}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P80560}. Note=Predominantly found on dense-core secretory granules. Sorting to secretory granules in part is dependent of the N-terminal propeptide domain of the precursor and its interaction with CPE (By similarity). Transiently found at the cell membrane, when secretory vesicles fuse with the cell membrane to release their cargo. Is then endocytosed and recycled to secretory vesicles involving clathrin-dependent AP2-mediated endocytosis (PubMed:15882444). Recycled via STX6- but not TTTGN1/TGN38-containing compartments (By similarity). {ECO:0000250|UniProtKB:P80560, ECO:0000269|PubMed:15882444, ECO:0000305}.; SUBCELLULAR LOCATION: [IA-2beta60]: Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000305}.
InterPro domains:
- IPR029021: Protein-tyrosine phosphatase-like (homologous_superfamily) [703-1001]
- IPR000387: Tyrosine-specific protein phosphatases domain (domain) [913-985]
- IPR021613: Protein-tyrosine phosphatase receptor IA-2 ectodomain (domain) [498-586]
- IPR038112: Protein-tyrosine phosphatase receptor IA-2, ectodomain superfamily (homologous_superfamily) [490-588]
- IPR003595: Protein-tyrosine phosphatase, catalytic (domain) [891-993]
- IPR033522: Receptor-type tyrosine-protein phosphatase-like N/N2 (family) [6-1004]
- IPR016130: Protein-tyrosine phosphatase, active site (active_site) [932-942]
- IPR000242: Tyrosine-specific protein phosphatase, PTPase domain (domain) [733-996]
Sequence:
MGLPLPLLLLLLLPPPLPRALPAPASARGRQLPGRLGCLFEDGLCGSLETCVNDGVFGRCQKVPALDTYRYEVSPGALLHLRIILQKLSRTGFTWQDDYTQRVIAQELSNLPKAYLWHEEASSPARSLQQNADNEKWFSLESEVALAKTLRRYLPYLELLSQAPTANAHPRIDHETRPVKGEDSSPENILTYVAHTSALTYPPATRVKYPDNLLRPLSRLQPDELSPKVDSDIDKQKLIAALGAYTAQRPPGENDPEPRYLVHSPMRAPRPFAAPALSQRWPLPPGDSKDSLSMGDDTLLRSLLKDLQQQAEVDRLGSLKLEEQADSIAGAIQSDPVEGSQESHGRGAEGQLREQADAPEEMLQDHRLPEVDDPAAYKEVSRLSFKLGDLLKDHGSPLLPEAPLLEKSSRAEMKKSEQPEEVLSSEEETAGVEHVKSRTYSKDLLERKPNSEPQPWRLEDQFQNRAPEVWEDEQNLKLAAQGPPSGGLQLEVQPSEEEQQGYILTGNNPLSPEKGKQLMDEVAHLLRVPSSFFADVKVLGPAVIFKVSANIQNMTTADVTKAAVDNKDELEKATGLTILQSGIRPKGKLKLLPHPEEQEDSTKFIVLTFLSIACILAVLLASSLAYCLRHNSHYKLKEKLSGLGADPSADATEAYQELCRQRMAVRPQDHSEGPHTSRINSVSSQLSDGPMPSPSARSSTSSWSEEPAQSNMDISTGHMILAYMEDHLKNKNRLEKEWEALCAYQAEPDSSLVAQREENAPKNRSLAVLTYDHSRILLKSENSHSNSDYINASPIMDHDPRNPAYIATQGPLPATVADFWQMVWESGCAVIVMLTPLSENGVRQCHHYWPDEGSNVYHVYEVNLVSEHIWCQDFLVRSFYLKNLQTNETRTVTQFHFLSWYDQGVPSSTRSLLDFRRKVNKCYRGRSCPIIVHCSDGAGRSGTYVLIDMVLNKMAKGAKEIDIAATLEHLRDQRPGMVQTKEQFEFALTAVAEEVNAILKALPQ
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0019899 (enzyme binding), GO:0051020 (GTPase binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0023052 (signaling), GO:0065008 (regulation of biological quality), GO:0042221 (response to chemical), GO:0009719 (response to endogenous stimulus), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0048522 (positive regulation of cellular process), GO:0042127 (regulation of cell population proliferation), GO:0035556 (intracellular signal transduction), GO:1901698 (response to nitrogen compound), GO:0070887 (cellular response to chemical stimulus), GO:0007166 (cell surface receptor signaling pathway), GO:1901700 (response to oxygen-containing compound), GO:0010817 (regulation of hormone levels), GO:0010033 (response to organic substance), GO:0009725 (response to hormone), GO:0008284 (positive regulation of cell population proliferation), GO:0043434 (response to peptide hormone), GO:1901652 (response to peptide), GO:0046683 (response to organophosphorus), GO:0009743 (response to carbohydrate), GO:0051591 (response to cAMP), GO:0034097 (response to cytokine), GO:0010243 (response to organonitrogen compound), GO:0071310 (cellular response to organic substance), GO:0014070 (response to organic cyclic compound), GO:0043627 (response to estrogen), GO:0019221 (cytokine-mediated signaling pathway), GO:0050678 (regulation of epithelial cell proliferation), GO:0019932 (second-messenger-mediated signaling), GO:0050679 (positive regulation of epithelial cell proliferation), GO:0061469 (regulation of type B pancreatic cell proliferation), GO:0032868 (response to insulin), GO:0014074 (response to purine-containing compound), GO:0034284 (response to monosaccharide), GO:0071345 (cellular response to cytokine stimulus), GO:0009746 (response to hexose), GO:0009749 (response to glucose)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0150034 (distal axon), GO:0042995 (cell projection), GO:0016020 (membrane), GO:0044297 (cell body), GO:0098793 (presynapse), GO:0071944 (cell periphery), GO:0030054 (cell junction), GO:0044306 (neuron projection terminus), GO:0036477 (somatodendritic compartment), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0030141 (secretory granule), GO:0043679 (axon terminus), GO:0120025 (plasma membrane bounded cell projection), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0045202 (synapse), GO:0043025 (neuronal cell body), GO:0005794 (Golgi apparatus), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0099503 (secretory vesicle), GO:0043231 (intracellular membrane-bounded organelle), GO:0043005 (neuron projection), GO:0031982 (vesicle), GO:0097708 (intracellular vesicle), GO:0030424 (axon)