ID PTPR2_MACNE Reviewed; 1013 AA. AC O02695; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1997, sequence version 1. DT 18-SEP-2019, entry version 113. DE RecName: Full=Receptor-type tyrosine-protein phosphatase N2; DE Short=R-PTP-N2; DE EC=3.1.3.-; DE EC=3.1.3.48; DE AltName: Full=M1851; DE Contains: DE RecName: Full=IA-2beta60; DE Flags: Precursor; GN Name=PTPRN2; OS Macaca nemestrina (Pig-tailed macaque). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Cercopithecidae; Cercopithecinae; Macaca. OX NCBI_TaxID=9545; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Pancreatic islet; RX PubMed=9100223; DOI=10.1007/bf03401670; RA Lagasse J., Jelinek L., Sexson S., Lofton-Day C.E., Breininger J., RA Sheppard P., Kindsvogel W., Hagopian W.A.; RT "An islet-cell protein tyrosine phosphatase is a likely precursor to RT the 37-kDa autoantigen in type 1 diabetes: human and macaque RT sequences, tissue distribution, unique and shared epitopes, and RT predictive autoantibodies."; RL Mol. Med. 3:163-173(1997). CC -!- FUNCTION: Plays a role in vesicle-mediated secretory processes. CC Required for normal accumulation of secretory vesicles in CC hippocampus, pituitary and pancreatic islets. Required for the CC accumulation of normal levels of insulin-containing vesicles and CC preventing their degradation. Plays a role in insulin secretion in CC response to glucose stimuli. Required for normal accumulation of CC the neurotransmitters norepinephrine, dopamine and serotonin in CC the brain. In females, but not in males, required for normal CC accumulation and secretion of pituitary hormones, such as CC luteinizing hormone (LH) and follicle-stimulating hormone (FSH). CC Required to maintain normal levels of renin expression and renin CC release. May regulate catalytic active protein-tyrosine CC phosphatases such as PTPRA through dimerization. Has CC phosphatidylinositol phosphatase activity; the PIPase activity is CC involved in its ability to regulate insulin secretion. Can CC dephosphorylate phosphatidylinositol 4,5-biphosphate, CC phosphatidylinositol 5-phosphate and phosphatidylinositol 3- CC phosphate. Regulates PI(4,5)P2 level in the plasma membrane and CC localization of cofilin at the plasma membrane and thus is CC indirectly involved in regulation of actin dynamics related to CC cell migration and metastasis; upon hydrolyzation of PI(4,5)P2 CC cofilin is released from the plasma membrane and acts in the CC cytoplasm in severing F-actin filaments. CC {ECO:0000250|UniProtKB:P80560, ECO:0000250|UniProtKB:Q63475, CC ECO:0000250|UniProtKB:Q92932}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] CC + phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, CC Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:46858, ChEBI:CHEBI:82620; EC=3.1.3.48; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10044}; CC -!- SUBUNIT: Self-associates. Interacts (via cytoplasmic domain) with CC PTPRN (via cytoplasmic domain). Interacts (precursor form) with CC CPE. Interacts with HAP1. Interacts with AP2A1 or AP2A2 and AP1G1; CC indicative for an association with adaptor protein complex 2 (AP- CC 2) and adaptor protein complex 1 (AP-1). Interacts with AP2M1; CC indicative for an association with adaptor protein complex 2 (AP- CC 2). Interacts with MYO5A. {ECO:0000250|UniProtKB:P80560, CC ECO:0000250|UniProtKB:Q63475}. CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle CC membrane {ECO:0000250|UniProtKB:P80560}; Single-pass type I CC membrane protein {ECO:0000250|UniProtKB:P80560}. Cytoplasmic CC vesicle, secretory vesicle, synaptic vesicle membrane CC {ECO:0000250|UniProtKB:P80560}; Single-pass type I membrane CC protein {ECO:0000250|UniProtKB:P80560}. Note=Predominantly found CC on dense-core secretory granules. Sorting to secretory granules in CC part is dependent of the N-terminal propeptide domain of the CC precursor and its interaction with CPE. Transiently found at the CC cell membrane, when secretory vesicles fuse with the cell membrane CC to release their cargo. Is then endocytosed and recycled to CC secretory vesicles involving clathrin-dependent AP2-mediated CC endocytosis. Recycled via STX6- but not TTTGN1/TGN38-containing CC compartments. {ECO:0000250|UniProtKB:P80560, CC ECO:0000250|UniProtKB:Q63475}. CC -!- TISSUE SPECIFICITY: Detected in pancreatic islets and adrenal CC medulla. {ECO:0000269|PubMed:9100223}. CC -!- DOMAIN: The tyrosine-based internalization signal is proposed to CC function in clathrin-mediated endocytosis and recycling. CC {ECO:0000250|UniProtKB:Q63475}. CC -!- DOMAIN: The leucine-based sorting signal is proposed to function CC in trafficking at the plasma membrane. CC {ECO:0000250|UniProtKB:P80560}. CC -!- PTM: Subject to proteolytic cleavage at multiple sites. CC {ECO:0000250|UniProtKB:P80560}. CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. CC Receptor class 8 subfamily. {ECO:0000305}. CC -!- CAUTION: Has no tyrosine-protein phosphatase activity at mild CC acidic conditions (pH 5.5). The in vivo relevance of the low PPase CC activity for the human protein at acidic conditions (pH 4.5) is CC questioned. This catalytic activity seems to be affected by the CC replacement of a highly conserved residue in the tyrosine-protein CC phosphatase domain. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U91574; AAC51186.1; -; mRNA. DR RefSeq; NP_001292849.1; NM_001305920.1. DR SMR; O02695; -. DR GeneID; 105474981; -. DR CTD; 5799; -. DR OrthoDB; 411281at2759; -. DR Proteomes; UP000233120; Whole Genome Shotgun Assembly. DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0030667; C:secretory granule membrane; ISS:UniProtKB. DR GO; GO:0030672; C:synaptic vesicle membrane; ISS:UniProtKB. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; ISS:UniProtKB. DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW. DR GO; GO:0007269; P:neurotransmitter secretion; ISS:UniProtKB. DR Gene3D; 3.30.70.2470; -; 1. DR Gene3D; 3.90.190.10; -; 1. DR InterPro; IPR033522; IA-2/IA-2_beta. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR000242; PTPase_domain. DR InterPro; IPR021613; Receptor_IA-2_dom. DR InterPro; IPR038112; Receptor_IA-2_ectodomain_sf. DR InterPro; IPR029403; RESP18_dom. DR InterPro; IPR016130; Tyr_Pase_AS. DR InterPro; IPR003595; Tyr_Pase_cat. DR InterPro; IPR000387; TYR_PHOSPHATASE_dom. DR PANTHER; PTHR46106:SF5; PTHR46106:SF5; 1. DR Pfam; PF11548; Receptor_IA-2; 1. DR Pfam; PF14948; RESP18; 1. DR Pfam; PF00102; Y_phosphatase; 1. DR PRINTS; PR00700; PRTYPHPHTASE. DR SMART; SM00194; PTPc; 1. DR SMART; SM00404; PTPc_motif; 1. DR SUPFAM; SSF52799; SSF52799; 1. DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1. DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1. DR PROSITE; PS50055; TYR_PHOSPHATASE_PTP; 1. PE 2: Evidence at transcript level; KW Acetylation; Cell junction; Complete proteome; Cytoplasmic vesicle; KW Glycoprotein; Hydrolase; Lipid metabolism; Membrane; KW Phospholipid metabolism; Phosphoprotein; Protein phosphatase; KW Receptor; Reference proteome; Signal; Synapse; Transmembrane; KW Transmembrane helix. FT SIGNAL 1 19 {ECO:0000255}. FT CHAIN 20 1013 Receptor-type tyrosine-protein FT phosphatase N2. FT /FTId=PRO_0000025455. FT CHAIN 500 1013 IA-2beta60. FT {ECO:0000250|UniProtKB:P80560}. FT /FTId=PRO_0000438069. FT TOPO_DOM 20 613 Extracellular. {ECO:0000255}. FT TRANSMEM 614 634 Helical. {ECO:0000255}. FT TOPO_DOM 635 1013 Cytoplasmic. {ECO:0000255}. FT DOMAIN 743 1003 Tyrosine-protein phosphatase. FT {ECO:0000255|PROSITE-ProRule:PRU00160}. FT REGION 1 419 Involved in localization to secretory FT granules; interaction with CPE. FT {ECO:0000250|UniProtKB:P80560}. FT REGION 943 949 Substrate binding. {ECO:0000250}. FT MOTIF 664 673 Tyrosine-based internalization motif. FT {ECO:0000250|UniProtKB:Q63475}. FT MOTIF 1002 1008 Leucine-based sorting signal. FT {ECO:0000250|UniProtKB:P80560}. FT ACT_SITE 943 943 Phosphocysteine intermediate. FT {ECO:0000255|PROSITE-ProRule:PRU00160, FT ECO:0000255|PROSITE-ProRule:PRU10044}. FT BINDING 911 911 Substrate. {ECO:0000250}. FT BINDING 988 988 Substrate. {ECO:0000250}. FT SITE 425 426 Cleavage. {ECO:0000250}. FT MOD_RES 434 434 Phosphoserine. FT {ECO:0000250|UniProtKB:P80560}. FT MOD_RES 435 435 Phosphoserine. FT {ECO:0000250|UniProtKB:P80560}. FT MOD_RES 690 690 Phosphoserine. FT {ECO:0000250|UniProtKB:Q63475}. FT MOD_RES 696 696 Phosphoserine. FT {ECO:0000250|UniProtKB:Q63475}. FT MOD_RES 968 968 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q92932}. FT CARBOHYD 562 562 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. SQ SEQUENCE 1013 AA; 111191 MW; 4808D43937A2EF59 CRC64; MALPLLLLLL LLLPPRVLPA APSSVPHGRQ LPGRLGCLLE EGLCGASEAC VNDGVFGRCQ KVPAMDFYRY EVSPVALQRL RVALQKLSGT GFTWQDDYTQ YVMDQELADL PKTYLRHPEA SGPARPSKHS IGSERRYSQE GGAALAKAFR RHLPFLEALS QAPASDALAR TRMAQDRPRA EGDDRFSKSI LTYVAHTSVL TYPPGPQAQL PEDLLPRTLS QLQPDELSPK VDSSVERHHL MAALSAYAAQ RPPAPPGKGS LEPQYLLRAP SRMPRPLLSP AVPQKWPSPL GDPEDPPSTG EGARIHTLLK DLQRQPAEAR GLSDLELDSM AELMAGLMQG MDHRGALGGP GKAALGESGE QADGPKAALR GESFPDDGVQ DDDDRLYQEV HRLSATLGGL LQDHGSRLSP GALPFAKPLK MERKKSERPE ASLSSEEETA GVENVKSQTY SKDLLGQQPH SEPGAGAFGE LQNQMPGPSE EEQSLPAGAQ EALGDGLQLE VKPSEEEARG YIVTDRDPLR PEEGRQLVED VARLLQMPSS TFADVEVLGP AVTFKVGANV QNVTTADVEK ATVDNKDKLE ETSGLKILQT GVGSKSKLKF LPPQAEQEDS TKFIALTLVS LACILGVLLA SGLIYCLRHS SQHRLKEKLS GLGRDPGADA TAAYQELCRQ RMATRPPDRP EGPHTSRISS VSSQFSDGPM PSPSARSSAS SWSEEPVQSN MDISTGHMIL SYMEDHLKNK NRLEKEWEAL CAYQAEPNSS LVAQKEENVP KNRSLAVLTY DHSRVLLKAE NSHSHSDYIN ASPIMDHDPR NPAYIATQGP LPATVADFWQ MVWESGCVVI VMLTPLTENG VRQCYHYWPD EGSNLYHIYE VNLVSEHIWC EDFLVRSFYL KNLQTNETRT VTQFHFLSWY DRGVPSSSRS LLDFRRKVNK CYRGRSCPII VHCSDGAGRS GTYVLIDMVL NKMAKGAKEI DIAATLEHLR DQRPGMVQTK EQFEFALTAV AEEVNAILKA LPQ //