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 24-JUL-2024, entry version 131. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; OC 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 the RT 37-kDa autoantigen in type 1 diabetes: human and macaque sequences, tissue RT distribution, unique and shared epitopes, and 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 hippocampus, CC pituitary and pancreatic islets. Required for the accumulation of CC normal levels of insulin-containing vesicles and preventing their CC degradation. Plays a role in insulin secretion in response to glucose CC stimuli. Required for normal accumulation of the neurotransmitters CC norepinephrine, dopamine and serotonin in the brain. In females, but CC not in males, required for normal accumulation and secretion of CC pituitary hormones, such as luteinizing hormone (LH) and follicle- CC stimulating hormone (FSH). Required to maintain normal levels of renin CC expression and renin release. May regulate catalytic active protein- CC tyrosine 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-phosphate. CC Regulates PI(4,5)P2 level in the plasma membrane and localization of CC cofilin at the plasma membrane and thus is indirectly involved in CC regulation of actin dynamics related to cell migration and metastasis; CC upon hydrolyzation of PI(4,5)P2 cofilin is released from the plasma CC membrane and acts in the 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, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU10044}; CC -!- SUBUNIT: Self-associates. Interacts (via cytoplasmic domain) with PTPRN CC (via cytoplasmic domain). Interacts (precursor form) with CPE. CC Interacts with HAP1. Interacts with AP2A1 or AP2A2 and AP1G1; CC indicative for an association with adaptor protein complex 2 (AP-2) and CC adaptor protein complex 1 (AP-1). Interacts with AP2M1; indicative for CC an association with adaptor protein complex 2 (AP-2). Interacts with CC MYO5A. {ECO:0000250|UniProtKB:P80560, ECO:0000250|UniProtKB:Q63475}. CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane CC {ECO:0000250|UniProtKB:P80560}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:P80560}. Cytoplasmic vesicle, secretory vesicle, CC synaptic vesicle membrane {ECO:0000250|UniProtKB:P80560}; Single-pass CC type I membrane protein {ECO:0000250|UniProtKB:P80560}. CC Note=Predominantly found on dense-core secretory granules. Sorting to CC secretory granules in part is dependent of the N-terminal propeptide CC domain of the precursor and its interaction with CPE. Transiently found CC at the cell membrane, when secretory vesicles fuse with the cell CC membrane 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 medulla. CC {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 in CC trafficking at the plasma membrane. {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 acidic CC conditions (pH 5.5). The in vivo relevance of the low PPase activity CC for the human protein at acidic conditions (pH 4.5) is questioned. This CC catalytic activity seems to be affected by the replacement of a highly CC conserved residue in the tyrosine-protein phosphatase domain. CC {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 AlphaFoldDB; O02695; -. DR SMR; O02695; -. DR STRING; 9545.ENSMNEP00000016459; -. DR GlyCosmos; O02695; 1 site, No reported glycans. DR GeneID; 105474981; -. DR KEGG; mni:105474981; -. DR CTD; 5799; -. DR OrthoDB; 2911650at2759; -. DR Proteomes; UP000233120; Whole Genome Shotgun Assembly. DR Proteomes; UP000694946; Unplaced. 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 GO; GO:0051046; P:regulation of secretion; IEA:TreeGrafter. DR CDD; cd14610; R-PTP-N2; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR Gene3D; 3.30.70.2470; Protein-tyrosine phosphatase receptor IA-2 ectodomain; 1. DR InterPro; IPR033522; IA-2/IA-2_beta. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR000242; PTP_cat. 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_Pase_dom. DR PANTHER; PTHR46106; IA-2 PROTEIN TYROSINE PHOSPHATASE, ISOFORM C; 1. DR PANTHER; PTHR46106:SF5; RECEPTOR-TYPE TYROSINE-PROTEIN PHOSPHATASE N2; 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 SMART; SM01305; RESP18; 1. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 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; Cytoplasmic vesicle; Glycoprotein; Hydrolase; KW Lipid metabolism; Membrane; Phospholipid metabolism; Phosphoprotein; KW Protein phosphatase; Receptor; Reference proteome; Signal; Synapse; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..19 FT /evidence="ECO:0000255" FT CHAIN 20..1013 FT /note="Receptor-type tyrosine-protein phosphatase N2" FT /id="PRO_0000025455" FT CHAIN 500..1013 FT /note="IA-2beta60" FT /evidence="ECO:0000250|UniProtKB:P80560" FT /id="PRO_0000438069" FT TOPO_DOM 20..613 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 614..634 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 635..1013 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 743..1003 FT /note="Tyrosine-protein phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT REGION 1..419 FT /note="Involved in localization to secretory granules; FT interaction with CPE" FT /evidence="ECO:0000250|UniProtKB:P80560" FT REGION 116..137 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 273..302 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 342..382 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 401..487 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 673..717 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 664..673 FT /note="Tyrosine-based internalization motif" FT /evidence="ECO:0000250|UniProtKB:Q63475" FT MOTIF 1002..1008 FT /note="Leucine-based sorting signal" FT /evidence="ECO:0000250|UniProtKB:P80560" FT COMPBIAS 276..294 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 418..434 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 437..456 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 685..717 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 943 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160, FT ECO:0000255|PROSITE-ProRule:PRU10044" FT BINDING 911 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 943..949 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 988 FT /ligand="substrate" FT /evidence="ECO:0000250" FT SITE 425..426 FT /note="Cleavage" FT /evidence="ECO:0000250" FT MOD_RES 434 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P80560" FT MOD_RES 435 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P80560" FT MOD_RES 690 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q63475" FT MOD_RES 696 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q63475" FT MOD_RES 968 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q92932" FT CARBOHYD 562 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="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 //