PTPR2_MOUSE
ID PTPR2_MOUSE Reviewed; 1001 AA.
AC P80560; O09134; P70328; Q1RLJ1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 178.
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=PTP IA-2beta {ECO:0000303|PubMed:8637868};
DE AltName: Full=Phogrin {ECO:0000303|PubMed:16262730, ECO:0000303|PubMed:21210912};
DE AltName: Full=Protein tyrosine phosphatase-NP;
DE Short=PTP-NP {ECO:0000303|PubMed:8681804};
DE Contains:
DE RecName: Full=IA-2beta71 {ECO:0000303|PubMed:17611635};
DE Contains:
DE RecName: Full=IA-2beta64 {ECO:0000303|PubMed:17611635};
DE Contains:
DE RecName: Full=IA-2beta60 {ECO:0000303|PubMed:17611635};
DE Flags: Precursor;
GN Name=Ptprn2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=ICR; TISSUE=Brain;
RX PubMed=8681804; DOI=10.1242/dev.122.7.2239;
RA Chiang M.-K., Flanagan J.G.;
RT "PTP-NP, a new member of the receptor protein tyrosine phosphatase family,
RT implicated in development of nervous system and pancreatic endocrine
RT cells.";
RL Development 122:2239-2250(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 282-1001, PROTEOLYTIC CLEAVAGE, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Neonatal brain;
RX PubMed=8637868; DOI=10.1073/pnas.93.6.2307;
RA Lu J., Li Q., Xie H., Chen Z.-J., Borovitskaya A.E., Maclaren N.K.,
RA Notkins A.L., Lan M.S.;
RT "Identification of a second transmembrane protein tyrosine phosphatase, IA-
RT 2beta, as an autoantigen in insulin-dependent diabetes mellitus: precursor
RT of the 37-kDa tryptic fragment.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:2307-2311(1996).
RN [3]
RP PROTEIN SEQUENCE OF 414-418 (IA-2BETA71), PROTEIN SEQUENCE OF 464-468
RP (IA-2BETA64), PROTEIN SEQUENCE OF 489-493 (IA-2BETA60), AND PROTEOLYTIC
RP CLEAVAGE.
RX PubMed=17611635;
RA Kawakami T., Saeki K., Takeyama N., Wu G., Sakudo A., Matsumoto Y.,
RA Hayashi T., Onodera T.;
RT "Detection of proteolytic cleavages of diabetes-associated protein IA-2
RT beta in the pancreas and the brain using novel anti-IA-2 beta monoclonal
RT antibodies.";
RL Int. J. Mol. Med. 20:177-185(2007).
RN [4]
RP FUNCTION, SELF-ASSOCIATION, AND INTERACTION WITH PTPRN AND PTPRA.
RX PubMed=12364328; DOI=10.1074/jbc.m208228200;
RA Gross S., Blanchetot C., Schepens J., Albet S., Lammers R., den Hertog J.,
RA Hendriks W.;
RT "Multimerization of the protein-tyrosine phosphatase (PTP)-like insulin-
RT dependent diabetes mellitus autoantigens IA-2 and IA-2beta with receptor
RT PTPs (RPTPs). Inhibition of RPTPalpha enzymatic activity.";
RL J. Biol. Chem. 277:48139-48145(2002).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=15485654; DOI=10.1016/j.bbrc.2004.09.147;
RA Vo Y.P., Hutton J.C., Angleson J.K.;
RT "Recycling of the dense-core vesicle membrane protein phogrin in Min6 beta-
RT cells.";
RL Biochem. Biophys. Res. Commun. 324:1004-1010(2004).
RN [6]
RP IDENTIFICATION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=15220191; DOI=10.2337/diabetes.53.7.1684;
RA Kubosaki A., Gross S., Miura J., Saeki K., Zhu M., Nakamura S.,
RA Hendriks W., Notkins A.L.;
RT "Targeted disruption of the IA-2beta gene causes glucose intolerance and
RT impairs insulin secretion but does not prevent the development of diabetes
RT in NOD mice.";
RL Diabetes 53:1684-1691(2004).
RN [7]
RP SUBCELLULAR LOCATION, LEUCINE-BASED SORTING SIGNAL, MUTAGENESIS OF
RP 990-GLU-GLU-991 AND 995-ILE-LEU-996, AND INTERACTION WITH AP2A1/2 AND
RP AP1G1.
RX PubMed=16262730; DOI=10.1111/j.1600-0854.2005.00353.x;
RA Torii S., Saito N., Kawano A., Zhao S., Izumi T., Takeuchi T.;
RT "Cytoplasmic transport signal is involved in phogrin targeting and
RT localization to secretory granules.";
RL Traffic 6:1213-1224(2005).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=16269463; DOI=10.1210/en.2005-0638;
RA Kubosaki A., Nakamura S., Clark A., Morris J.F., Notkins A.L.;
RT "Disruption of the transmembrane dense core vesicle proteins IA-2 and IA-
RT 2beta causes female infertility.";
RL Endocrinology 147:811-815(2006).
RN [9]
RP INDUCTION, AND FUNCTION.
RX PubMed=16418280; DOI=10.1073/pnas.0502470102;
RA Doi A., Shono T., Nishi M., Furuta H., Sasaki H., Nanjo K.;
RT "IA-2beta, but not IA-2, is induced by ghrelin and inhibits glucose-
RT stimulated insulin secretion.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:885-890(2006).
RN [10]
RP FUNCTION.
RX PubMed=19019914; DOI=10.1152/ajprenal.90543.2008;
RA Kim S.M., Theilig F., Qin Y., Cai T., Mizel D., Faulhaber-Walter R.,
RA Hirai H., Bachmann S., Briggs J.P., Notkins A.L., Schnermann J.;
RT "Dense-core vesicle proteins IA-2 and IA-2{beta} affect renin synthesis and
RT secretion through the {beta}-adrenergic pathway.";
RL Am. J. Physiol. 296:F382-F389(2009).
RN [11]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=19361477; DOI=10.1016/j.neuroscience.2009.01.022;
RA Nishimura T., Kubosaki A., Ito Y., Notkins A.L.;
RT "Disturbances in the secretion of neurotransmitters in IA-2/IA-2beta null
RT mice: changes in behavior, learning and lifespan.";
RL Neuroscience 159:427-437(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339; SER-422; SER-423 AND
RP SER-678, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Brown adipose tissue;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [13]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=21732083; DOI=10.1007/s00125-011-2221-6;
RA Cai T., Hirai H., Zhang G., Zhang M., Takahashi N., Kasai H., Satin L.S.,
RA Leapman R.D., Notkins A.L.;
RT "Deletion of Ia-2 and/or Ia-2beta in mice decreases insulin secretion by
RT reducing the number of dense core vesicles.";
RL Diabetologia 54:2347-2357(2011).
RN [14]
RP INTERACTION WITH CPE, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 990-GLU-GLU-991.
RX PubMed=21210912; DOI=10.1111/j.1600-0854.2011.01159.x;
RA Saito N., Takeuchi T., Kawano A., Hosaka M., Hou N., Torii S.;
RT "Luminal interaction of phogrin with carboxypeptidase E for effective
RT targeting to secretory granules.";
RL Traffic 12:499-506(2011).
RN [15]
RP INTERACTION WITH HAP1.
RX PubMed=21544547; DOI=10.1007/s00018-011-0692-8;
RA Cape A., Chen X., Wang C.E., O'Neill A., Lin Y.F., He J., Xu X.S., Yi H.,
RA Li H., Li S., Li X.J.;
RT "Loss of huntingtin-associated protein 1 impairs insulin secretion from
RT pancreatic beta-cells.";
RL Cell. Mol. Life Sci. 69:1305-1317(2012).
RN [16]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-259, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Plays a role in vesicle-mediated secretory processes
CC (PubMed:21732083). Required for normal accumulation of secretory
CC vesicles in hippocampus, pituitary and pancreatic islets. Required for
CC the accumulation of normal levels of insulin-containing vesicles and
CC preventing their degradation (PubMed:21732083). Plays a role in insulin
CC secretion in response to glucose stimuli (PubMed:15220191,
CC PubMed:16418280, PubMed:21732083). Required for normal accumulation of
CC the neurotransmitters norepinephrine, dopamine and serotonin in the
CC brain. In females, but not in males, required for normal accumulation
CC and secretion of pituitary hormones, such as luteinizing hormone (LH)
CC and follicle-stimulating hormone (FSH) (PubMed:16269463). Required to
CC maintain normal levels of renin expression and renin release
CC (PubMed:19019914). May regulate catalytic active protein-tyrosine
CC phosphatases such as PTPRA through dimerization (PubMed:12364328). 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 (PI(4,5)P2),
CC phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate
CC (By similarity). Regulates PI(4,5)P2 level in the plasma membrane and
CC localization of cofilin at the plasma membrane and thus is indirectly
CC involved in regulation of actin dynamics related to cell migration and
CC metastasis; upon hydrolyzation of PI(4,5)P2 cofilin is released from
CC the plasma membrane and acts in the cytoplasm in severing F-actin
CC filaments (By similarity). {ECO:0000250|UniProtKB:Q63475,
CC ECO:0000250|UniProtKB:Q92932, ECO:0000269|PubMed:12364328,
CC ECO:0000269|PubMed:15220191, ECO:0000269|PubMed:16269463,
CC ECO:0000269|PubMed:16418280, ECO:0000269|PubMed:19019914,
CC ECO:0000269|PubMed:21732083}.
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) (PubMed:12364328). Interacts (precursor form)
CC with CPE (PubMed:21210912). Interacts with HAP1 isoform A
CC (PubMed:21544547). Interacts with AP2A1 or AP2A2 and AP1G1; indicative
CC for an association with adaptor protein complex 2 (AP-2) and adaptor
CC protein complex 1 (AP-1) (PubMed:16262730). Interacts with AP2M1;
CC indicative for an association with adaptor protein complex 2 (AP-2).
CC Interacts with MYO5A (By similarity). {ECO:0000250|UniProtKB:Q63475,
CC ECO:0000269|PubMed:12364328, ECO:0000269|PubMed:16262730,
CC ECO:0000269|PubMed:21210912}.
CC -!- INTERACTION:
CC P80560; Q60673: Ptprn; NbExp=4; IntAct=EBI-8538944, EBI-8328895;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000269|PubMed:19361477}; Single-pass type I membrane protein
CC {ECO:0000305}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
CC membrane {ECO:0000269|PubMed:19361477}; Single-pass type I membrane
CC protein {ECO:0000305}. Note=Predominantly found on dense-core secretory
CC granules. Sorting to secretory granules in part is dependent of the N-
CC terminal pro domain of the precursor and its interaction with CPE.
CC Transiently found at the cell membrane, when secretory vesicles fuse
CC with the cell membrane to release their cargo. Is then endocytosed and
CC recycled to secretory vesicles involving clathrin-dependent AP2-
CC mediated endocytosis. Recycled via STX6- but not TTTGN1/TGN38-
CC containing compartments. {ECO:0000250|UniProtKB:Q63475,
CC ECO:0000269|PubMed:15485654, ECO:0000269|PubMed:21210912, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [IA-2beta60]: Cytoplasmic vesicle, secretory
CC vesicle membrane {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=Type 1-PTP-NP;
CC IsoId=P80560-1; Sequence=Displayed;
CC Name=2; Synonyms=Type 2-PTP-NP;
CC IsoId=P80560-2; Sequence=Not described;
CC -!- TISSUE SPECIFICITY: Detected in brain (PubMed:15220191,
CC PubMed:19361477). Detected in pancreas islets (at protein level)
CC (PubMed:8681804). Detected in pancreas and brain (PubMed:8681804,
CC PubMed:8637868). {ECO:0000269|PubMed:15220191,
CC ECO:0000269|PubMed:19361477, ECO:0000269|PubMed:8637868,
CC ECO:0000269|PubMed:8681804}.
CC -!- DEVELOPMENTAL STAGE: Expressed in early stages of pancreatic
CC development. First expressed in 8.5 dpc embryos in the dorsal part of
CC the midgut endoderm and by 9.5 dpc, in the pancreatic rudiment
CC specifically in early endocrine progenitor cells. At later stages
CC expressed in insulin- or glucagon-producing cells. During neural
CC development, the type 2 PTP-NP is expressed in early stages of
CC neurogenesis, and the type 1 weakly in the later stages.
CC {ECO:0000269|PubMed:8681804}.
CC -!- INDUCTION: By GHRL in brain, pancreas, and insulinoma cell lines.
CC {ECO:0000269|PubMed:16418280}.
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:0000305|PubMed:16262730}.
CC -!- PTM: Subject to proteolytic cleavage at multiple sites during
CC maturation of secretory granules. In the brain at least IA-2beta71, IA-
CC 2beta64 and IA-2beta60 have been detected, in the pancreas and a
CC pancreatic beta cell line only IA-2beta60 has been detected.
CC {ECO:0000269|PubMed:17611635, ECO:0000269|PubMed:8637868}.
CC -!- DISRUPTION PHENOTYPE: Mice appear healthy and normal, but display
CC mildly decreased glucose tolerance and impaired glucose-stimulated
CC insulin secretion (PubMed:15220191). Pancreatic islets from mice
CC lacking both Ptprn and Ptprn2 contain decreased numbers of insulin-
CC containing vesicles and show a further decrease in insulin secretion
CC after glucose stimuli (PubMed:21732083). Mice lacking both Ptprn and
CC Ptprn2 appear normal, but have lower levels of the neurotransmitters
CC norepinephrine, dopamine and serotonin in the brain. Likewise, they
CC have decreased numbers of synaptic vesicles in the hippocampus and show
CC decreased neurotransmitter release after K(+) stimulation; basal levels
CC of neurotransmitter release are unaffected. They show increased
CC anxiety-like behavior with strongly decreased exploratory activity and
CC rearing. Besides, they show defects in remembering conditioned
CC learning. With increasing age, mutant mice develop a tendency to suffer
CC seizures and display a reduced life span; roughly half of the mutant
CC mice are dead after 40 weeks (PubMed:19361477). The majority of female
CC mice deficient in both Ptprn and Ptprn2 are infertile or have small
CC litters, due to abnormalities of the estrous cycle and absence of
CC corpora lutea. These defects are due to decreased levels of luteinizing
CC hormone and follicle-stimulating hormone (FSH) in the pituitary and
CC decreased levels of luteinizing hormone (LH) in the blood plasma. In
CC contrast, male mice lacking both Ptprn and Ptprn2 display normal
CC hormone levels and normal fertility (PubMed:16269463).
CC {ECO:0000269|PubMed:15220191, ECO:0000269|PubMed:16269463,
CC ECO:0000269|PubMed:19361477, ECO:0000269|PubMed:21732083}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC {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; U57345; AAB06945.1; -; mRNA.
DR EMBL; U82439; AAB39996.1; -; mRNA.
DR EMBL; BN000315; CAG23871.1; -; Genomic_DNA.
DR EMBL; BN000293; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000294; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000295; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000296; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000297; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000298; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000299; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000300; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000301; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000302; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000303; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000304; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000305; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000306; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000307; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000308; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000309; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000310; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000311; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000312; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000313; CAG23871.1; JOINED; Genomic_DNA.
DR EMBL; BN000314; CAG23871.1; JOINED; Genomic_DNA.
DR CCDS; CCDS36576.1; -. [P80560-1]
DR RefSeq; NP_035345.2; NM_011215.2. [P80560-1]
DR AlphaFoldDB; P80560; -.
DR SMR; P80560; -.
DR BioGRID; 202504; 17.
DR IntAct; P80560; 4.
DR MINT; P80560; -.
DR STRING; 10090.ENSMUSP00000064046; -.
DR GlyGen; P80560; 1 site.
DR iPTMnet; P80560; -.
DR PhosphoSitePlus; P80560; -.
DR MaxQB; P80560; -.
DR PaxDb; P80560; -.
DR PRIDE; P80560; -.
DR ProteomicsDB; 301914; -. [P80560-1]
DR Antibodypedia; 1539; 378 antibodies from 31 providers.
DR DNASU; 19276; -.
DR Ensembl; ENSMUST00000070733; ENSMUSP00000064046; ENSMUSG00000056553. [P80560-1]
DR GeneID; 19276; -.
DR KEGG; mmu:19276; -.
DR UCSC; uc007phx.2; mouse. [P80560-1]
DR CTD; 5799; -.
DR MGI; MGI:107418; Ptprn2.
DR VEuPathDB; HostDB:ENSMUSG00000056553; -.
DR eggNOG; KOG0793; Eukaryota.
DR GeneTree; ENSGT00940000154095; -.
DR HOGENOM; CLU_007905_0_0_1; -.
DR InParanoid; P80560; -.
DR OMA; PDNGVHE; -.
DR PhylomeDB; P80560; -.
DR TreeFam; TF351976; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 19276; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Ptprn2; mouse.
DR PRO; PR:P80560; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P80560; protein.
DR Bgee; ENSMUSG00000056553; Expressed in dentate gyrus of hippocampal formation granule cell and 67 other tissues.
DR ExpressionAtlas; P80560; baseline and differential.
DR Genevisible; P80560; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; ISO:MGI.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0030141; C:secretory granule; IDA:MGI.
DR GO; GO:0030667; C:secretory granule membrane; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0043195; C:terminal bouton; ISO:MGI.
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; IMP:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0034260; P:negative regulation of GTPase activity; ISO:MGI.
DR GO; GO:0007269; P:neurotransmitter secretion; IMP:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
DR GO; GO:0051046; P:regulation of secretion; IBA:GO_Central.
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; PTP_cat.
DR InterPro; IPR021613; Receptor_IA-2_dom.
DR InterPro; IPR038112; Receptor_IA-2_ectodomain_sf.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR PANTHER; PTHR46106; PTHR46106; 1.
DR Pfam; PF11548; Receptor_IA-2; 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 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasmic vesicle;
KW Direct protein sequencing; Glycoprotein; Hydrolase; Lipid metabolism;
KW Membrane; Methylation; Phospholipid metabolism; Phosphoprotein;
KW Protein phosphatase; Receptor; Reference proteome; Signal; Synapse;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..1001
FT /note="Receptor-type tyrosine-protein phosphatase N2"
FT /id="PRO_0000025456"
FT CHAIN 414..1001
FT /note="IA-2beta71"
FT /evidence="ECO:0000305|PubMed:17611635"
FT /id="PRO_0000438090"
FT CHAIN 464..1001
FT /note="IA-2beta64"
FT /evidence="ECO:0000305|PubMed:17611635"
FT /id="PRO_0000438071"
FT CHAIN 489..1001
FT /note="IA-2beta60"
FT /evidence="ECO:0000305|PubMed:17611635"
FT /id="PRO_0000438072"
FT TOPO_DOM 28..600
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 601..621
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 622..1001
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 731..991
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 1..407
FT /note="Involved in localization to secretory granules;
FT interaction with CPE"
FT /evidence="ECO:0000269|PubMed:21210912"
FT REGION 271..296
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 308..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 394..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 663..705
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 652..661
FT /note="Tyrosine-based internalization motif"
FT /evidence="ECO:0000250|UniProtKB:Q63475"
FT MOTIF 990..996
FT /note="Leucine-based sorting signal"
FT /evidence="ECO:0000305|PubMed:16262730"
FT COMPBIAS 403..459
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 671..705
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 931
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 899
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 931..937
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 976
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 413..414
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT MOD_RES 259
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 422
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 423
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 678
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 684
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63475"
FT MOD_RES 697
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q63475"
FT MOD_RES 956
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q92932"
FT CARBOHYD 550
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 990..991
FT /note="EE->AA: Impairs localization to secretory granules,
FT promotes location at the TGN, decreases interaction with
FT alpha- and gamma-type adaptin subunits."
FT /evidence="ECO:0000269|PubMed:16262730,
FT ECO:0000269|PubMed:21210912"
FT MUTAGEN 995..996
FT /note="IL->AA: Impairs localization to secretory granules,
FT promotes location at the plasma membrane, defective ind
FT gamma endocytosis, highly decreases interaction with
FT alpha- and gamma-type adaptin subunits."
FT /evidence="ECO:0000269|PubMed:16262730"
FT CONFLICT 121
FT /note="A -> T (in Ref. 1; AAB06945)"
FT /evidence="ECO:0000305"
FT CONFLICT 266
FT /note="A -> S (in Ref. 1; AAB06945)"
FT /evidence="ECO:0000305"
FT CONFLICT 369
FT /note="E -> D (in Ref. 1; AAB06945)"
FT /evidence="ECO:0000305"
FT CONFLICT 370..371
FT /note="Missing (in Ref. 2; AAB39996)"
FT /evidence="ECO:0000305"
FT CONFLICT 395
FT /note="P -> H (in Ref. 1; AAB06945)"
FT /evidence="ECO:0000305"
FT CONFLICT 411
FT /note="I -> M (in Ref. 2; AAB39996)"
FT /evidence="ECO:0000305"
FT CONFLICT 414
FT /note="S -> L (in Ref. 2; AAB39996)"
FT /evidence="ECO:0000305"
FT CONFLICT 586
FT /note="L -> H (in Ref. 2; AAB39996)"
FT /evidence="ECO:0000305"
FT CONFLICT 662
FT /note="I -> V (in Ref. 1; AAB06945 and 2; AAB39996)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1001 AA; 111497 MW; 42B590A13CA89CB8 CRC64;
MGPPLPLLLL LLLPPPLPRA LPAPASARGR QLPGRLGCLF EDGLCGSLET CVNDGVFGRC
QKVPVMDTYR YEVPPGALLH LKVTLQKLSR TGFTWQDDYT QRVIAQELAN LPKAYLWHGE
ASGPARSLQQ NADNEKWFSL EREVALAKTL RRYLPYLELL SQTPTANAHS RIDHETRPAK
GEDSSPENIL TYVAHTSALT YPPATRAKYP DNLLRPFSRL QPDELSPKVD GDIDKQKLIA
ALGAYTAQRL PGENDPEPRY LVHGSARAPR PFSATALSQR WPPPPGDAKD SPSMDDDTLL
QSLLKDLQQN SEVDRLGPLK EEKADSVAGA IQSDPAEGSQ ESHGRGAEGQ PREQTDAPET
MLQDHRLSEV DDPVYKEVNR LSFQLGDLLK DYGSPLLPEG PLLEKSSREE IKKSEQPEEV
LSSEEETAGV EHVRSRTYSK DLFERKPNSE PQPRRLEDQF QNRAPELWED EESLKLAAQG
PPSGGLQLEV QPSEEQQGYI LTGNNPLSPE KGKQLMDQVA HILRVPSSFF ADIKVLGPAV
TFKVSANIQN MTTADVIKAA ADNKDQLEKA TGLTILQSGI RPKGKLKLLP HQEEQEDSTK
FILLTFLSIA CILGVLLASS LAYCLRHNSH YKLKDKLSGL GADPSADATE AYQELCRQRM
AIRPQDRSEG PHTSRINSVS SQFSDGPMPS PSARSSTSSW SEEPVQSNMD ISTGHMILAY
MEDHLKNKNR LEKEWEALCA YQAEPNSSLV AQREENAPKN RSLAVLTYDH SRILLKSQNS
HGSSDYINAS PIMDHDPRNP AYIATQGPLP ATVADFWQMV WESGCAVIVM LTPLSENGVR
QCHHYWPDEG SNLYHVYEVN LVSEHIWCQD FLVRSFYLKN LQTNETRTVT QFHFLSWYDQ
GVPSSTRSLL DFRRKVNKCY RGRSCPIIVH CSDGAGRSGT YVLIDMVLNK MAKGAKEIDI
AATLEHLRDQ RPGMVQTKEQ FEFALTAVAE EVNAILKALP Q
