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   27-MAR-2024, entry version 187.
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}.
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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   GlyCosmos; P80560; 1 site, No reported glycans.
DR   GlyGen; P80560; 1 site.
DR   iPTMnet; P80560; -.
DR   PhosphoSitePlus; P80560; -.
DR   SwissPalm; P80560; -.
DR   MaxQB; P80560; -.
DR   PaxDb; 10090-ENSMUSP00000064046; -.
DR   ProteomicsDB; 301914; -. [P80560-1]
DR   Antibodypedia; 1539; 396 antibodies from 31 providers.
DR   DNASU; 19276; -.
DR   Ensembl; ENSMUST00000070733.9; ENSMUSP00000064046.8; ENSMUSG00000056553.15. [P80560-1]
DR   GeneID; 19276; -.
DR   KEGG; mmu:19276; -.
DR   UCSC; uc007phx.2; mouse. [P80560-1]
DR   AGR; MGI:107418; -.
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; ENVQSHT; -.
DR   OrthoDB; 2911650at2759; -.
DR   PhylomeDB; P80560; -.
DR   TreeFam; TF351976; -.
DR   Reactome; R-MMU-6798695; Neutrophil degranulation.
DR   BioGRID-ORCS; 19276; 2 hits in 77 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 68 other cell types or tissues.
DR   ExpressionAtlas; P80560; baseline and differential.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; ISO:MGI.
DR   GO; GO:0098793; C:presynapse; 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:0016311; P:dephosphorylation; IEA:InterPro.
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:0007269; P:neurotransmitter secretion; IMP:UniProtKB.
DR   GO; GO:0051046; P:regulation of secretion; IBA:GO_Central.
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; 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; 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.
DR   Genevisible; P80560; MM.
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
//