PTN2_MOUSE
ID PTN2_MOUSE Reviewed; 406 AA.
AC Q06180; Q3V259; Q922E7;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 2;
DE Short=Protein-tyrosine phosphatase PTP-2;
DE EC=3.1.3.48;
DE AltName: Full=MPTP;
GN Name=Ptpn2; Synonyms=Ptpt;
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] (ISOFORM 2).
RX PubMed=1731319; DOI=10.1073/pnas.89.2.499;
RA Mosinger B. Jr., Tillmann U., Westphal H., Tremblay M.L.;
RT "Cloning and characterization of a mouse cDNA encoding a cytoplasmic
RT protein-tyrosine-phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:499-503(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6N; TISSUE=T-cell, and Testis;
RX PubMed=1283199; DOI=10.1007/bf00249698;
RA Miyasaka H., Li S.S.-L.;
RT "Molecular cloning, nucleotide sequence and expression of a cDNA encoding
RT an intracellular protein tyrosine phosphatase, PTPase-2, from mouse testis
RT and T-cells.";
RL Mol. Cell. Biochem. 118:91-98(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP DISRUPTION PHENOTYPE, FUNCTION IN IMMUNE SYSTEM DEVELOPMENT, AND TISSUE
RP SPECIFICITY.
RX PubMed=9271584; DOI=10.1084/jem.186.5.683;
RA You-Ten K.E., Muise E.S., Itie A., Michaliszyn E., Wagner J., Jothy S.,
RA Lapp W.S., Tremblay M.L.;
RT "Impaired bone marrow microenvironment and immune function in T cell
RT protein tyrosine phosphatase-deficient mice.";
RL J. Exp. Med. 186:683-693(1997).
RN [6]
RP FUNCTION IN PDGF SIGNALING.
RX PubMed=11498795; DOI=10.1038/sj.onc.1204648;
RA Ibarra-Sanchez M.J., Wagner J., Ong M.T., Lampron C., Tremblay M.L.;
RT "Murine embryonic fibroblasts lacking TC-PTP display delayed G1 phase
RT through defective NF-kappaB activation.";
RL Oncogene 20:4728-4739(2001).
RN [7]
RP FUNCTION IN CYTOKINE SIGNALING.
RX PubMed=11909529; DOI=10.1016/s0960-9822(02)00697-8;
RA Simoncic P.D., Lee-Loy A., Barber D.L., Tremblay M.L., McGlade C.J.;
RT "The T cell protein tyrosine phosphatase is a negative regulator of janus
RT family kinases 1 and 3.";
RL Curr. Biol. 12:446-453(2002).
RN [8]
RP FUNCTION IN DEPHOSPHORYLATION OF STAT1.
RX PubMed=12138178; DOI=10.1128/mcb.22.16.5662-5668.2002;
RA ten Hoeve J., de Jesus Ibarra-Sanchez M., Fu Y., Zhu W., Tremblay M.,
RA David M., Shuai K.;
RT "Identification of a nuclear Stat1 protein tyrosine phosphatase.";
RL Mol. Cell. Biol. 22:5662-5668(2002).
RN [9]
RP CAUTION.
RX PubMed=11773439; DOI=10.1210/mend.16.1.0761;
RA Aoki N., Matsuda T.;
RT "A nuclear protein tyrosine phosphatase TC-PTP is a potential negative
RT regulator of the PRL-mediated signaling pathway: dephosphorylation and
RT deactivation of signal transducer and activator of transcription 5a and 5b
RT by TC-PTP in nucleus.";
RL Mol. Endocrinol. 16:58-69(2002).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
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 [11]
RP RETRACTION NOTICE OF PUBMED:21183079, AND CAUTION.
RX PubMed=24319783; DOI=10.1210/me.2013-1264;
RA Aoki N., Matsuda T.;
RT "Retraction.";
RL Mol. Endocrinol. 27:1982-1982(2013).
RN [12]
RP DISRUPTION PHENOTYPE.
RX PubMed=14726372; DOI=10.1182/blood-2003-09-3153;
RA Heinonen K.M., Nestel F.P., Newell E.W., Charette G., Seemayer T.A.,
RA Tremblay M.L., Lapp W.S.;
RT "T-cell protein tyrosine phosphatase deletion results in progressive
RT systemic inflammatory disease.";
RL Blood 103:3457-3464(2004).
RN [13]
RP FUNCTION IN DEPHOSPHORYLATION OF PDGFRB, AND MUTAGENESIS OF CYS-216.
RX PubMed=14966296; DOI=10.1128/mcb.24.5.2190-2201.2004;
RA Persson C., Saevenhed C., Bourdeau A., Tremblay M.L., Markova B.,
RA Boehmer F.D., Haj F.G., Neel B.G., Elson A., Heldin C.H., Roennstrand L.,
RA Ostman A., Hellberg C.;
RT "Site-selective regulation of platelet-derived growth factor beta receptor
RT tyrosine phosphorylation by T-cell protein tyrosine phosphatase.";
RL Mol. Cell. Biol. 24:2190-2201(2004).
RN [14]
RP FUNCTION IN TUMOR NECROSIS FACTOR SIGNALING.
RX PubMed=15696169; DOI=10.1038/ni1169;
RA van Vliet C., Bukczynska P.E., Puryer M.A., Sadek C.M., Shields B.J.,
RA Tremblay M.L., Tiganis T.;
RT "Selective regulation of tumor necrosis factor-induced Erk signaling by Src
RT family kinases and the T cell protein tyrosine phosphatase.";
RL Nat. Immunol. 6:253-260(2005).
RN [15]
RP FUNCTION IN DEPHOSPHORYLATION OF CSF1R.
RX PubMed=16705167; DOI=10.1128/mcb.01932-05;
RA Simoncic P.D., Bourdeau A., Lee-Loy A., Rohrschneider L.R., Tremblay M.L.,
RA Stanley E.R., McGlade C.J.;
RT "T-cell protein tyrosine phosphatase (Tcptp) is a negative regulator of
RT colony-stimulating factor 1 signaling and macrophage differentiation.";
RL Mol. Cell. Biol. 26:4149-4160(2006).
RN [16]
RP FUNCTION IN DEPHOSPHORYLATION OF STAT6.
RX PubMed=17210636; DOI=10.1128/mcb.01234-06;
RA Lu X., Chen J., Sasmono R.T., Hsi E.D., Sarosiek K.A., Tiganis T.,
RA Lossos I.S.;
RT "T-cell protein tyrosine phosphatase, distinctively expressed in activated-
RT B-cell-like diffuse large B-cell lymphomas, is the nuclear phosphatase of
RT STAT6.";
RL Mol. Cell. Biol. 27:2166-2179(2007).
RN [17]
RP DISRUPTION PHENOTYPE, FUNCTION IN GLUCOSE HOMEOSTASIS, AND TISSUE
RP SPECIFICITY.
RX PubMed=20484139; DOI=10.2337/db09-1365;
RA Fukushima A., Loh K., Galic S., Fam B., Shields B., Wiede F.,
RA Tremblay M.L., Watt M.J., Andrikopoulos S., Tiganis T.;
RT "T-cell protein tyrosine phosphatase attenuates STAT3 and insulin signaling
RT in the liver to regulate gluconeogenesis.";
RL Diabetes 59:1906-1914(2010).
RN [18]
RP DISRUPTION PHENOTYPE, AND FUNCTION IN T-CELL RECEPTOR SIGNALING.
RX PubMed=22080863; DOI=10.1172/jci59492;
RA Wiede F., Shields B.J., Chew S.H., Kyparissoudis K., van Vliet C.,
RA Galic S., Tremblay M.L., Russell S.M., Godfrey D.I., Tiganis T.;
RT "T cell protein tyrosine phosphatase attenuates T cell signaling to
RT maintain tolerance in mice.";
RL J. Clin. Invest. 121:4758-4774(2011).
RN [19]
RP DISRUPTION PHENOTYPE.
RX PubMed=22124607; DOI=10.1007/s00125-011-2386-z;
RA Loh K., Merry T.L., Galic S., Wu B.J., Watt M.J., Zhang S., Zhang Z.Y.,
RA Neel B.G., Tiganis T.;
RT "T cell protein tyrosine phosphatase (TCPTP) deficiency in muscle does not
RT alter insulin signalling and glucose homeostasis in mice.";
RL Diabetologia 55:468-478(2012).
CC -!- FUNCTION: Non-receptor type tyrosine-specific phosphatase that
CC dephosphorylates receptor protein tyrosine kinases including INSR,
CC EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine
CC kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3 and
CC STAT6 either in the nucleus or the cytoplasm. Negatively regulates
CC numerous signaling pathways and biological processes like
CC hematopoiesis, inflammatory response, cell proliferation and
CC differentiation, and glucose homeostasis. Plays a multifaceted and
CC important role in the development of the immune system. Functions in T-
CC cell receptor signaling through dephosphorylation of FYN and LCK to
CC control T-cells differentiation and activation. Dephosphorylates CSF1R,
CC negatively regulating its downstream signaling and macrophage
CC differentiation. Negatively regulates cytokine (IL2/interleukin-2 and
CC interferon)-mediated signaling through dephosphorylation of the
CC cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that
CC propagate signaling downstream of the cytokine receptors. Also
CC regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine
CC signaling through dephosphorylation of STAT3 and STAT6 respectively. In
CC addition to the immune system, it is involved in anchorage-dependent,
CC negative regulation of EGF-stimulated cell growth. Activated by the
CC integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates
CC EGF signaling. Dephosphorylates PDGFRB and negatively regulates
CC platelet-derived growth factor receptor-beta signaling pathway and
CC therefore cell proliferation. Negatively regulates tumor necrosis
CC factor-mediated signaling downstream via MAPK through SRC
CC dephosphorylation. May also regulate the hepatocyte growth factor
CC receptor signaling pathway through dephosphorylation of the hepatocyte
CC growth factor receptor MET. Also plays an important role in glucose
CC homeostasis. For instance, negatively regulates the insulin receptor
CC signaling pathway through the dephosphorylation of INSR and control
CC gluconeogenesis and liver glucose production through negative
CC regulation of the IL6 signaling pathways. May also bind DNA.
CC {ECO:0000269|PubMed:11498795, ECO:0000269|PubMed:11909529,
CC ECO:0000269|PubMed:12138178, ECO:0000269|PubMed:14966296,
CC ECO:0000269|PubMed:15696169, ECO:0000269|PubMed:16705167,
CC ECO:0000269|PubMed:17210636, ECO:0000269|PubMed:20484139,
CC ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:9271584}.
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: Interacts with RMDN3. Isoform 1 interacts with TMED9. Isoform
CC 1 interacts with STX17; dephosphorylates STX17. Interacts with ITGA1
CC (via cytoplasmic domain); activates the phosphatase activity towards
CC EGFR. Interacts with TRAF2; probably involved in tumor necrosis factor-
CC mediated signaling. Interacts with MET (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum {ECO:0000250}.
CC Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000250}.
CC Note=Targeted to the endoplasmic reticulum by its C-terminal
CC hydrophobic region. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000250}. Cytoplasm
CC {ECO:0000250}. Cell membrane {ECO:0000250}. Note=Predominantly
CC localizes to chromatin. Able to shuttle between the nucleus and the
CC cytoplasm and to dephosphorylate plasma membrane receptors. Recruited
CC by activated ITGA1 at the plasma membrane (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=PTPB, TC-PTPb;
CC IsoId=Q06180-1; Sequence=Displayed;
CC Name=2; Synonyms=PTPA, TC-PTPa;
CC IsoId=Q06180-2; Sequence=VSP_012367;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. The highest expression
CC levels were found in ovary, testis, thymus and kidney.
CC {ECO:0000269|PubMed:20484139, ECO:0000269|PubMed:9271584}.
CC -!- PTM: [Isoform 2]: Specifically phosphorylated in a cell cycle-dependent
CC manner by cyclin-dependent kinases CDK1 and CDK2. Probably activated
CC through phosphorylation by PKR. {ECO:0000250|UniProtKB:P17706}.
CC -!- DISRUPTION PHENOTYPE: Newborn mice are viable and do not display
CC physical abnormalities. However, by 3 to 5 weeks of age they develop
CC hunched posture, diarrhea and anemia. They do not survive beyond 5
CC weeks of age due to severe anemia, hematopoietic defects and the
CC development of progressive systemic inflammatory disease. They display
CC splenomegaly, lymphadenopathy and thymic atrophy, associated with
CC altered B-cell differentiation, altered erythropoiesis, and impaired
CC T- and B-cell functions. The inflammatory disease is characterized by
CC high levels of circulating pro-inflammatory cytokines and lymphocytic
CC infiltrates in non-lymphoid tissues. Heterozygous Ptpn2+/- mice exhibit
CC decreased gluconeogenesis and hepatic glucose production while muscle-
CC specific disruption of Ptpn2 has no effect on insulin signaling and
CC glucose homeostasis in this tissue. {ECO:0000269|PubMed:14726372,
CC ECO:0000269|PubMed:20484139, ECO:0000269|PubMed:22080863,
CC ECO:0000269|PubMed:22124607, ECO:0000269|PubMed:9271584}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class 1 subfamily. {ECO:0000305}.
CC -!- CAUTION: Was reported to dephosphorylate STAT5A and STAT5B in the
CC nucleus to negatively regulate prolactin-mediated signaling pathway
CC (PubMed:11773439). However, the corresponding article has been
CC retracted (PubMed:24319783). {ECO:0000269|PubMed:11773439,
CC ECO:0000303|PubMed:24319783}.
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DR EMBL; M81477; AAA37446.1; -; mRNA.
DR EMBL; S52655; AAB25035.2; -; mRNA.
DR EMBL; BC008269; AAH08269.1; -; mRNA.
DR EMBL; AK076072; BAC36163.1; -; mRNA.
DR EMBL; AK132013; BAE20939.1; -; mRNA.
DR CCDS; CCDS37851.1; -. [Q06180-2]
DR CCDS; CCDS50311.1; -. [Q06180-1]
DR PIR; A38191; A38191.
DR RefSeq; NP_001120649.1; NM_001127177.1. [Q06180-1]
DR RefSeq; NP_033003.1; NM_008977.3. [Q06180-2]
DR RefSeq; XP_011245160.1; XM_011246858.2. [Q06180-2]
DR AlphaFoldDB; Q06180; -.
DR SMR; Q06180; -.
DR BioGRID; 202484; 27.
DR IntAct; Q06180; 5.
DR STRING; 10090.ENSMUSP00000112675; -.
DR iPTMnet; Q06180; -.
DR PhosphoSitePlus; Q06180; -.
DR EPD; Q06180; -.
DR jPOST; Q06180; -.
DR MaxQB; Q06180; -.
DR PaxDb; Q06180; -.
DR PeptideAtlas; Q06180; -.
DR PRIDE; Q06180; -.
DR ProteomicsDB; 301874; -. [Q06180-1]
DR ProteomicsDB; 301875; -. [Q06180-2]
DR Antibodypedia; 6936; 305 antibodies from 34 providers.
DR DNASU; 19255; -.
DR Ensembl; ENSMUST00000025420; ENSMUSP00000025420; ENSMUSG00000024539. [Q06180-2]
DR Ensembl; ENSMUST00000122412; ENSMUSP00000112675; ENSMUSG00000024539. [Q06180-1]
DR GeneID; 19255; -.
DR KEGG; mmu:19255; -.
DR UCSC; uc008fmu.2; mouse. [Q06180-2]
DR UCSC; uc008fmv.2; mouse. [Q06180-1]
DR CTD; 5771; -.
DR MGI; MGI:97806; Ptpn2.
DR VEuPathDB; HostDB:ENSMUSG00000024539; -.
DR eggNOG; KOG0789; Eukaryota.
DR GeneTree; ENSGT00940000154686; -.
DR InParanoid; Q06180; -.
DR OMA; NTAQMVQ; -.
DR OrthoDB; 411281at2759; -.
DR PhylomeDB; Q06180; -.
DR TreeFam; TF315897; -.
DR Reactome; R-MMU-6807004; Negative regulation of MET activity.
DR Reactome; R-MMU-877312; Regulation of IFNG signaling.
DR BioGRID-ORCS; 19255; 19 hits in 80 CRISPR screens.
DR ChiTaRS; Ptpn2; mouse.
DR PRO; PR:Q06180; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q06180; protein.
DR Bgee; ENSMUSG00000024539; Expressed in cleaving embryo and 253 other tissues.
DR ExpressionAtlas; Q06180; baseline and differential.
DR Genevisible; Q06180; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005178; F:integrin binding; ISO:MGI.
DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IMP:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0097677; F:STAT family protein binding; IPI:MGI.
DR GO; GO:0019905; F:syntaxin binding; ISO:MGI.
DR GO; GO:0030183; P:B cell differentiation; IMP:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0050922; P:negative regulation of chemotaxis; IMP:UniProtKB.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0060336; P:negative regulation of interferon-gamma-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:1902206; P:negative regulation of interleukin-2-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:1902215; P:negative regulation of interleukin-4-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0070104; P:negative regulation of interleukin-6-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0010888; P:negative regulation of lipid storage; IMP:UniProtKB.
DR GO; GO:1902227; P:negative regulation of macrophage colony-stimulating factor signaling pathway; IMP:UniProtKB.
DR GO; GO:0045650; P:negative regulation of macrophage differentiation; IMP:UniProtKB.
DR GO; GO:2000587; P:negative regulation of platelet-derived growth factor receptor-beta signaling pathway; IMP:UniProtKB.
DR GO; GO:1902233; P:negative regulation of positive thymic T cell selection; IMP:UniProtKB.
DR GO; GO:0061099; P:negative regulation of protein tyrosine kinase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IPI:MGI.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; IMP:UniProtKB.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IMP:UniProtKB.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IMP:UniProtKB.
DR GO; GO:1903899; P:positive regulation of PERK-mediated unfolded protein response; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:MGI.
DR GO; GO:1902202; P:regulation of hepatocyte growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; IMP:UniProtKB.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR012265; Ptpn1/Ptpn2.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR Pfam; PF00102; Y_phosphatase; 1.
DR PIRSF; PIRSF000926; Tyr-Ptase_nr1; 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 Alternative splicing; Cell membrane; Cytoplasm; Endoplasmic reticulum;
KW Hydrolase; Membrane; Nucleus; Phosphoprotein; Protein phosphatase;
KW Reference proteome; S-nitrosylation.
FT CHAIN 1..406
FT /note="Tyrosine-protein phosphatase non-receptor type 2"
FT /id="PRO_0000094753"
FT DOMAIN 5..275
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 341..406
FT /note="Endoplasmic reticulum location"
FT /evidence="ECO:0000250"
FT REGION 371..406
FT /note="Mediates interaction with STX17"
FT /evidence="ECO:0000250"
FT ACT_SITE 216
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 182
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 216..222
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 260
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 22
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 68
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 216
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17706"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17706"
FT MOD_RES 304
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17706"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT VAR_SEQ 377..406
FT /note="WLYWQPILTKMGFVSVILVGALVGWTLLFH -> PRLTDT (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:1283199,
FT ECO:0000303|PubMed:1731319"
FT /id="VSP_012367"
FT MUTAGEN 216
FT /note="C->S: Catalytically inactive. Unable to restore
FT phosphatase activity toward PDGFRB."
FT /evidence="ECO:0000269|PubMed:14966296"
FT MOD_RES Q06180-2:304
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17706"
SQ SEQUENCE 406 AA; 47360 MW; DFB881DF3C800DC3 CRC64;
MSATIEREFE ELDAQCRWQP LYLEIRNESH DYPHRVAKFP ENRNRNRYRD VSPYDHSRVK
LQSTENDYIN ASLVDIEEAQ RSYILTQGPL PNTCCHFWLM VWQQKTKAVV MLNRTVEKES
VKCAQYWPTD DREMVFKETG FSVKLLSEDV KSYYTVHLLQ LENINTGETR TISHFHYTTW
PDFGVPESPA SFLNFLFKVR ESGCLTPDHG PAVIHCSAGI GRSGTFSLVD TCLVLMEKGE
DVNVKQLLLN MRKYRMGLIQ TPDQLRFSYM AIIEGAKYTK GDSNIQKRWK ELSKEDLSPI
CDHSQNRVMV EKYNGKRIGS EDEKLTGLPS KVQDTVEESS ESILRKRIRE DRKATTAQKV
QQMKQRLNET ERKRKRWLYW QPILTKMGFV SVILVGALVG WTLLFH
