ID PTN11_HUMAN Reviewed; 593 AA. AC Q06124; A8K1D9; Q96HD7; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 11-DEC-2019, sequence version 3. DT 27-MAR-2024, entry version 260. DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 11; DE EC=3.1.3.48 {ECO:0000269|PubMed:26742426, ECO:0000269|PubMed:28074573}; DE AltName: Full=Protein-tyrosine phosphatase 1D; DE Short=PTP-1D; DE AltName: Full=Protein-tyrosine phosphatase 2C; DE Short=PTP-2C; DE AltName: Full=SH-PTP2; DE Short=SHP-2; DE Short=Shp2; DE AltName: Full=SH-PTP3; GN Name=PTPN11; Synonyms=PTP2C, SHPTP2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=T-cell; RX PubMed=1281790; DOI=10.1016/0014-5793(92)81500-l; RA Adachi M., Sekiya M., Miyachi T., Matsuno K., Hinoda Y., Imai K., Yachi A.; RT "Molecular cloning of a novel protein-tyrosine phosphatase SH-PTP3 with RT sequence similarity to the src-homology region 2."; RL FEBS Lett. 314:335-339(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=1280823; DOI=10.1073/pnas.89.23.11239; RA Freeman R.M. Jr., Plutzky J., Neel B.G.; RT "Identification of a human src homology 2-containing protein-tyrosine- RT phosphatase: a putative homolog of Drosophila corkscrew."; RL Proc. Natl. Acad. Sci. U.S.A. 89:11239-11243(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF CYS-459, AND TISSUE RP SPECIFICITY. RX PubMed=8216283; DOI=10.1006/bbrc.1993.2224; RA Bastien L., Ramachandran C., Liu S., Adam M.; RT "Cloning, expression and mutational analysis of SH-PTP2, human protein- RT tyrosine phosphatase."; RL Biochem. Biophys. Res. Commun. 196:124-133(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY. RC TISSUE=Umbilical cord; RX PubMed=7681589; DOI=10.1073/pnas.90.6.2197; RA Ahmad S., Banville D.L., Zhao Z., Fischer E.H., Shen S.H.; RT "A widely expressed human protein-tyrosine phosphatase containing src RT homology 2 domains."; RL Proc. Natl. Acad. Sci. U.S.A. 90:2197-2201(1993). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PHOSPHORYLATION. RX PubMed=7681217; DOI=10.1126/science.7681217; RA Vogel W., Lammers R., Huang J., Ullrich A.; RT "Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation."; RL Science 259:1611-1614(1993). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Eye; 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 [10] RP PHOSPHORYLATION, AND INTERACTION WITH PDGFRB. RX PubMed=7691811; DOI=10.1016/s0021-9258(20)80562-6; RA Lechleider R.J., Sugimoto S., Bennett A.M., Kashishian A.S., Cooper J.A., RA Shoelson S.E., Walsh C.T., Neel B.G.; RT "Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by RT its binding site, phosphotyrosine 1009, on the human platelet-derived RT growth factor receptor."; RL J. Biol. Chem. 268:21478-21481(1993). RN [11] RP PHOSPHORYLATION BY PDGFRB. RX PubMed=8041791; DOI=10.1073/pnas.91.15.7335; RA Bennett A.M., Tang T.L., Sugimoto S., Walsh C.T., Neel B.G.; RT "Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor RT receptor beta to Ras."; RL Proc. Natl. Acad. Sci. U.S.A. 91:7335-7339(1994). RN [12] RP INTERACTION WITH PTPNS1. RX PubMed=8810330; DOI=10.1074/jbc.271.41.25569; RA Ohnishi H., Kubota M., Ohtake A., Sato K., Sano S.; RT "Activation of protein-tyrosine phosphatase SH-PTP2 by a tyrosine-based RT activation motif of a novel brain molecule."; RL J. Biol. Chem. 271:25569-25574(1996). RN [13] RP INTERACTION WITH PTPNS1. RX PubMed=9062191; DOI=10.1038/386181a0; RA Kharitonenkov A., Chen Z., Sures I., Wang H., Schilling J., Ullrich A.; RT "A family of proteins that inhibit signalling through tyrosine kinase RT receptors."; RL Nature 386:181-186(1997). RN [14] RP INTERACTION WITH FLT1. RX PubMed=9600074; DOI=10.1006/bbrc.1998.8578; RA Igarashi K., Isohara T., Kato T., Shigeta K., Yamano T., Uno I.; RT "Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2."; RL Biochem. Biophys. Res. Commun. 246:95-99(1998). RN [15] RP INTERACTION WITH GAB2. RX PubMed=10068651; RA Nishida K., Yoshida Y., Itoh M., Fukada T., Ohtani T., Shirogane T., RA Atsumi T., Takahashi-Tezuka M., Ishihara K., Hibi M., Hirano T.; RT "Gab-family adapter proteins act downstream of cytokine and growth factor RT receptors and T- and B-cell antigen receptors."; RL Blood 93:1809-1816(1999). RN [16] RP INTERACTION WITH SIT1. RX PubMed=10209036; DOI=10.1084/jem.189.8.1181; RA Marie-Cardine A., Kirchgessner H., Bruyns E., Shevchenko A., Mann M., RA Autschbach F., Ratnofsky S., Meuer S., Schraven B.; RT "SHP2-interacting transmembrane adaptor protein (SIT), a novel disulfide- RT linked dimer regulating human T-cell activation."; RL J. Exp. Med. 189:1181-1194(1999). RN [17] RP FUNCTION, AND INTERACTION WITH EPHA2. RX PubMed=10655584; DOI=10.1038/35000008; RA Miao H., Burnett E., Kinch M., Simon E., Wang B.; RT "Activation of EphA2 kinase suppresses integrin function and causes focal- RT adhesion-kinase dephosphorylation."; RL Nat. Cell Biol. 2:62-69(2000). RN [18] RP INTERACTION WITH MZPL1, AND DEPHOSPHORYLATION OF MZPL1. RX PubMed=10681522; DOI=10.1074/jbc.275.8.5453; RA Zhao R., Zhao Z.J.; RT "Dissecting the interaction of SHP-2 with PZR, an immunoglobulin family RT protein containing immunoreceptor tyrosine-based inhibitory motifs."; RL J. Biol. Chem. 275:5453-5459(2000). RN [19] RP INTERACTION WITH FCRL3. RX PubMed=11162587; DOI=10.1006/bbrc.2000.4213; RA Xu M.-J., Zhao R., Zhao Z.J.; RT "Molecular cloning and characterization of SPAP1, an inhibitory receptor."; RL Biochem. Biophys. Res. Commun. 280:768-775(2001). RN [20] RP INTERACTION WITH CD84. RX PubMed=11389028; DOI=10.1182/blood.v97.12.3867; RA Sayos J., Martin M., Chen A., Simarro M., Howie D., Morra M., Engel P., RA Terhorst C.; RT "Cell surface receptors Ly-9 and CD84 recruit the X-linked RT lymphoproliferative disease gene product SAP."; RL Blood 97:3867-3874(2001). RN [21] RP INTERACTION WITH CD84. RX PubMed=11414741; DOI=10.1006/clim.2001.5035; RA Lewis J., Eiben L.J., Nelson D.L., Cohen J.I., Nichols K.E., Ochs H.D., RA Notarangelo L.D., Duckett C.S.; RT "Distinct interactions of the X-linked lymphoproliferative syndrome gene RT product SAP with cytoplasmic domains of members of the CD2 receptor RT family."; RL Clin. Immunol. 100:15-23(2001). RN [22] RP INTERACTION WITH SIT1. RX PubMed=11433379; RX DOI=10.1002/1521-4141(200106)31:6<1825::aid-immu1825>3.0.co;2-v; RA Pfrepper K.-I., Marie-Cardine A., Simeoni L., Kuramitsu Y., Leo A., RA Spicka J., Hilgert I., Scherer J., Schraven B.; RT "Structural and functional dissection of the cytoplasmic domain of the RT transmembrane adaptor protein SIT (SHP2-interacting transmembrane adaptor RT protein)."; RL Eur. J. Immunol. 31:1825-1836(2001). RN [23] RP INTERACTION WITH FER AND PECAM1. RX PubMed=12972546; DOI=10.1091/mbc.e03-02-0080; RA Kogata N., Masuda M., Kamioka Y., Yamagishi A., Endo A., Okada M., RA Mochizuki N.; RT "Identification of Fer tyrosine kinase localized on microtubules as a RT platelet endothelial cell adhesion molecule-1 phosphorylating kinase in RT vascular endothelial cells."; RL Mol. Biol. Cell 14:3553-3564(2003). RN [24] RP INTERACTION WITH FCRL4. RX PubMed=14597715; DOI=10.1073/pnas.1935944100; RA Ehrhardt G.R.A., Davis R.S., Hsu J.T., Leu C.-M., Ehrhardt A., Cooper M.D.; RT "The inhibitory potential of Fc receptor homolog 4 on memory B cells."; RL Proc. Natl. Acad. Sci. U.S.A. 100:13489-13494(2003). RN [25] RP REVIEW ON ROLE IN KIT SIGNALING. RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6; RA Ronnstrand L.; RT "Signal transduction via the stem cell factor receptor/c-Kit."; RL Cell. Mol. Life Sci. 61:2535-2548(2004). RN [26] RP INTERACTION WITH FLT4. RX PubMed=15102829; DOI=10.1074/jbc.m314015200; RA Wang J.F., Zhang X., Groopman J.E.; RT "Activation of vascular endothelial growth factor receptor-3 and its RT downstream signaling promote cell survival under oxidative stress."; RL J. Biol. Chem. 279:27088-27097(2004). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [28] RP INTERACTION WITH ANKHD1. RX PubMed=16956752; DOI=10.1016/j.bbadis.2006.07.010; RA Traina F., Favaro P.M.B., Medina Sde S., Duarte Ada S., Winnischofer S.M., RA Costa F.F., Saad S.T.O.; RT "ANKHD1, ankyrin repeat and KH domain containing 1, is overexpressed in RT acute leukemias and is associated with SHP2 in K562 cells."; RL Biochim. Biophys. Acta 1762:828-834(2006). RN [29] RP INTERACTION WITH ROS1. RX PubMed=16885344; DOI=10.1158/0008-5472.can-06-1193; RA Charest A., Wilker E.W., McLaughlin M.E., Lane K., Gowda R., Coven S., RA McMahon K., Kovach S., Feng Y., Yaffe M.B., Jacks T., Housman D.; RT "ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase- RT 2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling RT axis to form glioblastoma in mice."; RL Cancer Res. 66:7473-7481(2006). RN [30] RP INTERACTION WITH FCRL6. RX PubMed=17213291; DOI=10.1182/blood-2006-06-030023; RA Wilson T.J., Presti R.M., Tassi I., Overton E.T., Cella M., Colonna M.; RT "FcRL6, a new ITIM-bearing receptor on cytolytic cells, is broadly RT expressed by lymphocytes following HIV-1 infection."; RL Blood 109:3786-3793(2007). RN [31] RP INTERACTION WITH CLEC12B. RX PubMed=17562706; DOI=10.1074/jbc.m704250200; RA Hoffmann S.C., Schellack C., Textor S., Konold S., Schmitz D., Cerwenka A., RA Pflanz S., Watzl C.; RT "Identification of CLEC12B, an inhibitory receptor on myeloid cells."; RL J. Biol. Chem. 282:22370-22375(2007). RN [32] RP INTERACTION WITH TERT, AND FUNCTION. RX PubMed=18829466; DOI=10.1074/jbc.m805138200; RA Jakob S., Schroeder P., Lukosz M., Buchner N., Spyridopoulos I., RA Altschmied J., Haendeler J.; RT "Nuclear protein tyrosine phosphatase Shp-2 is one important negative RT regulator of nuclear export of telomerase reverse transcriptase."; RL J. Biol. Chem. 283:33155-33161(2008). RN [33] RP FUNCTION. RX PubMed=18559669; DOI=10.1083/jcb.200710187; RA Lee H.H., Chang Z.F.; RT "Regulation of RhoA-dependent ROCKII activation by Shp2."; RL J. Cell Biol. 181:999-1012(2008). RN [34] RP INTERACTION WITH KIR2DL1. RX PubMed=18604210; DOI=10.1038/ni.1635; RA Yu M.-C., Su L.-L., Zou L., Liu Y., Wu N., Kong L., Zhuang Z.-H., Sun L., RA Liu H.P., Hu J.-H., Li D., Strominger J.L., Zang J.-W., Pei G., Ge B.-X.; RT "An essential function for beta-arrestin 2 in the inhibitory signaling of RT natural killer cells."; RL Nat. Immunol. 9:898-907(2008). RN [35] RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [36] RP FUNCTION, INTERACTION WITH NEDD9, AND MUTAGENESIS OF CYS-459. RX PubMed=19275884; DOI=10.1016/j.bbrc.2009.03.010; RA Yo K., Iwata S., Hashizume Y., Kondo S., Nomura S., Hosono O., Kawasaki H., RA Tanaka H., Dang N.H., Morimoto C.; RT "SHP-2 inhibits tyrosine phosphorylation of Cas-L and regulates cell RT migration."; RL Biochem. Biophys. Res. Commun. 382:210-214(2009). RN [37] RP INTERACTION WITH GAREM1. RX PubMed=19509291; DOI=10.1074/jbc.m109.021139; RA Tashiro K., Tsunematsu T., Okubo H., Ohta T., Sano E., Yamauchi E., RA Taniguchi H., Konishi H.; RT "GAREM, a novel adaptor protein for growth factor receptor-bound protein 2, RT contributes to cellular transformation through the activation of RT extracellular signal-regulated kinase signaling."; RL J. Biol. Chem. 284:20206-20214(2009). RN [38] RP INTERACTION WITH PECAM1. RX PubMed=19342684; DOI=10.4049/jimmunol.0803192; RA Dasgupta B., Dufour E., Mamdouh Z., Muller W.A.; RT "A novel and critical role for tyrosine 663 in platelet endothelial cell RT adhesion molecule-1 trafficking and transendothelial migration."; RL J. Immunol. 182:5041-5051(2009). RN [39] RP INTERACTION WITH FCRL3. RX PubMed=19843936; DOI=10.4049/jimmunol.0901982; RA Kochi Y., Myouzen K., Yamada R., Suzuki A., Kurosaki T., Nakamura Y., RA Yamamoto K.; RT "FCRL3, an autoimmune susceptibility gene, has inhibitory potential on B- RT cell receptor-mediated signaling."; RL J. Immunol. 183:5502-5510(2009). RN [40] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-62 AND TYR-580, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [41] RP PHOSPHORYLATION, AND INTERACTION WITH PDGFRB. RX PubMed=20494825; DOI=10.1016/j.cellsig.2010.05.004; RA Wardega P., Heldin C.H., Lennartsson J.; RT "Mutation of tyrosine residue 857 in the PDGF beta-receptor affects cell RT proliferation but not migration."; RL Cell. Signal. 22:1363-1368(2010). RN [42] RP INVOLVEMENT IN MC. RX PubMed=20577567; DOI=10.1371/journal.pgen.1000991; RA Sobreira N.L., Cirulli E.T., Avramopoulos D., Wohler E., Oswald G.L., RA Stevens E.L., Ge D., Shianna K.V., Smith J.P., Maia J.M., Gumbs C.E., RA Pevsner J., Thomas G., Valle D., Hoover-Fong J.E., Goldstein D.B.; RT "Whole-genome sequencing of a single proband together with linkage analysis RT identifies a Mendelian disease gene."; RL PLoS Genet. 6:E1000991-E1000991(2010). RN [43] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [44] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [45] RP INTERACTION WITH MPIG6B. RX PubMed=23112346; DOI=10.1126/scisignal.2002936; RA Mazharian A., Wang Y.J., Mori J., Bem D., Finney B., Heising S., Gissen P., RA White J.G., Berndt M.C., Gardiner E.E., Nieswandt B., Douglas M.R., RA Campbell R.D., Watson S.P., Senis Y.A.; RT "Mice lacking the ITIM-containing receptor G6b-B exhibit RT macrothrombocytopenia and aberrant platelet function."; RL Sci. Signal. 5:RA78-RA78(2012). RN [46] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-580, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [47] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [48] RP INTERACTION WITH CLEC12B, AND PHOSPHORYLATION AT TYR-542. RX PubMed=34310951; DOI=10.1016/j.jid.2021.05.035; RA Montaudie H., Sormani L., Dadone-Montaudie B., Heim M., Cardot-Leccia N., RA Tulic M.K., Beranger G., Gay A.S., Debayle D., Cheli Y., Raymond J.H., RA Sohier P., Petit V., Rocchi S., Gesbert F., Larue L., Passeron T.; RT "CLEC12B Decreases Melanoma Proliferation by Repressing Signal Transducer RT and Activator of Transcription 3."; RL J. Invest. Dermatol. 142:425-434(2022). RN [49] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 3-526 (ISOFORM 2). RX PubMed=9491886; DOI=10.1016/s0092-8674(00)80938-1; RA Hof P., Pluskey S., Dhe-Paganon S., Eck M.J., Shoelson S.E.; RT "Crystal structure of the tyrosine phosphatase SHP-2."; RL Cell 92:441-450(1998). RN [50] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 237-529. RX PubMed=19167335; DOI=10.1016/j.cell.2008.11.038; RA Barr A.J., Ugochukwu E., Lee W.H., King O.N.F., Filippakopoulos P., RA Alfano I., Savitsky P., Burgess-Brown N.A., Mueller S., Knapp S.; RT "Large-scale structural analysis of the classical human protein tyrosine RT phosphatome."; RL Cell 136:352-363(2009). RN [51] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 262-528 IN COMPLEX WITH INHIBITOR, RP AND CATALYTIC ACTIVITY. RX PubMed=20170098; DOI=10.1021/jm901645u; RA Zhang X., He Y., Liu S., Yu Z., Jiang Z.X., Yang Z., Dong Y., RA Nabinger S.C., Wu L., Gunawan A.M., Wang L., Chan R.J., Zhang Z.Y.; RT "Salicylic acid based small molecule inhibitor for the oncogenic Src RT homology-2 domain containing protein tyrosine phosphatase-2 (SHP2)."; RL J. Med. Chem. 53:2482-2493(2010). RN [52] RP VARIANTS NS1 GLY-61; CYS-63; GLY-72; SER-72; ASP-76; ARG-79; VAL-282; RP ASP-308 AND VAL-504. RX PubMed=11704759; DOI=10.1038/ng772; RA Tartaglia M., Mehler E.L., Goldberg R., Zampino G., Brunner H.G., RA Kremer H., van der Burgt I., Crosby A.H., Ion A., Jeffery S., Kalidas K., RA Patton M.A., Kucherlapati R.S., Gelb B.D.; RT "Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, RT cause Noonan syndrome."; RL Nat. Genet. 29:465-468(2001). RN [53] RP ERRATUM OF PUBMED:11704759. RA Tartaglia M., Mehler E.L., Goldberg R., Zampino G., Brunner H.G., RA Kremer H., van der Burgt I., Crosby A.H., Ion A., Jeffery S., Kalidas K., RA Patton M.A., Kucherlapati R.S., Gelb B.D.; RL Nat. Genet. 29:491-491(2001). RN [54] RP ERRATUM OF PUBMED:11704759. RA Tartaglia M., Mehler E.L., Goldberg R., Zampino G., Brunner H.G., RA Kremer H., van der Burgt I., Crosby A.H., Ion A., Jeffery S., Kalidas K., RA Patton M.A., Kucherlapati R.S., Gelb B.D.; RL Nat. Genet. 30:123-123(2001). RN [55] RP VARIANTS NS1 ALA-42; ALA-60; ASN-61; GLY-61; ASP-62; CYS-63; GLY-72; RP ILE-73; ASP-76; ARG-79; ALA-106; ASP-139; CYS-279; VAL-282; LEU-285; RP SER-285; ASP-308; SER-308; VAL-309; LYS-501 AND VAL-504. RX PubMed=11992261; DOI=10.1086/340847; RA Tartaglia M., Kalidas K., Shaw A., Song X., Musat D.L., van der Burgt I., RA Brunner H.G., Bertola D.R., Crosby A.H., Ion A., Kucherlapati R.S., RA Jeffery S., Patton M.A., Gelb B.D.; RT "PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype- RT phenotype correlation, and phenotypic heterogeneity."; RL Am. J. Hum. Genet. 70:1555-1563(2002). RN [56] RP VARIANTS LPRD1 CYS-279 AND MET-468. RX PubMed=12058348; DOI=10.1086/341528; RA Digilio M.C., Conti E., Sarkozy A., Mingarelli R., Dottorini T., Marino B., RA Pizzuti A., Dallapiccola B.; RT "Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 RT gene."; RL Am. J. Hum. Genet. 71:389-394(2002). RN [57] RP VARIANTS NS1 ASP-62; CYS-63 AND THR-502. RX PubMed=12325025; DOI=10.1002/humu.10129; RA Maheshwari M., Belmont J., Fernbach S., Ho T., Molinari L., Yakub I., RA Yu F., Combes A., Towbin J.A., Craigen W.J., Gibbs R.A.; RT "PTPN11 mutations in Noonan syndrome type I: detection of recurrent RT mutations in exons 3 and 13."; RL Hum. Mutat. 20:298-304(2002). RN [58] RP VARIANTS NS1 GLY-61; CYS-63; SER-72; ILE-73; SER-285 AND ASP-308. RX PubMed=12161469; DOI=10.1210/jcem.87.8.8694; RA Kosaki K., Suzuki T., Muroya K., Hasegawa T., Sato S., Matsuo N., RA Kosaki R., Nagai T., Hasegawa Y., Ogata T.; RT "PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in RT seven Japanese patients with Noonan syndrome."; RL J. Clin. Endocrinol. Metab. 87:3529-3533(2002). RN [59] RP VARIANT NS1 ARG-79. RX PubMed=12529711; DOI=10.1038/sj.ejhg.5200915; RA Schollen E., Matthijs G., Gewillig M., Fryns J.-P., Legius E.; RT "PTPN11 mutation in a large family with Noonan syndrome and dizygous RT twinning."; RL Eur. J. Hum. Genet. 11:85-88(2003). RN [60] RP VARIANTS NS1 LYS-58; ASN-61; GLY-61; CYS-63; GLN-69; LEU-71; SER-72; RP ILE-73; ASP-76; ARG-79; ASP-139; ARG-256; VAL-282 AND ASP-308. RX PubMed=12634870; DOI=10.1038/sj.ejhg.5200935; RA Musante L., Kehl H.G., Majewski F., Meinecke P., Schweiger S., RA Gillessen-Kaesbach G., Wieczorek D., Hinkel G.K., Tinschert S., RA Hoeltzenbein M., Ropers H.-H., Kalscheuer V.M.; RT "Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 RT patients with Noonan syndrome and five patients with cardio-facio-cutaneous RT syndrome."; RL Eur. J. Hum. Genet. 11:201-206(2003). RN [61] RP ERRATUM OF PUBMED:12634870. RA Musante L., Kehl H.G., Majewski F., Meinecke P., Schweiger S., RA Gillessen-Kaesbach G., Wieczorek D., Hinkel G.K., Tinschert S., RA Hoeltzenbein M., Ropers H.-H., Kalscheuer V.M.; RL Eur. J. Hum. Genet. 11:551-551(2003). RN [62] RP VARIANT NS1 THR-502. RX PubMed=12739139; DOI=10.1007/s00431-003-1227-6; RA Kondoh T., Ishii E., Aoki Y., Shimizu T., Zaitsu M., Matsubara Y., RA Moriuchi H.; RT "Noonan syndrome with leukaemoid reaction and overproduction of RT catecholamines: a case report."; RL Eur. J. Pediatr. 162:548-549(2003). RN [63] RP VARIANT LPRD1 PRO-506. RX PubMed=14961557; DOI=10.1002/humu.9149; RA Conti E., Dottorini T., Sarkozy A., Tiller G.E., Esposito G., Pizzuti A., RA Dallapiccola B.; RT "A novel PTPN11 mutation in LEOPARD syndrome."; RL Hum. Mutat. 21:654-654(2003). RN [64] RP VARIANTS NS1 ILE-2; ALA-42; ASP-62; CYS-63; GLY-72; PRO-79; ALA-106; RP CYS-279; ASP-308; SER-308; MET-468; ARG-503; VAL-504 AND PHE-560. RX PubMed=12960218; DOI=10.1136/jmg.40.9.704; RA Sarkozy A., Conti E., Seripa D., Digilio M.C., Grifone N., Tandoi C., RA Fazio V.M., Di Ciommo V., Marino B., Pizzuti A., Dallapiccola B.; RT "Correlation between PTPN11 gene mutations and congenital heart defects in RT Noonan and LEOPARD syndromes."; RL J. Med. Genet. 40:704-708(2003). RN [65] RP VARIANTS JMML TYR-61; VAL-61; LYS-69; THR-72; VAL-72; ALA-76; GLY-76; RP LYS-76; VAL-76; ALA-503 AND ARG-503, VARIANTS MYELODYSPLASTIC SYNDROME RP VAL-60; VAL-61; LYS-69; LEU-71 AND ALA-76, VARIANTS NS1 ASP-62 AND ILE-73, RP AND VARIANT ACUTE MYELOID LEUKEMIA LYS-71. RX PubMed=12717436; DOI=10.1038/ng1156; RA Tartaglia M., Niemeyer C.M., Fragale A., Song X., Buechner J., Jung A., RA Haehlen K., Hasle H., Licht J.D., Gelb B.D.; RT "Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, RT myelodysplastic syndromes and acute myeloid leukemia."; RL Nat. Genet. 34:148-150(2003). RN [66] RP VARIANT NS1 MET-411. RX PubMed=15384080; DOI=10.1002/ajmg.a.30270; RA Bertola D.R., Pereira A.C., de Oliveira P.S.L., Kim C.A., Krieger J.E.; RT "Clinical variability in a Noonan syndrome family with a new PTPN11 gene RT mutation."; RL Am. J. Med. Genet. A 130:378-383(2004). RN [67] RP VARIANTS LPRD1 THR-461 AND ALA-464. RX PubMed=15389709; DOI=10.1002/ajmg.a.30281; RA Yoshida R., Nagai T., Hasegawa T., Kinoshita E., Tanaka T., Ogata T.; RT "Two novel and one recurrent PTPN11 mutations in LEOPARD syndrome."; RL Am. J. Med. Genet. A 130:432-434(2004). RN [68] RP VARIANTS LPRD1 CYS-279; SER-279; MET-468 AND PRO-510. RX PubMed=15520399; DOI=10.1136/jmg.2004.021451; RG French collaborative Noonan study group; RA Keren B., Hadchouel A., Saba S., Sznajer Y., Bonneau D., Leheup B., RA Boute O., Gaillard D., Lacombe D., Layet V., Marlin S., Mortier G., RA Toutain A., Beylot C., Baumann C., Verloes A., Cave H.; RT "PTPN11 mutations in patients with LEOPARD syndrome: a French multicentric RT experience."; RL J. Med. Genet. 41:E117-E117(2004). RN [69] RP VARIANTS LPRD1 CYS-279; SER-279; ALA-464; MET-468; TRP-498; LEU-498 AND RP PRO-506. RX PubMed=15121796; DOI=10.1136/jmg.2003.013466; RA Sarkozy A., Conti E., Digilio M.C., Marino B., Morini E., Pacileo G., RA Wilson M., Calabro R., Pizzuti A., Dallapiccola B.; RT "Clinical and molecular analysis of 30 patients with multiple lentigines RT LEOPARD syndrome."; RL J. Med. Genet. 41:E68-E68(2004). RN [70] RP VARIANT NS1 ARG-506. RX PubMed=15948193; DOI=10.1002/ajmg.a.30813; RA Bertola D.R., Pereira A.C., Passetti F., de Oliveira P.S.L., Messiaen L., RA Gelb B.D., Kim C.A., Krieger J.E.; RT "Neurofibromatosis-Noonan syndrome: molecular evidence of the concurrence RT of both disorders in a patient."; RL Am. J. Med. Genet. A 136:242-245(2005). RN [71] RP VARIANT NS1 GLU-510. RX PubMed=15889278; DOI=10.1007/s00431-005-1679-y; RA Takahashi K., Kogaki S., Kurotobi S., Nasuno S., Ohta M., Okabe H., RA Wada K., Sakai N., Taniike M., Ozono K.; RT "A novel mutation in the PTPN11 gene in a patient with Noonan syndrome and RT rapidly progressive hypertrophic cardiomyopathy."; RL Eur. J. Pediatr. 164:497-500(2005). RN [72] RP VARIANT LPRD1 PRO-506. RX PubMed=15690106; DOI=10.1007/s10038-004-0212-x; RA Kalidas K., Shaw A.C., Crosby A.H., Newbury-Ecob R., Greenhalgh L., RA Temple I.K., Law C., Patel A., Patton M.A., Jeffery S.; RT "Genetic heterogeneity in LEOPARD syndrome: two families with no mutations RT in PTPN11."; RL J. Hum. Genet. 50:21-25(2005). RN [73] RP VARIANT LPRD1 GLU-510. RX PubMed=16733669; DOI=10.1007/s00431-006-0163-7; RA Digilio M.C., Sarkozy A., Pacileo G., Limongelli G., Marino B., RA Dallapiccola B.; RT "PTPN11 gene mutations: linking the Gln510Glu mutation to the 'LEOPARD RT syndrome phenotype'."; RL Eur. J. Pediatr. 165:803-805(2006). RN [74] RP VARIANT LPRD1 CYS-279. RX PubMed=16679933; DOI=10.1097/01.mph.0000199590.21797.0b; RA Ucar C., Calyskan U., Martini S., Heinritz W.; RT "Acute myelomonocytic leukemia in a boy with LEOPARD syndrome (PTPN11 gene RT mutation positive)."; RL J. Pediatr. Hematol. Oncol. 28:123-125(2006). RN [75] RP VARIANT NS1 ALA-59. RX PubMed=19020799; DOI=10.1007/s10038-008-0343-6; RA Ko J.M., Kim J.M., Kim G.H., Yoo H.W.; RT "PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype RT correlation in Korean patients with Noonan syndrome."; RL J. Hum. Genet. 53:999-1006(2008). RN [76] RP VARIANT NS1 SER-491, VARIANT LPRD1 TRP-498, CHARACTERIZATION OF VARIANTS RP NS1 SER-491, AND CHARACTERIZATION OF VARIANT LPRD1 TRP-498. RX PubMed=24891296; DOI=10.1002/ajmg.a.36620; RA Edwards J.J., Martinelli S., Pannone L., Lo I.F., Shi L., Edelmann L., RA Tartaglia M., Luk H.M., Gelb B.D.; RT "A PTPN11 allele encoding a catalytically impaired SHP2 protein in a RT patient with a Noonan syndrome phenotype."; RL Am. J. Med. Genet. A 164:2351-2355(2014). RN [77] RP VARIANT JMML LYS-76, CHARACTERIZATION OF VARIANT JMML LYS-76, VARIANTS RP LPRD1 CYS-279; MET-468; PRO-506 AND GLU-510, CHARACTERIZATION OF VARIANTS RP LPRD1 CYS-279; MET-468; PRO-506 AND GLU-510, FUNCTION, CATALYTIC ACTIVITY, RP INTERACTION WITH CDC73, AND SUBCELLULAR LOCATION. RX PubMed=26742426; DOI=10.1016/j.bbrc.2015.12.117; RA Noda S., Takahashi A., Hayashi T., Tanuma S., Hatakeyama M.; RT "Determination of the catalytic activity of LEOPARD syndrome-associated RT SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in RT Wnt signaling."; RL Biochem. Biophys. Res. Commun. 469:1133-1139(2016). RN [78] RP VARIANTS NS1 HIS-261; PHE-261; ARG-262; PHE-262 AND GLN-265, RP CHARACTERIZATION OF VARIANTS NS1 HIS-261; PHE-261; ARG-262; PHE-262 AND RP GLN-265, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=28074573; DOI=10.1002/humu.23175; RA Pannone L., Bocchinfuso G., Flex E., Rossi C., Baldassarre G., RA Lissewski C., Pantaleoni F., Consoli F., Lepri F., Magliozzi M., RA Anselmi M., Delle Vigne S., Sorge G., Karaer K., Cuturilo G., Sartorio A., RA Tinschert S., Accadia M., Digilio M.C., Zampino G., De Luca A., Cav e H., RA Zenker M., Gelb B.D., Dallapiccola B., Stella L., Ferrero G.B., RA Martinelli S., Tartaglia M.; RT "Structural, Functional, and Clinical Characterization of a Novel PTPN11 RT Mutation Cluster Underlying Noonan Syndrome."; RL Hum. Mutat. 38:451-459(2017). CC -!- FUNCTION: Acts downstream of various receptor and cytoplasmic protein CC tyrosine kinases to participate in the signal transduction from the CC cell surface to the nucleus (PubMed:10655584, PubMed:18559669, CC PubMed:18829466, PubMed:26742426, PubMed:28074573). Positively CC regulates MAPK signal transduction pathway (PubMed:28074573). CC Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573). CC Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its CC RhoA binding activity (PubMed:18559669). Dephosphorylates CDC73 CC (PubMed:26742426). Dephosphorylates SOX9 on tyrosine residues, leading CC to inactivate SOX9 and promote ossification (By similarity). CC Dephosphorylates tyrosine-phosphorylated NEDD9/CAS-L (PubMed:19275884). CC {ECO:0000250|UniProtKB:P35235, ECO:0000269|PubMed:10655584, CC ECO:0000269|PubMed:18559669, ECO:0000269|PubMed:18829466, CC ECO:0000269|PubMed:19275884, ECO:0000269|PubMed:26742426, CC ECO:0000269|PubMed:28074573}. 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, ECO:0000269|PubMed:20170098, CC ECO:0000269|PubMed:26742426, ECO:0000269|PubMed:28074573}; CC -!- SUBUNIT: Interacts with phosphorylated LIME1 and BCAR3. Interacts with CC SHB and INPP5D/SHIP1 (By similarity). Interacts with MILR1 (tyrosine- CC phosphorylated). Interacts with FLT1 (tyrosine-phosphorylated), FLT3 CC (tyrosine-phosphorylated), FLT4 (tyrosine-phosphorylated), KIT and CC GRB2. Interacts with PDGFRA (tyrosine phosphorylated). Interacts (via CC SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity). CC Interacts with PTPNS1 and CD84. Interacts with phosphorylated SIT1 and CC MPZL1. Interacts with FCRL4, FCRL6 and ANKHD1. Interacts with KIR2DL1; CC the interaction is enhanced by ARRB2. Interacts with GAB2. Interacts CC with TERT; the interaction retains TERT in the nucleus. Interacts with CC PECAM1 and FER. Interacts with EPHA2 (activated); participates in CC PTK2/FAK1 dephosphorylation in EPHA2 downstream signaling. Interacts CC with ROS1; mediates PTPN11 phosphorylation. Interacts with PDGFRB CC (tyrosine phosphorylated); this interaction increases the PTPN11 CC phosphatase activity. Interacts with GAREM1 isoform 1 (tyrosine CC phosphorylated); the interaction increases MAPK/ERK activity and does CC not affect the GRB2/SOS complex formation. Interacts with CDC73 CC (PubMed:26742426). Interacts with CEACAM1 (via cytoplasmic domain); CC this interaction depends on the monomer/dimer equilibrium and is CC phosphorylation-dependent (By similarity). Interacts with MPIG6B (via CC ITIM motif) (PubMed:23112346). Interacts with SIGLEC10 (By similarity). CC Interacts with FCRL3 (via phosphorylated ITIM motifs) (PubMed:11162587, CC PubMed:19843936). Interacts with CLEC12B (via ITIM motif); this CC interaction triggers dephosphorylation and activation of PTPN11. CC Interacts (via SH2 domains) with NEDD9/CAS-L; the interaction is CC enhanced when NEDD9/CAS-L is tyrosine phosphorylated (PubMed:19275884). CC {ECO:0000250|UniProtKB:P35235, ECO:0000250|UniProtKB:P41499, CC ECO:0000269|PubMed:10068651, ECO:0000269|PubMed:10209036, CC ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:10681522, CC ECO:0000269|PubMed:11162587, ECO:0000269|PubMed:11389028, CC ECO:0000269|PubMed:11414741, ECO:0000269|PubMed:11433379, CC ECO:0000269|PubMed:12972546, ECO:0000269|PubMed:14597715, CC ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:16885344, CC ECO:0000269|PubMed:16956752, ECO:0000269|PubMed:17213291, CC ECO:0000269|PubMed:17562706, ECO:0000269|PubMed:18604210, CC ECO:0000269|PubMed:18829466, ECO:0000269|PubMed:19275884, CC ECO:0000269|PubMed:19342684, ECO:0000269|PubMed:19509291, CC ECO:0000269|PubMed:19843936, ECO:0000269|PubMed:20170098, CC ECO:0000269|PubMed:20494825, ECO:0000269|PubMed:23112346, CC ECO:0000269|PubMed:26742426, ECO:0000269|PubMed:34310951, CC ECO:0000269|PubMed:7691811, ECO:0000269|PubMed:8810330, CC ECO:0000269|PubMed:9062191, ECO:0000269|PubMed:9600074}. CC -!- INTERACTION: CC Q06124; P10275: AR; NbExp=12; IntAct=EBI-297779, EBI-608057; CC Q06124; P32239: CCKBR; NbExp=5; IntAct=EBI-297779, EBI-1753137; CC Q06124; Q9BZW8: CD244; NbExp=5; IntAct=EBI-297779, EBI-1580565; CC Q06124; P20138: CD33; NbExp=5; IntAct=EBI-297779, EBI-3906571; CC Q06124; Q08345: DDR1; NbExp=4; IntAct=EBI-297779, EBI-711879; CC Q06124; P00533: EGFR; NbExp=5; IntAct=EBI-297779, EBI-297353; CC Q06124; P29317: EPHA2; NbExp=3; IntAct=EBI-297779, EBI-702104; CC Q06124; P04626: ERBB2; NbExp=3; IntAct=EBI-297779, EBI-641062; CC Q06124; Q8WU20: FRS2; NbExp=4; IntAct=EBI-297779, EBI-1104330; CC Q06124; Q13480: GAB1; NbExp=42; IntAct=EBI-297779, EBI-517684; CC Q06124; Q9UQC2: GAB2; NbExp=4; IntAct=EBI-297779, EBI-975200; CC Q06124; P62993: GRB2; NbExp=10; IntAct=EBI-297779, EBI-401755; CC Q06124; P08069: IGF1R; NbExp=5; IntAct=EBI-297779, EBI-475981; CC Q06124; P06213: INSR; NbExp=3; IntAct=EBI-297779, EBI-475899; CC Q06124; P35568: IRS1; NbExp=3; IntAct=EBI-297779, EBI-517592; CC Q06124; P43628: KIR2DL3; NbExp=4; IntAct=EBI-297779, EBI-8632435; CC Q06124; P10721: KIT; NbExp=29; IntAct=EBI-297779, EBI-1379503; CC Q06124; P08581: MET; NbExp=13; IntAct=EBI-297779, EBI-1039152; CC Q06124; O95297: MPZL1; NbExp=4; IntAct=EBI-297779, EBI-963338; CC Q06124; Q15116: PDCD1; NbExp=3; IntAct=EBI-297779, EBI-4314328; CC Q06124; P09619: PDGFRB; NbExp=8; IntAct=EBI-297779, EBI-641237; CC Q06124; P16284: PECAM1; NbExp=7; IntAct=EBI-297779, EBI-716404; CC Q06124; P49023: PXN; NbExp=3; IntAct=EBI-297779, EBI-702209; CC Q06124; P49247: RPIA; NbExp=4; IntAct=EBI-297779, EBI-744831; CC Q06124; Q13049: TRIM32; NbExp=5; IntAct=EBI-297779, EBI-742790; CC Q06124; P68105: EEF1A1; Xeno; NbExp=2; IntAct=EBI-297779, EBI-7645934; CC Q06124; Q71V39: EEF1A2; Xeno; NbExp=2; IntAct=EBI-297779, EBI-7645815; CC Q06124; P35570: Irs1; Xeno; NbExp=3; IntAct=EBI-297779, EBI-520230; CC Q06124; P97710: Sirpa; Xeno; NbExp=3; IntAct=EBI-297779, EBI-7945080; CC Q06124-2; Q6P1J9: CDC73; NbExp=2; IntAct=EBI-17635971, EBI-930143; CC Q06124-2; Q13480: GAB1; NbExp=2; IntAct=EBI-17635971, EBI-517684; CC Q06124-2; O75496: GMNN; NbExp=3; IntAct=EBI-17635971, EBI-371669; CC Q06124-2; Q9UKI8: TLK1; NbExp=3; IntAct=EBI-17635971, EBI-740492; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26742426}. Nucleus CC {ECO:0000269|PubMed:26742426}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=PTP2C; CC IsoId=Q06124-2; Sequence=Displayed; CC Name=2; Synonyms=PTP2Ci; CC IsoId=Q06124-1; Sequence=VSP_060437; CC Name=3; CC IsoId=Q06124-3; Sequence=VSP_060438, VSP_060439; CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in heart, CC brain, and skeletal muscle. {ECO:0000269|PubMed:1280823, CC ECO:0000269|PubMed:7681589, ECO:0000269|PubMed:8216283}. CC -!- DOMAIN: The SH2 domains repress phosphatase activity. Binding of these CC domains to phosphotyrosine-containing proteins relieves this auto- CC inhibition, possibly by inducing a conformational change in the enzyme. CC -!- PTM: Phosphorylated on Tyr-542 and Tyr-580 upon receptor protein CC tyrosine kinase activation; which creates a binding site for GRB2 and CC other SH2-containing proteins. Phosphorylated upon activation of the CC receptor-type kinase FLT3. Phosphorylated upon activation of the CC receptor-type kinase PDGFRA (By similarity). Phosphorylated by CC activated PDGFRB. {ECO:0000250, ECO:0000269|PubMed:20494825, CC ECO:0000269|PubMed:34310951, ECO:0000269|PubMed:7681217, CC ECO:0000269|PubMed:7691811, ECO:0000269|PubMed:8041791}. CC -!- DISEASE: LEOPARD syndrome 1 (LPRD1) [MIM:151100]: A disorder CC characterized by lentigines, electrocardiographic conduction CC abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities CC of genitalia, retardation of growth, and sensorineural deafness. CC {ECO:0000269|PubMed:12058348, ECO:0000269|PubMed:14961557, CC ECO:0000269|PubMed:15121796, ECO:0000269|PubMed:15389709, CC ECO:0000269|PubMed:15520399, ECO:0000269|PubMed:15690106, CC ECO:0000269|PubMed:16679933, ECO:0000269|PubMed:16733669, CC ECO:0000269|PubMed:24891296, ECO:0000269|PubMed:26742426}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Noonan syndrome 1 (NS1) [MIM:163950]: A form of Noonan CC syndrome, a disease characterized by short stature, facial dysmorphic CC features such as hypertelorism, a downward eyeslant and low-set CC posteriorly rotated ears, and a high incidence of congenital heart CC defects and hypertrophic cardiomyopathy. Other features can include a CC short neck with webbing or redundancy of skin, deafness, motor delay, CC variable intellectual deficits, multiple skeletal defects, CC cryptorchidism, and bleeding diathesis. Individuals with Noonan CC syndrome are at risk of juvenile myelomonocytic leukemia, a CC myeloproliferative disorder characterized by excessive production of CC myelomonocytic cells. Some patients with NS1 develop multiple giant CC cell lesions of the jaw or other bony or soft tissues, which are CC classified as pigmented villonodular synovitis (PVNS) when occurring in CC the jaw or joints. {ECO:0000269|PubMed:11704759, CC ECO:0000269|PubMed:11992261, ECO:0000269|PubMed:12161469, CC ECO:0000269|PubMed:12325025, ECO:0000269|PubMed:12529711, CC ECO:0000269|PubMed:12634870, ECO:0000269|PubMed:12717436, CC ECO:0000269|PubMed:12739139, ECO:0000269|PubMed:12960218, CC ECO:0000269|PubMed:15384080, ECO:0000269|PubMed:15889278, CC ECO:0000269|PubMed:15948193, ECO:0000269|PubMed:19020799, CC ECO:0000269|PubMed:24891296, ECO:0000269|PubMed:28074573}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. Mutations in PTPN11 account for more than 50% of the cases. CC -!- DISEASE: Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: An CC aggressive pediatric myelodysplastic syndrome/myeloproliferative CC disorder characterized by malignant transformation in the hematopoietic CC stem cell compartment with proliferation of differentiated progeny. CC Patients have splenomegaly, enlarged lymph nodes, rashes, and CC hemorrhages. {ECO:0000269|PubMed:12717436, CC ECO:0000269|PubMed:26742426}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Metachondromatosis (MC) [MIM:156250]: A skeletal disorder with CC radiologic features of both multiple exostoses and Ollier disease, CC characterized by the presence of exostoses, commonly of the bones of CC the hands and feet, and enchondromas of the metaphyses of long bones CC and iliac crest. {ECO:0000269|PubMed:20577567}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non- CC receptor class 2 subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41910/PTPN11"; 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; D13540; BAA02740.2; -; mRNA. DR EMBL; L03535; AAA36611.1; -; mRNA. DR EMBL; L07527; AAA17022.1; -; mRNA. DR EMBL; L08807; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; X70766; CAA50045.1; -; mRNA. DR EMBL; BT007106; AAP35770.1; -; mRNA. DR EMBL; AK289854; BAF82543.1; -; mRNA. DR EMBL; CH471054; EAW98012.1; -; Genomic_DNA. DR EMBL; BC008692; AAH08692.1; -; mRNA. DR CCDS; CCDS58280.1; -. [Q06124-3] DR CCDS; CCDS81741.1; -. [Q06124-1] DR CCDS; CCDS9163.1; -. [Q06124-2] DR PIR; JN0805; JN0805. DR RefSeq; NP_001317366.1; NM_001330437.1. [Q06124-1] DR RefSeq; NP_002825.3; NM_002834.4. [Q06124-2] DR RefSeq; NP_542168.1; NM_080601.2. [Q06124-3] DR PDB; 2SHP; X-ray; 2.00 A; A/B=1-525. DR PDB; 3B7O; X-ray; 1.60 A; A=237-529. DR PDB; 3MOW; X-ray; 2.30 A; A=262-528. DR PDB; 3O5X; X-ray; 2.00 A; A=262-528. DR PDB; 3TKZ; X-ray; 1.80 A; A=1-106. DR PDB; 3TL0; X-ray; 2.05 A; A=1-106. DR PDB; 3ZM0; X-ray; 1.50 A; A=248-527. DR PDB; 3ZM1; X-ray; 1.40 A; A=248-527. DR PDB; 3ZM2; X-ray; 1.50 A; A=248-527. DR PDB; 3ZM3; X-ray; 1.50 A; A=248-527. DR PDB; 4DGP; X-ray; 2.30 A; A=1-528. DR PDB; 4DGX; X-ray; 2.30 A; A=1-528. DR PDB; 4GWF; X-ray; 2.10 A; A/B=1-539. DR PDB; 4H1O; X-ray; 2.20 A; A=1-539. DR PDB; 4H34; X-ray; 2.70 A; A=1-539. DR PDB; 4JE4; X-ray; 2.31 A; A=1-103. DR PDB; 4JEG; X-ray; 2.30 A; A=97-217. DR PDB; 4JMG; X-ray; 1.40 A; B=575-587. DR PDB; 4NWF; X-ray; 2.10 A; A/B=1-539. DR PDB; 4NWG; X-ray; 2.45 A; A/B=1-539. DR PDB; 4OHD; X-ray; 2.70 A; A=1-528. DR PDB; 4OHE; X-ray; 2.51 A; A=1-528. DR PDB; 4OHH; X-ray; 2.70 A; A=1-528. DR PDB; 4OHI; X-ray; 2.20 A; A=1-528. DR PDB; 4OHL; X-ray; 2.40 A; A/B=1-528. DR PDB; 4PVG; X-ray; 2.40 A; A=240-528. DR PDB; 4QSY; X-ray; 2.10 A; A=1-106. DR PDB; 4RDD; X-ray; 1.60 A; A=262-528. DR PDB; 5BK8; X-ray; 2.25 A; A=1-528. DR PDB; 5DF6; X-ray; 1.78 A; A=1-222. DR PDB; 5EHP; X-ray; 1.85 A; A/B=1-525. DR PDB; 5EHR; X-ray; 1.70 A; A/B=1-525. DR PDB; 5I6V; X-ray; 1.87 A; A/B=1-525. DR PDB; 5IBM; X-ray; 2.18 A; A/B=1-525. DR PDB; 5IBS; X-ray; 2.32 A; A/B=1-525. DR PDB; 5X7B; X-ray; 2.45 A; A=1-220. DR PDB; 5X94; X-ray; 2.60 A; A/B=1-220. DR PDB; 5XZR; X-ray; 2.80 A; A=1-534. DR PDB; 6ATD; X-ray; 2.50 A; A/B=1-526. DR PDB; 6BMR; X-ray; 2.21 A; A/B=1-525. DR PDB; 6BMU; X-ray; 2.12 A; A/B=1-525. DR PDB; 6BMV; X-ray; 2.05 A; A/B=1-525. DR PDB; 6BMW; X-ray; 2.10 A; A/B=1-525. DR PDB; 6BMX; X-ray; 2.42 A; A/B=1-525. DR PDB; 6BMY; X-ray; 2.09 A; A/B=1-525. DR PDB; 6BN5; X-ray; 2.22 A; A/B=1-525. DR PDB; 6CMP; X-ray; 1.80 A; A/B=1-529. DR PDB; 6CMQ; X-ray; 2.90 A; A/B/C/D=106-529. DR PDB; 6CMR; X-ray; 2.21 A; A=1-529. DR PDB; 6CMS; X-ray; 2.68 A; A=1-529. DR PDB; 6CRF; X-ray; 2.62 A; A/B=1-525. DR PDB; 6CRG; X-ray; 2.75 A; A/B=1-525. DR PDB; 6MD7; X-ray; 1.96 A; A/B=1-525. DR PDB; 6MD9; X-ray; 2.12 A; A/B=1-525. DR PDB; 6MDA; X-ray; 2.21 A; A/B=1-525. DR PDB; 6MDB; X-ray; 2.34 A; A/B=1-525. DR PDB; 6MDC; X-ray; 2.14 A; A/B=1-525. DR PDB; 6MDD; X-ray; 2.05 A; A/B=1-525. DR PDB; 6R5G; NMR; -; A=105-220. DR PDB; 6WU8; X-ray; 2.40 A; A/B=1-530. DR PDB; 7EMN; X-ray; 3.00 A; A/B=1-534. DR PDB; 7JVM; X-ray; 2.17 A; A/B=1-525. DR PDB; 7JVN; X-ray; 1.92 A; A/B=1-525. DR PDB; 7R75; X-ray; 2.83 A; A=1-530. DR PDB; 7R7D; X-ray; 2.60 A; A/B=1-530. DR PDB; 7R7I; X-ray; 2.85 A; A/B=1-530. DR PDB; 7R7L; X-ray; 3.00 A; A/B=1-530. DR PDB; 7RCT; X-ray; 1.80 A; A/B=1-525. DR PDB; 7TVJ; X-ray; 2.39 A; A/D=224-525. DR PDB; 7VXG; X-ray; 2.10 A; A/B/C/D=1-525. DR PDB; 7XHQ; X-ray; 2.20 A; A/B=1-525. DR PDB; 8B5Y; X-ray; 1.83 A; A/B=1-525. DR PDB; 8CBH; X-ray; 2.24 A; A/B=1-525. DR PDB; 8GWW; X-ray; 3.00 A; A/B=1-525. DR PDB; 8T6D; X-ray; 2.40 A; A/B=1-525. DR PDB; 8T6G; X-ray; 1.84 A; A/B=1-525. DR PDB; 8T7Q; X-ray; 2.10 A; A/B=1-525. DR PDB; 8T8Q; X-ray; 2.27 A; A/B=1-525. DR PDB; 8WFY; X-ray; 2.60 A; A/B=1-525. DR PDBsum; 2SHP; -. DR PDBsum; 3B7O; -. DR PDBsum; 3MOW; -. DR PDBsum; 3O5X; -. DR PDBsum; 3TKZ; -. DR PDBsum; 3TL0; -. DR PDBsum; 3ZM0; -. DR PDBsum; 3ZM1; -. DR PDBsum; 3ZM2; -. DR PDBsum; 3ZM3; -. DR PDBsum; 4DGP; -. DR PDBsum; 4DGX; -. DR PDBsum; 4GWF; -. DR PDBsum; 4H1O; -. DR PDBsum; 4H34; -. DR PDBsum; 4JE4; -. DR PDBsum; 4JEG; -. DR PDBsum; 4JMG; -. DR PDBsum; 4NWF; -. DR PDBsum; 4NWG; -. DR PDBsum; 4OHD; -. DR PDBsum; 4OHE; -. DR PDBsum; 4OHH; -. DR PDBsum; 4OHI; -. DR PDBsum; 4OHL; -. DR PDBsum; 4PVG; -. DR PDBsum; 4QSY; -. DR PDBsum; 4RDD; -. DR PDBsum; 5BK8; -. DR PDBsum; 5DF6; -. DR PDBsum; 5EHP; -. DR PDBsum; 5EHR; -. DR PDBsum; 5I6V; -. DR PDBsum; 5IBM; -. DR PDBsum; 5IBS; -. DR PDBsum; 5X7B; -. DR PDBsum; 5X94; -. DR PDBsum; 5XZR; -. DR PDBsum; 6ATD; -. DR PDBsum; 6BMR; -. DR PDBsum; 6BMU; -. DR PDBsum; 6BMV; -. DR PDBsum; 6BMW; -. DR PDBsum; 6BMX; -. DR PDBsum; 6BMY; -. DR PDBsum; 6BN5; -. DR PDBsum; 6CMP; -. DR PDBsum; 6CMQ; -. DR PDBsum; 6CMR; -. DR PDBsum; 6CMS; -. DR PDBsum; 6CRF; -. DR PDBsum; 6CRG; -. DR PDBsum; 6MD7; -. DR PDBsum; 6MD9; -. DR PDBsum; 6MDA; -. DR PDBsum; 6MDB; -. DR PDBsum; 6MDC; -. DR PDBsum; 6MDD; -. DR PDBsum; 6R5G; -. DR PDBsum; 6WU8; -. DR PDBsum; 7EMN; -. DR PDBsum; 7JVM; -. DR PDBsum; 7JVN; -. DR PDBsum; 7R75; -. DR PDBsum; 7R7D; -. DR PDBsum; 7R7I; -. DR PDBsum; 7R7L; -. DR PDBsum; 7RCT; -. DR PDBsum; 7TVJ; -. DR PDBsum; 7VXG; -. DR PDBsum; 7XHQ; -. DR PDBsum; 8B5Y; -. DR PDBsum; 8CBH; -. DR PDBsum; 8GWW; -. DR PDBsum; 8T6D; -. DR PDBsum; 8T6G; -. DR PDBsum; 8T7Q; -. DR PDBsum; 8T8Q; -. DR PDBsum; 8WFY; -. DR AlphaFoldDB; Q06124; -. DR SASBDB; Q06124; -. DR SMR; Q06124; -. DR BioGRID; 111745; 326. DR CORUM; Q06124; -. DR DIP; DIP-516N; -. DR ELM; Q06124; -. DR IntAct; Q06124; 219. DR MINT; Q06124; -. DR STRING; 9606.ENSP00000489597; -. DR BindingDB; Q06124; -. DR ChEMBL; CHEMBL3864; -. DR DrugBank; DB02779; Dodecyltrimethylammonium. DR DrugCentral; Q06124; -. DR GuidetoPHARMACOLOGY; 3203; -. DR MoonDB; Q06124; Predicted. DR DEPOD; PTPN11; -. DR GlyGen; Q06124; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q06124; -. DR MetOSite; Q06124; -. DR PhosphoSitePlus; Q06124; -. DR BioMuta; PTPN11; -. DR DMDM; 84028248; -. DR CPTAC; CPTAC-1556; -. DR EPD; Q06124; -. DR jPOST; Q06124; -. DR MassIVE; Q06124; -. DR MaxQB; Q06124; -. DR PaxDb; 9606-ENSP00000340944; -. DR PeptideAtlas; Q06124; -. DR ProteomicsDB; 58414; -. [Q06124-1] DR ProteomicsDB; 58415; -. [Q06124-2] DR ProteomicsDB; 58416; -. [Q06124-3] DR Pumba; Q06124; -. DR TopDownProteomics; Q06124-2; -. [Q06124-2] DR Antibodypedia; 3948; 1662 antibodies from 48 providers. DR CPTC; Q06124; 2 antibodies. DR DNASU; 5781; -. DR Ensembl; ENST00000351677.7; ENSP00000340944.3; ENSG00000179295.19. [Q06124-2] DR Ensembl; ENST00000392597.5; ENSP00000376376.1; ENSG00000179295.19. [Q06124-3] DR Ensembl; ENST00000635625.1; ENSP00000489597.1; ENSG00000179295.19. [Q06124-1] DR GeneID; 5781; -. DR KEGG; hsa:5781; -. DR MANE-Select; ENST00000351677.7; ENSP00000340944.3; NM_002834.5; NP_002825.3. DR UCSC; uc001ttw.2; human. [Q06124-2] DR AGR; HGNC:9644; -. DR CTD; 5781; -. DR DisGeNET; 5781; -. DR GeneCards; PTPN11; -. DR GeneReviews; PTPN11; -. DR HGNC; HGNC:9644; PTPN11. DR HPA; ENSG00000179295; Low tissue specificity. DR MalaCards; PTPN11; -. DR MIM; 151100; phenotype. DR MIM; 156250; phenotype. DR MIM; 163950; phenotype. DR MIM; 176876; gene. DR MIM; 607785; phenotype. DR neXtProt; NX_Q06124; -. DR OpenTargets; ENSG00000179295; -. DR Orphanet; 86834; Juvenile myelomonocytic leukemia. DR Orphanet; 2499; Metachondromatosis. DR Orphanet; 648; Noonan syndrome. DR Orphanet; 500; Noonan syndrome with multiple lentigines. DR PharmGKB; PA33986; -. DR VEuPathDB; HostDB:ENSG00000179295; -. DR eggNOG; KOG0790; Eukaryota. DR GeneTree; ENSGT00940000153876; -. DR HOGENOM; CLU_001645_9_10_1; -. DR InParanoid; Q06124; -. DR OMA; CEIDIHR; -. DR OrthoDB; 2911650at2759; -. DR PhylomeDB; Q06124; -. DR TreeFam; TF351632; -. DR BRENDA; 3.1.3.48; 2681. DR PathwayCommons; Q06124; -. DR Reactome; R-HSA-1059683; Interleukin-6 signaling. DR Reactome; R-HSA-109704; PI3K Cascade. DR Reactome; R-HSA-110056; MAPK3 (ERK1) activation. DR Reactome; R-HSA-112411; MAPK1 (ERK2) activation. DR Reactome; R-HSA-114604; GPVI-mediated activation cascade. DR Reactome; R-HSA-1170546; Prolactin receptor signaling. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-1295596; Spry regulation of FGF signaling. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-180292; GAB1 signalosome. DR Reactome; R-HSA-186763; Downstream signal transduction. DR Reactome; R-HSA-210990; PECAM1 interactions. DR Reactome; R-HSA-210993; Tie2 Signaling. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-2586552; Signaling by Leptin. DR Reactome; R-HSA-388841; Costimulation by the CD28 family. DR Reactome; R-HSA-389513; CTLA4 inhibitory signaling. DR Reactome; R-HSA-389948; PD-1 signaling. DR Reactome; R-HSA-391160; Signal regulatory protein family interactions. DR Reactome; R-HSA-418886; Netrin mediated repulsion signals. DR Reactome; R-HSA-432142; Platelet sensitization by LDL. DR Reactome; R-HSA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling. DR Reactome; R-HSA-5654689; PI-3K cascade:FGFR1. DR Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling. DR Reactome; R-HSA-5654695; PI-3K cascade:FGFR2. DR Reactome; R-HSA-5654700; FRS-mediated FGFR2 signaling. DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling. DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3. DR Reactome; R-HSA-5654712; FRS-mediated FGFR4 signaling. DR Reactome; R-HSA-5654720; PI-3K cascade:FGFR4. DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling. DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling. DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling. DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-HSA-877312; Regulation of IFNG signaling. DR Reactome; R-HSA-8853659; RET signaling. DR Reactome; R-HSA-8854691; Interleukin-20 family signaling. DR Reactome; R-HSA-8865999; MET activates PTPN11. DR Reactome; R-HSA-8934593; Regulation of RUNX1 Expression and Activity. DR Reactome; R-HSA-9008059; Interleukin-37 signaling. DR Reactome; R-HSA-9028731; Activated NTRK2 signals through FRS2 and FRS3. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR Reactome; R-HSA-912694; Regulation of IFNA/IFNB signaling. DR Reactome; R-HSA-936964; Activation of IRF3, IRF7 mediated by TBK1, IKBKE. DR Reactome; R-HSA-9607240; FLT3 Signaling. DR Reactome; R-HSA-9645135; STAT5 Activation. DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF). DR Reactome; R-HSA-9680350; Signaling by CSF1 (M-CSF) in myeloid cells. DR Reactome; R-HSA-9702518; STAT5 activation downstream of FLT3 ITD mutants. DR Reactome; R-HSA-9703648; Signaling by FLT3 ITD and TKD mutants. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR SABIO-RK; Q06124; -. DR SignaLink; Q06124; -. DR SIGNOR; Q06124; -. DR BioGRID-ORCS; 5781; 554 hits in 1181 CRISPR screens. DR ChiTaRS; PTPN11; human. DR EvolutionaryTrace; Q06124; -. DR GeneWiki; PTPN11; -. DR GenomeRNAi; 5781; -. DR Pharos; Q06124; Tchem. DR PRO; PR:Q06124; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q06124; Protein. DR Bgee; ENSG00000179295; Expressed in medial globus pallidus and 210 other cell types or tissues. DR ExpressionAtlas; Q06124; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB. DR GO; GO:0045296; F:cadherin binding; IPI:ARUK-UCL. DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:ARUK-UCL. DR GO; GO:0005158; F:insulin receptor binding; IPI:BHF-UCL. DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProt. DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; IDA:FlyBase. DR GO; GO:0051428; F:peptide hormone receptor binding; IEA:Ensembl. DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:UniProtKB. DR GO; GO:0001784; F:phosphotyrosine residue binding; IMP:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISS:ARUK-UCL. DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:ARUK-UCL. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB. DR GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central. DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IPI:BHF-UCL. DR GO; GO:0036302; P:atrioventricular canal development; IMP:BHF-UCL. DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl. DR GO; GO:0060020; P:Bergmann glial cell differentiation; IEA:Ensembl. DR GO; GO:0007420; P:brain development; IMP:BHF-UCL. DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IMP:UniProtKB. DR GO; GO:0021697; P:cerebellar cortex formation; IEA:Ensembl. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome. DR GO; GO:0000077; P:DNA damage checkpoint signaling; IEA:Ensembl. DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0038127; P:ERBB signaling pathway; IDA:UniProtKB. DR GO; GO:0060325; P:face morphogenesis; IMP:BHF-UCL. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IMP:FlyBase. DR GO; GO:0048806; P:genitalia development; IMP:BHF-UCL. DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl. DR GO; GO:0007507; P:heart development; IMP:BHF-UCL. DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl. DR GO; GO:0042445; P:hormone metabolic process; IEA:Ensembl. DR GO; GO:0009755; P:hormone-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0048839; P:inner ear development; IMP:BHF-UCL. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0061582; P:intestinal epithelial cell migration; IEA:Ensembl. DR GO; GO:0035855; P:megakaryocyte development; IEA:Ensembl. DR GO; GO:0032528; P:microvillus organization; IEA:Ensembl. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:0048609; P:multicellular organismal reproductive process; IEA:Ensembl. DR GO; GO:0033629; P:negative regulation of cell adhesion mediated by integrin; IEA:Ensembl. DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; ISS:UniProtKB. DR GO; GO:0051463; P:negative regulation of cortisol secretion; IEA:Ensembl. DR GO; GO:0060125; P:negative regulation of growth hormone secretion; IEA:Ensembl. DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:Ensembl. DR GO; GO:0032480; P:negative regulation of type I interferon production; IDA:UniProt. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IEA:Ensembl. DR GO; GO:0035265; P:organ growth; IEA:Ensembl. DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IDA:UniProtKB. DR GO; GO:0030220; P:platelet formation; IEA:Ensembl. DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:0046326; P:positive regulation of glucose import; IDA:BHF-UCL. DR GO; GO:0046887; P:positive regulation of hormone secretion; IEA:Ensembl. DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:ARUK-UCL. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:ARUK-UCL. DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0045778; P:positive regulation of ossification; ISS:UniProtKB. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:ARUK-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:ARUK-UCL. DR GO; GO:0006470; P:protein dephosphorylation; IMP:UniProtKB. DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; IMP:UniProtKB. DR GO; GO:0046825; P:regulation of protein export from nucleus; IEA:Ensembl. DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IDA:BHF-UCL. DR GO; GO:0060338; P:regulation of type I interferon-mediated signaling pathway; TAS:Reactome. DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome. DR GO; GO:0006641; P:triglyceride metabolic process; IEA:Ensembl. DR CDD; cd14605; PTPc-N11; 1. DR CDD; cd09931; SH2_C-SH2_SHP_like; 1. DR CDD; cd10340; SH2_N-SH2_SHP_like; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR Gene3D; 3.30.505.10; SH2 domain; 2. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR000242; PTP_cat. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR016130; Tyr_Pase_AS. DR InterPro; IPR003595; Tyr_Pase_cat. DR InterPro; IPR000387; Tyr_Pase_dom. DR InterPro; IPR012152; Tyr_Pase_non-rcpt_typ-6/11. DR PANTHER; PTHR46559; TYROSINE-PROTEIN PHOSPHATASE NON-RECEPTOR TYPE 11; 1. DR PANTHER; PTHR46559:SF1; TYROSINE-PROTEIN PHOSPHATASE NON-RECEPTOR TYPE 11; 1. DR Pfam; PF00017; SH2; 2. DR Pfam; PF00102; Y_phosphatase; 1. DR PIRSF; PIRSF000929; Tyr-Ptase_nr_6; 1. DR PRINTS; PR00700; PRTYPHPHTASE. DR PRINTS; PR00401; SH2DOMAIN. DR SMART; SM00194; PTPc; 1. DR SMART; SM00404; PTPc_motif; 1. DR SMART; SM00252; SH2; 2. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1. DR SUPFAM; SSF55550; SH2 domain; 2. DR PROSITE; PS50001; SH2; 2. DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1. DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1. DR PROSITE; PS50055; TYR_PHOSPHATASE_PTP; 1. DR Genevisible; Q06124; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Deafness; KW Disease variant; Hydrolase; Nucleus; Phosphoprotein; Protein phosphatase; KW Reference proteome; Repeat; SH2 domain. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..593 FT /note="Tyrosine-protein phosphatase non-receptor type 11" FT /id="PRO_0000094767" FT DOMAIN 6..102 FT /note="SH2 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 112..216 FT /note="SH2 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 247..517 FT /note="Tyrosine-protein phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT REGION 548..571 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 459 FT /note="Phosphocysteine intermediate" FT BINDING 425 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 459..465 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 506 FT /ligand="substrate" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylthreonine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 62 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 66 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P35235" FT MOD_RES 542 FT /note="Phosphotyrosine; by PDGFR" FT /evidence="ECO:0000269|PubMed:34310951" FT MOD_RES 580 FT /note="Phosphotyrosine; by PDGFR" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 407 FT /note="G -> GQALL (in isoform 2)" FT /id="VSP_060437" FT VAR_SEQ 460 FT /note="S -> R (in isoform 3)" FT /id="VSP_060438" FT VAR_SEQ 461..593 FT /note="Missing (in isoform 3)" FT /id="VSP_060439" FT VARIANT 2 FT /note="T -> I (in NS1; dbSNP:rs267606990)" FT /evidence="ECO:0000269|PubMed:12960218" FT /id="VAR_027183" FT VARIANT 42 FT /note="T -> A (in NS1; dbSNP:rs397507501)" FT /evidence="ECO:0000269|PubMed:11992261, FT ECO:0000269|PubMed:12960218" FT /id="VAR_015601" FT VARIANT 58 FT /note="N -> K (in NS1; dbSNP:rs397507506)" FT /evidence="ECO:0000269|PubMed:12634870" FT /id="VAR_027184" FT VARIANT 59 FT /note="T -> A (in NS1; dbSNP:rs886043790)" FT /evidence="ECO:0000269|PubMed:19020799" FT /id="VAR_066060" FT VARIANT 60 FT /note="G -> A (in NS1; dbSNP:rs397507509)" FT /evidence="ECO:0000269|PubMed:11992261" FT /id="VAR_015602" FT VARIANT 60 FT /note="G -> V (in myelodysplastic syndrome; FT dbSNP:rs397507509)" FT /evidence="ECO:0000269|PubMed:12717436" FT /id="VAR_015990" FT VARIANT 61 FT /note="D -> G (in NS1; dbSNP:rs121918461)" FT /evidence="ECO:0000269|PubMed:11704759, FT ECO:0000269|PubMed:11992261, ECO:0000269|PubMed:12161469, FT ECO:0000269|PubMed:12634870" FT /id="VAR_015603" FT VARIANT 61 FT /note="D -> N (in NS1; dbSNP:rs397507510)" FT /evidence="ECO:0000269|PubMed:11992261, FT ECO:0000269|PubMed:12634870" FT /id="VAR_015604" FT VARIANT 61 FT /note="D -> V (in JMML; also in myelodysplastic syndrome; FT dbSNP:rs121918461)" FT /evidence="ECO:0000269|PubMed:12717436" FT /id="VAR_015991" FT VARIANT 61 FT /note="D -> Y (in JMML; dbSNP:rs397507510)" FT /evidence="ECO:0000269|PubMed:12717436" FT /id="VAR_015992" FT VARIANT 62 FT /note="Y -> D (in NS1; also in Noonan patients manifesting FT juvenile myelomonocytic leukemia; dbSNP:rs121918460)" FT /evidence="ECO:0000269|PubMed:11992261, FT ECO:0000269|PubMed:12325025, ECO:0000269|PubMed:12717436, FT ECO:0000269|PubMed:12960218" FT /id="VAR_015605" FT VARIANT 63 FT /note="Y -> C (in NS1; dbSNP:rs121918459)" FT /evidence="ECO:0000269|PubMed:11704759, FT ECO:0000269|PubMed:11992261, ECO:0000269|PubMed:12161469, FT ECO:0000269|PubMed:12325025, ECO:0000269|PubMed:12634870, FT ECO:0000269|PubMed:12960218" FT /id="VAR_015606" FT VARIANT 69 FT /note="E -> K (in JMML; also in myelodysplastic syndrome; FT dbSNP:rs397507511)" FT /evidence="ECO:0000269|PubMed:12717436" FT /id="VAR_015993" FT VARIANT 69 FT /note="E -> Q (in NS1; dbSNP:rs397507511)" FT /evidence="ECO:0000269|PubMed:12634870" FT /id="VAR_027185" FT VARIANT 71 FT /note="F -> K (in acute myeloid leukemia; requires 2 FT nucleotide substitutions)" FT /evidence="ECO:0000269|PubMed:12717436" FT /id="VAR_015994" FT VARIANT 71 FT /note="F -> L (in NS1; also found in myelodysplastic FT syndrome; dbSNP:rs397507512)" FT /evidence="ECO:0000269|PubMed:12634870, FT ECO:0000269|PubMed:12717436" FT /id="VAR_015995" FT VARIANT 72 FT /note="A -> G (in NS1; dbSNP:rs121918454)" FT /evidence="ECO:0000269|PubMed:11704759, FT ECO:0000269|PubMed:11992261, ECO:0000269|PubMed:12960218" FT /id="VAR_015607" FT VARIANT 72 FT /note="A -> S (in NS1; dbSNP:rs121918453)" FT /evidence="ECO:0000269|PubMed:11704759, FT ECO:0000269|PubMed:12161469, ECO:0000269|PubMed:12634870" FT /id="VAR_015608" FT VARIANT 72 FT /note="A -> T (in JMML; dbSNP:rs121918453)" FT /evidence="ECO:0000269|PubMed:12717436" FT /id="VAR_015996" FT VARIANT 72 FT /note="A -> V (in JMML; dbSNP:rs121918454)" FT /evidence="ECO:0000269|PubMed:12717436" FT /id="VAR_015997" FT VARIANT 73 FT /note="T -> I (in NS1; also in Noonan patients manifesting FT juvenile myelomonocytic leukemia; dbSNP:rs121918462)" FT /evidence="ECO:0000269|PubMed:11992261, FT ECO:0000269|PubMed:12161469, ECO:0000269|PubMed:12634870, FT ECO:0000269|PubMed:12717436" FT /id="VAR_015609" FT VARIANT 76 FT /note="E -> A (in JMML; also in myelodysplastic syndrome; FT dbSNP:rs121918465)" FT /evidence="ECO:0000269|PubMed:12717436" FT /id="VAR_015998" FT VARIANT 76 FT /note="E -> D (in NS1; dbSNP:rs397507514)" FT /evidence="ECO:0000269|PubMed:11704759, FT ECO:0000269|PubMed:11992261, ECO:0000269|PubMed:12634870" FT /id="VAR_015610" FT VARIANT 76 FT /note="E -> G (in JMML; dbSNP:rs121918465)" FT /evidence="ECO:0000269|PubMed:12717436" FT /id="VAR_015999" FT VARIANT 76 FT /note="E -> K (in JMML; increases protein tyrosine FT phosphatase activity against CDC73; dbSNP:rs121918464)" FT /evidence="ECO:0000269|PubMed:12717436, FT ECO:0000269|PubMed:26742426" FT /id="VAR_016000" FT VARIANT 76 FT /note="E -> V (in JMML; dbSNP:rs121918465)" FT /evidence="ECO:0000269|PubMed:12717436" FT /id="VAR_016001" FT VARIANT 79 FT /note="Q -> P (in NS1)" FT /evidence="ECO:0000269|PubMed:12960218" FT /id="VAR_027186" FT VARIANT 79 FT /note="Q -> R (in NS1; dbSNP:rs121918466)" FT /evidence="ECO:0000269|PubMed:11704759, FT ECO:0000269|PubMed:11992261, ECO:0000269|PubMed:12529711, FT ECO:0000269|PubMed:12634870" FT /id="VAR_015611" FT VARIANT 106 FT /note="D -> A (in NS1; dbSNP:rs397507517)" FT /evidence="ECO:0000269|PubMed:11992261, FT ECO:0000269|PubMed:12960218" FT /id="VAR_015612" FT VARIANT 139 FT /note="E -> D (in NS1; dbSNP:rs397507520)" FT /evidence="ECO:0000269|PubMed:11992261, FT ECO:0000269|PubMed:12634870" FT /id="VAR_015613" FT VARIANT 256 FT /note="Q -> R (in NS1; dbSNP:rs397507523)" FT /evidence="ECO:0000269|PubMed:12634870" FT /id="VAR_027187" FT VARIANT 261 FT /note="L -> F (in NS1; increases MAPK signaling; increases FT protein tyrosine phosphatase activity; changed substrate FT selectivity for GAB1; dbSNP:rs397507525)" FT /evidence="ECO:0000269|PubMed:28074573" FT /id="VAR_078101" FT VARIANT 261 FT /note="L -> H (in NS1; increases MAPK signaling; increased FT protein tyrosine phosphatase activity; dbSNP:rs765642157)" FT /evidence="ECO:0000269|PubMed:28074573" FT /id="VAR_078102" FT VARIANT 262 FT /note="L -> F (in NS1; increases MAPK signaling; increased FT protein tyrosine phosphatase activity)" FT /evidence="ECO:0000269|PubMed:28074573" FT /id="VAR_078103" FT VARIANT 262 FT /note="L -> R (in NS1; increases MAPK signaling; increased FT protein tyrosine phosphatase activity; dbSNP:rs397507526)" FT /evidence="ECO:0000269|PubMed:28074573" FT /id="VAR_078104" FT VARIANT 265 FT /note="R -> Q (in NS1; increases MAPK signaling; increased FT protein tyrosine phosphatase activity; dbSNP:rs376607329)" FT /evidence="ECO:0000269|PubMed:28074573" FT /id="VAR_078105" FT VARIANT 279 FT /note="Y -> C (in NS1 and LPRD1; does not affect FT subcellular location; decreases protein tyrosine FT phosphatase activity against CDC73; dbSNP:rs121918456)" FT /evidence="ECO:0000269|PubMed:11992261, FT ECO:0000269|PubMed:12058348, ECO:0000269|PubMed:12960218, FT ECO:0000269|PubMed:15121796, ECO:0000269|PubMed:15520399, FT ECO:0000269|PubMed:16679933, ECO:0000269|PubMed:26742426" FT /id="VAR_015614" FT VARIANT 279 FT /note="Y -> S (in LPRD1; dbSNP:rs121918456)" FT /evidence="ECO:0000269|PubMed:15121796, FT ECO:0000269|PubMed:15520399" FT /id="VAR_027188" FT VARIANT 282 FT /note="I -> V (in NS1; dbSNP:rs397507529)" FT /evidence="ECO:0000269|PubMed:11704759, FT ECO:0000269|PubMed:11992261, ECO:0000269|PubMed:12634870" FT /id="VAR_015615" FT VARIANT 285 FT /note="F -> L (in NS1; dbSNP:rs397507531)" FT /evidence="ECO:0000269|PubMed:11992261" FT /id="VAR_015617" FT VARIANT 285 FT /note="F -> S (in NS1; dbSNP:rs121918463)" FT /evidence="ECO:0000269|PubMed:11992261, FT ECO:0000269|PubMed:12161469" FT /id="VAR_015616" FT VARIANT 308 FT /note="N -> D (in NS1; common mutation; dbSNP:rs28933386)" FT /evidence="ECO:0000269|PubMed:11704759, FT ECO:0000269|PubMed:11992261, ECO:0000269|PubMed:12161469, FT ECO:0000269|PubMed:12634870, ECO:0000269|PubMed:12960218" FT /id="VAR_015619" FT VARIANT 308 FT /note="N -> S (in NS1; some patients also manifest giant FT cell lesions of bone and soft tissue; dbSNP:rs121918455)" FT /evidence="ECO:0000269|PubMed:11992261, FT ECO:0000269|PubMed:12960218" FT /id="VAR_015618" FT VARIANT 309 FT /note="I -> V (in NS1; uncertain significance; FT dbSNP:rs201787206)" FT /evidence="ECO:0000269|PubMed:11992261" FT /id="VAR_015620" FT VARIANT 411 FT /note="T -> M (in NS1; dbSNP:rs121918467)" FT /evidence="ECO:0000269|PubMed:15384080" FT /id="VAR_027189" FT VARIANT 461 FT /note="A -> T (in LPRD1; dbSNP:rs121918468)" FT /evidence="ECO:0000269|PubMed:15389709" FT /id="VAR_027190" FT VARIANT 464 FT /note="G -> A (in LPRD1; dbSNP:rs121918469)" FT /evidence="ECO:0000269|PubMed:15121796, FT ECO:0000269|PubMed:15389709" FT /id="VAR_027191" FT VARIANT 468 FT /note="T -> M (in LPRD1; does not affect subcellular FT location; decreases protein tyrosine phosphatase activity FT against CDC73; dbSNP:rs121918457)" FT /evidence="ECO:0000269|PubMed:12058348, FT ECO:0000269|PubMed:12960218, ECO:0000269|PubMed:15121796, FT ECO:0000269|PubMed:15520399, ECO:0000269|PubMed:26742426" FT /id="VAR_015621" FT VARIANT 491 FT /note="P -> S (in NS1; increased phosphatase activity; FT dbSNP:rs397507539)" FT /evidence="ECO:0000269|PubMed:24891296" FT /id="VAR_071706" FT VARIANT 498 FT /note="R -> L (in LPRD1; dbSNP:rs397507542)" FT /evidence="ECO:0000269|PubMed:15121796" FT /id="VAR_027192" FT VARIANT 498 FT /note="R -> W (in LPRD1; reduced phosphatase activity; FT dbSNP:rs397507541)" FT /evidence="ECO:0000269|PubMed:15121796, FT ECO:0000269|PubMed:24891296" FT /id="VAR_027193" FT VARIANT 501 FT /note="R -> K (in NS1; dbSNP:rs397507543)" FT /evidence="ECO:0000269|PubMed:11992261" FT /id="VAR_015622" FT VARIANT 502 FT /note="S -> T (in NS1; dbSNP:rs121918458)" FT /evidence="ECO:0000269|PubMed:12325025, FT ECO:0000269|PubMed:12739139" FT /id="VAR_015623" FT VARIANT 503 FT /note="G -> A (in JMML; dbSNP:rs397507546)" FT /evidence="ECO:0000269|PubMed:12717436" FT /id="VAR_016002" FT VARIANT 503 FT /note="G -> R (in NS1 and JMML; JMML patient also shows FT growth retardation and pulmonic stenosis; FT dbSNP:rs397507545)" FT /evidence="ECO:0000269|PubMed:12717436, FT ECO:0000269|PubMed:12960218" FT /id="VAR_016003" FT VARIANT 504 FT /note="M -> V (in NS1; dbSNP:rs397507547)" FT /evidence="ECO:0000269|PubMed:11704759, FT ECO:0000269|PubMed:11992261, ECO:0000269|PubMed:12960218" FT /id="VAR_015624" FT VARIANT 506 FT /note="Q -> P (in LPRD1; does not affect subcellular FT location; decreases protein tyrosine phosphatase activity FT against CDC73; dbSNP:rs397509345)" FT /evidence="ECO:0000269|PubMed:14961557, FT ECO:0000269|PubMed:15121796, ECO:0000269|PubMed:15690106, FT ECO:0000269|PubMed:26742426" FT /id="VAR_027194" FT VARIANT 506 FT /note="Q -> R (in NS1)" FT /evidence="ECO:0000269|PubMed:15948193" FT /id="VAR_027195" FT VARIANT 510 FT /note="Q -> E (in NS1 and LPRD1; does not affect FT subcellular location; decreases protein tyrosine FT phosphatase activity against CDC73; dbSNP:rs397507549)" FT /evidence="ECO:0000269|PubMed:15889278, FT ECO:0000269|PubMed:16733669, ECO:0000269|PubMed:26742426" FT /id="VAR_076499" FT VARIANT 510 FT /note="Q -> P (in LPRD1; dbSNP:rs121918470)" FT /evidence="ECO:0000269|PubMed:15520399" FT /id="VAR_027196" FT VARIANT 560 FT /note="L -> F (in NS1; uncertain significance; FT dbSNP:rs397516797)" FT /evidence="ECO:0000269|PubMed:12960218" FT /id="VAR_027197" FT MUTAGEN 459 FT /note="C->S: Abolishes phosphatase activity. Enhances FT interaction with NEDD9." FT /evidence="ECO:0000269|PubMed:19275884, FT ECO:0000269|PubMed:8216283" FT CONFLICT 535 FT /note="S -> R (in Ref. 3; BAA02740)" FT /evidence="ECO:0000305" FT CONFLICT 548 FT /note="S -> P (in Ref. 3; BAA02740)" FT /evidence="ECO:0000305" FT TURN 4..6 FT /evidence="ECO:0007829|PDB:5X7B" FT HELIX 13..23 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 28..33 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 35..37 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 41..47 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 50..57 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 59..61 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 63..65 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 70..73 FT /evidence="ECO:0007829|PDB:5EHR" FT HELIX 74..82 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 83..85 FT /evidence="ECO:0007829|PDB:4OHD" FT STRAND 87..90 FT /evidence="ECO:0007829|PDB:3TKZ" FT STRAND 91..93 FT /evidence="ECO:0007829|PDB:5BK8" FT HELIX 107..109 FT /evidence="ECO:0007829|PDB:4DGX" FT STRAND 113..116 FT /evidence="ECO:0007829|PDB:6CMP" FT HELIX 119..129 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 134..139 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 141..143 FT /evidence="ECO:0007829|PDB:5DF6" FT STRAND 147..153 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 154..156 FT /evidence="ECO:0007829|PDB:5DF6" FT STRAND 157..159 FT /evidence="ECO:0007829|PDB:6CMP" FT STRAND 161..164 FT /evidence="ECO:0007829|PDB:6CMP" FT STRAND 166..175 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 178..184 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 187..189 FT /evidence="ECO:0007829|PDB:5EHR" FT HELIX 190..199 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 202..204 FT /evidence="ECO:0007829|PDB:5DF6" FT STRAND 205..207 FT /evidence="ECO:0007829|PDB:7R7D" FT STRAND 208..210 FT /evidence="ECO:0007829|PDB:4JEG" FT STRAND 218..222 FT /evidence="ECO:0007829|PDB:4OHD" FT HELIX 223..225 FT /evidence="ECO:0007829|PDB:5EHR" FT HELIX 226..234 FT /evidence="ECO:0007829|PDB:5EHR" FT STRAND 235..237 FT /evidence="ECO:0007829|PDB:6CMQ" FT HELIX 251..253 FT /evidence="ECO:0007829|PDB:3ZM1" FT HELIX 256..258 FT /evidence="ECO:0007829|PDB:4PVG" FT HELIX 259..262 FT /evidence="ECO:0007829|PDB:3B7O" FT HELIX 266..269 FT /evidence="ECO:0007829|PDB:3ZM1" FT HELIX 271..276 FT /evidence="ECO:0007829|PDB:3ZM1" FT STRAND 277..279 FT /evidence="ECO:0007829|PDB:6CMP" FT HELIX 286..288 FT /evidence="ECO:0007829|PDB:3ZM1" FT STRAND 289..291 FT /evidence="ECO:0007829|PDB:3ZM1" FT STRAND 299..301 FT /evidence="ECO:0007829|PDB:7RCT" FT STRAND 304..310 FT /evidence="ECO:0007829|PDB:3ZM1" FT TURN 312..315 FT /evidence="ECO:0007829|PDB:6CMP" FT STRAND 319..321 FT /evidence="ECO:0007829|PDB:4RDD" FT HELIX 323..325 FT /evidence="ECO:0007829|PDB:5EHP" FT STRAND 327..331 FT /evidence="ECO:0007829|PDB:3ZM1" FT HELIX 335..337 FT /evidence="ECO:0007829|PDB:3ZM1" FT HELIX 338..347 FT /evidence="ECO:0007829|PDB:3ZM1" FT STRAND 352..355 FT /evidence="ECO:0007829|PDB:3ZM1" FT STRAND 359..361 FT /evidence="ECO:0007829|PDB:3ZM1" FT STRAND 364..366 FT /evidence="ECO:0007829|PDB:3ZM0" FT STRAND 376..380 FT /evidence="ECO:0007829|PDB:3ZM1" FT STRAND 383..392 FT /evidence="ECO:0007829|PDB:3ZM1" FT STRAND 394..405 FT /evidence="ECO:0007829|PDB:3ZM1" FT TURN 406..408 FT /evidence="ECO:0007829|PDB:7R7D" FT HELIX 409..411 FT /evidence="ECO:0007829|PDB:5I6V" FT STRAND 413..420 FT /evidence="ECO:0007829|PDB:3ZM1" FT STRAND 425..427 FT /evidence="ECO:0007829|PDB:3ZM1" FT STRAND 430..432 FT /evidence="ECO:0007829|PDB:3ZM1" FT HELIX 433..447 FT /evidence="ECO:0007829|PDB:3ZM1" FT STRAND 449..451 FT /evidence="ECO:0007829|PDB:7R7I" FT STRAND 455..463 FT /evidence="ECO:0007829|PDB:3ZM1" FT HELIX 464..482 FT /evidence="ECO:0007829|PDB:3ZM1" FT STRAND 484..488 FT /evidence="ECO:0007829|PDB:5EHR" FT HELIX 490..498 FT /evidence="ECO:0007829|PDB:3ZM1" FT HELIX 508..524 FT /evidence="ECO:0007829|PDB:3ZM1" FT STRAND 581..585 FT /evidence="ECO:0007829|PDB:4JMG" SQ SEQUENCE 593 AA; 68011 MW; 9CDBEFFA5E6CCB45 CRC64; MTSRRWFHPN ITGVEAENLL LTRGVDGSFL ARPSKSNPGD FTLSVRRNGA VTHIKIQNTG DYYDLYGGEK FATLAELVQY YMEHHGQLKE KNGDVIELKY PLNCADPTSE RWFHGHLSGK EAEKLLTEKG KHGSFLVRES QSHPGDFVLS VRTGDDKGES NDGKSKVTHV MIRCQELKYD VGGGERFDSL TDLVEHYKKN PMVETLGTVL QLKQPLNTTR INAAEIESRV RELSKLAETT DKVKQGFWEE FETLQQQECK LLYSRKEGQR QENKNKNRYK NILPFDHTRV VLHDGDPNEP VSDYINANII MPEFETKCNN SKPKKSYIAT QGCLQNTVND FWRMVFQENS RVIVMTTKEV ERGKSKCVKY WPDEYALKEY GVMRVRNVKE SAAHDYTLRE LKLSKVGQGN TERTVWQYHF RTWPDHGVPS DPGGVLDFLE EVHHKQESIM DAGPVVVHCS AGIGRTGTFI VIDILIDIIR EKGVDCDIDV PKTIQMVRSQ RSGMVQTEAQ YRFIYMAVQH YIETLQRRIE EEQKSKRKGH EYTNIKYSLA DQTSGDQSPL PPCTPTPPCA EMREDSARVY ENVGLMQQQK SFR //