PTN11_HUMAN
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 03-AUG-2022, entry version 251.
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 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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 [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. 30:123-123(2001).
RN [54]
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 [55]
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 [56]
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 [57]
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 [58]
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 [59]
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 [60]
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 [61]
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 [62]
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 [63]
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 [64]
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 [65]
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 [66]
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 [67]
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 [68]
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 [69]
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 [70]
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 [71]
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 [72]
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 [73]
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 [74]
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 [75]
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 [76]
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 [77]
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 {ECO:0000250|UniProtKB:P35235, ECO:0000269|PubMed:10655584,
CC ECO:0000269|PubMed:18559669, ECO:0000269|PubMed:18829466,
CC ECO:0000269|PubMed:26742426, 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 {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:19342684,
CC ECO:0000269|PubMed:19509291, ECO:0000269|PubMed:19843936,
CC ECO:0000269|PubMed:20170098, ECO:0000269|PubMed:20494825,
CC ECO:0000269|PubMed:23112346, ECO:0000269|PubMed:26742426,
CC ECO:0000269|PubMed:34310951, ECO:0000269|PubMed:7691811,
CC ECO:0000269|PubMed:8810330, ECO:0000269|PubMed:9062191,
CC 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=4; IntAct=EBI-297779, EBI-297353;
CC Q06124; P29317: EPHA2; NbExp=2; 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=4; IntAct=EBI-297779, EBI-475981;
CC Q06124; P06213: INSR; NbExp=2; 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="http://atlasgeneticsoncology.org/Genes/PTPN11ID41910ch12q24.html";
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; 7VXG; X-ray; 2.10 A; A/B/C/D=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; 7VXG; -.
DR AlphaFoldDB; Q06124; -.
DR SASBDB; Q06124; -.
DR SMR; Q06124; -.
DR BioGRID; 111745; 263.
DR CORUM; Q06124; -.
DR DIP; DIP-516N; -.
DR ELM; Q06124; -.
DR IntAct; Q06124; 203.
DR MINT; Q06124; -.
DR STRING; 9606.ENSP00000340944; -.
DR BindingDB; Q06124; -.
DR ChEMBL; CHEMBL3864; -.
DR DrugBank; DB02779; Dodecyltrimethylammonium.
DR DrugCentral; Q06124; -.
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; Q06124; -.
DR PeptideAtlas; Q06124; -.
DR PRIDE; Q06124; -.
DR ProteomicsDB; 58414; -. [Q06124-1]
DR ProteomicsDB; 58415; -. [Q06124-2]
DR ProteomicsDB; 58416; -. [Q06124-3]
DR TopDownProteomics; Q06124-2; -. [Q06124-2]
DR Antibodypedia; 3948; 1479 antibodies from 48 providers.
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 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; KYYIATQ; -.
DR OrthoDB; 411281at2759; -.
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/IKK epsilon.
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-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; 536 hits in 1079 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 208 other tissues.
DR ExpressionAtlas; Q06124; baseline and differential.
DR Genevisible; Q06124; HS.
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: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:0033277; P:abortive mitotic cell cycle; IEA:Ensembl.
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: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 Gene3D; 3.30.505.10; -; 2.
DR Gene3D; 3.90.190.10; -; 1.
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 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; SSF52799; 1.
DR SUPFAM; SSF55550; SSF55550; 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.
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; unknown pathological 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; unknown pathological significance;
FT dbSNP:rs397516797)"
FT /evidence="ECO:0000269|PubMed:12960218"
FT /id="VAR_027197"
FT MUTAGEN 459
FT /note="C->S: Abolishes phosphatase activity."
FT /evidence="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
