PTN11_MOUSE
ID PTN11_MOUSE Reviewed; 593 AA.
AC P35235; Q3TQ84; Q64509; Q6PCL5;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2019, sequence version 3.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 11;
DE EC=3.1.3.48 {ECO:0000250|UniProtKB:Q06124};
DE AltName: Full=Protein-tyrosine phosphatase SYP;
DE AltName: Full=SH-PTP2;
DE Short=SHP-2;
DE Short=Shp2;
GN Name=Ptpn11;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=BALB/cJ; TISSUE=Brain;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain, and Mammary tumor;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-552 (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=8096088; DOI=10.1126/science.8096088;
RA Feng G.-S., Hui C.-C., Pawson T.;
RT "SH2-containing phosphotyrosine phosphatase as a target of protein-tyrosine
RT kinases.";
RL Science 259:1607-1611(1993).
RN [5]
RP TISSUE SPECIFICITY.
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 INTERACTION WITH PDGFRA AND GRB2, AND PHOSPHORYLATION.
RX PubMed=8943348; DOI=10.1128/mcb.16.12.6926;
RA Bazenet C.E., Gelderloos J.A., Kazlauskas A.;
RT "Phosphorylation of tyrosine 720 in the platelet-derived growth factor
RT alpha receptor is required for binding of Grb2 and SHP-2 but not for
RT activation of Ras or cell proliferation.";
RL Mol. Cell. Biol. 16:6926-6936(1996).
RN [7]
RP INTERACTION WITH INPP5D.
RX PubMed=9110989; DOI=10.1074/jbc.272.17.10998;
RA Liu L., Damen J.E., Ware M.D., Krystal G.;
RT "Interleukin-3 induces the association of the inositol 5-phosphatase SHIP
RT with SHP2.";
RL J. Biol. Chem. 272:10998-11001(1997).
RN [8]
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 [9]
RP INTERACTION WITH INPP5D.
RX PubMed=9393882; DOI=10.1038/sj.onc.1201422;
RA Sattler M., Salgia R., Shrikhande G., Verma S., Choi J.-L.,
RA Rohrschneider L.R., Griffin J.D.;
RT "The phosphatidylinositol polyphosphate 5-phosphatase SHIP and the protein
RT tyrosine phosphatase SHP-2 form a complex in hematopoietic cells which can
RT be regulated by BCR/ABL and growth factors.";
RL Oncogene 15:2379-2384(1997).
RN [10]
RP INTERACTION WITH FLT1.
RX PubMed=9722576; DOI=10.1074/jbc.273.36.23410;
RA Ito N., Wernstedt C., Engstrom U., Claesson-Welsh L.;
RT "Identification of vascular endothelial growth factor receptor-1 tyrosine
RT phosphorylation sites and binding of SH2 domain-containing molecules.";
RL J. Biol. Chem. 273:23410-23418(1998).
RN [11]
RP INTERACTION WITH KIT.
RX PubMed=9528781; DOI=10.1128/mcb.18.4.2089;
RA Kozlowski M., Larose L., Lee F., Le D.M., Rottapel R., Siminovitch K.A.;
RT "SHP-1 binds and negatively modulates the c-Kit receptor by interaction
RT with tyrosine 569 in the c-Kit juxtamembrane domain.";
RL Mol. Cell. Biol. 18:2089-2099(1998).
RN [12]
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 [13]
RP INTERACTION WITH CEACAM1.
RX PubMed=9867848; DOI=10.1074/jbc.274.1.335;
RA Huber M., Izzi L., Grondin P., Houde C., Kunath T., Veillette A.,
RA Beauchemin N.;
RT "The carboxyl-terminal region of biliary glycoprotein controls its tyrosine
RT phosphorylation and association with protein-tyrosine phosphatases SHP-1
RT and SHP-2 in epithelial cells.";
RL J. Biol. Chem. 274:335-344(1999).
RN [14]
RP INTERACTION WITH LILRB4A.
RX PubMed=10026201; DOI=10.1074/jbc.274.9.5791;
RA Lu-Kuo J.M., Joyal D.M., Austen K.F., Katz H.R.;
RT "gp49B1 inhibits IgE-initiated mast cell activation through both
RT immunoreceptor tyrosine-based inhibitory motifs, recruitment of src
RT homology 2 domain-containing phosphatase-1, and suppression of early and
RT late calcium mobilization.";
RL J. Biol. Chem. 274:5791-5796(1999).
RN [15]
RP INTERACTION WITH TEK/TIE2.
RX PubMed=10521483; DOI=10.1074/jbc.274.43.30896;
RA Jones N., Master Z., Jones J., Bouchard D., Gunji Y., Sasaki H., Daly R.,
RA Alitalo K., Dumont D.J.;
RT "Identification of Tek/Tie2 binding partners. Binding to a multifunctional
RT docking site mediates cell survival and migration.";
RL J. Biol. Chem. 274:30896-30905(1999).
RN [16]
RP PHOSPHORYLATION, AND INTERACTION WITH GRB2.
RX PubMed=10080542; DOI=10.1002/jlb.65.3.372;
RA Zhang S., Mantel C., Broxmeyer H.E.;
RT "Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and
RT their association with Grb2 and Shc in Baf3/Flt3 cells.";
RL J. Leukoc. Biol. 65:372-380(1999).
RN [17]
RP INTERACTION WITH BCAR3.
RX PubMed=10896938; DOI=10.1074/jbc.m003074200;
RA Gotoh T., Cai D., Tian X., Feig L.A., Lerner A.;
RT "p130Cas regulates the activity of AND-34, a novel Ral, Rap1, and R-Ras
RT guanine nucleotide exchange factor.";
RL J. Biol. Chem. 275:30118-30123(2000).
RN [18]
RP INTERACTION WITH SHB.
RX PubMed=12181353; DOI=10.1091/mbc.e02-02-0103;
RA Cross M.J., Lu L., Magnusson P., Nyqvist D., Holmqvist K., Welsh M.,
RA Claesson-Welsh L.;
RT "The Shb adaptor protein binds to tyrosine 766 in the FGFR-1 and regulates
RT the Ras/MEK/MAPK pathway via FRS2 phosphorylation in endothelial cells.";
RL Mol. Biol. Cell 13:2881-2893(2002).
RN [19]
RP INTERACTION WITH LIME1.
RX PubMed=14610044; DOI=10.1084/jem.20030232;
RA Hur E.M., Son M., Lee O.-H., Choi Y.B., Park C., Lee H., Yun Y.;
RT "LIME, a novel transmembrane adaptor protein, associates with p56lck and
RT mediates T cell activation.";
RL J. Exp. Med. 198:1463-1473(2003).
RN [20]
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 [21]
RP INTERACTION WITH FLT3.
RX PubMed=16684964; DOI=10.1182/blood-2005-07-008896;
RA Heiss E., Masson K., Sundberg C., Pedersen M., Sun J., Bengtsson S.,
RA Ronnstrand L.;
RT "Identification of Y589 and Y599 in the juxtamembrane domain of Flt3 as
RT ligand-induced autophosphorylation sites involved in binding of Src family
RT kinases and the protein tyrosine phosphatase SHP2.";
RL Blood 108:1542-1550(2006).
RN [22]
RP INTERACTION WITH ROS1, AND PHOSPHORYLATION AT TYR-542 AND TYR-580.
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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-62, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-62 AND TYR-66, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [25]
RP INTERACTION WITH CEACAM1.
RX PubMed=19948503; DOI=10.1083/jcb.200904150;
RA Mueller M.M., Klaile E., Vorontsova O., Singer B.B., Obrink B.;
RT "Homophilic adhesion and CEACAM1-S regulate dimerization of CEACAM1-L and
RT recruitment of SHP-2 and c-Src.";
RL J. Cell Biol. 187:569-581(2009).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-62, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [27]
RP INTERACTION WITH MILR1.
RX PubMed=20526344; DOI=10.1038/ni.1886;
RA Hitomi K., Tahara-Hanaoka S., Someya S., Fujiki A., Tada H., Sugiyama T.,
RA Shibayama S., Shibuya K., Shibuya A.;
RT "An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-
RT mediated immediate hypersensitivity reactions.";
RL Nat. Immunol. 11:601-607(2010).
RN [28]
RP FUNCTION.
RX PubMed=14967142; DOI=10.1016/s1097-2765(04)00050-4;
RA Zhang S.Q., Yang W., Kontaridis M.I., Bivona T.G., Wen G., Araki T.,
RA Luo J., Thompson J.A., Schraven B.L., Philips M.R., Neel B.G.;
RT "Shp2 regulates SRC family kinase activity and Ras/Erk activation by
RT controlling Csk recruitment.";
RL Mol. Cell 13:341-355(2004).
RN [29]
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 [30]
RP INTERACTION WITH SIGLEC10.
RX PubMed=23374343; DOI=10.1016/j.cell.2013.01.011;
RA Chen W., Han C., Xie B., Hu X., Yu Q., Shi L., Wang Q., Li D., Wang J.,
RA Zheng P., Liu Y., Cao X.;
RT "Induction of Siglec-G by RNA viruses inhibits the innate immune response
RT by promoting RIG-I degradation.";
RL Cell 152:467-478(2013).
RN [31]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29644115; DOI=10.1038/s41413-018-0013-z;
RA Zuo C., Wang L., Kamalesh R.M., Bowen M.E., Moore D.C., Dooner M.S.,
RA Reginato A.M., Wu Q., Schorl C., Song Y., Warman M.L., Neel B.G.,
RA Ehrlich M.G., Yang W.;
RT "SHP2 regulates skeletal cell fate by modifying SOX9 expression and
RT transcriptional activity.";
RL Bone Res. 6:12-12(2018).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 4-103 IN COMPLEX WITH PDGFRB, AND
RP INTERACTION WITH PDGFRB.
RX PubMed=7521735; DOI=10.1016/s0969-2126(00)00044-7;
RA Lee C.-H., Kominos D., Jacques S., Margolis B., Schlessinger J.,
RA Shoelson S.E., Kuriyan J.;
RT "Crystal structures of peptide complexes of the amino-terminal SH2 domain
RT of the Syp tyrosine phosphatase.";
RL Structure 2:423-438(1994).
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:14967142). Positively regulates
CC MAPK signal transduction pathway (By similarity). Dephosphorylates
CC GAB1, ARHGAP35 and EGFR (By similarity). Dephosphorylates ROCK2 at
CC 'Tyr-722' resulting in stimulation of its RhoA binding activity (By
CC similarity). Dephosphorylates CDC73 (By similarity). Dephosphorylates
CC SOX9 on tyrosine residues, leading to inactivate SOX9 and promote
CC ossification (PubMed:29644115). {ECO:0000250|UniProtKB:Q06124,
CC ECO:0000269|PubMed:14967142, ECO:0000269|PubMed:29644115}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10044};
CC -!- SUBUNIT: Interacts with CD84 and with phosphorylated SIT1 and MZPL1.
CC Interacts with FCRL4, FCRL6 and ANKHD1. Interacts with GAREM1 (tyrosine
CC phosphorylated); the interaction increases MAPK/ERK activity and does
CC not affect the GRB2/SOS complex formation (By similarity). Interacts
CC with PTPNS1 and BCAR3. Interacts with phosphorylated LIME1. Interacts
CC with SHB and INPP5D/SHIP1. Interacts with KIR2DL1; the interaction is
CC enhanced by ARRB2 (By similarity). Interacts with GAB2. Interacts with
CC 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 (By
CC similarity). Interacts with MILR1 (tyrosine phosphorylated). Interacts
CC with FLT1 (tyrosine-phosphorylated), FLT3 (tyrosine-phosphorylated),
CC FLT4 (tyrosine-phosphorylated), KIT and GRB2. Interacts with ROS1;
CC mediates PTPN11 phosphorylation. Interacts with PDGFRA (tyrosine
CC phosphorylated). Interacts with PDGFRB (tyrosine phosphorylated); this
CC interaction increases the PTPN11 phosphatase activity. Interacts (via
CC SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with
CC CEACAM1 (via cytoplasmic domain); this interaction depends on the
CC monomer/dimer equilibrium and is phosphorylation-dependent
CC (PubMed:19948503, PubMed:9867848). Interacts with MPIG6B (via ITIM
CC motif) (PubMed:23112346). Interacts with SIGLEC10 (PubMed:23374343).
CC Interacts with Lilrb4a (when tyrosine phosphorylated)
CC (PubMed:10026201). Interacts with SIGLEC10 (By similarity). Interacts
CC with CLEC12B (via ITIM motif); this interaction triggers
CC dephosphorylation and activation of PTPN11.
CC {ECO:0000250|UniProtKB:P41499, ECO:0000250|UniProtKB:Q06124,
CC ECO:0000269|PubMed:10026201, ECO:0000269|PubMed:10068651,
CC ECO:0000269|PubMed:10080542, ECO:0000269|PubMed:10521483,
CC ECO:0000269|PubMed:10896938, ECO:0000269|PubMed:12181353,
CC ECO:0000269|PubMed:14610044, ECO:0000269|PubMed:16684964,
CC ECO:0000269|PubMed:16885344, ECO:0000269|PubMed:19948503,
CC ECO:0000269|PubMed:20526344, ECO:0000269|PubMed:23112346,
CC ECO:0000269|PubMed:23374343, ECO:0000269|PubMed:7521735,
CC ECO:0000269|PubMed:8943348, ECO:0000269|PubMed:9062191,
CC ECO:0000269|PubMed:9110989, ECO:0000269|PubMed:9393882,
CC ECO:0000269|PubMed:9528781, ECO:0000269|PubMed:9722576,
CC ECO:0000269|PubMed:9867848}.
CC -!- INTERACTION:
CC P35235; P30999: Ctnnd1; NbExp=3; IntAct=EBI-397236, EBI-529924;
CC P35235; P16879: Fes; NbExp=2; IntAct=EBI-397236, EBI-771815;
CC P35235; Q60631: Grb2; NbExp=3; IntAct=EBI-397236, EBI-1688;
CC P35235; P28776: Ido1; NbExp=5; IntAct=EBI-397236, EBI-4410822;
CC P35235; P97484: Lilrb3; NbExp=2; IntAct=EBI-397236, EBI-15728641;
CC P35235; P15209: Ntrk2; NbExp=2; IntAct=EBI-397236, EBI-309647;
CC P35235; Q8K4V6: Pirb; NbExp=3; IntAct=EBI-397236, EBI-8602514;
CC P35235; P70196: Traf6; NbExp=2; IntAct=EBI-397236, EBI-448028;
CC P35235; P62993: GRB2; Xeno; NbExp=7; IntAct=EBI-397236, EBI-401755;
CC P35235; P10721: KIT; Xeno; NbExp=2; IntAct=EBI-397236, EBI-1379503;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P35235-2; Sequence=Displayed;
CC Name=2;
CC IsoId=P35235-1; Sequence=VSP_060440;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, heart and kidney.
CC {ECO:0000269|PubMed:7681217}.
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 by activated PDGFRB (By
CC similarity). Phosphorylated upon activation of the receptor-type kinase
CC PDGFRA. {ECO:0000250, ECO:0000269|PubMed:10080542,
CC ECO:0000269|PubMed:16885344, ECO:0000269|PubMed:8943348}.
CC -!- DISRUPTION PHENOTYPE: Conditional deletion in limb and head mesenchyme
CC leads to increased cartilage mass and deficient ossification:
CC osteochondroprogenitors become chondrocytes and not osteoblasts caused
CC by inability of PTPN11/SHP2 to mediate tyrosine dephosphorylation of
CC SOX9. {ECO:0000269|PubMed:29644115}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class 2 subfamily. {ECO:0000305}.
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DR EMBL; D84372; BAA12328.1; -; mRNA.
DR EMBL; AK159501; BAE35134.1; -; mRNA.
DR EMBL; AK159587; BAE35207.1; -; mRNA.
DR EMBL; AK163809; BAE37500.1; -; mRNA.
DR EMBL; BC057398; AAH57398.1; -; mRNA.
DR EMBL; BC059278; AAH59278.1; -; mRNA.
DR EMBL; L08663; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS39247.1; -. [P35235-1]
DR CCDS; CCDS51637.1; -. [P35235-2]
DR PIR; A46209; A46209.
DR RefSeq; NP_001103462.1; NM_001109992.1. [P35235-2]
DR RefSeq; NP_035332.1; NM_011202.3. [P35235-1]
DR PDB; 1AYA; X-ray; 2.05 A; A/B=4-103.
DR PDB; 1AYB; X-ray; 3.00 A; A=4-103.
DR PDB; 1AYC; X-ray; 2.30 A; A=4-103.
DR PDB; 1AYD; X-ray; 2.20 A; A=4-103.
DR PDBsum; 1AYA; -.
DR PDBsum; 1AYB; -.
DR PDBsum; 1AYC; -.
DR PDBsum; 1AYD; -.
DR AlphaFoldDB; P35235; -.
DR SMR; P35235; -.
DR BioGRID; 202477; 42.
DR CORUM; P35235; -.
DR DIP; DIP-29669N; -.
DR IntAct; P35235; 33.
DR MINT; P35235; -.
DR STRING; 10090.ENSMUSP00000098333; -.
DR ChEMBL; CHEMBL2620; -.
DR iPTMnet; P35235; -.
DR PhosphoSitePlus; P35235; -.
DR EPD; P35235; -.
DR MaxQB; P35235; -.
DR PaxDb; P35235; -.
DR PeptideAtlas; P35235; -.
DR PRIDE; P35235; -.
DR ProteomicsDB; 301936; -. [P35235-2]
DR ProteomicsDB; 301937; -. [P35235-2]
DR Antibodypedia; 3948; 1479 antibodies from 48 providers.
DR DNASU; 19247; -.
DR Ensembl; ENSMUST00000054547; ENSMUSP00000058757; ENSMUSG00000043733. [P35235-1]
DR Ensembl; ENSMUST00000100770; ENSMUSP00000098333; ENSMUSG00000043733. [P35235-2]
DR GeneID; 19247; -.
DR KEGG; mmu:19247; -.
DR UCSC; uc008zio.2; mouse. [P35235-2]
DR UCSC; uc008zip.2; mouse. [P35235-2]
DR CTD; 5781; -.
DR MGI; MGI:99511; Ptpn11.
DR VEuPathDB; HostDB:ENSMUSG00000043733; -.
DR eggNOG; KOG0790; Eukaryota.
DR GeneTree; ENSGT00940000153876; -.
DR HOGENOM; CLU_001645_9_10_1; -.
DR InParanoid; P35235; -.
DR OMA; KYYIATQ; -.
DR OrthoDB; 411281at2759; -.
DR PhylomeDB; P35235; -.
DR TreeFam; TF351632; -.
DR Reactome; R-MMU-1059683; Interleukin-6 signaling.
DR Reactome; R-MMU-109704; PI3K Cascade.
DR Reactome; R-MMU-110056; MAPK3 (ERK1) activation.
DR Reactome; R-MMU-112411; MAPK1 (ERK2) activation.
DR Reactome; R-MMU-114604; GPVI-mediated activation cascade.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-1295596; Spry regulation of FGF signaling.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR Reactome; R-MMU-180292; GAB1 signalosome.
DR Reactome; R-MMU-186763; Downstream signal transduction.
DR Reactome; R-MMU-210990; PECAM1 interactions.
DR Reactome; R-MMU-210993; Tie2 Signaling.
DR Reactome; R-MMU-388841; Costimulation by the CD28 family.
DR Reactome; R-MMU-389513; CTLA4 inhibitory signaling.
DR Reactome; R-MMU-389948; PD-1 signaling.
DR Reactome; R-MMU-432142; Platelet sensitization by LDL.
DR Reactome; R-MMU-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-MMU-5654689; PI-3K cascade:FGFR1.
DR Reactome; R-MMU-5654693; FRS-mediated FGFR1 signaling.
DR Reactome; R-MMU-5654695; PI-3K cascade:FGFR2.
DR Reactome; R-MMU-5654700; FRS-mediated FGFR2 signaling.
DR Reactome; R-MMU-5654706; FRS-mediated FGFR3 signaling.
DR Reactome; R-MMU-5654710; PI-3K cascade:FGFR3.
DR Reactome; R-MMU-5654712; FRS-mediated FGFR4 signaling.
DR Reactome; R-MMU-5654720; PI-3K cascade:FGFR4.
DR Reactome; R-MMU-5654726; Negative regulation of FGFR1 signaling.
DR Reactome; R-MMU-5654727; Negative regulation of FGFR2 signaling.
DR Reactome; R-MMU-5654732; Negative regulation of FGFR3 signaling.
DR Reactome; R-MMU-5654733; Negative regulation of FGFR4 signaling.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-8853659; RET signaling.
DR Reactome; R-MMU-8854691; Interleukin-20 family signaling.
DR Reactome; R-MMU-8865999; MET activates PTPN11.
DR Reactome; R-MMU-8934593; Regulation of RUNX1 Expression and Activity.
DR Reactome; R-MMU-912694; Regulation of IFNA/IFNB signaling.
DR Reactome; R-MMU-936964; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR Reactome; R-MMU-9674555; Signaling by CSF3 (G-CSF).
DR SABIO-RK; P35235; -.
DR BioGRID-ORCS; 19247; 25 hits in 76 CRISPR screens.
DR ChiTaRS; Ptpn11; mouse.
DR EvolutionaryTrace; P35235; -.
DR PRO; PR:P35235; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P35235; protein.
DR Bgee; ENSMUSG00000043733; Expressed in renal corpuscle and 241 other tissues.
DR Genevisible; P35235; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0044853; C:plasma membrane raft; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0045296; F:cadherin binding; ISO:MGI.
DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:UniProtKB.
DR GO; GO:0031748; F:D1 dopamine receptor binding; ISO:MGI.
DR GO; GO:0005158; F:insulin receptor binding; ISO:MGI.
DR GO; GO:0043560; F:insulin receptor substrate binding; ISO:MGI.
DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; IMP:MGI.
DR GO; GO:0051428; F:peptide hormone receptor binding; IPI:MGI.
DR GO; GO:0043274; F:phospholipase binding; ISO:MGI.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IMP:MGI.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:MGI.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; ISO:MGI.
DR GO; GO:0033277; P:abortive mitotic cell cycle; IMP:MGI.
DR GO; GO:0036302; P:atrioventricular canal development; ISO:MGI.
DR GO; GO:0007409; P:axonogenesis; IMP:MGI.
DR GO; GO:0060020; P:Bergmann glial cell differentiation; IMP:MGI.
DR GO; GO:0007420; P:brain development; ISO:MGI.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:MGI.
DR GO; GO:0021697; P:cerebellar cortex formation; IMP:MGI.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:MGI.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IGI:MGI.
DR GO; GO:0038127; P:ERBB signaling pathway; ISO:MGI.
DR GO; GO:0060325; P:face morphogenesis; ISO:MGI.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0048806; P:genitalia development; ISO:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR GO; GO:0007507; P:heart development; ISO:MGI.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IMP:MGI.
DR GO; GO:0042445; P:hormone metabolic process; IMP:MGI.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IDA:MGI.
DR GO; GO:0048839; P:inner ear development; ISO:MGI.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IMP:MGI.
DR GO; GO:0061582; P:intestinal epithelial cell migration; IMP:MGI.
DR GO; GO:0006629; P:lipid metabolic process; IMP:MGI.
DR GO; GO:0035855; P:megakaryocyte development; IMP:MGI.
DR GO; GO:0032528; P:microvillus organization; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0048609; P:multicellular organismal reproductive process; IMP:MGI.
DR GO; GO:0033629; P:negative regulation of cell adhesion mediated by integrin; IMP:MGI.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0051463; P:negative regulation of cortisol secretion; IMP:MGI.
DR GO; GO:0060125; P:negative regulation of growth hormone secretion; IMP:MGI.
DR GO; GO:0046888; P:negative regulation of hormone secretion; IMP:MGI.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IMP:MGI.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IMP:MGI.
DR GO; GO:0035265; P:organ growth; IMP:MGI.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; ISS:UniProtKB.
DR GO; GO:0030220; P:platelet formation; IGI:MGI.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IGI:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IGI:MGI.
DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; ISO:MGI.
DR GO; GO:0046326; P:positive regulation of glucose import; ISO:MGI.
DR GO; GO:0046887; P:positive regulation of hormone secretion; IMP:MGI.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IMP:ARUK-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IGI:ARUK-UCL.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IGI:MGI.
DR GO; GO:0045778; P:positive regulation of ossification; IMP:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0009967; P:positive regulation of signal transduction; IMP:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IGI:ARUK-UCL.
DR GO; GO:0006470; P:protein dephosphorylation; ISO:MGI.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
DR GO; GO:0043408; P:regulation of MAPK cascade; IMP:MGI.
DR GO; GO:0046825; P:regulation of protein export from nucleus; IMP:MGI.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; IMP:MGI.
DR GO; GO:0006641; P:triglyceride metabolic process; IMP:MGI.
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; Hydrolase;
KW Phosphoprotein; Protein phosphatase; Reference proteome; Repeat;
KW SH2 domain.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q06124"
FT CHAIN 2..593
FT /note="Tyrosine-protein phosphatase non-receptor type 11"
FT /id="PRO_0000094768"
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..521
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT ACT_SITE 459
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
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:0000250|UniProtKB:Q06124"
FT MOD_RES 62
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:18034455, ECO:0007744|PubMed:21183079"
FT MOD_RES 66
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 542
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000269|PubMed:16885344"
FT MOD_RES 580
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000269|PubMed:16885344"
FT VAR_SEQ 407
FT /note="G -> GQALL (in isoform 2)"
FT /id="VSP_060440"
FT CONFLICT 390
FT /note="E -> G (in Ref. 2; BAE37500)"
FT /evidence="ECO:0000305"
FT HELIX 13..22
FT /evidence="ECO:0007829|PDB:1AYA"
FT STRAND 28..33
FT /evidence="ECO:0007829|PDB:1AYA"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:1AYA"
FT STRAND 41..47
FT /evidence="ECO:0007829|PDB:1AYA"
FT STRAND 50..55
FT /evidence="ECO:0007829|PDB:1AYA"
FT STRAND 63..68
FT /evidence="ECO:0007829|PDB:1AYA"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:1AYA"
FT HELIX 74..83
FT /evidence="ECO:0007829|PDB:1AYA"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:1AYD"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:1AYD"
SQ SEQUENCE 593 AA; 68035 MW; 6C71EEEECCF7F159 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 EVHHKQESIV DAGPVVVHCS AGIGRTGTFI VIDILIDIIR
EKGVDCDIDV PKTIQMVRSQ RSGMVQTEAQ YRFIYMAVQH YIETLQRRIE EEQKSKRKGH
EYTNIKYSLV DQTSGDQSPL PPCTPTPPCA EMREDSARVY ENVGLMQQQR SFR
