PTN6_HUMAN
ID PTN6_HUMAN Reviewed; 595 AA.
AC P29350; A8K306; G3V0F8; Q969V8; Q9UK67;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 241.
DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 6;
DE EC=3.1.3.48;
DE AltName: Full=Hematopoietic cell protein-tyrosine phosphatase;
DE AltName: Full=Protein-tyrosine phosphatase 1C;
DE Short=PTP-1C;
DE AltName: Full=Protein-tyrosine phosphatase SHP-1;
DE AltName: Full=SH-PTP1;
GN Name=PTPN6; Synonyms=HCP, PTP1C;
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).
RX PubMed=1732748; DOI=10.1128/mcb.12.2.836-846.1992;
RA Yi T., Cleveland J.L., Ihle J.N.;
RT "Protein tyrosine phosphatase containing SH2 domains: characterization,
RT preferential expression in hematopoietic cells, and localization to human
RT chromosome 12p12-p13.";
RL Mol. Cell. Biol. 12:836-846(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Mammary gland;
RX PubMed=1652101; DOI=10.1038/352736a0;
RA Shen S.H., Bastien L., Posner B.I., Chretien P.;
RT "A protein-tyrosine phosphatase with sequence similarity to the SH2 domain
RT of the protein-tyrosine kinases.";
RL Nature 352:736-739(1991).
RN [3]
RP ERRATUM OF PUBMED:1652101, AND SEQUENCE REVISION.
RA Shen S.H., Bastien L., Posner B.I., Chretien P.;
RL Nature 353:868-868(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1736296; DOI=10.1073/pnas.89.3.1123;
RA Plutzky J., Neel B.G., Rosenberg R.D.;
RT "Isolation of a src homology 2-containing tyrosine phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:1123-1127(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2 AND 3).
RX PubMed=7665165; DOI=10.1006/geno.1995.1020;
RA Banville D., Stocco R., Shen S.H.;
RT "Human protein tyrosine phosphatase 1C (PTPN6) gene structure: alternate
RT promoter usage and exon skipping generate multiple transcripts.";
RL Genomics 27:165-173(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9074930; DOI=10.1101/gr.7.3.268;
RA Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A.;
RT "Large-scale sequencing in human chromosome 12p13: experimental and
RT computational gene structure determination.";
RL Genome Res. 7:268-280(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RX PubMed=10497187; DOI=10.1074/jbc.274.40.28301;
RA Jin Y.J., Yu C.L., Burakoff S.J.;
RT "Human 70-kDa SHP-1L differs from 68-kDa SHP-1 in its C-terminal structure
RT and catalytic activity.";
RL J. Biol. Chem. 274:28301-28307(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
RA Oka T., Ouchida M.;
RT "Gene silencing of SHP-1 gene in leukemias/lymphomas by aberrant
RT methylation.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Umbilical cord blood;
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [11]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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 [13]
RP PHOSPHORYLATION.
RX PubMed=7781604; DOI=10.1002/j.1460-2075.1995.tb07249.x;
RA Li R.Y., Gaits F., Ragab A., Ragab-Thomas J.M.F., Chap H.;
RT "Tyrosine phosphorylation of an SH2-containing protein tyrosine phosphatase
RT is coupled to platelet thrombin receptor via a pertussis toxin-sensitive
RT heterotrimeric G-protein.";
RL EMBO J. 14:2519-2526(1995).
RN [14]
RP INTERACTION WITH LILRB1.
RX PubMed=9285411; DOI=10.1016/s1074-7613(00)80529-4;
RA Cosman D., Fanger N., Borges L., Kubin M., Chin W., Peterson L., Hsu M.-L.;
RT "A novel immunoglobulin superfamily receptor for cellular and viral MHC
RT class I molecules.";
RL Immunity 7:273-282(1997).
RN [15]
RP INTERACTION WITH LILRB4.
RX PubMed=9151699; DOI=10.1084/jem.185.10.1743;
RA Cella M., Doehring C., Samaridis J., Dessing M., Brockhaus M.,
RA Lanzavecchia A., Colonna M.;
RT "A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages,
RT and dendritic cells involved in antigen processing.";
RL J. Exp. Med. 185:1743-1751(1997).
RN [16]
RP INTERACTION WITH LILRB2.
RX PubMed=9842885;
RX DOI=10.1002/(sici)1521-4141(199811)28:11<3423::aid-immu3423>3.0.co;2-2;
RA Fanger N.A., Cosman D., Peterson L., Braddy S.C., Maliszewski C.R.,
RA Borges L.;
RT "The MHC class I binding proteins LIR-1 and LIR-2 inhibit Fc receptor-
RT mediated signaling in monocytes.";
RL Eur. J. Immunol. 28:3423-3434(1998).
RN [17]
RP INTERACTION WITH SIRPA.
RX PubMed=9712903; DOI=10.1074/jbc.273.35.22719;
RA Veillette A., Thibaudeau E., Latour S.;
RT "High expression of inhibitory receptor SHPS-1 and its association with
RT protein tyrosine phosphatase SHP-1 in macrophages.";
RL J. Biol. Chem. 273:22719-22728(1998).
RN [18]
RP INTERACTION WITH LYN, AND PHOSPHORYLATION AT TYR-564.
RX PubMed=10574931; DOI=10.1074/jbc.274.49.34663;
RA Yoshida K., Kharbanda S., Kufe D.;
RT "Functional interaction between SHPTP1 and the Lyn tyrosine kinase in the
RT apoptotic response to DNA damage.";
RL J. Biol. Chem. 274:34663-34668(1999).
RN [19]
RP INTERACTION WITH FCRL2 AND 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=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 [21]
RP FUNCTION IN ROS1 DEPHOSPHORYLATION, AND INTERACTION WITH ROS1.
RX PubMed=11266449; DOI=10.1083/jcb.152.2.325;
RA Keilhack H., Mueller M., Boehmer S.A., Frank C., Weidner K.M.,
RA Birchmeier W., Ligensa T., Berndt A., Kosmehl H., Guenther B., Mueller T.,
RA Birchmeier C., Boehmer F.D.;
RT "Negative regulation of Ros receptor tyrosine kinase signaling. An
RT epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1.";
RL J. Cell Biol. 152:325-334(2001).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [23]
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 [24]
RP INTERACTION WITH CD300LF.
RX PubMed=15184070; DOI=10.1016/j.bbrc.2004.05.065;
RA Sui L., Li N., Liu Q., Zhang W., Wan T., Wang B., Luo K., Sun H., Cao X.;
RT "IgSF13, a novel human inhibitory receptor of the immunoglobulin
RT superfamily, is preferentially expressed in dendritic cells and
RT monocytes.";
RL Biochem. Biophys. Res. Commun. 319:920-928(2004).
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 REVIEW ON ROLE IN KIT SIGNALING.
RX PubMed=16129412; DOI=10.1016/j.bbrc.2005.08.055;
RA Roskoski R. Jr.;
RT "Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.";
RL Biochem. Biophys. Res. Commun. 337:1-13(2005).
RN [27]
RP INTERACTION WITH LILRB4.
RX PubMed=16493035; DOI=10.4049/jimmunol.176.5.2790;
RA Kim-Schulze S., Scotto L., Vlad G., Piazza F., Lin H., Liu Z.,
RA Cortesini R., Suciu-Foca N.;
RT "Recombinant Ig-like transcript 3-Fc modulates T cell responses via
RT induction of Th anergy and differentiation of CD8+ T suppressor cells.";
RL J. Immunol. 176:2790-2798(2006).
RN [28]
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 [29]
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 [30]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PDPK1.
RX PubMed=19591923; DOI=10.1016/j.cellsig.2009.06.010;
RA Sephton C.F., Zhang D., Lehmann T.M., Pennington P.R., Scheid M.P.,
RA Mousseau D.D.;
RT "The nuclear localization of 3'-phosphoinositide-dependent kinase-1 is
RT dependent on its association with the protein tyrosine phosphatase SHP-1.";
RL Cell. Signal. 21:1634-1644(2009).
RN [31]
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 [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-64, AND IDENTIFICATION BY
RP 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 [33]
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 [34]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CDK2.
RX PubMed=21262353; DOI=10.1016/j.cellsig.2011.01.019;
RA Fiset A., Xu E., Bergeron S., Marette A., Pelletier G., Siminovitch K.A.,
RA Olivier M., Beauchemin N., Faure R.L.;
RT "Compartmentalized CDK2 is connected with SHP-1 and beta-catenin and
RT regulates insulin internalization.";
RL Cell. Signal. 23:911-919(2011).
RN [35]
RP INTERACTION WITH FCRL6.
RX PubMed=20933011; DOI=10.1016/j.imlet.2010.09.023;
RA Kulemzin S.V., Zamoshnikova A.Y., Yurchenko M.Y., Vitak N.Y.,
RA Najakshin A.M., Fayngerts S.A., Chikaev N.A., Reshetnikova E.S.,
RA Kashirina N.M., Peclo M.M., Rutkevich P.N., Shevelev A.Y.,
RA Yanushevskaya E.V., Baranov K.O., Mamonkin M., Vlasik T.N., Sidorenko S.P.,
RA Taranin A.V., Mechetina L.V.;
RT "FCRL6 receptor: expression and associated proteins.";
RL Immunol. Lett. 134:174-182(2011).
RN [36]
RP INTERACTION WITH EGFR.
RX PubMed=21258366; DOI=10.1038/ncb2158;
RA Hsu J.M., Chen C.T., Chou C.K., Kuo H.P., Li L.Y., Lin C.Y., Lee H.J.,
RA Wang Y.N., Liu M., Liao H.W., Shi B., Lai C.C., Bedford M.T., Tsai C.H.,
RA Hung M.C.;
RT "Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation
RT negatively modulates EGFR-mediated ERK activation.";
RL Nat. Cell Biol. 13:174-181(2011).
RN [37]
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 [38]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [39]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 248-399.
RX PubMed=9774441; DOI=10.1074/jbc.273.43.28199;
RA Yang J., Liang X., Niu T., Meng W., Zhao Z., Zhou G.W.;
RT "Crystal structure of the catalytic domain of protein-tyrosine phosphatase
RT SHP-1.";
RL J. Biol. Chem. 273:28199-28207(1998).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-532, AND DOMAIN SH2.
RX PubMed=12482860; DOI=10.1074/jbc.m210430200;
RA Yang J., Liu L., He D., Song X., Liang X., Zhao Z.J., Zhou G.W.;
RT "Crystal structure of human protein-tyrosine phosphatase SHP-1.";
RL J. Biol. Chem. 278:6516-6520(2003).
RN [42]
RP STRUCTURE BY NMR OF 110-214.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structures of the SH2 domain of human protein-tyrosine
RT phosphatase SHP-1.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [43]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS), AND DOMAIN SH2.
RX PubMed=21465528; DOI=10.1002/jcb.23125;
RA Wang W., Liu L., Song X., Mo Y., Komma C., Bellamy H.D., Zhao Z.J.,
RA Zhou G.W.;
RT "Crystal structure of human protein tyrosine phosphatase SHP-1 in the open
RT conformation.";
RL J. Cell. Biochem. 112:2062-2071(2011).
CC -!- FUNCTION: Modulates signaling by tyrosine phosphorylated cell surface
CC receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may
CC interact with other cellular components to modulate its own phosphatase
CC activity against interacting substrates. Together with MTUS1, induces
CC UBE2V2 expression upon angiotensin II stimulation. Plays a key role in
CC hematopoiesis. {ECO:0000269|PubMed:11266449}.
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: Monomer. Interacts with MTUS1 (By similarity). Interacts with
CC MILR1 (tyrosine-phosphorylated) (By similarity). Interacts with KIT (By
CC similarity). Interacts with SIRPA/PTPNS1 (PubMed:9712903). Interacts
CC with LILRB1 and LILRB2 (PubMed:9285411, PubMed:9842885). Interacts with
CC LILRB4 (PubMed:9151699, PubMed:16493035). Interacts with FCRL2 and
CC FCRL4 (PubMed:11162587, PubMed:14597715). Interacts with FCRL3 and
CC FCRL6 (tyrosine phosphorylated form) (PubMed:20933011, PubMed:11162587,
CC PubMed:19843936). Interacts with CD84 (PubMed:11414741). Interacts with
CC CD300LF (PubMed:15184070). Interacts with CDK2 (PubMed:21262353).
CC Interacts with KIR2DL1; the interaction is enhanced by ARRB2
CC (PubMed:18604210). Interacts (via SH2 1 domain) with ROS1; the
CC interaction is direct and promotes ROS1 dephosphorylation
CC (PubMed:11266449). Interacts with EGFR; inhibits EGFR-dependent
CC activation of MAPK/ERK (PubMed:21258366). Interacts with LYN
CC (PubMed:10574931). Interacts with the tyrosine phosphorylated form of
CC PDPK1 (PubMed:19591923). Interacts with CEACAM1 (via cytoplasmic
CC domain); this interaction depends on the monomer/dimer equilibrium and
CC is phosphorylation-dependent (By similarity). Interacts with MPIG6B
CC (via ITIM motif) (PubMed:23112346). Interacts with moesin/MSN.
CC Interacts with CLEC12B (via ITIM motif). {ECO:0000250|UniProtKB:P29351,
CC ECO:0000250|UniProtKB:P81718, ECO:0000269|PubMed:10574931,
CC ECO:0000269|PubMed:11162587, ECO:0000269|PubMed:11266449,
CC ECO:0000269|PubMed:11414741, ECO:0000269|PubMed:14597715,
CC ECO:0000269|PubMed:15184070, ECO:0000269|PubMed:16493035,
CC ECO:0000269|PubMed:17562706, ECO:0000269|PubMed:18604210,
CC ECO:0000269|PubMed:19591923, ECO:0000269|PubMed:19843936,
CC ECO:0000269|PubMed:20933011, ECO:0000269|PubMed:21258366,
CC ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:23112346,
CC ECO:0000269|PubMed:9151699, ECO:0000269|PubMed:9285411,
CC ECO:0000269|PubMed:9712903, ECO:0000269|PubMed:9842885}.
CC -!- INTERACTION:
CC P29350; Q14790: CASP8; NbExp=3; IntAct=EBI-78260, EBI-78060;
CC P29350; P20273: CD22; NbExp=4; IntAct=EBI-78260, EBI-78277;
CC P29350; Q9BZW8: CD244; NbExp=2; IntAct=EBI-78260, EBI-1580565;
CC P29350; P20138: CD33; NbExp=10; IntAct=EBI-78260, EBI-3906571;
CC P29350; P11049: CD37; NbExp=4; IntAct=EBI-78260, EBI-6139068;
CC P29350; P19235: EPOR; NbExp=11; IntAct=EBI-78260, EBI-617321;
CC P29350; P31994: FCGR2B; NbExp=3; IntAct=EBI-78260, EBI-724784;
CC P29350; Q13643: FHL3; NbExp=3; IntAct=EBI-78260, EBI-741101;
CC P29350; P62993: GRB2; NbExp=3; IntAct=EBI-78260, EBI-401755;
CC P29350; P08069: IGF1R; NbExp=3; IntAct=EBI-78260, EBI-475981;
CC P29350; P35968: KDR; NbExp=2; IntAct=EBI-78260, EBI-1005487;
CC P29350; P43626: KIR2DL1; NbExp=4; IntAct=EBI-78260, EBI-8684277;
CC P29350; P43628: KIR2DL3; NbExp=13; IntAct=EBI-78260, EBI-8632435;
CC P29350; Q6GTX8: LAIR1; NbExp=5; IntAct=EBI-78260, EBI-965864;
CC P29350; P06239: LCK; NbExp=5; IntAct=EBI-78260, EBI-1348;
CC P29350; Q8NHL6: LILRB1; NbExp=4; IntAct=EBI-78260, EBI-2805262;
CC P29350; Q8N423: LILRB2; NbExp=3; IntAct=EBI-78260, EBI-2816428;
CC P29350; O75022: LILRB3; NbExp=4; IntAct=EBI-78260, EBI-2830524;
CC P29350; Q8NHJ6: LILRB4; NbExp=4; IntAct=EBI-78260, EBI-2805248;
CC P29350; Q9H492: MAP1LC3A; NbExp=2; IntAct=EBI-78260, EBI-720768;
CC P29350; O94916-1: NFAT5; NbExp=4; IntAct=EBI-78260, EBI-15828651;
CC P29350; P16284: PECAM1; NbExp=4; IntAct=EBI-78260, EBI-716404;
CC P29350; Q9UKJ1: PILRA; NbExp=5; IntAct=EBI-78260, EBI-965833;
CC P29350; P08922: ROS1; NbExp=2; IntAct=EBI-78260, EBI-7371065;
CC P29350; Q8N1K5: THEMIS; NbExp=4; IntAct=EBI-78260, EBI-2873538;
CC P29350; O35274: Ppp1r9b; Xeno; NbExp=2; IntAct=EBI-78260, EBI-80022;
CC P29350; B7UM99: tir; Xeno; NbExp=4; IntAct=EBI-78260, EBI-2504426;
CC P29350; Q7DB77: tir; Xeno; NbExp=2; IntAct=EBI-78260, EBI-6480811;
CC P29350-3; Q05397: PTK2; NbExp=3; IntAct=EBI-7399369, EBI-702142;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=In neurons, translocates
CC into the nucleus after treatment with angiotensin II (By similarity).
CC Shuttles between the cytoplasm and nucleus via its association with
CC PDPK1. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Long;
CC IsoId=P29350-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P29350-3; Sequence=VSP_007775;
CC Name=3; Synonyms=Short;
CC IsoId=P29350-2; Sequence=VSP_005129, VSP_005130;
CC Name=4; Synonyms=70-kDa, SHP-1L;
CC IsoId=P29350-4; Sequence=VSP_044447;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in hematopoietic cells.
CC Isoform 2 is expressed in non-hematopoietic cells.
CC -!- DOMAIN: The N-terminal SH2 domain functions as an auto-inhibitory
CC domain, blocking the catalytic domain in the ligand-free close
CC conformation. {ECO:0000269|PubMed:12482860,
CC ECO:0000269|PubMed:21465528}.
CC -!- PTM: Phosphorylated on tyrosine residues. Binding of KITLG/SCF to KIT
CC increases tyrosine phosphorylation (By similarity). Phosphorylation at
CC Tyr-564 enhances phosphatase activity. {ECO:0000250,
CC ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:7781604}.
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/PTPN6ID41920ch12p13.html";
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DR EMBL; M74903; AAA35963.1; -; mRNA.
DR EMBL; X62055; CAA43982.1; -; mRNA.
DR EMBL; M77273; AAA36610.1; -; mRNA.
DR EMBL; U15528; AAA82880.1; -; Genomic_DNA.
DR EMBL; U15536; AAA82880.1; JOINED; Genomic_DNA.
DR EMBL; U15535; AAA82880.1; JOINED; Genomic_DNA.
DR EMBL; U15534; AAA82880.1; JOINED; Genomic_DNA.
DR EMBL; U15533; AAA82880.1; JOINED; Genomic_DNA.
DR EMBL; U15532; AAA82880.1; JOINED; Genomic_DNA.
DR EMBL; U15531; AAA82880.1; JOINED; Genomic_DNA.
DR EMBL; U15530; AAA82880.1; JOINED; Genomic_DNA.
DR EMBL; U15529; AAA82880.1; JOINED; Genomic_DNA.
DR EMBL; U15528; AAA82879.1; -; Genomic_DNA.
DR EMBL; U15537; AAA82879.1; JOINED; Genomic_DNA.
DR EMBL; U15535; AAA82879.1; JOINED; Genomic_DNA.
DR EMBL; U15534; AAA82879.1; JOINED; Genomic_DNA.
DR EMBL; U15533; AAA82879.1; JOINED; Genomic_DNA.
DR EMBL; U15532; AAA82879.1; JOINED; Genomic_DNA.
DR EMBL; U15531; AAA82879.1; JOINED; Genomic_DNA.
DR EMBL; U15530; AAA82879.1; JOINED; Genomic_DNA.
DR EMBL; U15529; AAA82879.1; JOINED; Genomic_DNA.
DR EMBL; U47924; AAB51322.1; -; Genomic_DNA.
DR EMBL; U47924; AAB51323.1; -; Genomic_DNA.
DR EMBL; AF178946; AAD53317.1; -; mRNA.
DR EMBL; AB079851; BAC81774.1; -; Genomic_DNA.
DR EMBL; AB079851; BAC81775.1; -; Genomic_DNA.
DR EMBL; AK290421; BAF83110.1; -; mRNA.
DR EMBL; CH471116; EAW88703.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88704.1; -; Genomic_DNA.
DR EMBL; BC002523; AAH02523.1; -; mRNA.
DR EMBL; BC007667; AAH07667.1; -; mRNA.
DR CCDS; CCDS41744.1; -. [P29350-3]
DR CCDS; CCDS44820.1; -. [P29350-1]
DR CCDS; CCDS44821.1; -. [P29350-4]
DR PIR; B42031; S20825.
DR RefSeq; NP_002822.2; NM_002831.5. [P29350-1]
DR RefSeq; NP_536858.1; NM_080548.4. [P29350-3]
DR RefSeq; NP_536859.1; NM_080549.3. [P29350-4]
DR RefSeq; XP_011519290.1; XM_011520988.1. [P29350-3]
DR PDB; 1FPR; X-ray; 2.50 A; A=243-526.
DR PDB; 1GWZ; X-ray; 2.50 A; A=243-541.
DR PDB; 1X6C; NMR; -; A=110-214.
DR PDB; 2B3O; X-ray; 2.80 A; A=1-532.
DR PDB; 2RMX; NMR; -; A=110-214.
DR PDB; 2YU7; NMR; -; A=110-214.
DR PDB; 3PS5; X-ray; 3.10 A; A=1-595.
DR PDB; 4GRY; X-ray; 1.70 A; A=243-528.
DR PDB; 4GRZ; X-ray; 1.37 A; A=243-528.
DR PDB; 4GS0; X-ray; 1.80 A; A/B=243-528.
DR PDB; 4HJP; X-ray; 1.40 A; A=243-528.
DR PDB; 4HJQ; X-ray; 1.80 A; A/B=243-528.
DR PDB; 6SM5; X-ray; 2.75 A; A=100-214.
DR PDBsum; 1FPR; -.
DR PDBsum; 1GWZ; -.
DR PDBsum; 1X6C; -.
DR PDBsum; 2B3O; -.
DR PDBsum; 2RMX; -.
DR PDBsum; 2YU7; -.
DR PDBsum; 3PS5; -.
DR PDBsum; 4GRY; -.
DR PDBsum; 4GRZ; -.
DR PDBsum; 4GS0; -.
DR PDBsum; 4HJP; -.
DR PDBsum; 4HJQ; -.
DR PDBsum; 6SM5; -.
DR AlphaFoldDB; P29350; -.
DR SMR; P29350; -.
DR BioGRID; 111742; 222.
DR DIP; DIP-31002N; -.
DR IntAct; P29350; 124.
DR MINT; P29350; -.
DR STRING; 9606.ENSP00000391592; -.
DR BindingDB; P29350; -.
DR ChEMBL; CHEMBL3166; -.
DR DrugBank; DB01133; Tiludronic acid.
DR DrugCentral; P29350; -.
DR MoonDB; P29350; Predicted.
DR DEPOD; PTPN6; -.
DR GlyGen; P29350; 2 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; P29350; -.
DR PhosphoSitePlus; P29350; -.
DR BioMuta; PTPN6; -.
DR DMDM; 131469; -.
DR OGP; P29350; -.
DR EPD; P29350; -.
DR jPOST; P29350; -.
DR MassIVE; P29350; -.
DR MaxQB; P29350; -.
DR PaxDb; P29350; -.
DR PeptideAtlas; P29350; -.
DR PRIDE; P29350; -.
DR ProteomicsDB; 32184; -.
DR ProteomicsDB; 54543; -. [P29350-1]
DR ProteomicsDB; 54544; -. [P29350-2]
DR ProteomicsDB; 54545; -. [P29350-3]
DR Antibodypedia; 728; 1038 antibodies from 49 providers.
DR CPTC; P29350; 3 antibodies.
DR DNASU; 5777; -.
DR Ensembl; ENST00000318974.14; ENSP00000326010.9; ENSG00000111679.17. [P29350-1]
DR Ensembl; ENST00000399448.5; ENSP00000382376.1; ENSG00000111679.17. [P29350-3]
DR Ensembl; ENST00000456013.5; ENSP00000391592.1; ENSG00000111679.17. [P29350-4]
DR GeneID; 5777; -.
DR KEGG; hsa:5777; -.
DR MANE-Select; ENST00000318974.14; ENSP00000326010.9; NM_002831.6; NP_002822.2.
DR UCSC; uc001qsb.3; human. [P29350-1]
DR CTD; 5777; -.
DR DisGeNET; 5777; -.
DR GeneCards; PTPN6; -.
DR HGNC; HGNC:9658; PTPN6.
DR HPA; ENSG00000111679; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 176883; gene.
DR neXtProt; NX_P29350; -.
DR OpenTargets; ENSG00000111679; -.
DR PharmGKB; PA34002; -.
DR VEuPathDB; HostDB:ENSG00000111679; -.
DR eggNOG; KOG0790; Eukaryota.
DR GeneTree; ENSGT00940000159480; -.
DR InParanoid; P29350; -.
DR OMA; VKIMCEN; -.
DR OrthoDB; 411281at2759; -.
DR PhylomeDB; P29350; -.
DR TreeFam; TF351632; -.
DR BRENDA; 3.1.3.48; 2681.
DR PathwayCommons; P29350; -.
DR Reactome; R-HSA-114604; GPVI-mediated activation cascade.
DR Reactome; R-HSA-1433559; Regulation of KIT signaling.
DR Reactome; R-HSA-201556; Signaling by ALK.
DR Reactome; R-HSA-210990; PECAM1 interactions.
DR Reactome; R-HSA-388841; Costimulation by the CD28 family.
DR Reactome; R-HSA-389948; PD-1 signaling.
DR Reactome; R-HSA-391160; Signal regulatory protein family interactions.
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-5690714; CD22 mediated BCR regulation.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR Reactome; R-HSA-877312; Regulation of IFNG signaling.
DR Reactome; R-HSA-9008059; Interleukin-37 signaling.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling.
DR Reactome; R-HSA-912694; Regulation of IFNA/IFNB signaling.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR Reactome; R-HSA-982772; Growth hormone receptor signaling.
DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR SignaLink; P29350; -.
DR SIGNOR; P29350; -.
DR BioGRID-ORCS; 5777; 15 hits in 1083 CRISPR screens.
DR ChiTaRS; PTPN6; human.
DR EvolutionaryTrace; P29350; -.
DR GeneWiki; PTPN6; -.
DR GenomeRNAi; 5777; -.
DR Pharos; P29350; Tchem.
DR PRO; PR:P29350; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P29350; protein.
DR Bgee; ENSG00000111679; Expressed in granulocyte and 191 other tissues.
DR ExpressionAtlas; P29350; baseline and differential.
DR Genevisible; P29350; HS.
DR GO; GO:0042105; C:alpha-beta T cell receptor complex; IEA:Ensembl.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR GO; GO:0050839; F:cell adhesion molecule binding; IEA:Ensembl.
DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; IBA:GO_Central.
DR GO; GO:0140031; F:phosphorylation-dependent protein binding; IPI:UniProtKB.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IMP:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IMP:UniProtKB.
DR GO; GO:0042169; F:SH2 domain binding; IEA:Ensembl.
DR GO; GO:0017124; F:SH3 domain binding; IEA:Ensembl.
DR GO; GO:0005001; F:transmembrane receptor protein tyrosine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0033277; P:abortive mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IDA:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR GO; GO:1905867; P:epididymis development; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR GO; GO:0035855; P:megakaryocyte development; IEA:Ensembl.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; NAS:UniProtKB.
DR GO; GO:0002924; P:negative regulation of humoral immune response mediated by circulating immunoglobulin; IEA:Ensembl.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISS:ARUK-UCL.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IEA:Ensembl.
DR GO; GO:0033007; P:negative regulation of mast cell activation involved in immune response; IEA:Ensembl.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IMP:BHF-UCL.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IEA:Ensembl.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISS:ARUK-UCL.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IMP:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0070527; P:platelet aggregation; IEA:Ensembl.
DR GO; GO:0030220; P:platelet formation; IEA:Ensembl.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:BHF-UCL.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; TAS:ProtInc.
DR GO; GO:0045577; P:regulation of B cell differentiation; IEA:Ensembl.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IMP:BHF-UCL.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl.
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:0042098; P:T cell proliferation; IEA:Ensembl.
DR GO; GO:0050852; P:T cell receptor signaling pathway; 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; Alternative splicing; Cytoplasm; Hydrolase; Nucleus;
KW Phosphoprotein; Protein phosphatase; Reference proteome; Repeat;
KW SH2 domain.
FT CHAIN 1..595
FT /note="Tyrosine-protein phosphatase non-receptor type 6"
FT /id="PRO_0000094758"
FT DOMAIN 4..100
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 110..213
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 244..515
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 535..595
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 554..589
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 453
FT /note="Phosphocysteine intermediate"
FT BINDING 419
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 453..459
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 500
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P81718"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29351"
FT MOD_RES 64
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 377
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29351"
FT MOD_RES 536
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29351"
FT MOD_RES 564
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000269|PubMed:10574931"
FT VAR_SEQ 1..39
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:1652101"
FT /id="VSP_005129"
FT VAR_SEQ 1..3
FT /note="MVR -> MLSRG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007775"
FT VAR_SEQ 40..44
FT /note="SLSVR -> MLSRG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:1652101"
FT /id="VSP_005130"
FT VAR_SEQ 559..595
FT /note="HKEDVYENLHTKNKREEKVKKQRSADKEKSKGSLKRK -> SLESSAGTVAA
FT SPVRRGGQRGLPVPGPPVLSPDLHQLPVLAPLHPAADTRRMCMRTCTLRTRGRRK (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:10497187"
FT /id="VSP_044447"
FT CONFLICT 6
FT /note="H -> L (in Ref. 5; AAA82880)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="L -> V (in Ref. 4; AAA36610 and 7; AAD53317)"
FT /evidence="ECO:0000305"
FT CONFLICT 146
FT /note="V -> E (in Ref. 5; AAA82880/AAA82879)"
FT /evidence="ECO:0000305"
FT HELIX 11..21
FT /evidence="ECO:0007829|PDB:2B3O"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:2B3O"
FT STRAND 33..45
FT /evidence="ECO:0007829|PDB:2B3O"
FT STRAND 48..55
FT /evidence="ECO:0007829|PDB:2B3O"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:2B3O"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:2B3O"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:2B3O"
FT HELIX 72..80
FT /evidence="ECO:0007829|PDB:2B3O"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:2B3O"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:2B3O"
FT STRAND 111..114
FT /evidence="ECO:0007829|PDB:6SM5"
FT HELIX 117..126
FT /evidence="ECO:0007829|PDB:6SM5"
FT STRAND 132..137
FT /evidence="ECO:0007829|PDB:6SM5"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:6SM5"
FT STRAND 145..157
FT /evidence="ECO:0007829|PDB:6SM5"
FT STRAND 162..172
FT /evidence="ECO:0007829|PDB:6SM5"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:6SM5"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:6SM5"
FT HELIX 187..197
FT /evidence="ECO:0007829|PDB:6SM5"
FT STRAND 199..202
FT /evidence="ECO:0007829|PDB:6SM5"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:6SM5"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:2B3O"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:3PS5"
FT HELIX 244..256
FT /evidence="ECO:0007829|PDB:4GRZ"
FT TURN 257..259
FT /evidence="ECO:0007829|PDB:4HJP"
FT HELIX 263..266
FT /evidence="ECO:0007829|PDB:4GRZ"
FT HELIX 268..273
FT /evidence="ECO:0007829|PDB:4GRZ"
FT STRAND 275..278
FT /evidence="ECO:0007829|PDB:1GWZ"
FT TURN 283..285
FT /evidence="ECO:0007829|PDB:4GRZ"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:4GRZ"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:4GS0"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:3PS5"
FT TURN 297..300
FT /evidence="ECO:0007829|PDB:4GRZ"
FT STRAND 301..307
FT /evidence="ECO:0007829|PDB:4GRZ"
FT STRAND 309..312
FT /evidence="ECO:0007829|PDB:1GWZ"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:1FPR"
FT STRAND 321..324
FT /evidence="ECO:0007829|PDB:4GRZ"
FT HELIX 329..331
FT /evidence="ECO:0007829|PDB:4GRZ"
FT HELIX 332..341
FT /evidence="ECO:0007829|PDB:4GRZ"
FT STRAND 346..349
FT /evidence="ECO:0007829|PDB:4GRZ"
FT STRAND 353..355
FT /evidence="ECO:0007829|PDB:4GRZ"
FT STRAND 356..358
FT /evidence="ECO:0007829|PDB:1FPR"
FT STRAND 371..374
FT /evidence="ECO:0007829|PDB:4GRZ"
FT STRAND 377..386
FT /evidence="ECO:0007829|PDB:4GRZ"
FT STRAND 388..399
FT /evidence="ECO:0007829|PDB:4GRZ"
FT HELIX 400..402
FT /evidence="ECO:0007829|PDB:2B3O"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:1FPR"
FT STRAND 407..414
FT /evidence="ECO:0007829|PDB:4GRZ"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:2B3O"
FT STRAND 424..426
FT /evidence="ECO:0007829|PDB:4GRZ"
FT HELIX 427..442
FT /evidence="ECO:0007829|PDB:4GRZ"
FT STRAND 443..445
FT /evidence="ECO:0007829|PDB:4HJQ"
FT STRAND 449..452
FT /evidence="ECO:0007829|PDB:4GRZ"
FT STRAND 454..457
FT /evidence="ECO:0007829|PDB:4GRZ"
FT HELIX 458..476
FT /evidence="ECO:0007829|PDB:4GRZ"
FT HELIX 484..492
FT /evidence="ECO:0007829|PDB:4GRZ"
FT HELIX 502..523
FT /evidence="ECO:0007829|PDB:4GRZ"
SQ SEQUENCE 595 AA; 67561 MW; 4D7736C21D3542D2 CRC64;
MVRWFHRDLS GLDAETLLKG RGVHGSFLAR PSRKNQGDFS LSVRVGDQVT HIRIQNSGDF
YDLYGGEKFA TLTELVEYYT QQQGVLQDRD GTIIHLKYPL NCSDPTSERW YHGHMSGGQA
ETLLQAKGEP WTFLVRESLS QPGDFVLSVL SDQPKAGPGS PLRVTHIKVM CEGGRYTVGG
LETFDSLTDL VEHFKKTGIE EASGAFVYLR QPYYATRVNA ADIENRVLEL NKKQESEDTA
KAGFWEEFES LQKQEVKNLH QRLEGQRPEN KGKNRYKNIL PFDHSRVILQ GRDSNIPGSD
YINANYIKNQ LLGPDENAKT YIASQGCLEA TVNDFWQMAW QENSRVIVMT TREVEKGRNK
CVPYWPEVGM QRAYGPYSVT NCGEHDTTEY KLRTLQVSPL DNGDLIREIW HYQYLSWPDH
GVPSEPGGVL SFLDQINQRQ ESLPHAGPII VHCSAGIGRT GTIIVIDMLM ENISTKGLDC
DIDIQKTIQM VRAQRSGMVQ TEAQYKFIYV AIAQFIETTK KKLEVLQSQK GQESEYGNIT
YPPAMKNAHA KASRTSSKHK EDVYENLHTK NKREEKVKKQ RSADKEKSKG SLKRK
