PTN2_HUMAN
ID PTN2_HUMAN Reviewed; 415 AA.
AC P17706; A8K955; A8MXU3; K7ENG3; Q96AU5; Q96HR2;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 2;
DE EC=3.1.3.48;
DE AltName: Full=T-cell protein-tyrosine phosphatase;
DE Short=TCPTP;
GN Name=PTPN2; Synonyms=PTPT;
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), AND TISSUE SPECIFICITY.
RC TISSUE=T-cell;
RX PubMed=2546150; DOI=10.1073/pnas.86.14.5257;
RA Cool D., Tonks N.K., Charbonneau H., Walsh K.A., Fischer E.H., Krebs E.G.;
RT "cDNA isolated from a human T-cell library encodes a member of the protein-
RT tyrosine-phosphatase family.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:5257-5261(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain, and 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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 350-415 (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=1731319; DOI=10.1073/pnas.89.2.499;
RA Mosinger B. Jr., Tillmann U., Westphal H., Tremblay M.L.;
RT "Cloning and characterization of a mouse cDNA encoding a cytoplasmic
RT protein-tyrosine-phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:499-503(1992).
RN [8]
RP SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), AND MUTAGENESIS OF
RP 350-ARG--ARG-352 AND LYS-380.
RX PubMed=7593185; DOI=10.1083/jcb.131.3.631;
RA Lorenzen J.A., Dadabay C.Y., Fischer E.H.;
RT "COOH-terminal sequence motifs target the T cell protein tyrosine
RT phosphatase to the ER and nucleus.";
RL J. Cell Biol. 131:631-643(1995).
RN [9]
RP ACTIVITY REGULATION.
RX PubMed=9361013; DOI=10.1074/jbc.272.46.29322;
RA Hao L., Tiganis T., Tonks N.K., Charbonneau H.;
RT "The noncatalytic C-terminal segment of the T cell protein tyrosine
RT phosphatase regulates activity via an intramolecular mechanism.";
RL J. Biol. Chem. 272:29322-29329(1997).
RN [10]
RP FUNCTION IN DEPHOSPHORYLATION OF EGFR AND SHC1, MUTAGENESIS OF ASP-182, AND
RP SUBCELLULAR LOCATION (ISOFORM 2).
RX PubMed=9488479; DOI=10.1128/mcb.18.3.1622;
RA Tiganis T., Bennett A.M., Ravichandran K.S., Tonks N.K.;
RT "Epidermal growth factor receptor and the adaptor protein p52Shc are
RT specific substrates of T-cell protein tyrosine phosphatase.";
RL Mol. Cell. Biol. 18:1622-1634(1998).
RN [11]
RP FUNCTION IN DEPHOSPHORYLATION OF INSR.
RX PubMed=10734133; DOI=10.1074/jbc.275.13.9792;
RA Waelchli S., Curchod M.L., Gobert R.P., Arkinstall S.,
RA Hooft van Huijsduijnen R.;
RT "Identification of tyrosine phosphatases that dephosphorylate the insulin
RT receptor. A brute force approach based on 'substrate-trapping' mutants.";
RL J. Biol. Chem. 275:9792-9796(2000).
RN [12]
RP FUNCTION IN DEPHOSPHORYLATION OF STAT3(ISOFORM 2).
RX PubMed=12359225; DOI=10.1016/s0006-291x(02)02291-x;
RA Yamamoto T., Sekine Y., Kashima K., Kubota A., Sato N., Aoki N.,
RA Matsuda T.;
RT "The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates
RT interleukin-6-mediated signaling pathway through STAT3 dephosphorylation.";
RL Biochem. Biophys. Res. Commun. 297:811-817(2002).
RN [13]
RP FUNCTION IN DEPHOSPHORYLATION OF JAK1 AND JAK3, AND INTERACTION WITH JAK1
RP AND JAK3.
RX PubMed=11909529; DOI=10.1016/s0960-9822(02)00697-8;
RA Simoncic P.D., Lee-Loy A., Barber D.L., Tremblay M.L., McGlade C.J.;
RT "The T cell protein tyrosine phosphatase is a negative regulator of janus
RT family kinases 1 and 3.";
RL Curr. Biol. 12:446-453(2002).
RN [14]
RP FUNCTION IN DEPHOSPHORYLATION OF STAT1.
RX PubMed=12138178; DOI=10.1128/mcb.22.16.5662-5668.2002;
RA ten Hoeve J., de Jesus Ibarra-Sanchez M., Fu Y., Zhu W., Tremblay M.,
RA David M., Shuai K.;
RT "Identification of a nuclear Stat1 protein tyrosine phosphatase.";
RL Mol. Cell. Biol. 22:5662-5668(2002).
RN [15]
RP FUNCTION IN DEPHOSPHORYLATION OF INSR, MUTAGENESIS OF ASP-182, AND
RP SUBCELLULAR LOCATION (ISOFORM 2).
RX PubMed=12612081; DOI=10.1128/mcb.23.6.2096-2108.2003;
RA Galic S., Klingler-Hoffmann M., Fodero-Tavoletti M.T., Puryer M.A.,
RA Meng T.C., Tonks N.K., Tiganis T.;
RT "Regulation of insulin receptor signaling by the protein tyrosine
RT phosphatase TCPTP.";
RL Mol. Cell. Biol. 23:2096-2108(2003).
RN [16]
RP PHOSPHORYLATION AT SER-304 BY CDK1 AND CDK2 (ISOFORM 2), AND MUTAGENESIS OF
RP SER-304.
RX PubMed=15030318; DOI=10.1042/bj20031780;
RA Bukczynska P., Klingler-Hoffmann M., Mitchelhill K.I., Lam M.H.,
RA Ciccomancini M., Tonks N.K., Sarcevic B., Kemp B.E., Tiganis T.;
RT "The T-cell protein tyrosine phosphatase is phosphorylated on Ser-304 by
RT cyclin-dependent protein kinases in mitosis.";
RL Biochem. J. 380:939-949(2004).
RN [17]
RP FUNCTION IN DEPHOSPHORYLATION OF PDGFRB.
RX PubMed=14966296; DOI=10.1128/mcb.24.5.2190-2201.2004;
RA Persson C., Saevenhed C., Bourdeau A., Tremblay M.L., Markova B.,
RA Boehmer F.D., Haj F.G., Neel B.G., Elson A., Heldin C.H., Roennstrand L.,
RA Ostman A., Hellberg C.;
RT "Site-selective regulation of platelet-derived growth factor beta receptor
RT tyrosine phosphorylation by T-cell protein tyrosine phosphatase.";
RL Mol. Cell. Biol. 24:2190-2201(2004).
RN [18]
RP INTERACTION WITH RMDN3.
RX PubMed=15609043; DOI=10.1007/s00418-004-0732-7;
RA Stenzinger A., Kajosch T., Tag C., Porsche A., Welte I., Hofer H.W.,
RA Steger K., Wimmer M.;
RT "The novel protein PTPIP51 exhibits tissue- and cell-specific expression.";
RL Histochem. Cell Biol. 123:19-28(2005).
RN [19]
RP FUNCTION IN DEPHOSPHORYLATION OF EGFR, INTERACTION WITH ITGA1, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15592458; DOI=10.1038/ncb1209;
RA Mattila E., Pellinen T., Nevo J., Vuoriluoto K., Arjonen A., Ivaska J.;
RT "Negative regulation of EGFR signalling through integrin-alpha1beta1-
RT mediated activation of protein tyrosine phosphatase TCPTP.";
RL Nat. Cell Biol. 7:78-85(2005).
RN [20]
RP INTERACTION WITH TRAF2.
RX PubMed=15696169; DOI=10.1038/ni1169;
RA van Vliet C., Bukczynska P.E., Puryer M.A., Sadek C.M., Shields B.J.,
RA Tremblay M.L., Tiganis T.;
RT "Selective regulation of tumor necrosis factor-induced Erk signaling by Src
RT family kinases and the T cell protein tyrosine phosphatase.";
RL Nat. Immunol. 6:253-260(2005).
RN [21]
RP PHOSPHORYLATION BY PKR.
RX PubMed=16431927; DOI=10.1074/jbc.m504977200;
RA Wang S., Raven J.F., Baltzis D., Kazemi S., Brunet D.V., Hatzoglou M.,
RA Tremblay M.L., Koromilas A.E.;
RT "The catalytic activity of the eukaryotic initiation factor-2alpha kinase
RT PKR is required to negatively regulate Stat1 and Stat3 via activation of
RT the T-cell protein-tyrosine phosphatase.";
RL J. Biol. Chem. 281:9439-9449(2006).
RN [22]
RP INTERACTION WITH TMED9.
RX PubMed=16595549; DOI=10.1242/jcs.02885;
RA Gupta V., Swarup G.;
RT "Evidence for a role of transmembrane protein p25 in localization of
RT protein tyrosine phosphatase TC48 to the ER.";
RL J. Cell Sci. 119:1703-1714(2006).
RN [23]
RP FUNCTION IN DEPHOSPHORYLATION OF STAT6 (ISOFORM 2), AND INDUCTION BY IL4.
RX PubMed=17210636; DOI=10.1128/mcb.01234-06;
RA Lu X., Chen J., Sasmono R.T., Hsi E.D., Sarosiek K.A., Tiganis T.,
RA Lossos I.S.;
RT "T-cell protein tyrosine phosphatase, distinctively expressed in activated-
RT B-cell-like diffuse large B-cell lymphomas, is the nuclear phosphatase of
RT STAT6.";
RL Mol. Cell. Biol. 27:2166-2179(2007).
RN [24]
RP FUNCTION IN DEPHOSPHORYLATION OF MET, AND INTERACTION WITH MET.
RX PubMed=18819921; DOI=10.1074/jbc.m805916200;
RA Sangwan V., Paliouras G.N., Abella J.V., Dube N., Monast A., Tremblay M.L.,
RA Park M.;
RT "Regulation of the Met receptor-tyrosine kinase by the protein-tyrosine
RT phosphatase 1B and T-cell phosphatase.";
RL J. Biol. Chem. 283:34374-34383(2008).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298 AND SER-304, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304, AND IDENTIFICATION BY
RP 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 [27]
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 [28]
RP FUNCTION IN DEPHOSPHORYLATION OF LCK AND FYN.
RX PubMed=22080863; DOI=10.1172/jci59492;
RA Wiede F., Shields B.J., Chew S.H., Kyparissoudis K., van Vliet C.,
RA Galic S., Tremblay M.L., Russell S.M., Godfrey D.I., Tiganis T.;
RT "T cell protein tyrosine phosphatase attenuates T cell signaling to
RT maintain tolerance in mice.";
RL J. Clin. Invest. 121:4758-4774(2011).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [30]
RP INTERACTION WITH STX17, AND SUBCELLULAR LOCATION.
RX PubMed=23006999; DOI=10.1016/j.bbamcr.2012.09.003;
RA Muppirala M., Gupta V., Swarup G.;
RT "Tyrosine phosphorylation of a SNARE protein, Syntaxin 17: Implications for
RT membrane trafficking in the early secretory pathway.";
RL Biochim. Biophys. Acta 1823:2109-2119(2012).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293; SER-298 AND SER-304, AND
RP IDENTIFICATION BY 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 [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298 AND SER-304, AND
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 [33]
RP X-RAY CRYSTALLOGRAPHY (2.56 ANGSTROMS) OF 1-314, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=11907034; DOI=10.1074/jbc.m200567200;
RA Iversen L.F., Moller K.B., Pedersen A.K., Peters G.H., Petersen A.S.,
RA Andersen H.S., Branner S., Mortensen S.B., Moller N.P.;
RT "Structure determination of T cell protein-tyrosine phosphatase.";
RL J. Biol. Chem. 277:19982-19990(2002).
CC -!- FUNCTION: Non-receptor type tyrosine-specific phosphatase that
CC dephosphorylates receptor protein tyrosine kinases including INSR,
CC EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine
CC kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3 and
CC STAT6 either in the nucleus or the cytoplasm. Negatively regulates
CC numerous signaling pathways and biological processes like
CC hematopoiesis, inflammatory response, cell proliferation and
CC differentiation, and glucose homeostasis. Plays a multifaceted and
CC important role in the development of the immune system. Functions in T-
CC cell receptor signaling through dephosphorylation of FYN and LCK to
CC control T-cells differentiation and activation. Dephosphorylates CSF1R,
CC negatively regulating its downstream signaling and macrophage
CC differentiation. Negatively regulates cytokine (IL2/interleukin-2 and
CC interferon)-mediated signaling through dephosphorylation of the
CC cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that
CC propagate signaling downstream of the cytokine receptors. Also
CC regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine
CC signaling through dephosphorylation of STAT3 and STAT6 respectively. In
CC addition to the immune system, it is involved in anchorage-dependent,
CC negative regulation of EGF-stimulated cell growth. Activated by the
CC integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates
CC EGF signaling. Dephosphorylates PDGFRB and negatively regulates
CC platelet-derived growth factor receptor-beta signaling pathway and
CC therefore cell proliferation. Negatively regulates tumor necrosis
CC factor-mediated signaling downstream via MAPK through SRC
CC dephosphorylation. May also regulate the hepatocyte growth factor
CC receptor signaling pathway through dephosphorylation of the hepatocyte
CC growth factor receptor MET. Also plays an important role in glucose
CC homeostasis. For instance, negatively regulates the insulin receptor
CC signaling pathway through the dephosphorylation of INSR and control
CC gluconeogenesis and liver glucose production through negative
CC regulation of the IL6 signaling pathways. May also bind DNA.
CC {ECO:0000269|PubMed:10734133, ECO:0000269|PubMed:11909529,
CC ECO:0000269|PubMed:12138178, ECO:0000269|PubMed:12612081,
CC ECO:0000269|PubMed:14966296, ECO:0000269|PubMed:15592458,
CC ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:22080863,
CC ECO:0000269|PubMed:9488479}.
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.48 mM for p-nitrophenyl phosphate (at pH 6.5 and 25 degrees
CC Celsius) {ECO:0000269|PubMed:11907034};
CC -!- SUBUNIT: Interacts with RMDN3. Isoform 1 interacts with TMED9. Isoform
CC 1 interacts with STX17; dephosphorylates STX17. Interacts with ITGA1
CC (via cytoplasmic domain); activates the phosphatase activity towards
CC EGFR. Interacts with TRAF2; probably involved in tumor necrosis factor-
CC mediated signaling. Interacts with MET. {ECO:0000269|PubMed:11909529,
CC ECO:0000269|PubMed:15592458, ECO:0000269|PubMed:15609043,
CC ECO:0000269|PubMed:15696169, ECO:0000269|PubMed:16595549,
CC ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:23006999}.
CC -!- INTERACTION:
CC P17706; P10912: GHR; NbExp=8; IntAct=EBI-984930, EBI-286316;
CC P17706; Q2GHU2: ECH_0166; Xeno; NbExp=4; IntAct=EBI-984930, EBI-26585631;
CC P17706-1; P49755: TMED10; NbExp=5; IntAct=EBI-4409481, EBI-998422;
CC P17706-1; Q9BVK6: TMED9; NbExp=5; IntAct=EBI-4409481, EBI-1056827;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum
CC {ECO:0000269|PubMed:7593185}. Endoplasmic reticulum-Golgi intermediate
CC compartment {ECO:0000269|PubMed:7593185}. Note=Targeted to the
CC endoplasmic reticulum by its C-terminal hydrophobic region.
CC {ECO:0000269|PubMed:7593185}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus. Cytoplasm. Cell membrane.
CC Note=Predominantly localizes to chromatin (By similarity). Able to
CC shuttle between the nucleus and the cytoplasm and to dephosphorylate
CC plasma membrane receptors (PubMed:9488479). Recruited by activated
CC ITGA1 at the plasma membrane. {ECO:0000250,
CC ECO:0000269|PubMed:9488479}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=PTPB, p48TC, TC48, TC-PTPb;
CC IsoId=P17706-1; Sequence=Displayed;
CC Name=2; Synonyms=PTPA, p45TC, TC45, TC-PTPa;
CC IsoId=P17706-2; Sequence=VSP_005125;
CC Name=3;
CC IsoId=P17706-3; Sequence=VSP_043383, VSP_005125;
CC Name=4;
CC IsoId=P17706-4; Sequence=VSP_054821, VSP_005125;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Isoform 2 is probably the
CC major isoform. Isoform 1 is expressed in T-cells and in placenta.
CC {ECO:0000269|PubMed:1731319, ECO:0000269|PubMed:2546150}.
CC -!- INDUCTION: Up-regulated by IL4/interleukin-4 (at protein level).
CC {ECO:0000269|PubMed:17210636}.
CC -!- PTM: [Isoform 2]: Specifically phosphorylated in a cell cycle-dependent
CC manner by cyclin-dependent kinases CDK1 and CDK2. Probably activated
CC through phosphorylation by PKR. {ECO:0000269|PubMed:15030318,
CC ECO:0000269|PubMed:16431927}.
CC -!- MISCELLANEOUS: [Isoform 1]: Minor isoform.
CC -!- MISCELLANEOUS: [Isoform 2]: Major isoform. Contains a nuclear location
CC signal at positions 377-381 (PubMed:7593185) and an autoinhibitory
CC region acting through intramolecular interactions is found at positions
CC 353-387. {ECO:0000269|PubMed:15030318, ECO:0000305|PubMed:7593185}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class 1 subfamily. {ECO:0000305}.
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DR EMBL; M25393; AAA65997.1; -; mRNA.
DR EMBL; AK292570; BAF85259.1; -; mRNA.
DR EMBL; EF445017; ACA06062.1; -; Genomic_DNA.
DR EMBL; EF445017; ACA06064.1; -; Genomic_DNA.
DR EMBL; AP001077; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002449; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP005482; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471113; EAX01532.1; -; Genomic_DNA.
DR EMBL; CH471113; EAX01539.1; -; Genomic_DNA.
DR EMBL; BC008244; AAH08244.1; -; mRNA.
DR EMBL; BC016727; AAH16727.1; -; mRNA.
DR EMBL; M81478; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS11863.1; -. [P17706-2]
DR CCDS; CCDS11864.1; -. [P17706-3]
DR CCDS; CCDS11865.1; -. [P17706-1]
DR CCDS; CCDS59306.1; -. [P17706-4]
DR PIR; A33899; A33899.
DR RefSeq; NP_001193942.1; NM_001207013.1. [P17706-4]
DR RefSeq; NP_002819.2; NM_002828.3. [P17706-1]
DR RefSeq; NP_536347.1; NM_080422.2. [P17706-2]
DR RefSeq; NP_536348.1; NM_080423.2. [P17706-3]
DR PDB; 1L8K; X-ray; 2.56 A; A=1-314.
DR PDB; 6ZZ4; X-ray; 2.43 A; A/B=1-314.
DR PDB; 7F5N; X-ray; 1.93 A; A/B/C=1-314.
DR PDB; 7F5O; X-ray; 1.70 A; A/B/C=1-302.
DR PDBsum; 1L8K; -.
DR PDBsum; 6ZZ4; -.
DR PDBsum; 7F5N; -.
DR PDBsum; 7F5O; -.
DR AlphaFoldDB; P17706; -.
DR SMR; P17706; -.
DR BioGRID; 111737; 190.
DR CORUM; P17706; -.
DR IntAct; P17706; 59.
DR MINT; P17706; -.
DR STRING; 9606.ENSP00000311857; -.
DR BindingDB; P17706; -.
DR ChEMBL; CHEMBL3807; -.
DR TCDB; 8.A.128.1.13; the signaling adaptor protein karap/dap12/tyrobp (sap) family.
DR DEPOD; PTPN2; -.
DR GlyGen; P17706; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P17706; -.
DR MetOSite; P17706; -.
DR PhosphoSitePlus; P17706; -.
DR BioMuta; PTPN2; -.
DR DMDM; 229462762; -.
DR EPD; P17706; -.
DR jPOST; P17706; -.
DR MassIVE; P17706; -.
DR MaxQB; P17706; -.
DR PaxDb; P17706; -.
DR PeptideAtlas; P17706; -.
DR PRIDE; P17706; -.
DR ProteomicsDB; 53507; -. [P17706-1]
DR ProteomicsDB; 53508; -. [P17706-2]
DR ProteomicsDB; 53509; -. [P17706-3]
DR Antibodypedia; 6936; 305 antibodies from 34 providers.
DR CPTC; P17706; 1 antibody.
DR DNASU; 5771; -.
DR Ensembl; ENST00000309660.10; ENSP00000311857.3; ENSG00000175354.20. [P17706-1]
DR Ensembl; ENST00000327283.7; ENSP00000320298.3; ENSG00000175354.20. [P17706-2]
DR Ensembl; ENST00000353319.8; ENSP00000320546.3; ENSG00000175354.20. [P17706-3]
DR Ensembl; ENST00000591115.5; ENSP00000466936.1; ENSG00000175354.20. [P17706-4]
DR GeneID; 5771; -.
DR KEGG; hsa:5771; -.
DR MANE-Select; ENST00000309660.10; ENSP00000311857.3; NM_002828.4; NP_002819.2.
DR UCSC; uc002krl.4; human. [P17706-1]
DR CTD; 5771; -.
DR DisGeNET; 5771; -.
DR GeneCards; PTPN2; -.
DR HGNC; HGNC:9650; PTPN2.
DR HPA; ENSG00000175354; Tissue enhanced (lymphoid).
DR MalaCards; PTPN2; -.
DR MIM; 176887; gene.
DR neXtProt; NX_P17706; -.
DR OpenTargets; ENSG00000175354; -.
DR Orphanet; 206; NON RARE IN EUROPE: Crohn disease.
DR Orphanet; 771; NON RARE IN EUROPE: Ulcerative colitis.
DR Orphanet; 85410; Oligoarticular juvenile idiopathic arthritis.
DR Orphanet; 85408; Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis.
DR PharmGKB; PA33993; -.
DR VEuPathDB; HostDB:ENSG00000175354; -.
DR eggNOG; KOG0789; Eukaryota.
DR GeneTree; ENSGT00940000154686; -.
DR HOGENOM; CLU_001645_9_0_1; -.
DR InParanoid; P17706; -.
DR OMA; NTAQMVQ; -.
DR OrthoDB; 411281at2759; -.
DR PhylomeDB; P17706; -.
DR TreeFam; TF315897; -.
DR BRENDA; 3.1.3.48; 2681.
DR PathwayCommons; P17706; -.
DR Reactome; R-HSA-6807004; Negative regulation of MET activity.
DR Reactome; R-HSA-877312; Regulation of IFNG signaling. [P17706-2]
DR Reactome; R-HSA-9008059; Interleukin-37 signaling.
DR SABIO-RK; P17706; -.
DR SignaLink; P17706; -.
DR SIGNOR; P17706; -.
DR BioGRID-ORCS; 5771; 26 hits in 1085 CRISPR screens.
DR ChiTaRS; PTPN2; human.
DR EvolutionaryTrace; P17706; -.
DR GeneWiki; PTPN2; -.
DR GenomeRNAi; 5771; -.
DR Pharos; P17706; Tchem.
DR PRO; PR:P17706; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; P17706; protein.
DR Bgee; ENSG00000175354; Expressed in tendon of biceps brachii and 205 other tissues.
DR ExpressionAtlas; P17706; baseline and differential.
DR Genevisible; P17706; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB.
DR GO; GO:0097677; F:STAT family protein binding; IEA:Ensembl.
DR GO; GO:0019905; F:syntaxin binding; IPI:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0050922; P:negative regulation of chemotaxis; ISS:UniProtKB.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0060336; P:negative regulation of interferon-gamma-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:1902206; P:negative regulation of interleukin-2-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:1902215; P:negative regulation of interleukin-4-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0070104; P:negative regulation of interleukin-6-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0010888; P:negative regulation of lipid storage; ISS:UniProtKB.
DR GO; GO:1902227; P:negative regulation of macrophage colony-stimulating factor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045650; P:negative regulation of macrophage differentiation; ISS:UniProtKB.
DR GO; GO:2000587; P:negative regulation of platelet-derived growth factor receptor-beta signaling pathway; ISS:UniProtKB.
DR GO; GO:1902233; P:negative regulation of positive thymic T cell selection; ISS:UniProtKB.
DR GO; GO:0061099; P:negative regulation of protein tyrosine kinase activity; IEA:Ensembl.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; IDA:UniProtKB.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IDA:UniProtKB.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; ISS:UniProtKB.
DR GO; GO:1903899; P:positive regulation of PERK-mediated unfolded protein response; IEA:Ensembl.
DR GO; GO:1902202; P:regulation of hepatocyte growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0060334; P:regulation of interferon-gamma-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR012265; Ptpn1/Ptpn2.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR Pfam; PF00102; Y_phosphatase; 1.
DR PIRSF; PIRSF000926; Tyr-Ptase_nr1; 1.
DR PRINTS; PR00700; PRTYPHPHTASE.
DR SMART; SM00194; PTPc; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50055; TYR_PHOSPHATASE_PTP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cytoplasm;
KW Endoplasmic reticulum; Hydrolase; Membrane; Nucleus; Phosphoprotein;
KW Protein phosphatase; Reference proteome; S-nitrosylation.
FT CHAIN 1..415
FT /note="Tyrosine-protein phosphatase non-receptor type 2"
FT /id="PRO_0000094752"
FT DOMAIN 5..275
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 346..415
FT /note="Endoplasmic reticulum location"
FT REGION 376..415
FT /note="Mediates interaction with STX17"
FT /evidence="ECO:0000269|PubMed:23006999"
FT ACT_SITE 216
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 182
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 216..222
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 260
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 22
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 68
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 216
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 304
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT VAR_SEQ 165
FT /note="N -> NYIENLWITLYLKLLMLDVKRSLK (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_054821"
FT VAR_SEQ 347..380
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043383"
FT VAR_SEQ 382..415
FT /note="WLYWQPILTKMGFMSVILVGAFVGWTLFFQQNAL -> PRLTDT (in
FT isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1731319"
FT /id="VSP_005125"
FT MUTAGEN 182
FT /note="D->A: Substrate-trapping mutant; catalytically
FT inactive it forms a stable complex with physiological
FT substrates including INSR and EGFR. Accumulates in the
FT cytoplasm upon stimulation by insulin or EGF; isoform 2."
FT /evidence="ECO:0000269|PubMed:12612081,
FT ECO:0000269|PubMed:9488479"
FT MUTAGEN 222
FT /note="R->M: Impairs phosphatase activity."
FT MUTAGEN 304
FT /note="S->A: Alters phosphorylation by cyclin-dependent
FT kinases of isoform 2 but has no effect on its phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:15030318"
FT MUTAGEN 350..352
FT /note="RKR->QQQ: Alters location to the endoplasmic
FT reticulum; isoform 1."
FT /evidence="ECO:0000269|PubMed:7593185"
FT MUTAGEN 380
FT /note="K->Q: Prevents location to the nucleus; isoform 2."
FT /evidence="ECO:0000269|PubMed:7593185"
FT CONFLICT 407
FT /note="T -> R (in Ref. 1; AAA65997 and 7; M81478)"
FT /evidence="ECO:0000305"
FT HELIX 4..14
FT /evidence="ECO:0007829|PDB:7F5O"
FT HELIX 18..28
FT /evidence="ECO:0007829|PDB:7F5O"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:7F5O"
FT HELIX 40..45
FT /evidence="ECO:0007829|PDB:7F5O"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:7F5O"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:7F5O"
FT STRAND 68..76
FT /evidence="ECO:0007829|PDB:7F5O"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:7F5O"
FT STRAND 81..86
FT /evidence="ECO:0007829|PDB:7F5O"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:7F5O"
FT HELIX 94..104
FT /evidence="ECO:0007829|PDB:7F5O"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:7F5O"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:7F5O"
FT STRAND 129..132
FT /evidence="ECO:0007829|PDB:7F5O"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:7F5O"
FT TURN 137..140
FT /evidence="ECO:0007829|PDB:7F5O"
FT STRAND 141..150
FT /evidence="ECO:0007829|PDB:7F5O"
FT STRAND 152..163
FT /evidence="ECO:0007829|PDB:7F5O"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:7F5O"
FT STRAND 169..177
FT /evidence="ECO:0007829|PDB:7F5O"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:1L8K"
FT HELIX 189..200
FT /evidence="ECO:0007829|PDB:7F5O"
FT TURN 201..205
FT /evidence="ECO:0007829|PDB:7F5O"
FT STRAND 212..221
FT /evidence="ECO:0007829|PDB:7F5O"
FT HELIX 222..235
FT /evidence="ECO:0007829|PDB:7F5O"
FT STRAND 236..239
FT /evidence="ECO:0007829|PDB:1L8K"
FT HELIX 244..252
FT /evidence="ECO:0007829|PDB:7F5O"
FT HELIX 262..275
FT /evidence="ECO:0007829|PDB:7F5O"
FT HELIX 286..293
FT /evidence="ECO:0007829|PDB:7F5O"
FT TURN 294..296
FT /evidence="ECO:0007829|PDB:7F5N"
FT MOD_RES P17706-2:304
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15030318,
FT ECO:0000305|PubMed:7593185"
SQ SEQUENCE 415 AA; 48473 MW; 0207694A4F058E68 CRC64;
MPTTIEREFE ELDTQRRWQP LYLEIRNESH DYPHRVAKFP ENRNRNRYRD VSPYDHSRVK
LQNAENDYIN ASLVDIEEAQ RSYILTQGPL PNTCCHFWLM VWQQKTKAVV MLNRIVEKES
VKCAQYWPTD DQEMLFKETG FSVKLLSEDV KSYYTVHLLQ LENINSGETR TISHFHYTTW
PDFGVPESPA SFLNFLFKVR ESGSLNPDHG PAVIHCSAGI GRSGTFSLVD TCLVLMEKGD
DINIKQVLLN MRKYRMGLIQ TPDQLRFSYM AIIEGAKCIK GDSSIQKRWK ELSKEDLSPA
FDHSPNKIMT EKYNGNRIGL EEEKLTGDRC TGLSSKMQDT MEENSESALR KRIREDRKAT
TAQKVQQMKQ RLNENERKRK RWLYWQPILT KMGFMSVILV GAFVGWTLFF QQNAL
