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P17706 (PTN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein phosphatase non-receptor type 2

EC=3.1.3.48
Alternative name(s):
T-cell protein-tyrosine phosphatase
Short name=TCPTP
Gene names
Name:PTPN2
Synonyms:PTPT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length415 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3, STAT5A, STAT5B and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the development of the immune system. Functions in T-cell receptor signaling through dephosphorylation of FYN and LCK to control T-cells differentiation and activation. Dephosphorylates CSF1R, negatively regulating its downstream signaling and macrophage differentiation. Negatively regulates cytokine (IL2/interleukin-2 and interferon)-mediated signaling through dephosphorylation of the cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that propagate signaling downstream of the cytokine receptors. Also regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine signaling through dephosphorylation of STAT3 and STAT6 respectively. Beside the immune system, it is involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth. Activated by the integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates EGF signaling. Dephosphorylates PDGFRB and negatively regulates platelet-derived growth factor receptor-beta signaling pathway and therefore cell proliferation. Negatively regulates tumor necrosis factor-mediated signaling downstream via MAPK through SRC dephosphorylation. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of the hepatocyte growth factor receptor MET. Plays also an important role in glucose homeostasis. For instance, negatively regulates the insulin receptor signaling pathway through the dephosphorylation of INSR and control gluconeogenesis and liver glucose production through negative regulation of the IL6 signaling pathways. Finally, it negatively regulates prolactin-mediated signaling pathway through dephosphorylation of STAT5A and STAT5B. May also bind DNA. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.19 Ref.23 Ref.24 Ref.28

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Subunit structure

Interacts with RMDN3. Isoform 1 interacts with TMED9. Isoform 1 interacts with STX17; dephosphorylates STX17. Interacts with ITGA1 (via cytoplasmic domain); activates the phosphatase activity towards EGFR. Interacts with TRAF2; probably involved in tumor necrosis factor-mediated signaling. Interacts with MET. Ref.13 Ref.18 Ref.19 Ref.20 Ref.22 Ref.24 Ref.30

Subcellular location

Isoform 1: Endoplasmic reticulum. Endoplasmic reticulum-Golgi intermediate compartment. Note: Targeted to the endoplasmic reticulum by its C-terminal hydrophobic region (Ref.8). Ref.8 Ref.10 Ref.15 Ref.19 Ref.30

Isoform 2: Nucleus. Cytoplasm. Cell membrane. Note: Predominantly localizes to chromatin By similarity. Able to shuttle between the nucleus and the cytoplasm and to dephosphorylate plasma membrane receptors (Ref.10). Recruited by activated ITGA1 at the plasma membrane. Ref.8 Ref.10 Ref.15 Ref.19 Ref.30

Tissue specificity

Ubiquitously expressed. Isoform 2 is probably the major isoform. Isoform 1 is expressed in T-cells and in placenta. Ref.1 Ref.7

Induction

Up-regulated by IL4/interleukin-4 (at protein level). Ref.9 Ref.23

Post-translational modification

Isoform 2:Specifically phosphorylated in a cell cycle-dependent manner by cyclin-dependent kinases. Probably activated through phosphorylation by PKR. Ref.16 Ref.21

Sequence similarities

Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily.

Contains 1 tyrosine-protein phosphatase domain.

Biophysicochemical properties

Kinetic parameters:

KM=0.48 mM for p-nitrophenyl phosphate (at pH 6.5 and 25 degrees Celsius) Ref.31

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Endoplasmic reticulum
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   Molecular functionHydrolase
Protein phosphatase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

T cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

erythrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

glucose homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

insulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

negative regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of T cell receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from mutant phenotype Ref.19. Source: UniProtKB

negative regulation of chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of epidermal growth factor receptor signaling pathway

Inferred from mutant phenotype Ref.19. Source: UniProtKB

negative regulation of inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of insulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of interferon-gamma-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of interleukin-2-mediated signaling pathway

Inferred from mutant phenotype Ref.13. Source: UniProtKB

negative regulation of interleukin-4-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-6-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of lipid storage

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of macrophage colony-stimulating factor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of macrophage differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of platelet-derived growth factor receptor-beta signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of positive thymic T cell selection

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of prolactin signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of tumor necrosis factor-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of type I interferon-mediated signaling pathway

Inferred from mutant phenotype Ref.13. Source: UniProtKB

negative regulation of tyrosine phosphorylation of Stat1 protein

Inferred from mutant phenotype Ref.14. Source: UniProtKB

negative regulation of tyrosine phosphorylation of Stat3 protein

Inferred from direct assay Ref.12. Source: UniProtKB

negative regulation of tyrosine phosphorylation of Stat5 protein

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of tyrosine phosphorylation of Stat6 protein

Inferred from electronic annotation. Source: Ensembl

positive regulation of gluconeogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of hepatocyte growth factor receptor signaling pathway

Inferred from mutant phenotype Ref.24. Source: UniProtKB

   Cellular_componentendoplasmic reticulum

Inferred from direct assay PubMed 10940933Ref.8. Source: UniProtKB

endoplasmic reticulum-Golgi intermediate compartment

Inferred from direct assay Ref.30. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.15Ref.8. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein tyrosine phosphatase activity

Inferred from direct assay Ref.15Ref.30Ref.14. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P17706-1)

Also known as: PTPB; p48TC; TC48; TC-PTPb;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Minor isoform.
Isoform 2 (identifier: P17706-2)

Also known as: PTPA; p45TC; TC45; TC-PTPa;

The sequence of this isoform differs from the canonical sequence as follows:
     382-415: WLYWQPILTKMGFMSVILVGAFVGWTLFFQQNAL → PRLTDT
Note: Major isoform. Contains a nuclear location signal at positions 377-381 (PubMed:7593185) and an autoinhibitory region acting through intramolecular interactions is found at positions 353-387.
Isoform 3 (identifier: P17706-3)

The sequence of this isoform differs from the canonical sequence as follows:
     347-380: Missing.
     382-415: WLYWQPILTKMGFMSVILVGAFVGWTLFFQQNAL → PRLTDT
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 415415Tyrosine-protein phosphatase non-receptor type 2
PRO_0000094752

Regions

Domain5 – 275271Tyrosine-protein phosphatase
Region216 – 2227Substrate binding By similarity
Region346 – 41570Endoplasmic reticulum location
Region376 – 41540Mediates interaction with STX17

Sites

Active site2161Phosphocysteine intermediate By similarity
Binding site1821Substrate By similarity
Binding site2601Substrate By similarity

Amino acid modifications

Modified residue2981Phosphoserine Ref.25
Modified residue3041Phosphoserine; by CDK1 and CDK2; in isoform 2 Ref.16 Ref.25 Ref.26 Ref.29

Natural variations

Alternative sequence347 – 38034Missing in isoform 3.
VSP_043383
Alternative sequence382 – 41534WLYWQ…QQNAL → PRLTDT in isoform 2 and isoform 3.
VSP_005125

Experimental info

Mutagenesis1821D → A: Substrate-trapping mutant; catalytically inactive it forms a stable complex with physiological substrates including INSR and EGFR. Accumulates in the cytoplasm upon stimulation by insulin or EGF; isoform 2. Ref.10 Ref.15
Mutagenesis2221R → M: Impairs phosphatase activity.
Mutagenesis3041S → A: Alters phosphorylation by cyclin-dependent kinases of isoform 2 but has no effect on its phosphatase activity. Ref.16
Mutagenesis350 – 3523RKR → QQQ: Alters location to the endoplasmic reticulum; isoform 1. Ref.8
Mutagenesis3801K → Q: Prevents location to the nucleus; isoform 2. Ref.8
Sequence conflict4071T → R in AAA65997. Ref.1
Sequence conflict4071T → R in M81478. Ref.7

Secondary structure

............................................... 415
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PTPB) (p48TC) (TC48) (TC-PTPb) [UniParc].

Last modified May 5, 2009. Version 2.
Checksum: 0207694A4F058E68

FASTA41548,473
        10         20         30         40         50         60 
MPTTIEREFE ELDTQRRWQP LYLEIRNESH DYPHRVAKFP ENRNRNRYRD VSPYDHSRVK 

        70         80         90        100        110        120 
LQNAENDYIN ASLVDIEEAQ RSYILTQGPL PNTCCHFWLM VWQQKTKAVV MLNRIVEKES 

       130        140        150        160        170        180 
VKCAQYWPTD DQEMLFKETG FSVKLLSEDV KSYYTVHLLQ LENINSGETR TISHFHYTTW 

       190        200        210        220        230        240 
PDFGVPESPA SFLNFLFKVR ESGSLNPDHG PAVIHCSAGI GRSGTFSLVD TCLVLMEKGD 

       250        260        270        280        290        300 
DINIKQVLLN MRKYRMGLIQ TPDQLRFSYM AIIEGAKCIK GDSSIQKRWK ELSKEDLSPA 

       310        320        330        340        350        360 
FDHSPNKIMT EKYNGNRIGL EEEKLTGDRC TGLSSKMQDT MEENSESALR KRIREDRKAT 

       370        380        390        400        410 
TAQKVQQMKQ RLNENERKRK RWLYWQPILT KMGFMSVILV GAFVGWTLFF QQNAL 

« Hide

Isoform 2 (PTPA) (p45TC) (TC45) (TC-PTPa) [UniParc].

Checksum: 0F3E622EBA5A92CB
Show »

FASTA38745,168
Isoform 3 [UniParc].

Checksum: 5AE668EB7D76CB93
Show »

FASTA35340,990

References

« Hide 'large scale' references
[1]"cDNA isolated from a human T-cell library encodes a member of the protein-tyrosine-phosphatase family."
Cool D., Tonks N.K., Charbonneau H., Walsh K.A., Fischer E.H., Krebs E.G.
Proc. Natl. Acad. Sci. U.S.A. 86:5257-5261(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: T-cell.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[3]NHLBI resequencing and genotyping service (RS&G)
Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"DNA sequence and analysis of human chromosome 18."
Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. expand/collapse author list , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.
Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
Tissue: Brain and Eye.
[7]"Cloning and characterization of a mouse cDNA encoding a cytoplasmic protein-tyrosine-phosphatase."
Mosinger B. Jr., Tillmann U., Westphal H., Tremblay M.L.
Proc. Natl. Acad. Sci. U.S.A. 89:499-503(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 350-415 (ISOFORM 2), TISSUE SPECIFICITY.
[8]"COOH-terminal sequence motifs target the T cell protein tyrosine phosphatase to the ER and nucleus."
Lorenzen J.A., Dadabay C.Y., Fischer E.H.
J. Cell Biol. 131:631-643(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), MUTAGENESIS OF 350-ARG--ARG-352 AND LYS-380.
[9]"The noncatalytic C-terminal segment of the T cell protein tyrosine phosphatase regulates activity via an intramolecular mechanism."
Hao L., Tiganis T., Tonks N.K., Charbonneau H.
J. Biol. Chem. 272:29322-29329(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[10]"Epidermal growth factor receptor and the adaptor protein p52Shc are specific substrates of T-cell protein tyrosine phosphatase."
Tiganis T., Bennett A.M., Ravichandran K.S., Tonks N.K.
Mol. Cell. Biol. 18:1622-1634(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEPHOSPHORYLATION OF EGFR AND SHC1, MUTAGENESIS OF ASP-182, SUBCELLULAR LOCATION (ISOFORM 2).
[11]"Identification of tyrosine phosphatases that dephosphorylate the insulin receptor. A brute force approach based on 'substrate-trapping' mutants."
Waelchli S., Curchod M.L., Gobert R.P., Arkinstall S., Hooft van Huijsduijnen R.
J. Biol. Chem. 275:9792-9796(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEPHOSPHORYLATION OF INSR.
[12]"The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation."
Yamamoto T., Sekine Y., Kashima K., Kubota A., Sato N., Aoki N., Matsuda T.
Biochem. Biophys. Res. Commun. 297:811-817(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEPHOSPHORYLATION OF STAT3(ISOFORM 2).
[13]"The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3."
Simoncic P.D., Lee-Loy A., Barber D.L., Tremblay M.L., McGlade C.J.
Curr. Biol. 12:446-453(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEPHOSPHORYLATION OF JAK1 AND JAK3, INTERACTION WITH JAK1 AND JAK3.
[14]"Identification of a nuclear Stat1 protein tyrosine phosphatase."
ten Hoeve J., de Jesus Ibarra-Sanchez M., Fu Y., Zhu W., Tremblay M., David M., Shuai K.
Mol. Cell. Biol. 22:5662-5668(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEPHOSPHORYLATION OF STAT1.
[15]"Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP."
Galic S., Klingler-Hoffmann M., Fodero-Tavoletti M.T., Puryer M.A., Meng T.C., Tonks N.K., Tiganis T.
Mol. Cell. Biol. 23:2096-2108(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEPHOSPHORYLATION OF INSR, MUTAGENESIS OF ASP-182, SUBCELLULAR LOCATION (ISOFORM 2).
[16]"The T-cell protein tyrosine phosphatase is phosphorylated on Ser-304 by cyclin-dependent protein kinases in mitosis."
Bukczynska P., Klingler-Hoffmann M., Mitchelhill K.I., Lam M.H., Ciccomancini M., Tonks N.K., Sarcevic B., Kemp B.E., Tiganis T.
Biochem. J. 380:939-949(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-304 BY CDK1 AND CDK2 (ISOFORM 2), MUTAGENESIS OF SER-304.
[17]"Site-selective regulation of platelet-derived growth factor beta receptor tyrosine phosphorylation by T-cell protein tyrosine phosphatase."
Persson C., Saevenhed C., Bourdeau A., Tremblay M.L., Markova B., Boehmer F.D., Haj F.G., Neel B.G., Elson A., Heldin C.H., Roennstrand L., Ostman A., Hellberg C.
Mol. Cell. Biol. 24:2190-2201(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEPHOSPHORYLATION OF PDGFRB.
[18]"The novel protein PTPIP51 exhibits tissue- and cell-specific expression."
Stenzinger A., Kajosch T., Tag C., Porsche A., Welte I., Hofer H.W., Steger K., Wimmer M.
Histochem. Cell Biol. 123:19-28(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RMDN3.
[19]"Negative regulation of EGFR signalling through integrin-alpha1beta1-mediated activation of protein tyrosine phosphatase TCPTP."
Mattila E., Pellinen T., Nevo J., Vuoriluoto K., Arjonen A., Ivaska J.
Nat. Cell Biol. 7:78-85(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEPHOSPHORYLATION OF EGFR, INTERACTION WITH ITGA1, SUBCELLULAR LOCATION.
[20]"Selective regulation of tumor necrosis factor-induced Erk signaling by Src family kinases and the T cell protein tyrosine phosphatase."
van Vliet C., Bukczynska P.E., Puryer M.A., Sadek C.M., Shields B.J., Tremblay M.L., Tiganis T.
Nat. Immunol. 6:253-260(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRAF2.
[21]"The catalytic activity of the eukaryotic initiation factor-2alpha kinase PKR is required to negatively regulate Stat1 and Stat3 via activation of the T-cell protein-tyrosine phosphatase."
Wang S., Raven J.F., Baltzis D., Kazemi S., Brunet D.V., Hatzoglou M., Tremblay M.L., Koromilas A.E.
J. Biol. Chem. 281:9439-9449(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY PKR.
[22]"Evidence for a role of transmembrane protein p25 in localization of protein tyrosine phosphatase TC48 to the ER."
Gupta V., Swarup G.
J. Cell Sci. 119:1703-1714(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TMED9.
[23]"T-cell protein tyrosine phosphatase, distinctively expressed in activated-B-cell-like diffuse large B-cell lymphomas, is the nuclear phosphatase of STAT6."
Lu X., Chen J., Sasmono R.T., Hsi E.D., Sarosiek K.A., Tiganis T., Lossos I.S.
Mol. Cell. Biol. 27:2166-2179(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEPHOSPHORYLATION OF STAT6 (ISOFORM 2), INDUCTION BY IL4.
[24]"Regulation of the Met receptor-tyrosine kinase by the protein-tyrosine phosphatase 1B and T-cell phosphatase."
Sangwan V., Paliouras G.N., Abella J.V., Dube N., Monast A., Tremblay M.L., Park M.
J. Biol. Chem. 283:34374-34383(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEPHOSPHORYLATION OF MET, INTERACTION WITH MET.
[25]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298 AND SER-304, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[26]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[27]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice."
Wiede F., Shields B.J., Chew S.H., Kyparissoudis K., van Vliet C., Galic S., Tremblay M.L., Russell S.M., Godfrey D.I., Tiganis T.
J. Clin. Invest. 121:4758-4774(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEPHOSPHORYLATION OF LCK AND FYN.
[29]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[30]"Tyrosine phosphorylation of a SNARE protein, Syntaxin 17: Implications for membrane trafficking in the early secretory pathway."
Muppirala M., Gupta V., Swarup G.
Biochim. Biophys. Acta 1823:2109-2119(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STX17, SUBCELLULAR LOCATION.
[31]"Structure determination of T cell protein-tyrosine phosphatase."
Iversen L.F., Moller K.B., Pedersen A.K., Peters G.H., Petersen A.S., Andersen H.S., Branner S., Mortensen S.B., Moller N.P.
J. Biol. Chem. 277:19982-19990(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.56 ANGSTROMS) OF 1-314, BIOPHYSICOCHEMICAL PROPERTIES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M25393 mRNA. Translation: AAA65997.1.
AK292570 mRNA. Translation: BAF85259.1.
EF445017 Genomic DNA. Translation: ACA06062.1.
EF445017 Genomic DNA. Translation: ACA06064.1.
AP001077 Genomic DNA. No translation available.
AP002449 Genomic DNA. No translation available.
AP005482 Genomic DNA. No translation available.
CH471113 Genomic DNA. Translation: EAX01532.1.
CH471113 Genomic DNA. Translation: EAX01539.1.
BC008244 mRNA. Translation: AAH08244.1.
BC016727 mRNA. Translation: AAH16727.1.
M81478 mRNA. No translation available.
PIRA33899.
RefSeqNP_002819.2. NM_002828.3.
NP_536347.1. NM_080422.2.
NP_536348.1. NM_080423.2.
UniGeneHs.654527.
Hs.663373.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1L8KX-ray2.56A1-314[»]
ProteinModelPortalP17706.
SMRP17706. Positions 5-277.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111737. 14 interactions.
IntActP17706. 14 interactions.
MINTMINT-3975566.
STRING9606.ENSP00000311857.

Chemistry

BindingDBP17706.
ChEMBLCHEMBL3807.

PTM databases

PhosphoSiteP17706.

Polymorphism databases

DMDM229462762.

Proteomic databases

PaxDbP17706.
PRIDEP17706.

Protocols and materials databases

DNASU5771.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000309660; ENSP00000311857; ENSG00000175354. [P17706-1]
ENST00000327283; ENSP00000320298; ENSG00000175354. [P17706-2]
ENST00000353319; ENSP00000320546; ENSG00000175354. [P17706-3]
GeneID5771.
KEGGhsa:5771.
UCSCuc002krm.3. human. [P17706-3]
uc002krp.3. human. [P17706-1]

Organism-specific databases

CTD5771.
GeneCardsGC18M012864.
HGNCHGNC:9650. PTPN2.
HPAHPA015004.
HPA046176.
MIM176887. gene.
neXtProtNX_P17706.
Orphanet206. Crohn disease.
85408. Juvenile rheumatoid factor-negative polyarthritis.
85410. Oligoarticular juvenile arthritis.
771. Ulcerative colitis.
PharmGKBPA33993.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5599.
HOGENOMHOG000273908.
HOVERGENHBG008321.
InParanoidP17706.
KOK01104.
OMANTAQKVQ.
OrthoDBEOG7RV9G4.
PhylomeDBP17706.
TreeFamTF315897.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkP17706.

Gene expression databases

ArrayExpressP17706.
BgeeP17706.
CleanExHS_PTPN2.
GenevestigatorP17706.

Family and domain databases

InterProIPR012265. Ptpn1/Ptpn2.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
[Graphical view]
PfamPF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFPIRSF000926. Tyr-Ptase_nr1. 1 hit.
PRINTSPR00700. PRTYPHPHTASE.
SMARTSM00194. PTPc. 1 hit.
[Graphical view]
PROSITEPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPTPN2. human.
EvolutionaryTraceP17706.
GeneWikiPTPN2.
GenomeRNAi5771.
NextBio22446.
PROP17706.
SOURCESearch...

Entry information

Entry namePTN2_HUMAN
AccessionPrimary (citable) accession number: P17706
Secondary accession number(s): A8K955 expand/collapse secondary AC list , A8MXU3, Q96AU5, Q96HR2
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: May 5, 2009
Last modified: March 19, 2014
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM