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P35233

- PTN2_RAT

UniProt

P35233 - PTN2_RAT

Protein

Tyrosine-protein phosphatase non-receptor type 2

Gene

Ptpn2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 116 (01 Oct 2014)
      Sequence version 2 (16 Nov 2011)
      Previous versions | rss
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    Functioni

    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. In addition to 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 By similarity.By similarity

    Catalytic activityi

    Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei182 – 1821SubstrateBy similarity
    Active sitei216 – 2161Phosphocysteine intermediatePROSITE-ProRule annotation
    Binding sitei260 – 2601SubstrateBy similarity

    GO - Molecular functioni

    1. DNA binding Source: RGD
    2. non-membrane spanning protein tyrosine phosphatase activity Source: RGD
    3. protein tyrosine phosphatase activity Source: UniProtKB

    GO - Biological processi

    1. B cell differentiation Source: UniProtKB
    2. erythrocyte differentiation Source: UniProtKB
    3. glucose homeostasis Source: UniProtKB
    4. insulin receptor signaling pathway Source: UniProtKB
    5. negative regulation of cell proliferation Source: UniProtKB
    6. negative regulation of chemotaxis Source: UniProtKB
    7. negative regulation of epidermal growth factor receptor signaling pathway Source: UniProtKB
    8. negative regulation of ERK1 and ERK2 cascade Source: UniProtKB
    9. negative regulation of inflammatory response Source: UniProtKB
    10. negative regulation of insulin receptor signaling pathway Source: UniProtKB
    11. negative regulation of interferon-gamma-mediated signaling pathway Source: UniProtKB
    12. negative regulation of interleukin-2-mediated signaling pathway Source: UniProtKB
    13. negative regulation of interleukin-4-mediated signaling pathway Source: UniProtKB
    14. negative regulation of interleukin-6-mediated signaling pathway Source: UniProtKB
    15. negative regulation of lipid storage Source: UniProtKB
    16. negative regulation of macrophage colony-stimulating factor signaling pathway Source: UniProtKB
    17. negative regulation of macrophage differentiation Source: UniProtKB
    18. negative regulation of platelet-derived growth factor receptor-beta signaling pathway Source: UniProtKB
    19. negative regulation of positive thymic T cell selection Source: UniProtKB
    20. negative regulation of prolactin signaling pathway Source: UniProtKB
    21. negative regulation of T cell receptor signaling pathway Source: UniProtKB
    22. negative regulation of tumor necrosis factor-mediated signaling pathway Source: UniProtKB
    23. negative regulation of type I interferon-mediated signaling pathway Source: UniProtKB
    24. negative regulation of tyrosine phosphorylation of Stat1 protein Source: UniProtKB
    25. negative regulation of tyrosine phosphorylation of Stat3 protein Source: UniProtKB
    26. negative regulation of tyrosine phosphorylation of Stat5 protein Source: UniProtKB
    27. negative regulation of tyrosine phosphorylation of Stat6 protein Source: UniProtKB
    28. peptidyl-tyrosine dephosphorylation Source: UniProtKB
    29. positive regulation of gluconeogenesis Source: UniProtKB
    30. regulation of hepatocyte growth factor receptor signaling pathway Source: UniProtKB
    31. T cell differentiation Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Enzyme and pathway databases

    ReactomeiREACT_196448. Regulation of IFNG signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein phosphatase non-receptor type 2 (EC:3.1.3.48)
    Alternative name(s):
    Protein-tyrosine phosphatase PTP-S
    Gene namesi
    Name:Ptpn2
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi620710. Ptpn2.

    Subcellular locationi

    Cytoplasm. Endoplasmic reticulum-Golgi intermediate compartment By similarity
    Note: Targeted to the endoplasmic reticulum by its C-terminal hydrophobic region.By similarity
    Isoform 1 : Endoplasmic reticulum 1 Publication. Nucleus membrane 1 Publication
    Isoform 2 : Nucleus By similarity. Cytoplasm By similarity. Cell membrane By similarity
    Note: Predominantly localizes to chromatin. Able to shuttle between the nucleus and the cytoplasm and to dephosphorylate plasma membrane receptors. Recruited by activated ITGA1 at the plasma membrane By similarity.By similarity

    GO - Cellular componenti

    1. endoplasmic reticulum Source: UniProtKB
    2. endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB
    3. nuclear membrane Source: UniProtKB-SubCell
    4. nucleus Source: UniProtKB
    5. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 416416Tyrosine-protein phosphatase non-receptor type 2PRO_0000094754Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei298 – 2981PhosphoserineBy similarity
    Modified residuei304 – 3041Phosphoserine; by CDK1 and CDK2; in isoform 2By similarity

    Post-translational modificationi

    Isoform 2 is specifically phosphorylated in a cell cycle-dependent manner by cyclin-dependent kinases. Probably activated through phosphorylation by PKR By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP35233.
    PRIDEiP35233.

    Expressioni

    Tissue specificityi

    Does not show tissue- or cell-type specificity although levels of transcription show variability. Macrophages showed higher levels of expression than lymphocytes.

    Gene expression databases

    GenevestigatoriP35233.

    Interactioni

    Subunit structurei

    Interacts with RMDN3. Interacts with TMED9. 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 By similarity.By similarity

    Protein-protein interaction databases

    IntActiP35233. 2 interactions.
    STRINGi10116.ENSRNOP00000023763.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini5 – 275271Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni216 – 2227Substrate bindingBy similarity
    Regioni341 – 41070Endoplasmic reticulum locationBy similarityAdd
    BLAST
    Regioni371 – 41040May mediate interaction with STX17By similarityAdd
    BLAST

    Sequence similaritiesi

    Contains 1 tyrosine-protein phosphatase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG5599.
    HOGENOMiHOG000273908.
    HOVERGENiHBG008321.
    InParanoidiP35233.
    KOiK18026.

    Family and domain databases

    Gene3Di3.90.190.10. 1 hit.
    InterProiIPR029021. Prot-tyrosine_phosphatase-like.
    IPR012265. Ptpn1/Ptpn2.
    IPR000387. Tyr/Dual-sp_Pase.
    IPR016130. Tyr_Pase_AS.
    IPR000242. Tyr_Pase_rcpt/non-rcpt.
    [Graphical view]
    PfamiPF00102. Y_phosphatase. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000926. Tyr-Ptase_nr1. 1 hit.
    PRINTSiPR00700. PRTYPHPHTASE.
    SMARTiSM00194. PTPc. 1 hit.
    [Graphical view]
    SUPFAMiSSF52799. SSF52799. 1 hit.
    PROSITEiPS00383. TYR_PHOSPHATASE_1. 1 hit.
    PS50056. TYR_PHOSPHATASE_2. 1 hit.
    PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P35233-1) [UniParc]FASTAAdd to Basket

    Also known as: PTP-S4

    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.

    « Hide

    MSATIEREFE ELDAQCRWQP LYLEIRNESH DYPHRVAKFP ENRNRNRYRD    50
    VSPYDHSRVK LQSAENDYIN ASLVDIEEAQ RSYILTQGPL PNTCCHFWLM 100
    VWQQKTRAVV MLNRTVEKES VKCAQYWPTD DREMVFKETG FSVKLLSEDV 150
    KSYYTVHLLQ LENINSGETR TISHFHYTTW PDFGVPESPA SFLNFLFKVR 200
    ESGSLNPDHG PAVIHCSAGI GRSGTFSLVD TCLVLMEKGE DVNVKQILLS 250
    MRKYRMGLIQ TPDQLRFSYM AIIEGAKYTK GDSNIQKRWK ELSKEDLSPV 300
    CRHSQNRTMT EKYNGKRIGS EDEKLTGLSS KVPDTVEESS ESILRKRIRE 350
    DRKATTAQKV QQMRQRLNET ERKRKRWLYW QPILTKMGFV SVILVGALVG 400
    WTLLFQLNVL PRLTDT 416
    Length:416
    Mass (Da):48,446
    Last modified:November 16, 2011 - v2
    Checksum:iE8FB1E670FFC5308
    GO
    Isoform 2 (identifier: P35233-2) [UniParc]FASTAAdd to Basket

    Also known as: PTP-S2

    The sequence of this isoform differs from the canonical sequence as follows:
         377-410: Missing.

    Show »
    Length:382
    Mass (Da):44,544
    Checksum:i0455FE00D3162D8F
    GO
    Isoform 3 (identifier: P35233-3) [UniParc]FASTAAdd to Basket

    Also known as: PTP-S3

    The sequence of this isoform differs from the canonical sequence as follows:
         287-305: Missing.

    Note: Minor.

    Show »
    Length:397
    Mass (Da):46,138
    Checksum:i5B7F4DD9463D779F
    GO
    Isoform 4 (identifier: P35233-4) [UniParc]FASTAAdd to Basket

    Also known as: PTP-S1

    The sequence of this isoform differs from the canonical sequence as follows:
         287-305: Missing.
         377-410: Missing.

    Note: Minor.

    Show »
    Length:363
    Mass (Da):42,236
    Checksum:iB417C04466D24715
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei287 – 30519Missing in isoform 3 and isoform 4. 2 PublicationsVSP_042001Add
    BLAST
    Alternative sequencei377 – 41034Missing in isoform 2 and isoform 4. 2 PublicationsVSP_042002Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X58828 mRNA. Translation: CAA41633.1.
    BC078758 mRNA. Translation: AAH78758.1.
    PIRiS14294.
    RefSeqiNP_446442.1. NM_053990.1. [P35233-4]
    UniGeneiRn.33497.

    Genome annotation databases

    GeneIDi117063.
    KEGGirno:117063.
    UCSCiRGD:620710. rat. [P35233-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X58828 mRNA. Translation: CAA41633.1 .
    BC078758 mRNA. Translation: AAH78758.1 .
    PIRi S14294.
    RefSeqi NP_446442.1. NM_053990.1. [P35233-4 ]
    UniGenei Rn.33497.

    3D structure databases

    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P35233. 2 interactions.
    STRINGi 10116.ENSRNOP00000023763.

    Proteomic databases

    PaxDbi P35233.
    PRIDEi P35233.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 117063.
    KEGGi rno:117063.
    UCSCi RGD:620710. rat. [P35233-1 ]

    Organism-specific databases

    CTDi 5771.
    RGDi 620710. Ptpn2.

    Phylogenomic databases

    eggNOGi COG5599.
    HOGENOMi HOG000273908.
    HOVERGENi HBG008321.
    InParanoidi P35233.
    KOi K18026.

    Enzyme and pathway databases

    Reactomei REACT_196448. Regulation of IFNG signaling.

    Miscellaneous databases

    NextBioi 619930.
    PROi P35233.

    Gene expression databases

    Genevestigatori P35233.

    Family and domain databases

    Gene3Di 3.90.190.10. 1 hit.
    InterProi IPR029021. Prot-tyrosine_phosphatase-like.
    IPR012265. Ptpn1/Ptpn2.
    IPR000387. Tyr/Dual-sp_Pase.
    IPR016130. Tyr_Pase_AS.
    IPR000242. Tyr_Pase_rcpt/non-rcpt.
    [Graphical view ]
    Pfami PF00102. Y_phosphatase. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000926. Tyr-Ptase_nr1. 1 hit.
    PRINTSi PR00700. PRTYPHPHTASE.
    SMARTi SM00194. PTPc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52799. SSF52799. 1 hit.
    PROSITEi PS00383. TYR_PHOSPHATASE_1. 1 hit.
    PS50056. TYR_PHOSPHATASE_2. 1 hit.
    PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning and expression of a protein-tyrosine phosphatase showing homology with transcription factors Fos and Jun."
      Swarup G., Kamatkar S., Radha V., Rema V.
      FEBS Lett. 280:65-69(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
      Tissue: Spleen.
    2. "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] (ISOFORM 4).
      Tissue: Testis.
    3. "Binding of a protein-tyrosine phosphatase to DNA through its carboxy-terminal noncatalytic domain."
      Radha V., Kamatkar S., Swarup G.
      Biochemistry 32:2194-2201(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: DNA-BINDING.
    4. "Alternative splicing generates four different forms of a non-transmembrane protein tyrosine phosphatase mRNA."
      Reddy R.S., Swarup G.
      DNA Cell Biol. 14:1007-1015(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE SPLICING.
    5. "Two splice variants of a tyrosine phosphatase differ in substrate specificity, DNA binding, and subcellular location."
      Kamatkar S., Radha V., Nambirajan S., Reddy R.S., Swarup G.
      J. Biol. Chem. 271:26755-26761(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION (ISOFORMS 1 AND 2).

    Entry informationi

    Entry nameiPTN2_RAT
    AccessioniPrimary (citable) accession number: P35233
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: November 16, 2011
    Last modified: October 1, 2014
    This is version 116 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3