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P35233

- PTN2_RAT

UniProt

P35233 - PTN2_RAT

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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

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
Complete GO annotation...

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. nucleus Source: UniProtKB
  4. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

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

        10         20         30         40         50
MSATIEREFE ELDAQCRWQP LYLEIRNESH DYPHRVAKFP ENRNRNRYRD
60 70 80 90 100
VSPYDHSRVK LQSAENDYIN ASLVDIEEAQ RSYILTQGPL PNTCCHFWLM
110 120 130 140 150
VWQQKTRAVV MLNRTVEKES VKCAQYWPTD DREMVFKETG FSVKLLSEDV
160 170 180 190 200
KSYYTVHLLQ LENINSGETR TISHFHYTTW PDFGVPESPA SFLNFLFKVR
210 220 230 240 250
ESGSLNPDHG PAVIHCSAGI GRSGTFSLVD TCLVLMEKGE DVNVKQILLS
260 270 280 290 300
MRKYRMGLIQ TPDQLRFSYM AIIEGAKYTK GDSNIQKRWK ELSKEDLSPV
310 320 330 340 350
CRHSQNRTMT EKYNGKRIGS EDEKLTGLSS KVPDTVEESS ESILRKRIRE
360 370 380 390 400
DRKATTAQKV QQMRQRLNET ERKRKRWLYW QPILTKMGFV SVILVGALVG
410
WTLLFQLNVL PRLTDT
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

« Hide 'large scale' publications
  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 29, 2014
This is version 117 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