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P35233 (PTN2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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):
Protein-tyrosine phosphatase PTP-S
Gene names
Name:Ptpn2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length416 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 By similarity.

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Subunit structure

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.

Subcellular location

Cytoplasm. Endoplasmic reticulum-Golgi intermediate compartment By similarity. Note: Targeted to the endoplasmic reticulum by its C-terminal hydrophobic region By similarity. Ref.5

Isoform 1: Endoplasmic reticulum. Nucleus membrane Ref.5.

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. Ref.5

Tissue specificity

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

Post-translational modification

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

Sequence similarities

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

Contains 1 tyrosine-protein phosphatase domain.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Endoplasmic reticulum
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   Molecular functionHydrolase
Protein phosphatase
   PTMPhosphoprotein
   Technical termComplete 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

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 sequence or structural similarity. 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 sequence or structural similarity. 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 sequence or structural similarity. Source: UniProtKB

negative regulation of interleukin-4-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of interleukin-6-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

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 sequence or structural similarity. Source: UniProtKB

negative regulation of tyrosine phosphorylation of Stat1 protein

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of tyrosine phosphorylation of Stat3 protein

Inferred from sequence or structural similarity. 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 sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of gluconeogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of hepatocyte growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentendoplasmic reticulum

Inferred from sequence or structural similarity. Source: UniProtKB

endoplasmic reticulum-Golgi intermediate compartment

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionDNA binding

Traceable author statement Ref.1. Source: RGD

non-membrane spanning protein tyrosine phosphatase activity

Inferred from direct assay Ref.4. Source: RGD

protein tyrosine phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P35233-1)

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.
Isoform 2 (identifier: P35233-2)

Also known as: PTP-S2;

The sequence of this isoform differs from the canonical sequence as follows:
     377-410: Missing.
Isoform 3 (identifier: P35233-3)

Also known as: PTP-S3;

The sequence of this isoform differs from the canonical sequence as follows:
     287-305: Missing.
Note: Minor.
Isoform 4 (identifier: P35233-4)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 416416Tyrosine-protein phosphatase non-receptor type 2
PRO_0000094754

Regions

Domain5 – 275271Tyrosine-protein phosphatase
Region216 – 2227Substrate binding By similarity
Region341 – 41070Endoplasmic reticulum location By similarity
Region371 – 41040May mediate interaction with STX17 By similarity

Sites

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

Amino acid modifications

Modified residue2981Phosphoserine By similarity
Modified residue3041Phosphoserine; by CDK1 and CDK2; in isoform 2 By similarity

Natural variations

Alternative sequence287 – 30519Missing in isoform 3 and isoform 4.
VSP_042001
Alternative sequence377 – 41034Missing in isoform 2 and isoform 4.
VSP_042002

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PTP-S4) [UniParc].

Last modified November 16, 2011. Version 2.
Checksum: E8FB1E670FFC5308

FASTA41648,446
        10         20         30         40         50         60 
MSATIEREFE ELDAQCRWQP LYLEIRNESH DYPHRVAKFP ENRNRNRYRD VSPYDHSRVK 

        70         80         90        100        110        120 
LQSAENDYIN ASLVDIEEAQ RSYILTQGPL PNTCCHFWLM VWQQKTRAVV MLNRTVEKES 

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

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

       250        260        270        280        290        300 
DVNVKQILLS MRKYRMGLIQ TPDQLRFSYM AIIEGAKYTK GDSNIQKRWK ELSKEDLSPV 

       310        320        330        340        350        360 
CRHSQNRTMT EKYNGKRIGS EDEKLTGLSS KVPDTVEESS ESILRKRIRE DRKATTAQKV 

       370        380        390        400        410 
QQMRQRLNET ERKRKRWLYW QPILTKMGFV SVILVGALVG WTLLFQLNVL PRLTDT 

« Hide

Isoform 2 (PTP-S2) [UniParc].

Checksum: 0455FE00D3162D8F
Show »

FASTA38244,544
Isoform 3 (PTP-S3) [UniParc].

Checksum: 5B7F4DD9463D779F
Show »

FASTA39746,138
Isoform 4 (PTP-S1) [UniParc].

Checksum: B417C04466D24715
Show »

FASTA36342,236

References

« Hide 'large scale' references
[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).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X58828 mRNA. Translation: CAA41633.1.
BC078758 mRNA. Translation: AAH78758.1.
PIRS14294.
RefSeqNP_446442.1. NM_053990.1. [P35233-4]
UniGeneRn.33497.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP35233. 2 interactions.
STRING10116.ENSRNOP00000023763.

Proteomic databases

PaxDbP35233.
PRIDEP35233.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID117063.
KEGGrno:117063.
UCSCRGD:620710. rat. [P35233-1]

Organism-specific databases

CTD5771.
RGD620710. Ptpn2.

Phylogenomic databases

eggNOGCOG5599.
HOGENOMHOG000273908.
HOVERGENHBG008321.
InParanoidP35233.
KOK18026.

Gene expression databases

GenevestigatorP35233.

Family and domain databases

Gene3D3.90.190.10. 1 hit.
InterProIPR029021. Prot-tyrosine_phosphatase-like.
IPR012265. 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]
SUPFAMSSF52799. SSF52799. 1 hit.
PROSITEPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio619930.
PROP35233.

Entry information

Entry namePTN2_RAT
AccessionPrimary (citable) accession number: P35233
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: November 16, 2011
Last modified: June 11, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families