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Protein

Tyrosine-protein phosphatase non-receptor type 2

Gene

Ptpn2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 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. May also bind DNA.10 Publications

Caution

Was reported to dephosphorylate STAT5A and STAT5B in the nucleus to negatively regulate prolactin-mediated signaling pathway (PubMed:11773439). However, the corresponding article has been retracted (PubMed:24319783).1 Publication1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei182SubstrateBy similarity1
Active sitei216Phosphocysteine intermediatePROSITE-ProRule annotation1
Binding sitei260SubstrateBy similarity1

GO - Molecular functioni

GO - Biological processi

  • B cell differentiation Source: UniProtKB
  • erythrocyte differentiation Source: UniProtKB
  • glucose homeostasis Source: UniProtKB
  • insulin receptor signaling pathway Source: MGI
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of chemotaxis Source: UniProtKB
  • negative regulation of epidermal growth factor receptor signaling pathway Source: UniProtKB
  • negative regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • negative regulation of inflammatory response Source: UniProtKB
  • negative regulation of insulin receptor signaling pathway Source: UniProtKB
  • negative regulation of interferon-gamma-mediated signaling pathway Source: UniProtKB
  • negative regulation of interleukin-2-mediated signaling pathway Source: UniProtKB
  • negative regulation of interleukin-4-mediated signaling pathway Source: UniProtKB
  • negative regulation of interleukin-6-mediated signaling pathway Source: UniProtKB
  • negative regulation of lipid storage Source: UniProtKB
  • negative regulation of macrophage colony-stimulating factor signaling pathway Source: UniProtKB
  • negative regulation of macrophage differentiation Source: UniProtKB
  • negative regulation of platelet-derived growth factor receptor-beta signaling pathway Source: UniProtKB
  • negative regulation of positive thymic T cell selection Source: UniProtKB
  • negative regulation of protein tyrosine kinase activity Source: ParkinsonsUK-UCL
  • negative regulation of T cell receptor signaling pathway Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II Source: MGI
  • negative regulation of tumor necrosis factor-mediated signaling pathway Source: UniProtKB
  • negative regulation of type I interferon-mediated signaling pathway Source: UniProtKB
  • negative regulation of tyrosine phosphorylation of STAT protein Source: UniProtKB
  • peptidyl-tyrosine dephosphorylation Source: UniProtKB
  • positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
  • positive regulation of gluconeogenesis Source: UniProtKB
  • positive regulation of PERK-mediated unfolded protein response Source: ParkinsonsUK-UCL
  • protein dephosphorylation Source: MGI
  • regulation of hepatocyte growth factor receptor signaling pathway Source: UniProtKB
  • T cell differentiation Source: UniProtKB

Keywordsi

Molecular functionHydrolase, Protein phosphatase

Enzyme and pathway databases

ReactomeiR-MMU-6807004 Negative regulation of MET activity
R-MMU-877312 Regulation of IFNG signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein phosphatase non-receptor type 2 (EC:3.1.3.48)
Short name:
Protein-tyrosine phosphatase PTP-2
Alternative name(s):
MPTP
Gene namesi
Name:Ptpn2
Synonyms:Ptpt
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:97806 Ptpn2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Newborn mice are viable and do not display physical abnormalities. However, by 3 to 5 weeks of age they develop hunched posture, diarrhea and anemia. They do not survive beyond 5 weeks of age due to severe anemia, hematopoietic defects and the development of progressive systemic inflammatory disease. They display splenomegaly, lymphadenopathy and thymic atrophy, associated with altered B-cell differentiation, altered erythropoiesis, and impaired T- and B-cell functions. The inflammatory disease is characterized by high levels of circulating proinflammatory cytokines and lymphocytic infiltrates in non-lymphoid tissues. Heterozygous Ptpn2+/- mice exhibit decreased gluconeogenesis and hepatic glucose production while muscle-specific disruption of Ptpn2 has no effect on insulin signaling and glucose homeostasis in this tissue.5 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi216C → S: Catalytically inactive. Unable to restore phosphatase activity toward PDGFRB. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000947531 – 406Tyrosine-protein phosphatase non-receptor type 2Add BLAST406

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei22PhosphotyrosineBy similarity1
Modified residuei52PhosphoserineBy similarity1
Modified residuei68PhosphotyrosineBy similarity1
Modified residuei216S-nitrosocysteineBy similarity1
Modified residuei293PhosphoserineBy similarity1
Modified residuei298PhosphoserineBy similarity1
Modified residuei304PhosphoserineBy similarity1
Modified residuei320PhosphoserineCombined sources1
Modified residuei339PhosphoserineBy similarity1
Isoform 2 (identifier: Q06180-2)
Modified residuei304PhosphoserineBy similarity1

Post-translational modificationi

Isoform 2: Specifically phosphorylated in a cell cycle-dependent manner by cyclin-dependent kinases CDK1 and CDK2. Probably activated through phosphorylation by PKR.By similarity

Keywords - PTMi

Phosphoprotein, S-nitrosylation

Proteomic databases

MaxQBiQ06180
PaxDbiQ06180
PeptideAtlasiQ06180
PRIDEiQ06180

PTM databases

iPTMnetiQ06180
PhosphoSitePlusiQ06180

Expressioni

Tissue specificityi

Ubiquitously expressed. The highest expression levels were found in ovary, testis, thymus and kidney.2 Publications

Gene expression databases

BgeeiENSMUSG00000024539
CleanExiMM_PTPN2
ExpressionAtlasiQ06180 baseline and differential
GenevisibleiQ06180 MM

Interactioni

Subunit structurei

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 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202484, 5 interactors
IntActiQ06180, 7 interactors
MINTiQ06180
STRINGi10090.ENSMUSP00000112675

Structurei

3D structure databases

ProteinModelPortaliQ06180
SMRiQ06180
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini5 – 275Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST271

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni216 – 222Substrate bindingBy similarity7
Regioni341 – 406Endoplasmic reticulum locationBy similarityAdd BLAST66
Regioni371 – 406Mediates interaction with STX17By similarityAdd BLAST36

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0789 Eukaryota
COG5599 LUCA
GeneTreeiENSGT00900000140785
HOGENOMiHOG000273908
HOVERGENiHBG008321
InParanoidiQ06180
KOiK18026
OMAiWQQLYLE
OrthoDBiEOG091G082B
PhylomeDBiQ06180
TreeFamiTF315897

Family and domain databases

Gene3Di3.90.190.10, 1 hit
InterProiView protein in InterPro
IPR029021 Prot-tyrosine_phosphatase-like
IPR000242 PTPase_domain
IPR012265 Ptpn1/Ptpn2
IPR016130 Tyr_Pase_AS
IPR003595 Tyr_Pase_cat
IPR000387 TYR_PHOSPHATASE_dom
PfamiView protein in Pfam
PF00102 Y_phosphatase, 1 hit
PIRSFiPIRSF000926 Tyr-Ptase_nr1, 1 hit
PRINTSiPR00700 PRTYPHPHTASE
SMARTiView protein in SMART
SM00194 PTPc, 1 hit
SM00404 PTPc_motif, 1 hit
SUPFAMiSSF52799 SSF52799, 1 hit
PROSITEiView protein in PROSITE
PS00383 TYR_PHOSPHATASE_1, 1 hit
PS50056 TYR_PHOSPHATASE_2, 1 hit
PS50055 TYR_PHOSPHATASE_PTP, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q06180-1) [UniParc]FASTAAdd to basket
Also known as: PTPB, 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.

« Hide

        10         20         30         40         50
MSATIEREFE ELDAQCRWQP LYLEIRNESH DYPHRVAKFP ENRNRNRYRD
60 70 80 90 100
VSPYDHSRVK LQSTENDYIN ASLVDIEEAQ RSYILTQGPL PNTCCHFWLM
110 120 130 140 150
VWQQKTKAVV MLNRTVEKES VKCAQYWPTD DREMVFKETG FSVKLLSEDV
160 170 180 190 200
KSYYTVHLLQ LENINTGETR TISHFHYTTW PDFGVPESPA SFLNFLFKVR
210 220 230 240 250
ESGCLTPDHG PAVIHCSAGI GRSGTFSLVD TCLVLMEKGE DVNVKQLLLN
260 270 280 290 300
MRKYRMGLIQ TPDQLRFSYM AIIEGAKYTK GDSNIQKRWK ELSKEDLSPI
310 320 330 340 350
CDHSQNRVMV EKYNGKRIGS EDEKLTGLPS KVQDTVEESS ESILRKRIRE
360 370 380 390 400
DRKATTAQKV QQMKQRLNET ERKRKRWLYW QPILTKMGFV SVILVGALVG

WTLLFH
Length:406
Mass (Da):47,360
Last modified:January 4, 2005 - v2
Checksum:iDFB881DF3C800DC3
GO
Isoform 2 (identifier: Q06180-2) [UniParc]FASTAAdd to basket
Also known as: PTPA, TC-PTPa

The sequence of this isoform differs from the canonical sequence as follows:
     377-406: WLYWQPILTKMGFVSVILVGALVGWTLLFH → PRLTDT

Show »
Length:382
Mass (Da):44,573
Checksum:iBFE174ABC0963929
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012367377 – 406WLYWQ…TLLFH → PRLTDT in isoform 2. 2 PublicationsAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81477 mRNA Translation: AAA37446.1
S52655 mRNA Translation: AAB25035.2
BC008269 mRNA Translation: AAH08269.1
AK076072 mRNA Translation: BAC36163.1
AK132013 mRNA Translation: BAE20939.1
CCDSiCCDS37851.1 [Q06180-2]
CCDS50311.1 [Q06180-1]
PIRiA38191
RefSeqiNP_001120649.1, NM_001127177.1 [Q06180-1]
NP_033003.1, NM_008977.3 [Q06180-2]
XP_011245160.1, XM_011246858.2 [Q06180-2]
UniGeneiMm.260433

Genome annotation databases

EnsembliENSMUST00000025420; ENSMUSP00000025420; ENSMUSG00000024539 [Q06180-2]
ENSMUST00000122412; ENSMUSP00000112675; ENSMUSG00000024539 [Q06180-1]
GeneIDi19255
KEGGimmu:19255
UCSCiuc008fmu.2 mouse [Q06180-2]
uc008fmv.2 mouse [Q06180-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPTN2_MOUSE
AccessioniPrimary (citable) accession number: Q06180
Secondary accession number(s): Q3V259, Q922E7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: January 4, 2005
Last modified: March 28, 2018
This is version 164 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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