Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Tyrosine-protein phosphatase non-receptor type 2

Gene

Ptpn2

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity

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

Keywordsi

Molecular functionHydrolase, Protein phosphatase

Enzyme and pathway databases

ReactomeiR-RNO-6807004 Negative regulation of MET activity
R-RNO-877312 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 18

Organism-specific databases

RGDi620710 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000947541 – 416Tyrosine-protein phosphatase non-receptor type 2Add BLAST416

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 residuei320PhosphoserineBy similarity1
Modified residuei339PhosphoserineBy similarity1
Isoform 2 (identifier: P35233-2)
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

PaxDbiP35233
PRIDEiP35233

PTM databases

PhosphoSitePlusiP35233

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

BgeeiENSRNOG00000017453

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

GO - Molecular functioni

Protein-protein interaction databases

IntActiP35233, 1 interactor
STRINGi10116.ENSRNOP00000063665

Structurei

3D structure databases

SMRiP35233
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 – 410Endoplasmic reticulum locationBy similarityAdd BLAST70
Regioni371 – 410May mediate interaction with STX17By similarityAdd BLAST40

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0789 Eukaryota
COG5599 LUCA
GeneTreeiENSGT00900000140785
HOGENOMiHOG000273908
HOVERGENiHBG008321
InParanoidiP35233
KOiK18026
OMAiWQQLYLE

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 (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_042001287 – 305Missing in isoform 3 and isoform 4. 2 PublicationsAdd BLAST19
Alternative sequenceiVSP_042002377 – 410Missing in isoform 2 and isoform 4. 2 PublicationsAdd BLAST34

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

EnsembliENSRNOT00000023763; ENSRNOP00000023763; ENSRNOG00000017453 [P35233-4]
GeneIDi117063
KEGGirno:117063
UCSCiRGD:620710 rat [P35233-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPTN2_RAT
AccessioniPrimary (citable) accession number: P35233
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: November 16, 2011
Last modified: May 23, 2018
This is version 145 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

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health