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P29352 (PTN22_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein phosphatase non-receptor type 22

EC=3.1.3.48
Alternative name(s):
Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP
PEST-domain phosphatase
Short name=PEP
Gene names
Name:Ptpn22
Synonyms:Ptpn8
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length802 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules. Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue. Dephosphorylates ZAP70 at its activating 'Tyr-492' residue. Dephosphorylates the immune system activator SKAP2 By similarity. Ref.3

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Subunit structure

Interacts with CBL By similarity. Interacts with CSK. Interacts with LPXN. Ref.3 Ref.4

Subcellular location

Cytoplasm Ref.3.

Tissue specificity

Spleen, thymus, lymph node and bone marrow.

Post-translational modification

Phosphorylation on Ser-35 by PKC/PRKCD abrogates its ability to dephosphorylate and inactivate the SRC family kinases By similarity.

Sequence similarities

Belongs to the protein-tyrosine phosphatase family. Non-receptor class 4 subfamily.

Contains 1 tyrosine-protein phosphatase domain.

Ontologies

Keywords
   Biological processImmunity
   Cellular componentCytoplasm
   Molecular functionHydrolase
Protein phosphatase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell differentiation

Inferred from mutant phenotype PubMed 14752163. Source: MGI

T cell receptor signaling pathway

Inferred from mutant phenotype PubMed 14752163. Source: MGI

negative regulation of T cell activation

Inferred from mutant phenotype PubMed 21044313. Source: BHF-UCL

negative regulation of T cell receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

phosphoanandamide dephosphorylation

Inferred from direct assay PubMed 16938887. Source: BHF-UCL

protein dephosphorylation

Inferred from mutant phenotype PubMed 14752163. Source: MGI

regulation of natural killer cell proliferation

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 10940933. Source: UniProtKB

cytoplasmic side of plasma membrane

Inferred from direct assay PubMed 10940933. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 10940933. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from sequence or structural similarity. Source: BHF-UCL

   Molecular_functionSH3 domain binding

Inferred from physical interaction Ref.3. Source: BHF-UCL

kinase binding

Inferred from physical interaction Ref.3. Source: BHF-UCL

protein tyrosine phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 802802Tyrosine-protein phosphatase non-receptor type 22
PRO_0000094776

Regions

Domain24 – 289266Tyrosine-protein phosphatase
Region227 – 2337Substrate binding By similarity
Region613 – 6219Interaction with CSK

Sites

Active site2271Phosphocysteine intermediate By similarity
Binding site1951Substrate By similarity
Binding site2741Substrate By similarity

Amino acid modifications

Modified residue351Phosphoserine; by PKC/PRKCD By similarity
Modified residue6341Phosphoserine Ref.5
Modified residue6801Phosphoserine Ref.5
Modified residue6871Phosphoserine Ref.5

Experimental info

Sequence conflict911K → Q in AAH55377. Ref.2
Sequence conflict1411R → H in AAH55377. Ref.2

Secondary structure

... 802
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P29352 [UniParc].

Last modified December 1, 1992. Version 1.
Checksum: 0F1E45339BD4613E

FASTA80289,714
        10         20         30         40         50         60 
MDQREILQQL LKEAQKKKLN SEEFASEFLK LKRQSTKYKA DKIYPTTVAQ RPKNIKKNRY 

        70         80         90        100        110        120 
KDILPYDHSL VELSLLTSDE DSSYINASFI KGVYGPKAYI ATQGPLSTTL LDFWRMIWEY 

       130        140        150        160        170        180 
RILVIVMACM EFEMGKKKCE RYWAEPGETQ LQFGPFSISC EAEKKKSDYK IRTLKAKFNN 

       190        200        210        220        230        240 
ETRIIYQFHY KNWPDHDVPS SIDPILQLIW DMRCYQEDDC VPICIHCSAG CGRTGVICAV 

       250        260        270        280        290        300 
DYTWMLLKDG IIPKNFSVFN LIQEMRTQRP SLVQTQEQYE LVYSAVLELF KRHMDVISDN 

       310        320        330        340        350        360 
HLGREIQAQC SIPEQSLTVE ADSCPLDLPK NAMRDVKTTN QHSKQGAEAE STGGSSLGLR 

       370        380        390        400        410        420 
TSTMNAEEEL VLHSAKSSPS FNCLELNCGC NNKAVITRNG QARASPVVGE PLQKYQSLDF 

       430        440        450        460        470        480 
GSMLFGSCPS ALPINTADRY HNSKGPVKRT KSTPFELIQQ RKTNDLAVGD GFSCLESQLH 

       490        500        510        520        530        540 
EHYSLRELQV QRVAHVSSEE LNYSLPGACD ASCVPRHSPG ALRVHLYTSL AEDPYFSSSP 

       550        560        570        580        590        600 
PNSADSKMSF DLPEKQDGAT SPGALLPASS TTSFFYSNPH DSLVMNTLTS FSPPLNQETA 

       610        620        630        640        650        660 
VEAPSRRTDD EIPPPLPERT PESFIVVEEA GEPSPRVTES LPLVVTFGAS PECSGTSEMK 

       670        680        690        700        710        720 
SHDSVGFTPS KNVKLRSPKS DRHQDGSPPP PLPERTLESF FLADEDCIQA QAVQTSSTSY 

       730        740        750        760        770        780 
PETTENSTSS KQTLRTPGKS FTRSKSLKIF RNMKKSVCNS SSPSKPTERV QPKNSSSFLN 

       790        800 
FGFGNRFSKP KGPRNPPSAW NM 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences."
Matthews R.J., Bowne D.B., Flores E., Thomas M.L.
Mol. Cell. Biol. 12:2396-2405(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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].
Strain: C57BL/6NCr.
Tissue: Hematopoietic stem cell.
[3]"Association of inhibitory tyrosine protein kinase p50csk with protein tyrosine phosphatase PEP in T cells and other hemopoietic cells."
Cloutier J.-F., Veillette A.
EMBO J. 15:4909-4918(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 495-789, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CSK.
Tissue: Splenocyte.
[4]"Leupaxin binds to PEST domain tyrosine phosphatase PEP."
Watanabe N., Amano N., Ishizuka H., Mashima K.
Mol. Cell. Biochem. 269:13-17(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LPXN.
[5]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-634; SER-680 AND SER-687, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"A novel, specific interaction involving the Csk SH3 domain and its natural ligand."
Ghose R., Shekhtman A., Goger M.J., Ji H., Cowburn D.
Nat. Struct. Biol. 8:998-1004(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 612-629 IN COMPLEX WITH CSK.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M90388 mRNA. Translation: AAA39994.1.
BC055377 mRNA. Translation: AAH55377.1.
PIRB44390.
RefSeqNP_033005.1. NM_008979.2.
XP_006501211.1. XM_006501148.1.
XP_006501212.1. XM_006501149.1.
XP_006501213.1. XM_006501150.1.
UniGeneMm.395.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1JEGNMR-B605-629[»]
ProteinModelPortalP29352.
SMRP29352. Positions 3-297.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP29352. 2 interactions.
MINTMINT-1535132.

Chemistry

ChEMBLCHEMBL2157855.

PTM databases

PhosphoSiteP29352.

Proteomic databases

PRIDEP29352.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000029433; ENSMUSP00000029433; ENSMUSG00000027843.
GeneID19260.
KEGGmmu:19260.
UCSCuc008qtv.1. mouse.

Organism-specific databases

CTD26191.
MGIMGI:107170. Ptpn22.

Phylogenomic databases

eggNOGCOG5599.
GeneTreeENSGT00750000117233.
HOGENOMHOG000252955.
HOVERGENHBG103877.
InParanoidP29352.
KOK18024.
OMAADEDCMQ.
PhylomeDBP29352.
TreeFamTF351977.

Gene expression databases

ArrayExpressP29352.
BgeeP29352.
GenevestigatorP29352.

Family and domain databases

InterProIPR016276. Non-rcpt_Tyr_Pase_8/22.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
[Graphical view]
PfamPF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFPIRSF000930. PTPN8_PTPN22. 1 hit.
PRINTSPR00700. PRTYPHPHTASE.
SMARTSM00194. PTPc. 1 hit.
[Graphical view]
PROSITEPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPTPN22. mouse.
EvolutionaryTraceP29352.
NextBio296116.
PROP29352.
SOURCESearch...

Entry information

Entry namePTN22_MOUSE
AccessionPrimary (citable) accession number: P29352
Secondary accession number(s): Q7TMP9
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: April 16, 2014
This is version 119 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot