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Protein

Tyrosine-protein phosphatase non-receptor type 22

Gene

Ptpn22

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity). Associates with and probably dephosphorylates CBL (By similarity). Dephosphorylates LCK at its activating 'Tyr-394' residue (By similarity). Dephosphorylates ZAP70 at its activating 'Tyr-492' residue (By similarity). Dephosphorylates the immune system activator SKAP2 (By similarity). Positively regulates toll-like receptor (TLR)-induced type 1 interferon production (PubMed:23871208). Promotes host antiviral responses mediated by type 1 interferon (PubMed:23871208). Regulates NOD2-induced pro-inflammatory cytokine secretion and autophagy (PubMed:23991106).By similarity2 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei195SubstrateBy similarity1
Active sitei227Phosphocysteine intermediatePROSITE-ProRule annotation1
Binding sitei274SubstrateBy similarity1

GO - Molecular functioni

  • kinase binding Source: BHF-UCL
  • phosphatase activity Source: MGI
  • protein tyrosine kinase binding Source: Ensembl
  • protein tyrosine phosphatase activity Source: UniProtKB
  • SH3 domain binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: MGI

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • cellular response to muramyl dipeptide Source: UniProtKB
  • lipopolysaccharide-mediated signaling pathway Source: MGI
  • negative regulation of autophagy Source: MGI
  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of interleukin-6 secretion Source: UniProtKB
  • negative regulation of interleukin-8 secretion Source: UniProtKB
  • negative regulation of JUN kinase activity Source: MGI
  • negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKB
  • negative regulation of p38MAPK cascade Source: UniProtKB
  • negative regulation of T cell activation Source: BHF-UCL
  • negative regulation of T cell receptor signaling pathway Source: UniProtKB
  • negative regulation of tumor necrosis factor production Source: UniProtKB
  • phosphoanandamide dephosphorylation Source: BHF-UCL
  • positive regulation of CD8-positive, alpha-beta T cell proliferation Source: UniProtKB
  • positive regulation of defense response to virus by host Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of granzyme B production Source: UniProtKB
  • positive regulation of interferon-alpha secretion Source: UniProtKB
  • positive regulation of interferon-beta secretion Source: UniProtKB
  • positive regulation of interferon-gamma secretion Source: MGI
  • positive regulation of protein K63-linked ubiquitination Source: UniProtKB
  • positive regulation of toll-like receptor 3 signaling pathway Source: UniProtKB
  • positive regulation of toll-like receptor 4 signaling pathway Source: UniProtKB
  • positive regulation of toll-like receptor 7 signaling pathway Source: UniProtKB
  • positive regulation of toll-like receptor 9 signaling pathway Source: UniProtKB
  • positive regulation of transcription factor import into nucleus Source: UniProtKB
  • positive regulation of type I interferon production Source: MGI
  • protein dephosphorylation Source: MGI
  • regulation of calcium ion transmembrane transport Source: Ensembl
  • regulation of leukocyte migration Source: UniProtKB
  • regulation of natural killer cell proliferation Source: BHF-UCL
  • regulation of NIK/NF-kappaB signaling Source: UniProtKB
  • regulation of peptidyl-tyrosine phosphorylation Source: Ensembl
  • response to lipopolysaccharide Source: MGI
  • T cell differentiation Source: MGI
  • T cell receptor signaling pathway Source: MGI

Keywordsi

Molecular functionHydrolase, Protein phosphatase
Biological processAutophagy, Immunity

Enzyme and pathway databases

ReactomeiR-MMU-202427. Phosphorylation of CD3 and TCR zeta chains.
R-MMU-202430. Translocation of ZAP-70 to Immunological synapse.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Ptpn22
Synonyms:Ptpn8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:107170. Ptpn22.

Subcellular locationi

  • Cytoplasm 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoplasmic side of plasma membrane Source: UniProtKB
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: BHF-UCL

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2157855.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000947761 – 802Tyrosine-protein phosphatase non-receptor type 22Add BLAST802

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei35Phosphoserine; by PKC/PRKCDBy similarity1
Modified residuei452PhosphoserineCombined sources1
Modified residuei634PhosphoserineCombined sources1
Modified residuei680PhosphoserineCombined sources1
Modified residuei687PhosphoserineCombined sources1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP29352.
MaxQBiP29352.
PaxDbiP29352.
PRIDEiP29352.

PTM databases

iPTMnetiP29352.
PhosphoSitePlusiP29352.

Expressioni

Tissue specificityi

Spleen, thymus, lymph node and bone marrow.

Gene expression databases

BgeeiENSMUSG00000027843.
ExpressionAtlasiP29352. baseline and differential.
GenevisibleiP29352. MM.

Interactioni

Subunit structurei

Interacts with CBL (By similarity). Interacts with CSK (PubMed:8890164, PubMed:11685249). Interacts with LPXN (PubMed:15786712). Interacts with TRAF3 (via MATH domain); the interaction promotes TRAF3 polyubiquitination (PubMed:23871208).By similarity4 Publications

GO - Molecular functioni

  • kinase binding Source: BHF-UCL
  • protein tyrosine kinase binding Source: Ensembl
  • SH3 domain binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: MGI

Protein-protein interaction databases

ELMiP29352.
IntActiP29352. 3 interactors.
MINTiMINT-1535132.
STRINGi10090.ENSMUSP00000029433.

Structurei

Secondary structure

1802
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi621 – 624Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JEGNMR-B605-629[»]
ProteinModelPortaliP29352.
SMRiP29352.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP29352.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 289Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST266

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni227 – 233Substrate bindingBy similarity7
Regioni613 – 621Interaction with CSK1 Publication9

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0789. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00880000137849.
HOGENOMiHOG000252955.
HOVERGENiHBG103877.
InParanoidiP29352.
KOiK18024.
OMAiPLQKHQS.
OrthoDBiEOG091G0B5O.
PhylomeDBiP29352.
TreeFamiTF351977.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiView protein in InterPro
IPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR016276. PTPN22.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
PfamiView protein in Pfam
PF00102. Y_phosphatase. 1 hit.
PIRSFiPIRSF000930. PTPN8_PTPN22. 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.

Sequencei

Sequence statusi: Complete.

P29352-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDQREILQQL LKEAQKKKLN SEEFASEFLK LKRQSTKYKA DKIYPTTVAQ
60 70 80 90 100
RPKNIKKNRY KDILPYDHSL VELSLLTSDE DSSYINASFI KGVYGPKAYI
110 120 130 140 150
ATQGPLSTTL LDFWRMIWEY RILVIVMACM EFEMGKKKCE RYWAEPGETQ
160 170 180 190 200
LQFGPFSISC EAEKKKSDYK IRTLKAKFNN ETRIIYQFHY KNWPDHDVPS
210 220 230 240 250
SIDPILQLIW DMRCYQEDDC VPICIHCSAG CGRTGVICAV DYTWMLLKDG
260 270 280 290 300
IIPKNFSVFN LIQEMRTQRP SLVQTQEQYE LVYSAVLELF KRHMDVISDN
310 320 330 340 350
HLGREIQAQC SIPEQSLTVE ADSCPLDLPK NAMRDVKTTN QHSKQGAEAE
360 370 380 390 400
STGGSSLGLR TSTMNAEEEL VLHSAKSSPS FNCLELNCGC NNKAVITRNG
410 420 430 440 450
QARASPVVGE PLQKYQSLDF GSMLFGSCPS ALPINTADRY HNSKGPVKRT
460 470 480 490 500
KSTPFELIQQ RKTNDLAVGD GFSCLESQLH EHYSLRELQV QRVAHVSSEE
510 520 530 540 550
LNYSLPGACD ASCVPRHSPG ALRVHLYTSL AEDPYFSSSP PNSADSKMSF
560 570 580 590 600
DLPEKQDGAT SPGALLPASS TTSFFYSNPH DSLVMNTLTS FSPPLNQETA
610 620 630 640 650
VEAPSRRTDD EIPPPLPERT PESFIVVEEA GEPSPRVTES LPLVVTFGAS
660 670 680 690 700
PECSGTSEMK SHDSVGFTPS KNVKLRSPKS DRHQDGSPPP PLPERTLESF
710 720 730 740 750
FLADEDCIQA QAVQTSSTSY PETTENSTSS KQTLRTPGKS FTRSKSLKIF
760 770 780 790 800
RNMKKSVCNS SSPSKPTERV QPKNSSSFLN FGFGNRFSKP KGPRNPPSAW

NM
Length:802
Mass (Da):89,714
Last modified:December 1, 1992 - v1
Checksum:i0F1E45339BD4613E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti91K → Q in AAH55377 (PubMed:15489334).Curated1
Sequence conflicti141R → H in AAH55377 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M90388 mRNA. Translation: AAA39994.1.
BC055377 mRNA. Translation: AAH55377.1.
CCDSiCCDS38577.1.
PIRiB44390.
RefSeqiNP_033005.1. NM_008979.2.
XP_006501211.1. XM_006501148.3.
XP_006501212.1. XM_006501149.3.
XP_006501213.1. XM_006501150.2.
XP_011238343.1. XM_011240041.2.
XP_011238344.1. XM_011240042.2.
UniGeneiMm.395.

Genome annotation databases

EnsembliENSMUST00000029433; ENSMUSP00000029433; ENSMUSG00000027843.
GeneIDi19260.
KEGGimmu:19260.
UCSCiuc008qtv.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiPTN22_MOUSE
AccessioniPrimary (citable) accession number: P29352
Secondary accession number(s): Q7TMP9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: August 30, 2017
This is version 149 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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