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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei195 – 1951SubstrateBy similarity
Active sitei227 – 2271Phosphocysteine intermediatePROSITE-ProRule annotation
Binding sitei274 – 2741SubstrateBy similarity

GO - Molecular functioni

  • kinase binding Source: BHF-UCL
  • protein tyrosine phosphatase activity Source: UniProtKB
  • SH3 domain binding Source: BHF-UCL

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • 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 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
  • peptidyl-tyrosine dephosphorylation Source: MGI
  • 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 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
  • protein dephosphorylation Source: MGI
  • regulation of leukocyte migration Source: UniProtKB
  • regulation of natural killer cell proliferation Source: BHF-UCL
  • regulation of NIK/NF-kappaB signaling Source: UniProtKB
  • T cell differentiation Source: MGI
  • T cell receptor signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Autophagy, Immunity

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 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
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 802802Tyrosine-protein phosphatase non-receptor type 22PRO_0000094776Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei35 – 351Phosphoserine; by PKC/PRKCDBy similarity
Modified residuei634 – 6341Phosphoserine1 Publication
Modified residuei680 – 6801Phosphoserine1 Publication
Modified residuei687 – 6871Phosphoserine1 Publication

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

PRIDEiP29352.

PTM databases

PhosphoSiteiP29352.

Expressioni

Tissue specificityi

Spleen, thymus, lymph node and bone marrow.

Gene expression databases

BgeeiP29352.
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

Protein-protein interaction databases

IntActiP29352. 2 interactions.
MINTiMINT-1535132.
STRINGi10090.ENSMUSP00000029433.

Structurei

Secondary structure

1
802
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi621 – 6244Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JEGNMR-B605-629[»]
ProteinModelPortaliP29352.
SMRiP29352. Positions 3-297.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP29352.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 289266Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni227 – 2337Substrate bindingBy similarity
Regioni613 – 6219Interaction with CSK

Sequence similaritiesi

Contains 1 tyrosine-protein phosphatase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG5599.
GeneTreeiENSGT00770000120452.
HOGENOMiHOG000252955.
HOVERGENiHBG103877.
InParanoidiP29352.
KOiK18024.
OMAiADEDCMQ.
PhylomeDBiP29352.
TreeFamiTF351977.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR016276. PTPN22.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
[Graphical view]
PANTHERiPTHR19134:SF260. PTHR19134:SF260. 1 hit.
PfamiPF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFiPIRSF000930. PTPN8_PTPN22. 1 hit.
PRINTSiPR00700. PRTYPHPHTASE.
SMARTiSM00194. PTPc. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti91 – 911K → Q in AAH55377 (PubMed:15489334).Curated
Sequence conflicti141 – 1411R → H in AAH55377 (PubMed:15489334).Curated

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_006501148.2.
XP_006501212.1. XM_006501149.2.
XP_006501213.1. XM_006501150.2.
XP_011238342.1. XM_011240040.1.
XP_011238343.1. XM_011240041.1.
XP_011238344.1. XM_011240042.1.
UniGeneiMm.395.

Genome annotation databases

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

Cross-referencesi

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_006501148.2.
XP_006501212.1. XM_006501149.2.
XP_006501213.1. XM_006501150.2.
XP_011238342.1. XM_011240040.1.
XP_011238343.1. XM_011240041.1.
XP_011238344.1. XM_011240042.1.
UniGeneiMm.395.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JEGNMR-B605-629[»]
ProteinModelPortaliP29352.
SMRiP29352. Positions 3-297.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP29352. 2 interactions.
MINTiMINT-1535132.
STRINGi10090.ENSMUSP00000029433.

Chemistry

ChEMBLiCHEMBL2157855.

PTM databases

PhosphoSiteiP29352.

Proteomic databases

PRIDEiP29352.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi26191.
MGIiMGI:107170. Ptpn22.

Phylogenomic databases

eggNOGiCOG5599.
GeneTreeiENSGT00770000120452.
HOGENOMiHOG000252955.
HOVERGENiHBG103877.
InParanoidiP29352.
KOiK18024.
OMAiADEDCMQ.
PhylomeDBiP29352.
TreeFamiTF351977.

Miscellaneous databases

ChiTaRSiPtpn22. mouse.
EvolutionaryTraceiP29352.
NextBioi296116.
PROiP29352.
SOURCEiSearch...

Gene expression databases

BgeeiP29352.
ExpressionAtlasiP29352. baseline and differential.
GenevisibleiP29352. MM.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR016276. PTPN22.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
[Graphical view]
PANTHERiPTHR19134:SF260. PTHR19134:SF260. 1 hit.
PfamiPF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFiPIRSF000930. PTPN8_PTPN22. 1 hit.
PRINTSiPR00700. PRTYPHPHTASE.
SMARTiSM00194. PTPc. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: FUNCTION, INTERACTION WITH TRAF3.
  7. "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "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.

Entry informationi

Entry nameiPTN22_MOUSE
AccessioniPrimary (citable) accession number: P29352
Secondary accession number(s): Q7TMP9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: July 22, 2015
This is version 132 of the entry and version 1 of the sequence. [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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.