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Overview

Uniprot IDQ9Y2R2
Protein NameTyrosine-protein phosphatase non-receptor type 22
Gene NamePTPN22
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
337 KSTTKAAKMMNQQRT

Function

Acts as a 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 (PubMed:16461343, PubMed:18056643). Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue (PubMed:21719704). Dephosphorylates ZAP70 at its activating 'Tyr-493' residue (PubMed:16461343). Dephosphorylates the immune system activator SKAP2 (PubMed:21719704). Positively regulates toll-like receptor (TLR)-induced type 1 interferon production (PubMed:23871208). Promotes host antiviral responses mediated by type 1 interferon (By similarity). Regulates NOD2-induced pro-inflammatory cytokine secretion and autophagy (PubMed:23991106). Acts as an activator of NLRP3 inflammasome assembly by mediating dephosphorylation of 'Tyr-861' of NLRP3 (PubMed:27043286). Dephosphorylates phospho-anandamide (p-AEA), an endocannabinoid to anandamide (also called N-arachidonoylethanolamide) (By similarity)

Protein Sequence

10 MDQREILQKF 20 LDEAQSKKIT 30 KEEFANEFLK 40 LKRQSTKYKA 50 DKTYPTTVAE 60 KPKNIKKNRY 70 KDILPYDYSR 80 VELSLITSDE 90 DSSYINANFI 100 KGVYGPKAYI 110 ATQGPLSTTL 120 LDFWRMIWEY 130 SVLIIVMACM 140 EYEMGKKKCE 150 RYWAEPGEMQ 160 LEFGPFSVSC 170 EAEKRKSDYI 180 IRTLKVKFNS 190 ETRTIYQFHY 200 KNWPDHDVPS 210 SIDPILELIW 220 DVRCYQEDDS 230 VPICIHCSAG 240 CGRTGVICAI 250 DYTWMLLKDG 260 IIPENFSVFS 270 LIREMRTQRP 280 SLVQTQEQYE 290 LVYNAVLELF 300 KRQMDVIRDK 310 HSGTESQAKH 320 CIPEKNHTLQ 330 ADSYSPNLPK 340 STTKAAKMMN 350 QQRTKMEIKE 360 SSSFDFRTSE 370 ISAKEELVLH 380 PAKSSTSFDF 390 LELNYSFDKN 400 ADTTMKWQTK 410 AFPIVGEPLQ 420 KHQSLDLGSL 430 LFEGCSNSKP 440 VNAAGRYFNS 450 KVPITRTKST 460 PFELIQQRET 470 KEVDSKENFS 480 YLESQPHDSC 490 FVEMQAQKVM 500 HVSSAELNYS 510 LPYDSKHQIR 520 NASNVKHHDS 530 SALGVYSYIP 540 LVENPYFSSW 550 PPSGTSSKMS 560 LDLPEKQDGT 570 VFPSSLLPTS 580 STSLFSYYNS 590 HDSLSLNSPT 600 NISSLLNQES 610 AVLATAPRID 620 DEIPPPLPVR 630 TPESFIVVEE 640 AGEFSPNVPK 650 SLSSAVKVKI 660 GTSLEWGGTS 670 EPKKFDDSVI 680 LRPSKSVKLR 690 SPKSELHQDR 700 SSPPPPLPER 710 TLESFFLADE 720 DCMQAQSIET 730 YSTSYPDTME 740 NSTSSKQTLK 750 TPGKSFTRSK 760 SLKILRNMKK 770 SICNSCPPNK 780 PAESVQSNNS 790 SSFLNFGFAN 800 RFSKPKGPRN PPPTWNI

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0009898 cytoplasmic side of plasma membrane
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005634 nucleus
Cellular Component GO:0048471 perinuclear region of cytoplasm
Molecular Function GO:0019900 kinase binding
Molecular Function GO:0004726 non-membrane spanning protein tyrosine phosphatase activity
Molecular Function GO:0016791 phosphatase activity
Molecular Function GO:0004725 protein tyrosine phosphatase activity
Molecular Function GO:0017124 SH3 domain binding
Molecular Function GO:0031625 ubiquitin protein ligase binding
Biological Process GO:0006914 autophagy
Biological Process GO:0071225 cellular response to muramyl dipeptide
Biological Process GO:0006629 lipid metabolic process
Biological Process GO:0031663 lipopolysaccharide-mediated signaling pathway
Biological Process GO:0010507 negative regulation of autophagy
Biological Process GO:0010629 negative regulation of gene expression
Biological Process GO:0032715 negative regulation of interleukin-6 production
Biological Process GO:0032717 negative regulation of interleukin-8 production
Biological Process GO:0043508 negative regulation of JUN kinase activity
Biological Process GO:0070433 negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
Biological Process GO:1903753 negative regulation of p38MAPK cascade
Biological Process GO:0050868 negative regulation of T cell activation
Biological Process GO:0050860 negative regulation of T cell receptor signaling pathway
Biological Process GO:0032720 negative regulation of tumor necrosis factor production
Biological Process GO:0035644 phosphoanandamide dephosphorylation
Biological Process GO:0070374 positive regulation of ERK1 and ERK2 cascade
Biological Process GO:0010628 positive regulation of gene expression
Biological Process GO:1900227 positive regulation of NLRP3 inflammasome complex assembly
Biological Process GO:1902523 positive regulation of protein K63-linked ubiquitination
Biological Process GO:0034141 positive regulation of toll-like receptor 3 signaling pathway
Biological Process GO:0034145 positive regulation of toll-like receptor 4 signaling pathway
Biological Process GO:0032481 positive regulation of type I interferon production
Biological Process GO:0032729 positive regulation of type II interferon production
Biological Process GO:0050855 regulation of B cell receptor signaling pathway
Biological Process GO:0045088 regulation of innate immune response
Biological Process GO:0032817 regulation of natural killer cell proliferation
Biological Process GO:1901222 regulation of non-canonical NF-kappaB signal transduction
Biological Process GO:0032496 response to lipopolysaccharide
Biological Process GO:0030217 T cell differentiation
Biological Process GO:0050852 T cell receptor signaling pathway

Reference

[1] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.