CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-023691
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Tyrosine-protein phosphatase non-receptor type 22 
Protein Synonyms/Alias
 Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP; Lymphoid phosphatase; LyP; PEST-domain phosphatase; PEP 
Gene Name
 PTPN22 
Gene Synonyms/Alias
 PTPN8 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
17FLDEAQSKKITKEEFubiquitination[1]
18LDEAQSKKITKEEFAubiquitination[1]
21AQSKKITKEEFANEFubiquitination[1]
61NIKKNRYKDILPYDYubiquitination[1]
166SCEAEKRKSDYIIRTubiquitination[1]
309SGTESQAKHCIPEKNubiquitination[1]
315AKHCIPEKNHTLQADubiquitination[1, 2]
364RTSEISAKEELVLHPubiquitination[1]
396KNADTTMKWQTKAFPubiquitination[1]
400TTMKWQTKAFPIVGEubiquitination[1, 2]
411IVGEPLQKHQSLDLGubiquitination[1]
429FEGCSNSKPVNAAGRubiquitination[1]
441AGRYFNSKVPITRTKubiquitination[1]
448KVPITRTKSTPFELIubiquitination[1, 2]
461LIQQRETKEVDSKENubiquitination[1]
466ETKEVDSKENFSYLEubiquitination[1]
506YSLPYDSKHQIRNASubiquitination[1]
640EFSPNVPKSLSSAVKubiquitination[1]
647KSLSSAVKVKIGTSLubiquitination[1]
649LSSAVKVKIGTSLEWubiquitination[1]
664GGTSEPKKFDDSVILubiquitination[1]
770CNSCPPNKPAESVQSubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 
Functional Description
 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-493' residue. Dephosphorylates the immune system activator SKAP2. 
Sequence Annotation
 DOMAIN 24 289 Tyrosine-protein phosphatase.
 REGION 227 233 Substrate binding.
 ACT_SITE 227 227 Phosphocysteine intermediate (By
 BINDING 195 195 Substrate (By similarity).
 BINDING 274 274 Substrate.
 MOD_RES 35 35 Phosphoserine; by PKC/PRKCD.
 MOD_RES 635 635 Phosphoserine (By similarity).
 MOD_RES 692 692 Phosphoserine (By similarity).
 DISULFID 129 227  
Keyword
 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; Disulfide bond; Hydrolase; Immunity; Phosphoprotein; Polymorphism; Protein phosphatase; Reference proteome; Systemic lupus erythematosus. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 807 AA 
Protein Sequence
MDQREILQKF LDEAQSKKIT KEEFANEFLK LKRQSTKYKA DKTYPTTVAE KPKNIKKNRY 60
KDILPYDYSR VELSLITSDE DSSYINANFI KGVYGPKAYI ATQGPLSTTL LDFWRMIWEY 120
SVLIIVMACM EYEMGKKKCE RYWAEPGEMQ LEFGPFSVSC EAEKRKSDYI IRTLKVKFNS 180
ETRTIYQFHY KNWPDHDVPS SIDPILELIW DVRCYQEDDS VPICIHCSAG CGRTGVICAI 240
DYTWMLLKDG IIPENFSVFS LIREMRTQRP SLVQTQEQYE LVYNAVLELF KRQMDVIRDK 300
HSGTESQAKH CIPEKNHTLQ ADSYSPNLPK STTKAAKMMN QQRTKMEIKE SSSFDFRTSE 360
ISAKEELVLH PAKSSTSFDF LELNYSFDKN ADTTMKWQTK AFPIVGEPLQ KHQSLDLGSL 420
LFEGCSNSKP VNAAGRYFNS KVPITRTKST PFELIQQRET KEVDSKENFS YLESQPHDSC 480
FVEMQAQKVM HVSSAELNYS LPYDSKHQIR NASNVKHHDS SALGVYSYIP LVENPYFSSW 540
PPSGTSSKMS LDLPEKQDGT VFPSSLLPTS STSLFSYYNS HDSLSLNSPT NISSLLNQES 600
AVLATAPRID DEIPPPLPVR TPESFIVVEE AGEFSPNVPK SLSSAVKVKI GTSLEWGGTS 660
EPKKFDDSVI LRPSKSVKLR SPKSELHQDR SSPPPPLPER TLESFFLADE DCMQAQSIET 720
YSTSYPDTME NSTSSKQTLK TPGKSFTRSK SLKILRNMKK SICNSCPPNK PAESVQSNNS 780
SSFLNFGFAN RFSKPKGPRN PPPTWNI 807 
Gene Ontology
 GO:0009898; C:internal side of plasma membrane; IDA:UniProtKB.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
 GO:0019900; F:kinase binding; ISS:BHF-UCL.
 GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB.
 GO:0017124; F:SH3 domain binding; ISS:BHF-UCL.
 GO:0050868; P:negative regulation of T cell activation; IMP:BHF-UCL.
 GO:0050860; P:negative regulation of T cell receptor signaling pathway; IDA:UniProtKB.
 GO:0035644; P:phosphoanandamide dephosphorylation; ISS:BHF-UCL.
 GO:0050855; P:regulation of B cell receptor signaling pathway; NAS:BHF-UCL.
 GO:0045088; P:regulation of innate immune response; IC:BHF-UCL.
 GO:0032817; P:regulation of natural killer cell proliferation; IDA:BHF-UCL.
 GO:0030217; P:T cell differentiation; ISS:BHF-UCL.
 GO:0050852; P:T cell receptor signaling pathway; IEA:Compara. 
Interpro
 IPR016276; Non-rcpt_Tyr_Pase_8/22.
 IPR000387; Tyr/Dual-sp_Pase.
 IPR016130; Tyr_Pase_AS.
 IPR000242; Tyr_Pase_rcpt/non-rcpt. 
Pfam
 PF00102; Y_phosphatase 
SMART
 SM00194; PTPc 
PROSITE
 PS00383; TYR_PHOSPHATASE_1
 PS50056; TYR_PHOSPHATASE_2
 PS50055; TYR_PHOSPHATASE_PTP 
PRINTS
 PR00700; PRTYPHPHTASE.