Top PTPN22
Download FASTA sequences of PTPN22-substrates in Humans
Pathway ID Pathway Name Pathway Description (KEGG) R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains. Prior to T cell receptor (TCR) stimulation, CD4/CD8 associated Lck remains seperated from the TCR and is maintained in an inactive state by the action of Csk. Csk phosphorylates the negative regulatory tyrosine of Lck and inactivates the Lck kinase domain. Upon TCR stimulation, CD4/CD8 associated Lck co-localizes with the TCR leading to the phosphorylation of the CD3 and TCR subunit. Lck becomes activated by way of CD45-mediated dephosphorylation of negative regulatory tyrosine residues. The presence to PAG-bound Csk is further reduced via the dephosphorylation of PAG (step 1).
Lck is further activated by trans-autophosphorylation on the tyrosine residue on its activation loop (step 2). Active Lck further phosphorylates the tyrosine residues on CD3 chains. The signal-transducing CD3 delta/epsilon/gamma and TCR zeta chains contain a critical signaling motif known as the immunoreceptor tyrosine-based activation motif (ITAM). The two critical tyrosines of each ITAM motif are phosphorylated by Lck (step 3)
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse. The dual phosphorylated ITAMs recruit Syk kinase ZAP-70 via their tandem SH2 domains (step 4). ZAP-70 subsequently undergoes phosphorylation on multiple tyrosine residues for further activation. ZAP-70 includes both positive and negative regulatory sites. Tyrosine 493 is a conserved regulatory site found within the activation loop of the kinase domain. This site has shown to be a positive regulatory site required for ZAP-70 kinase activity and is phosphorylated by Lck (step 5). This phosphorylation contributes to the active conformation of the catalytic domain. Later ZAP-70 undergoes trans-autophosphorylation at Y315 and Y319 (step 6). These sites appear to be positive regulatory sites. ZAP-70 achieves its full activation after the trans-autophosphorylation. Activated ZAP-70 along with Lck phosphorylates the multiple tyrosine residues in the adaptor protein LAT (step 7)
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source ACTA1 Affinity Capture-MS physical 16461343 , (Europe PMC )NA BioGRID AKR7A2 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID CALR Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID CALU Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID CBL Affinity Capture-Western, anti bait coimmunoprecipitation physical, physical association 10068674 , (Europe PMC )0.40 BioGRID, IntAct, MINT CCDC138 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID CD247 Affinity Capture-Western, anti tag coimmunoprecipitation, pull down association, direct interaction, physical, physical association 16461343 , (Europe PMC )0.63 BioGRID, IntAct CD3E Affinity Capture-MS, Affinity Capture-Western, pull down association, physical 16461343 , (Europe PMC )0.35 BioGRID, IntAct CEP131 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID CLK1 Biochemical Activity physical 26167880 , (Europe PMC )NA BioGRID CSK Affinity Capture-MS, Proximity Label-MS physical 27432908 , 27880917 , (Europe PMC )NA BioGRID EGFR Affinity Capture-Luminescence, PCA, Two-hybrid, luminescence based mammalian interactome mapping, ubiquitin reconstruction physical, physical association 24658140 , 25402006 , (Europe PMC )0.51 BioGRID, IntAct EIF3E Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID GLUD1 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID GRB2 Affinity Capture-Western, anti bait coimmunoprecipitation, phage display direct interaction, physical, physical association 11882361 , (Europe PMC )0.54 BioGRID, IntAct, MINT HAX1 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID HSPB1 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID KIAA0753 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID KIF7 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID LCK Affinity Capture-MS, Affinity Capture-Western, phosphatase assay, pull down association, dephosphorylation reaction, direct interaction, physical 16461343 , 19167335 , 21719704 , (Europe PMC )0.78 BioGRID, IntAct LZTS2 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID MAD2L1BP Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID MAIP1 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID MED4 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID MIB1 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID NDUFA9 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID NDUFB10 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID PIBF1 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID PRKAR2A Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID PSTPIP2 Affinity Capture-MS physical 27432908 , 27880917 , (Europe PMC )NA BioGRID PTPN22 Affinity Capture-MS, Affinity Capture-Western, x-ray crystallography direct interaction, physical 10068674 , 18056643 , 27432908 , (Europe PMC )0.44 BioGRID, IntAct RCN1 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID RPS19BP1 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID SCO2 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID SDF4 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID SFXN4 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID SLC25A19 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID SPTA1 Affinity Capture-MS physical 16461343 , (Europe PMC )NA BioGRID SRPK2 Biochemical Activity physical 26167880 , (Europe PMC )NA BioGRID SSX2IP Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID TBC1D31 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID VAV1 Affinity Capture-MS, pull down association, physical 16461343 , (Europe PMC )0.35 BioGRID, IntAct VCP Affinity Capture-MS, pull down association, physical 16461343 , (Europe PMC )0.35 BioGRID, IntAct ZAP70 Affinity Capture-MS, Affinity Capture-Western, phosphatase assay, pull down association, dephosphorylation reaction, direct interaction, physical 16461343 , (Europe PMC )0.60 BioGRID, IntAct
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source CD247 Affinity Capture-Western, anti tag coimmunoprecipitation, pull down association, direct interaction, physical, physical association 16461343 , (Europe PMC )0.63 BioGRID, IntAct CD3E Affinity Capture-MS, Affinity Capture-Western, pull down association, physical 16461343 , (Europe PMC )0.35 BioGRID, IntAct CDH2 phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct EGFR Affinity Capture-Luminescence, PCA, Two-hybrid, luminescence based mammalian interactome mapping, ubiquitin reconstruction physical, physical association 24658140 , 25402006 , (Europe PMC )0.51 BioGRID, IntAct ERBB2 phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct GHR phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct GRB2 Affinity Capture-Western, anti bait coimmunoprecipitation, phage display direct interaction, physical, physical association 11882361 , (Europe PMC )0.54 BioGRID, IntAct, MINT LCK Affinity Capture-MS, Affinity Capture-Western, phosphatase assay, pull down association, dephosphorylation reaction, direct interaction, physical 16461343 , 19167335 , 21719704 , (Europe PMC )0.78 BioGRID, IntAct NTRK1 phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct PDGFRB phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct PDPK1 phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct PRKCD protein kinase assay direct interaction 18056643 , (Europe PMC )0.44 IntAct PSTPIP1 anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, pull down physical association 25040622 , (Europe PMC )0.59 IntAct, MINT PTPN22 Affinity Capture-MS, Affinity Capture-Western, x-ray crystallography direct interaction, physical 10068674 , 18056643 , 27432908 , (Europe PMC )0.44 BioGRID, IntAct SKAP2 anti tag coimmunoprecipitation, phosphatase assay, x-ray crystallography dephosphorylation reaction, direct interaction, physical association 21719704 , (Europe PMC )0.61 IntAct TRAF3 anti bait coimmunoprecipitation physical association 23871208 , (Europe PMC )0.40 IntAct VAV1 Affinity Capture-MS, pull down association, physical 16461343 , (Europe PMC )0.35 BioGRID, IntAct VCP Affinity Capture-MS, pull down association, physical 16461343 , (Europe PMC )0.35 BioGRID, IntAct WAS phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct ZAP70 Affinity Capture-MS, Affinity Capture-Western, phosphatase assay, pull down association, dephosphorylation reaction, direct interaction, physical 16461343 , (Europe PMC )0.60 BioGRID, IntAct
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source GRB2 Affinity Capture-Western, anti bait coimmunoprecipitation, phage display direct interaction, physical, physical association 11882361 , (Europe PMC )0.54 BioGRID, IntAct, MINT PSTPIP1 anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, pull down physical association 25040622 , (Europe PMC )0.59 IntAct, MINT
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source ACTA1 Affinity Capture-MS physical 16461343 , (Europe PMC )NA BioGRID AKR7A2 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID CALR Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID CALU Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID CBL Affinity Capture-Western, anti bait coimmunoprecipitation physical, physical association 10068674 , (Europe PMC )0.40 BioGRID, IntAct, MINT CCDC138 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID CD247 Affinity Capture-Western, anti tag coimmunoprecipitation, pull down association, direct interaction, physical, physical association 16461343 , (Europe PMC )0.63 BioGRID, IntAct CD3E Affinity Capture-MS, Affinity Capture-Western, pull down association, physical 16461343 , (Europe PMC )0.35 BioGRID, IntAct CDH2 phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct CEP131 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID CLK1 Biochemical Activity physical 26167880 , (Europe PMC )NA BioGRID CSK Affinity Capture-MS, Proximity Label-MS physical 27432908 , 27880917 , (Europe PMC )NA BioGRID EGFR Affinity Capture-Luminescence, PCA, Two-hybrid, luminescence based mammalian interactome mapping, ubiquitin reconstruction physical, physical association 24658140 , 25402006 , (Europe PMC )0.51 BioGRID, IntAct EIF3E Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID ERBB2 phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct GHR phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct GLUD1 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID GRB2 Affinity Capture-Western, anti bait coimmunoprecipitation, phage display direct interaction, physical, physical association 11882361 , (Europe PMC )0.54 BioGRID, IntAct, MINT HAX1 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID HSPB1 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID KIAA0753 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID KIF7 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID LCK Affinity Capture-MS, Affinity Capture-Western, phosphatase assay, pull down association, dephosphorylation reaction, direct interaction, physical 16461343 , 19167335 , 21719704 , (Europe PMC )0.78 BioGRID, IntAct LZTS2 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID MAD2L1BP Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID MAIP1 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID MED4 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID MIB1 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID NDUFA9 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID NDUFB10 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID NTRK1 phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct PDGFRB phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct PDPK1 phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct PIBF1 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID PRKAR2A Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID PRKCD protein kinase assay direct interaction 18056643 , (Europe PMC )0.44 IntAct PSTPIP1 anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, pull down physical association 25040622 , (Europe PMC )0.59 IntAct, MINT PSTPIP2 Affinity Capture-MS physical 27432908 , 27880917 , (Europe PMC )NA BioGRID PTPN22 Affinity Capture-MS, Affinity Capture-Western, x-ray crystallography direct interaction, physical 10068674 , 18056643 , 27432908 , (Europe PMC )0.44 BioGRID, IntAct RCN1 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID RPS19BP1 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID SCO2 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID SDF4 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID SFXN4 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID SKAP2 anti tag coimmunoprecipitation, phosphatase assay, x-ray crystallography dephosphorylation reaction, direct interaction, physical association 21719704 , (Europe PMC )0.61 IntAct SLC25A19 Affinity Capture-MS physical 27432908 , (Europe PMC )NA BioGRID SPTA1 Affinity Capture-MS physical 16461343 , (Europe PMC )NA BioGRID SRPK2 Biochemical Activity physical 26167880 , (Europe PMC )NA BioGRID SSX2IP Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID TBC1D31 Proximity Label-MS physical 27880917 , (Europe PMC )NA BioGRID TRAF3 anti bait coimmunoprecipitation physical association 23871208 , (Europe PMC )0.40 IntAct VAV1 Affinity Capture-MS, pull down association, physical 16461343 , (Europe PMC )0.35 BioGRID, IntAct VCP Affinity Capture-MS, pull down association, physical 16461343 , (Europe PMC )0.35 BioGRID, IntAct WAS phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct ZAP70 Affinity Capture-MS, Affinity Capture-Western, phosphatase assay, pull down association, dephosphorylation reaction, direct interaction, physical 16461343 , (Europe PMC )0.60 BioGRID, IntAct
Phosphorylating Kinases Phosphoresidues Detection Method PubMed IDs Source
Visualize a network of protein kinases and phosphatases phosphorylating and dephosphorylating this protein respectively
PRKCD S35_FLKLKRQsTKYKADK , in vitro, in vivo 18056643 ,(Europe PMC )HPRD, PhosphoSitePlus , Unknown S35_FLKLKRQsTKYKADK , S414_EPLQKHQsLDLGSLL , in vivo 18056643 , 20058876 ,(Europe PMC )HPRD,
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