Target name

P43403: Tyrosine-protein kinase ZAP-70


  Protein function

Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR).

  Database links

Uniprot primary ID P43403
PDB ID 1FBV 1U59 4A4C 4A4B 1M61 4K2R 2OZO 4XZ0 4XZ1 3ZNI 2OQ1 2Y1N 2CBL
DrugBank ID
BioGrid ID 113367
GuidetoPHARMACOLOGY ID 2285
PharmGKB ID PA37447
KEGG ID hsa:7535
DIP ID DIP-38781N
STRING ID 9606.ENSP00000264972
IntAct ID P43403
DMDM 1177044
BRENDA 2.7.10.2
Reactome R-HSA-202433 R-HSA-202430
SignaLink P43403
BioCyc
Entrez Gene (Gene ID) 7535
BindingDB P43403

  Model Performance Metrics

Fingerprint type Sensitivity SEN_std Specificity SPE_std Accuracy ACC_std F1-score F1-score_std AUC AUC_std MCC MCC_std Download model
FP2 fingerprints 0.829 0.003 0.933 0.008 0.881 0.003 0.874 0.005 0.937 0.005 0.764 0.005 Download
Estate fingerprints 0.841 0.009 0.775 0.011 0.808 0.008 0.812 0.004 0.869 0.003 0.612 0.010 Download
MACCS fingerprints 0.837 0.008 0.851 0.012 0.844 0.005 0.843 0.005 0.904 0.005 0.686 0.010 Download
Daylight fingerprints 0.860 0.007 0.922 0.007 0.891 0.003 0.888 0.004 0.936 0.005 0.786 0.010 Download
ECFP2 fingerprints 0.865 0.007 0.909 0.013 0.887 0.005 0.884 0.005 0.940 0.005 0.773 0.012 Download
ECFP4 fingerprints 0.846 0.010 0.954 0.008 0.900 0.008 0.896 0.008 0.942 0.004 0.808 0.013 Download
ECFP6 fingerprints 0.837 0.011 0.985 0.005 0.911 0.007 0.904 0.005 0.949 0.003 0.831 0.009 Download

  Download datasets

Positive dataset Negative dataset


Copyright @ 2012-2014 Computational Biology & Drug Design Group,
School of Pharmaceutical Sciences, Central South University. All rights reserved.

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