Target name

P43405: Tyrosine-protein kinase SYK


  Protein function

Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR plays also a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade. Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen.

  Database links

Uniprot primary ID P43405
PDB ID 4PX6 4PUZ 4FYO 4FYN 1A81 4DFN 4DFL 3FQE 3FQH 4RX8 4RX9 3FQS 1CSY 3SRV 1CSZ 4I0S 3BUW 4I0T 4GFG 3EMG 4PV0 4FZ6 4FZ7 3TUB 3TUC 3TUD 4F4P 4RX7 5CY3 4I0R 5CXH 1XBA 1XBC 1XBB 4FL2 4FL3 4FL1 5CXZ 3VF9 3VF8
DrugBank ID
BioGrid ID 112717
GuidetoPHARMACOLOGY ID 2230
PharmGKB ID PA36273
KEGG ID hsa:6850
DIP ID DIP-253N
STRING ID 9606.ENSP00000364898
IntAct ID P43405
DMDM 1174527
BRENDA 2.7.10.2
Reactome R-HSA-983695 R-HSA-2029485 R-HSA-912631 R-HSA-2029481 R-HSA-2029482 R-HSA-5621480 R-HSA-2454202 R-HSA-114604 R-HSA-2871796 R-HSA-451927 R-HSA-354192 R-HSA-2871809 R-HSA-5607764 R-HSA-2424491 R-HSA-2730905
SignaLink P43405
BioCyc
Entrez Gene (Gene ID) 6850
BindingDB P43405

  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 0.857 0.005 0.901 0.003 0.879 0.003 0.877 0.005 0.940 0.000 0.757 0.005 Download
Estate fingerprints 0.832 0.004 0.752 0.007 0.792 0.004 0.802 0.004 0.870 0.000 0.585 0.008 Download
MACCS fingerprints 0.817 0.008 0.779 0.007 0.798 0.006 0.802 0.006 0.888 0.004 0.597 0.009 Download
Daylight fingerprints 0.872 0.008 0.868 0.008 0.870 0.005 0.871 0.006 0.908 0.004 0.741 0.009 Download
ECFP2 fingerprints 0.877 0.005 0.875 0.007 0.876 0.005 0.878 0.004 0.940 0.000 0.751 0.006 Download
ECFP4 fingerprints 0.870 0.005 0.950 0.005 0.910 0.005 0.905 0.005 0.950 0.000 0.820 0.008 Download
ECFP6 fingerprints 0.843 0.008 0.977 0.000 0.910 0.005 0.904 0.005 0.950 0.000 0.829 0.006 Download

  Download datasets

Positive dataset Negative dataset


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School of Pharmaceutical Sciences, Central South University. All rights reserved.

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