Target Information
Target General Infomation | |||||
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Target ID |
T37952
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Former ID |
TTDI02237
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Target Name |
mRNA of SYK
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Gene Name |
SYK
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Synonyms |
Spleen tyrosine kinase (mRNA); Tyrosine-protein kinase SYK (mRNA); p72-Syk (mRNA); SYK
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Target Type |
Discontinued
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Disease | Asthma [ICD10: J45] | ||||
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 isrequired for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen.
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BioChemical Class |
Target of siRNA drug
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UniProt ID | |||||
EC Number |
EC 2.7.10.2
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Sequence |
MASSGMADSANHLPFFFGNITREEAEDYLVQGGMSDGLYLLRQSRNYLGGFALSVAHGRK
AHHYTIERELNGTYAIAGGRTHASPADLCHYHSQESDGLVCLLKKPFNRPQGVQPKTGPF EDLKENLIREYVKQTWNLQGQALEQAIISQKPQLEKLIATTAHEKMPWFHGKISREESEQ IVLIGSKTNGKFLIRARDNNGSYALCLLHEGKVLHYRIDKDKTGKLSIPEGKKFDTLWQL VEHYSYKADGLLRVLTVPCQKIGTQGNVNFGGRPQLPGSHPATWSAGGIISRIKSYSFPK PGHRKSSPAQGNRQESTVSFNPYEPELAPWAADKGPQREALPMDTEVYESPYADPEEIRP KEVYLDRKLLTLEDKELGSGNFGTVKKGYYQMKKVVKTVAVKILKNEANDPALKDELLAE ANVMQQLDNPYIVRMIGICEAESWMLVMEMAELGPLNKYLQQNRHVKDKNIIELVHQVSM GMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADENYYKAQTHGKWPVKWYA PECINYYKFSSKSDVWSFGVLMWEAFSYGQKPYRGMKGSEVTAMLEKGERMGCPAGCPRE MYDLMNLCWTYDVENRPGFAAVELRLRNYYYDVVN |
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Drugs and Mode of Action | |||||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | NF-kappa B signaling pathway | ||||
PI3K-Akt signaling pathway | |||||
Osteoclast differentiation | |||||
Platelet activation | |||||
Natural killer cell mediated cytotoxicity | |||||
B cell receptor signaling pathway | |||||
Fc epsilon RI signaling pathway | |||||
Fc gamma R-mediated phagocytosis | |||||
Tuberculosis | |||||
Epstein-Barr virus infection | |||||
Viral carcinogenesis | |||||
PANTHER Pathway | B cell activation | ||||
Pathway Interaction Database | Fc-epsilon receptor I signaling in mast cells | ||||
BCR signaling pathway | |||||
GMCSF-mediated signaling events | |||||
Atypical NF-kappaB pathway | |||||
Osteopontin-mediated events | |||||
FAS (CD95) signaling pathway | |||||
Thromboxane A2 receptor signaling | |||||
IL2-mediated signaling events | |||||
Class I PI3K signaling events | |||||
Alpha-synuclein signaling | |||||
PathWhiz Pathway | Fc Epsilon Receptor I Signaling in Mast Cells | ||||
Reactome | GPVI-mediated activation cascade | ||||
FCGR activation | |||||
Regulation of actin dynamics for phagocytic cup formation | |||||
Role of phospholipids in phagocytosis | |||||
DAP12 signaling | |||||
Fc epsilon receptor (FCERI) signaling | |||||
Role of LAT2/NTAL/LAB on calcium mobilization | |||||
FCERI mediated MAPK activation | |||||
FCERI mediated Ca+2 mobilization | |||||
Integrin alphaIIb beta3 signaling | |||||
Interleukin-2 signaling | |||||
CLEC7A (Dectin-1) signaling | |||||
Dectin-2 family | |||||
Regulation of signaling by CBL | |||||
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers | |||||
WikiPathways | IL-2 Signaling Pathway | ||||
IL-3 Signaling Pathway | |||||
Fc epsilon receptor (FCERI) signaling | |||||
Signaling by the B Cell Receptor (BCR) | |||||
Interleukin-2 signaling | |||||
Fcgamma receptor (FCGR) dependent phagocytosis | |||||
DAP12 interactions | |||||
B Cell Receptor Signaling Pathway | |||||
RANKL/RANK Signaling Pathway | |||||
Integrin alphaIIb beta3 signaling | |||||
GPVI-mediated activation cascade | |||||
Regulation of toll-like receptor signaling pathway | |||||
IL-5 Signaling Pathway | |||||
References |
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