General Information of the Protein
Protein ID
PT06075
Protein Name
Tyrosine-protein kinase SYK
Secondarily
Protein Name
Spleen tyrosine kinase
p72Syk
Gene Name
SYK
Sequence
MAGNAVDNANHLTYFFGNITREEAEDYLVQGGMTDGLYLLRQSRNYLGGFALSVAHNRKAHHYTIERELNGTYAISGGRAHASPADLCHYHSQEPEGLVCLLKKPFNRPPGVQPKTGPFEDLKENLIREYVKQTWNLQGQALEQAIISQKPQLEKLIATTAHEKMPWFHGNISRDESEQTVLIGSKTNGKFLIRARDNNGSFALCLLHEGKVLHYRIDRDKTGKLSIPEGKKFDTLWQLVEHYSYKPDGLLRVLTVPCQKIGVQMGHPGSSNAHPVTWSPGGIISRIKSYSFPKPGHKKPPPPQGSRPESTVSFNPYEPTGGAWGPDRGLQREALPMDTEVYESPYADPEEIRPKEVYLDRKLLTLEDNELGSGNFGTVKKGYYQMKKVVKTVAVKILKNEANDPALKDELLAEANVMQQLDNPYIVRMIGICEAESWMLVMEMAAWGPLNKYLQQNRHIKDKNIIELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADENYYKAQTHGKWPVKWYAPECINYFKFSSKSDVWSFGVLMWEAFSYGQKPYRGMKGSEVTAMLEKGERMGCPPGCPREMYDLMFLCWTYDVENRPGFAAVELRLRNYYYDVVN
    Show/Hide
Organism
Rattus norvegicus, Rat
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
TK protein kinase group
>
Tyrosine protein kinase Syk family
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 DEPTOR, 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 also plays 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. Required for the stimulation of neutrophil phagocytosis by IL15 (By similarity). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). 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. Also plays 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. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity).
    Show/Hide
Uniprot ID
Q64725
Ensembl ID
ENSG00000165025
Subcellular Location
Cell membrane
Cytoplasm
Cytosol
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000278 , RBL-2H3
Compound ID Compound Name Compound Formula
CP0259173
3-((5-methoxy-1-methyl-1H-indol-3-yl)methylene)-N-methyl-2-oxoindoline-5-carboxamide
   Show/Hide
C21H19N3O3
 1
1
EC50 = 100 nM
   TI
   LI
   LO
   TS
CP0130033
3-[1-(5-Methoxy-1-methyl-1H-indol-3-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-1H-indole-5-sulfonic acid methylamide
   Show/Hide
C20H19N3O4S
 1
1
EC50 = 110 nM
   TI
   LI
   LO
   TS
CP0016242
3-((1-methyl-1H-indol-3-yl)methylene)-2-oxoindoline-5-sulfonamide
   Show/Hide
C18H15N3O3S
 1
1
EC50 = 313 nM
   TI
   LI
   LO
   TS
CP0320547
3-((5-methoxy-1-methyl-1H-indol-3-yl)methylene)-2-oxoindoline-5-carboxylic acid
   Show/Hide
C20H16N2O4
 1
1
EC50 = 3500 nM
   TI
   LI
   LO
   TS
CP0170330
3-((1-(3-hydroxypropyl)-5-methoxy-1H-indol-3-yl)methylene)-2-oxoindoline-5-sulfonamide
   Show/Hide
C21H21N3O5S
 1
1
EC50 > 10000 nM
   TI
   LI
   LO
   TS
CP0259174
4-{5-Methoxy-3-[2-oxo-5-sulfamoyl-1,2-dihydro-indol-(3Z)-ylidenemethyl]-indol-1-yl}-butyramide
   Show/Hide
C22H22N4O5S
 1
1
EC50 > 10000 nM
   TI
   LI
   LO
   TS
CP0853513
10-(3-aminopropyl)-3,4-dimethylacridin-9(10H)-one oxalate
   Show/Hide
C20H22N2O5
 1
1
IC50 = 10000 nM
   TI
   LI
   LO
   TS