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IID50282
UniprotP48025
ProteinTyrosine-protein kinase SYK
GeneSyk
OrganismMus musculus
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
629
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 338-350 Hetero dimer : IID00652Complex
 Evidence NMR 2mc1 B Reference
       Region 2mc1 B 338-350 order
 Evidence NMR 2lct B Reference
       Region 2lct B 338-350 order
Seqphosphorylation
    313-313 Phosphoserine
    310-310 Phosphoserine
    291-291 Phosphoserine
    290-290 Phosphotyrosine
    289-289 Phosphoserine
    255-255 Phosphothreonine
    270-270 Phosphoserine
    201-201 Phosphoserine
    130-130 Phosphotyrosine
    46-46 Phosphotyrosine
    43-43 Phosphoserine
    27-27 Phosphotyrosine
    519-519 Phosphotyrosine; by autocatalysis
    625-625 Phosphotyrosine
    624-624 Phosphotyrosine
    623-623 Phosphotyrosine
    576-576 Phosphothreonine
    573-573 Phosphoserine
    540-540 Phosphotyrosine
    524-524 Phosphothreonine
    520-520 Phosphotyrosine
    311-311 Phosphothreonine
    501-501 Phosphotyrosine
    478-478 Phosphotyrosine
    358-358 Phosphotyrosine
    373-373 Phosphoserine
    378-378 Phosphothreonine
    344-344 Phosphoserine
    346-346 Phosphotyrosine
    342-342 Phosphotyrosine
    339-339 Phosphothreonine
    317-317 Phosphotyrosine; by LYN
 
Prediction
NeProc
Disorder 1-6,267-341
Order 7-266,342-402,408-629
ProS 267-341
AlphaFold
Disorder 1-7,262-331,512-512,514-528
Order 8-261,332-511,513-513,529-629
Pfam Hmmer
PF00017 14-91 3.8e-30
PF00017 167-243 1.7e-30
PF07714 364-620 6.1e-127
Function
Function in SwissProt
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. 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 (PubMed:19098920). 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. 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 (PubMed:26195794).