Protein: Tyrosine-protein kinase SYK (EC 2.7.10.2) (Spleen tyrosine kinase) [Cleaved into: 72 kDa tyrosine-protein kinase SYK; 40 kDa tyrosine-protein kinase SYK] (Q00655)
Organism: Sus scrofa (Pig)
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 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).
Subcellular location: [72 kDa tyrosine-protein kinase SYK]: Cell membrane {ECO:0000305}. Cytoplasm, cytosol. Note=Mainly associated with membranes.; SUBCELLULAR LOCATION: [40 kDa tyrosine-protein kinase SYK]: Cell membrane {ECO:0000305}. Cytoplasm, cytosol. Note=Equally distributed between membranes and cytosol.
Sequence: MADSANHLPFFFGQITREEAEDYLVQGGMSDGLYLLRQSRNYLGGFALSVAYDRKAHHYTIERELNGTYAISGGRTHGSPAELCHYHSQELDGLVCLLKNPFNRPPGVQPKTGPFEDLKENLIREYVKQTWNLQGQALEQAIISQKPQLEKLIATTAHEKMPWFHGKISRDESEQIVLIGSKTNGKFLIRARDNGSYALGLLHEGKVLHYRIDKDKTGKLSIPGGKNFDTLWQLVEHYSYKSDGLLRVLTVPCQKIGGQTGNDSFRPQLPSAHPATWSAGGIISRIKSYSFPKPGHRKASSPQGNRPESLVSYNPYESDRGPWANEREAQREALPMDTEVYESPYADPEEIRPKEVYLDRKLLTLEDKELGSGNFGTVKKGYYQMKKVVKTVAVKILKNEANDPALKDELLAEANVMQQLDNPYIVRMIGICEAESWMLVMEMAELGPLNKYLQQNRHVKDKNIIELVHQVSMGMKYLEECNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADENYYKAQTHGKWPVKWYAPECINYYKFSSKSDVWSFGVLMWEAFSYGQKPYRGMKGSEVSAMLEKGERMGCPPGCPREMYELMTLCWTYDVENRPGFVAVELRLRNYYYDVVN
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [368-620]
- IPR023420: Tyrosine-protein kinase SYK/ZAP-70, inter-SH2 domain superfamily (homologous_superfamily) [113-153]
- IPR035838: SYK/ZAP-70, N-terminal SH2 domain (domain) [8-111]
- IPR050198: Non-receptor tyrosine kinases involved in cell signaling (family) [140-616]
- IPR036860: SH2 domain superfamily (homologous_superfamily) [1-383]
- IPR001245: Serine-threonine/tyrosine-protein kinase, catalytic domain (domain) [367-616]
- IPR017441: Protein kinase, ATP binding site (binding_site) [370-395]
- IPR000719: Protein kinase domain (domain) [364-624]
- IPR012234: Tyrosine-protein kinase, non-receptor SYK/ZAP-70 (family) [1-628]
- IPR008266: Tyrosine-protein kinase, active site (active_site) [483-495]
- IPR020635: Tyrosine-protein kinase, catalytic domain (domain) [364-619]
- IPR000980: SH2 domain (domain) [8-253]
Interaction partners: - TYRO protein tyrosine kinase-binding protein
- 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma
- Proto-oncogene vav
- 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma
- Tyrosine-protein kinase
- Vav guanine nucleotide exchange factor 3.
- B-cell linker protein isoform 1.
- Tyrosine-protein phosphatase non-receptor type
- Vav guanine nucleotide exchange factor 2.
- E3 ubiquitin-protein ligase CBL
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0044237 (cellular metabolic process), GO:0048584 (positive regulation of response to stimulus), GO:0032879 (regulation of localization), GO:0002684 (positive regulation of immune system process), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0002682 (regulation of immune system process), GO:0071704 (organic substance metabolic process), GO:0051050 (positive regulation of transport), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0006793 (phosphorus metabolic process), GO:0002696 (positive regulation of leukocyte activation), GO:1903530 (regulation of secretion by cell), GO:0051049 (regulation of transport), GO:0050776 (regulation of immune response), GO:0051047 (positive regulation of secretion), GO:1901564 (organonitrogen compound metabolic process), GO:0002697 (regulation of immune effector process), GO:0019538 (protein metabolic process), GO:0050778 (positive regulation of immune response), GO:0060627 (regulation of vesicle-mediated transport), GO:0002699 (positive regulation of immune effector process), GO:0050865 (regulation of cell activation), GO:0043170 (macromolecule metabolic process), GO:1903532 (positive regulation of secretion by cell), GO:0043300 (regulation of leukocyte degranulation), GO:0036211 (protein modification process), GO:0043412 (macromolecule modification), GO:0002703 (regulation of leukocyte mediated immunity), GO:0033003 (regulation of mast cell activation), GO:0033006 (regulation of mast cell activation involved in immune response), GO:0043302 (positive regulation of leukocyte degranulation), GO:0017157 (regulation of exocytosis), GO:0051046 (regulation of secretion), GO:0006796 (phosphate-containing compound metabolic process), GO:0033008 (positive regulation of mast cell activation involved in immune response), GO:0045921 (positive regulation of exocytosis), GO:0033005 (positive regulation of mast cell activation), GO:0043306 (positive regulation of mast cell degranulation), GO:0016310 (phosphorylation), GO:0043304 (regulation of mast cell degranulation), GO:0002886 (regulation of myeloid leukocyte mediated immunity), GO:1903307 (positive regulation of regulated secretory pathway), GO:0006468 (protein phosphorylation), GO:1903305 (regulation of regulated secretory pathway), GO:0046777 (protein autophosphorylation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005829 (cytosol), GO:0005622 (intracellular anatomical structure)