Names & Taxonomy

Uniprot ID:
P43405
Entry Name:
KSYK_HUMAN
Status:
reviewed
Protein Names:
Tyrosine-protein kinase SYK (EC 2.7.10.2) (Spleen tyrosine kinase) (p72-Syk)
Gene Names:
SYK
Gene Names Primary:
SYK
Organism:
Homo sapiens (Human)

Structure

Length:
635
Sequence:
MASSGMADSANHLPFFFGNITREEAEDYLVQGGMSDGLYLLRQSRNYLGGFALSVAHGRKAHHYTIERELNGTYAIAGGRTHASPADLCHYHSQESDGLVCLLKKPFNRPQGVQPKTGPFEDLKENLIREYVKQTWNLQGQALEQAIISQKPQLEKLIATTAHEKMPWFHGKISREESEQIVLIGSKTNGKFLIRARDNNGSYALCLLHEGKVLHYRIDKDKTGKLSIPEGKKFDTLWQLVEHYSYKADGLLRVLTVPCQKIGTQGNVNFGGRPQLPGSHPATWSAGGIISRIKSYSFPKPGHRKSSPAQGNRQESTVSFNPYEPELAPWAADKGPQREALPMDTEVYESPYADPEEIRPKEVYLDRKLLTLEDKELGSGNFGTVKKGYYQMKKVVKTVAVKILKNEANDPALKDELLAEANVMQQLDNPYIVRMIGICEAESWMLVMEMAELGPLNKYLQQNRHVKDKNIIELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADENYYKAQTHGKWPVKWYAPECINYYKFSSKSDVWSFGVLMWEAFSYGQKPYRGMKGSEVTAMLEKGERMGCPAGCPREMYDLMNLCWTYDVENRPGFAAVELRLRNYYYDVVN
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell membrane

Function

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.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:
ENZYME REGULATION: Autoinhibited. Intramolecular binding of the interdomains A and B (also called linker region) to parts of the catalytic domain keep the catalytic center in an inactive conformation. The phosphorylation of the interdomains or the binding of the SH2 domains with dually phosphorylated ITAM domains on transmembrane proteins disrupt those intramolecular interactions allowing the kinase domain to adopt an active conformation. The phosphorylation of SYK and of the ITAM domains which is responsible for SYK activation is essentially mediated by SRC subfamily kinases, like LYN, upon transmembrane receptors engagement. May also be negatively regulated by PTPN6 through dephosphorylation. Downstream signaling adapters and intermediates like BLNK or RHOH may mediate positive and/or negative feedback regulation. Negatively regulated by CBL and CBLB through ubiquitination and probable degradation. Phosphorylates SH3BP2 which in turn may regulate SYK through LYN (By similarity).
Active Site:
ACT_SITE 494 494 Proton acceptor.
Gene Ontology Go:
B cell receptor complex
cytoplasm
cytosol
early phagosome
extrinsic component of cytoplasmic side of plasma membrane
nucleus
plasma membrane
protein complex
T cell receptor complex
ATP binding
integrin binding
non-membrane spanning protein tyrosine kinase activity
protein kinase activity
protein serine/threonine kinase activity
protein tyrosine kinase activity
receptor signaling protein tyrosine kinase activity
activation of JUN kinase activity
adaptive immune response
angiogenesis
B cell receptor signaling pathway
beta selection
blood coagulation
blood vessel morphogenesis
cell differentiation
cell proliferation
cellular response to low-density lipoprotein particle stimulus
cellular response to molecule of fungal origin
defense response to bacterium
Fc-epsilon receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
innate immune response
integrin-mediated signaling pathway
leukocyte activation involved in immune response
leukocyte cell-cell adhesion
leukotriene biosynthetic process
lymph vessel development
macrophage activation involved in immune response
neutrophil activation involved in immune response
neutrophil chemotaxis
organ morphogenesis
peptidyl-serine phosphorylation
peptidyl-tyrosine autophosphorylation
platelet activation
positive regulation of alpha-beta T cell differentiation
positive regulation of alpha-beta T cell proliferation
positive regulation of B cell differentiation
positive regulation of bone resorption
positive regulation of calcium-mediated signaling
positive regulation of cell adhesion mediated by integrin
positive regulation of cytokine secretion
positive regulation of gamma-delta T cell differentiation
positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process
positive regulation of interleukin-3 biosynthetic process
positive regulation of mast cell degranulation
positive regulation of peptidyl-tyrosine phosphorylation
positive regulation of receptor internalization
positive regulation of type I interferon production
protein phosphorylation
receptor internalization
regulation of arachidonic acid secretion
regulation of ERK1 and ERK2 cascade
regulation of neutrophil degranulation
regulation of phagocytosis
regulation of platelet activation
regulation of platelet aggregation
regulation of sequence-specific DNA binding transcription factor activity
regulation of superoxide anion generation
regulation of tumor necrosis factor-mediated signaling pathway
serotonin secretion by platelet
stimulatory C-type lectin receptor signaling pathway
transcription factor import into nucleus
transmembrane receptor protein tyrosine kinase signaling pathway
viral process
Gene Ontology Biological Process:
activation of JUN kinase activity
adaptive immune response
angiogenesis
B cell receptor signaling pathway
beta selection
blood coagulation
blood vessel morphogenesis
cell differentiation
cell proliferation
cellular response to low-density lipoprotein particle stimulus
cellular response to molecule of fungal origin
defense response to bacterium
Fc-epsilon receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
innate immune response
integrin-mediated signaling pathway
leukocyte activation involved in immune response
leukocyte cell-cell adhesion
leukotriene biosynthetic process
lymph vessel development
macrophage activation involved in immune response
neutrophil activation involved in immune response
neutrophil chemotaxis
organ morphogenesis
peptidyl-serine phosphorylation
peptidyl-tyrosine autophosphorylation
platelet activation
positive regulation of alpha-beta T cell differentiation
positive regulation of alpha-beta T cell proliferation
positive regulation of B cell differentiation
positive regulation of bone resorption
positive regulation of calcium-mediated signaling
positive regulation of cell adhesion mediated by integrin
positive regulation of cytokine secretion
positive regulation of gamma-delta T cell differentiation
positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process
positive regulation of interleukin-3 biosynthetic process
positive regulation of mast cell degranulation
positive regulation of peptidyl-tyrosine phosphorylation
positive regulation of receptor internalization
positive regulation of type I interferon production
protein phosphorylation
receptor internalization
regulation of arachidonic acid secretion
regulation of ERK1 and ERK2 cascade
regulation of neutrophil degranulation
regulation of phagocytosis
regulation of platelet activation
regulation of platelet aggregation
regulation of sequence-specific DNA binding transcription factor activity
regulation of superoxide anion generation
regulation of tumor necrosis factor-mediated signaling pathway
serotonin secretion by platelet
stimulatory C-type lectin receptor signaling pathway
transcription factor import into nucleus
transmembrane receptor protein tyrosine kinase signaling pathway
viral process
Gene Ontology Molecular Function:
ATP binding
integrin binding
non-membrane spanning protein tyrosine kinase activity
protein kinase activity
protein serine/threonine kinase activity
protein tyrosine kinase activity
receptor signaling protein tyrosine kinase activity
Gene Ontology Cellular Component:
B cell receptor complex
cytoplasm
cytosol
early phagosome
extrinsic component of cytoplasmic side of plasma membrane
nucleus
plasma membrane
protein complex
T cell receptor complex
Keywords:
3D-structure
ATP-binding
Adaptive immunity
Alternative splicing
Angiogenesis
Cell membrane
Complete proteome
Cytoplasm
Host-virus interaction
Immunity
Innate immunity
Kinase
Membrane
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
Repeat
SH2 domain
Transferase
Tyrosine-protein kinase
Ubl conjugation
Interacts With:
P22681; P20273; P11049; P07766; P00533; P04626; P21860; Q96IP4; P30273; P36888; Q13480; P06239; P08581; P19174; Q9NP31; P40763; P54274; Q8TF42; Q9UHP3

Publication

PubMed ID:
7513161 8163536 15164053 15489334 8168854 7895172 8986718 8657103 9535867 9857068 10458769 10449770 11162587 12456653 12387735 11940607 15388330 18369315 18818202 18088087 19369195 19690332 20154219 19909739 20713593 21269460 21469132 22019427 23299888 8590001 9698567