Syk
entrez
25155
canonical
uniprot
Q64725
canonical
ensembl
ENSRNOG00000012160
resolver
ensp
ENSRNOP00000016942
resolver
enst
ENSRNOT00000016942
resolver
genesymbol
Syk
resolver
uniprot
G3V7N4
resolver
uniprot_entry
G3V7N4_RAT
resolver
uniprot_entry
KSYK_RAT
resolver
activity_regulation
ACTIVITY 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 (By similarity). Phosphorylates SH3BP2 which in turn may regulate SYK through LYN (By similarity). {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MAGNAVDNANHLTYFFGNITREEAEDYLVQGGMTDGLYLLRQSRNYLGGFALSVAHNRKAHHYTIERELNGTYAISGGRAHASPADLCHYHSQEPEGLVCLLKKPFNRPPGVQPKTGPFEDLKENLIREYVKQTWNLQGQALEQAIISQKPQLEKLIATTAHEKMPWFHGNISRDESEQTVLIGSKTNGKFLIRARDNNGSFALCLLHEGKVLHYRIDRDKTGKLSIPEGKKFDTLWQLVEHYSYKPDGLLRVLTVPCQKIGVQMGHPGSSNAHPVTWSPGGIISRIKSYSFPKPGHKKPPPPQGSRPESTVSFNPYEPTGGAWGPDRGLQREALPMDTEVYESPYADPEEIRPKEVYLDRKLLTLEDNELGSGNFGTVKKGYYQMKKVVKTVAVKILKNEANDPALKDELLAEANVMQQLDNPYIVRMIGICEAESWMLVMEMAAWGPLNKYLQQNRHIKDKNIIELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADENYYKAQTHGKWPVKWYAPECINYFKFSSKSDVWSFGVLMWEAFSYGQKPYRGMKGSEVTAMLEKGERMGCPPGCPREMYDLMFLCWTYDVENRPGFAAVELRLRNYYYDVVN
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
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 DEPTOR, MYO1F, 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). Acts as a positive regulator of cGAS-STING signaling by mediating phosphorylation of MYO1F, thereby promoting plasma membrane localization and activation of CGAS (By similarity). {ECO:0000250|UniProtKB:P43405, ECO:0000250|UniProtKB:P48025, ECO:0000269|PubMed:8611520}.
uniprot
proteins
mass_dalton
71529
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated. Phosphorylated on tyrosine residues by LYN following receptors engagement. Phosphorylation on Tyr-317 creates a binding site for CBL, an adapter protein that serves as a negative regulator of BCR-stimulated calcium ion signaling (By similarity). Phosphorylation at Tyr-342 creates a binding site for VAV1 (By similarity). Phosphorylation on Tyr-342 and Tyr-346 enhances the phosphorylation and activation of phospholipase C-gamma and the early phase of calcium ion mobilization via a phosphoinositide 3-kinase-independent pathway (By similarity). Phosphorylated on tyrosine residues in response to IL15 (By similarity). Phosphorylation on Ser-291 is very common, it peaks 5 minutes after BCR stimulation, and creates a binding site for YWHAG (By similarity). Phosphorylation at Tyr-624 creates a binding site for BLNK (By similarity). Dephosphorylated by PTPN6 (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P43405}.; PTM: Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation. {ECO:0000250}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
SYK/ZAP-70 subfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
12077122
uniprot
proteins
pubmed
7759516
uniprot
proteins
pubmed
8611520
uniprot
proteins
sequence_length
629
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}. Cytoplasm, cytosol {ECO:0000305}.
uniprot
proteins