SYK
entrez
6850
canonical
uniprot
P43405
canonical
ensembl
ENSG00000165025
resolver
ensp
ENSP00000364898
resolver
ensp
ENSP00000364899
resolver
ensp
ENSP00000364904
resolver
ensp
ENSP00000364907
resolver
ensp
ENSP00000535936
resolver
ensp
ENSP00000535938
resolver
ensp
ENSP00000640543
resolver
ensp
ENSP00000677242
resolver
genesymbol
SYK
resolver
hgnc
HGNC:11491
resolver
uniprot
C3W981
resolver
uniprot_entry
C3W981_HUMAN
resolver
uniprot_entry
KSYK_HUMAN
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. Phosphorylates SH3BP2 which in turn may regulate SYK through LYN (By similarity). {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MASSGMADSANHLPFFFGNITREEAEDYLVQGGMSDGLYLLRQSRNYLGGFALSVAHGRKAHHYTIERELNGTYAIAGGRTHASPADLCHYHSQESDGLVCLLKKPFNRPQGVQPKTGPFEDLKENLIREYVKQTWNLQGQALEQAIISQKPQLEKLIATTAHEKMPWFHGKISREESEQIVLIGSKTNGKFLIRARDNNGSYALCLLHEGKVLHYRIDKDKTGKLSIPEGKKFDTLWQLVEHYSYKADGLLRVLTVPCQKIGTQGNVNFGGRPQLPGSHPATWSAGGIISRIKSYSFPKPGHRKSSPAQGNRQESTVSFNPYEPELAPWAADKGPQREALPMDTEVYESPYADPEEIRPKEVYLDRKLLTLEDKELGSGNFGTVKKGYYQMKKVVKTVAVKILKNEANDPALKDELLAEANVMQQLDNPYIVRMIGICEAESWMLVMEMAELGPLNKYLQQNRHVKDKNIIELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADENYYKAQTHGKWPVKWYAPECINYYKFSSKSDVWSFGVLMWEAFSYGQKPYRGMKGSEVTAMLEKGERMGCPAGCPREMYDLMNLCWTYDVENRPGFAAVELRLRNYYYDVVN
uniprot
proteins
disease_involvement
DISEASE: Immunodeficiency 82 with systemic inflammation (IMD82) [MIM:619381]: An autosomal dominant immunologic disorder with onset in early childhood. It is characterized by recurrent infections with various organisms, and multi-organ inflammation that manifests as colitis, hepatitis, arthritis and dermatitis. Patients have a propensity for the development of lymphoma, usually in adulthood. Disease severity is variable. {ECO:0000269|PubMed:33782605}. Note=The disease is caused by variants affecting the gene represented in this entry.
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 (PubMed:12387735, PubMed:33782605). Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains (PubMed:12387735, PubMed:9698567). The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains (PubMed:20154219). 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 (PubMed:8657103, PubMed:12456653, PubMed:15388330, PubMed:18369315, PubMed:34634301, PubMed:39694035, PubMed:8657103). 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 (PubMed:12456653). Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors (PubMed:12456653, PubMed:18369315). It also phosphorylates and activates PLCG1 and the PKC signaling pathway (PubMed:8657103). It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling (By similarity). In addition to its function downstream of BCR also plays a role in T-cell receptor signaling. Also plays 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 (By similarity). Required for the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770). 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 (PubMed:12387735). 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 (PubMed:20154219). 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 (PubMed:39694035). {ECO:0000250|UniProtKB:P48025, ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:12456653, ECO:0000269|PubMed:15123770, ECO:0000269|PubMed:15388330, ECO:0000269|PubMed:18369315, ECO:0000269|PubMed:19909739, ECO:0000269|PubMed:20154219, ECO:0000269|PubMed:33782605, ECO:0000269|PubMed:34634301, ECO:0000269|PubMed:39694035, ECO:0000269|PubMed:8657103, ECO:0000269|PubMed:9535867, ECO:0000269|PubMed:9698567}.
uniprot
proteins
mass_dalton
72066
uniprot
proteins
mutagenesis
MUTAGEN 297; /note="S->A: Abolishes YWHAG binding."; /evidence="ECO:0000269|PubMed:21469132"; MUTAGEN 630; /note="Y->F: Loss of interaction with BLNK."; /evidence="ECO:0000269|PubMed:18369315
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation. {ECO:0000250}.; PTM: Autophosphorylated. Phosphorylated on tyrosine residues by LYN following receptors engagement. Phosphorylation on Tyr-323 creates a binding site for CBL, an adapter protein that serves as a negative regulator of BCR-stimulated calcium ion signaling. Phosphorylation at Tyr-348 creates a binding site for VAV1. Phosphorylation on Tyr-348 and Tyr-352 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 (PubMed:15123770). Phosphorylation on Ser-297 is very common, it peaks 5 minutes after BCR stimulation, and creates a binding site for YWHAG. Phosphorylation at Tyr-630 creates a binding site for BLNK. Dephosphorylated by PTPN6. {ECO:0000250, ECO:0000269|PubMed:10458769, ECO:0000269|PubMed:15123770, ECO:0000269|PubMed:18369315, ECO:0000269|PubMed:21469132}.
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
10449770
uniprot
proteins
pubmed
10458769
uniprot
proteins
pubmed
11162587
uniprot
proteins
pubmed
11940607
uniprot
proteins
pubmed
12387735
uniprot
proteins
pubmed
12456653
uniprot
proteins
pubmed
15123770
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15388330
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18369315
uniprot
proteins
pubmed
18818202
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19843936
uniprot
proteins
pubmed
19909739
uniprot
proteins
pubmed
20154219
uniprot
proteins
pubmed
20713593
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21469132
uniprot
proteins
pubmed
22019427
uniprot
proteins
pubmed
23299888
uniprot
proteins
pubmed
24607955
uniprot
proteins
pubmed
33782605
uniprot
proteins
pubmed
34634301
uniprot
proteins
pubmed
39694035
uniprot
proteins
pubmed
7513161
uniprot
proteins
pubmed
7895172
uniprot
proteins
pubmed
8163536
uniprot
proteins
pubmed
8168854
uniprot
proteins
pubmed
8590001
uniprot
proteins
pubmed
8657103
uniprot
proteins
pubmed
8986718
uniprot
proteins
pubmed
9535867
uniprot
proteins
pubmed
9698567
uniprot
proteins
pubmed
9857068
uniprot
proteins
sequence_length
635
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}. Cytoplasm, cytosol {ECO:0000305}.
uniprot
proteins