UniProtKB - Q00655 (KSYK_PIG)
Tyrosine-protein kinase SYK
SYK
Functioni
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 (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. 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 (By similarity).
By similarity3 PublicationsCatalytic activityi
- EC:2.7.10.2PROSITE-ProRule annotation
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 395 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 487 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 370 – 378 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
- protein serine/threonine/tyrosine kinase activity Source: RHEA
GO - Biological processi
- adaptive immune response Source: UniProtKB
- angiogenesis Source: UniProtKB-KW
- B cell receptor signaling pathway Source: UniProtKB
- blood vessel morphogenesis Source: UniProtKB
- cellular response to low-density lipoprotein particle stimulus Source: UniProtKB
- cellular response to molecule of fungal origin Source: UniProtKB
- defense response to bacterium Source: UniProtKB
- innate immune response Source: UniProtKB
- integrin-mediated signaling pathway Source: UniProtKB
- interleukin-3-mediated signaling pathway Source: UniProtKB
- intracellular signal transduction Source: InterPro
- leukocyte activation involved in immune response Source: UniProtKB
- leukocyte cell-cell adhesion Source: UniProtKB
- lymph vessel development Source: UniProtKB
- macrophage activation involved in immune response Source: UniProtKB
- neutrophil activation involved in immune response Source: UniProtKB
- neutrophil chemotaxis Source: UniProtKB
- peptidyl-tyrosine phosphorylation Source: UniProtKB
- positive regulation of bone resorption Source: UniProtKB
- positive regulation of cell adhesion mediated by integrin Source: UniProtKB
- positive regulation of interleukin-4 production Source: UniProtKB
- receptor internalization Source: UniProtKB
- regulation of arachidonic acid secretion Source: UniProtKB
- regulation of ERK1 and ERK2 cascade Source: UniProtKB
- regulation of neutrophil degranulation Source: UniProtKB
- regulation of phagocytosis Source: UniProtKB
- regulation of platelet activation Source: UniProtKB
- regulation of platelet aggregation Source: UniProtKB
- regulation of superoxide anion generation Source: UniProtKB
- serotonin secretion by platelet Source: UniProtKB
Keywordsi
Molecular function | Kinase, Transferase, Tyrosine-protein kinase |
Biological process | Adaptive immunity, Angiogenesis, Immunity, Innate immunity |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.10.2, 6170 |
Names & Taxonomyi
Protein namesi | Recommended name: Tyrosine-protein kinase SYK (EC:2.7.10.2)Alternative name(s): Spleen tyrosine kinase Cleaved into the following 2 chains: |
Gene namesi | Name:SYK |
Organismi | Sus scrofa (Pig) |
Taxonomic identifieri | 9823 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Suina › Suidae › Sus |
Proteomesi |
|
Subcellular locationi
Plasma membrane
- Cell membrane Curated
Cytoplasm and Cytosol
Note: Mainly associated with membranes.
Plasma membrane
- Cell membrane Curated
Cytoplasm and Cytosol
Note: Equally distributed between membranes and cytosol.
Cytosol
- cytosol Source: Reactome
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
- early phagosome Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cytoplasm, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 341 | Y → F: Alters interaction with VAV1. 1 Publication | 1 | |
Mutagenesisi | 345 | Y → F: Moderately alters interaction with VAV1. 1 Publication | 1 | |
Mutagenesisi | 395 | K → R: Loss of kinase activity. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000024468 | 1 – 628 | 72 kDa tyrosine-protein kinase SYKAdd BLAST | 628 | |
ChainiPRO_0000024469 | 313 – 628 | 40 kDa tyrosine-protein kinase SYKAdd BLAST | 316 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 23 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 39 | PhosphoserineBy similarity | 1 | |
Modified residuei | 42 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 126 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 196 | PhosphoserineBy similarity | 1 | |
Modified residuei | 250 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 288 | PhosphoserineBy similarity | 1 | |
Modified residuei | 289 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 290 | PhosphoserineBy similarity | 1 | |
Modified residuei | 309 | PhosphoserineBy similarity | 1 | |
Modified residuei | 312 | PhosphoserineBy similarity | 1 | |
Modified residuei | 316 | Phosphotyrosine; by LYNBy similarity | 1 | |
Modified residuei | 338 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 341 | Phosphotyrosine1 Publication | 1 | |
Modified residuei | 343 | PhosphoserineBy similarity | 1 | |
Modified residuei | 345 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 357 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 372 | PhosphoserineBy similarity | 1 | |
Modified residuei | 377 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 477 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 500 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 518 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 519 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 523 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 539 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 572 | PhosphoserineBy similarity | 1 | |
Modified residuei | 622 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 623 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 624 | PhosphotyrosineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | Q00655 |
PRIDEi | Q00655 |
PTM databases
iPTMneti | Q00655 |
Expressioni
Tissue specificityi
Interactioni
Subunit structurei
Interacts with LYN; phosphorylates SYK.
Interacts with RHOH (phosphorylated); regulates mast cells activation (By similarity).
Interacts with NFAM1 (phosphorylated); probably involved in BCR signaling (By similarity).
Interacts with VAV1 (via SH2 domain); phosphorylates VAV1 upon BCR activation.
Interacts with GAB2 (phosphorylated); probably involved in IgE Fc receptor signaling (By similarity).
Interacts (via its SH2 domains) with CD79A (via its phosphorylated ITAM domain); the interaction stimulates SYK autophosphorylation and activation (By similarity).
Interacts (via SH2 domains) with FCER1G (via ITAM domain); activates SYK and mediates neutrophils and macrophages integrin-mediated activation (By similarity). Interaction with FCER1G in basophils triggers IL3-induced IL4 production (By similarity).
Interacts with ITGB2 and FGR; involved in ITGB2 downstream signaling (By similarity).
Interacts with ITGB3; upon activation by ITGB3 promotes platelet adhesion (By similarity).
Interacts (via SH2 domains) with TYROBP (via ITAM domain); involved in neutrophils and macrophages integrin-mediated activation (By similarity).
Interacts with MSN and SELPLG; mediates the selectin-dependent activation of SYK by SELPLG (By similarity).
Interacts with BLNK (via SH2 domain) (By similarity).
Interacts (via the second SH2 domain) with USP25 (via C-terminus); phosphorylates USP25 and regulates USP25 intracellular levels (By similarity).
Interacts (via SH2 domains) with CLEC1B (dimer) (By similarity).
Interacts with CLEC7A; participates in leukocyte activation in presence of fungal pathogens (By similarity).
Interacts (phosphorylated) with SLA; may regulate SYK through CBL recruitment (By similarity).
Interacts with YWHAG; attenuates BCR-induced membrane translocation and activation of SYK (By similarity).
Interacts (via SH2 domains) with GCSAM; the interaction increases after B-cell receptor stimulation, resulting in enhanced SYK autophosphorylation and activity (By similarity).
Interacts with TNS2; leading to the phosphorylation of SYK (By similarity).
Interacts with FLNA (via filamin repeat 5); docks SYK to the plasma membrane (By similarity).
Interacts CEACAM1; lipopolysaccharide activated neutrophils induce phosphorylation of SYK resulting in the formation of a complex including TLR4 and the phosphorylated form of SYK and CEACAM1, which in turn, recruits PTPN6 that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, which in turn, reduces the activity of the inflammasome (By similarity). Interacts (via SH2 domains) with CEACAM20 (phosphorylated form); the interaction further enhances CEACAM20 phosphorylation (By similarity).
Interacts with IL15RA (By similarity).
By similarityProtein-protein interaction databases
IntActi | Q00655, 1 interactor |
MINTi | Q00655 |
STRINGi | 9823.ENSSSCP00000010237 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 10 – 102 | SH2 1PROSITE-ProRule annotationAdd BLAST | 93 | |
Domaini | 163 – 253 | SH2 2PROSITE-ProRule annotationAdd BLAST | 91 | |
Domaini | 364 – 624 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 261 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 103 – 162 | Interdomain ABy similarityAdd BLAST | 60 | |
Regioni | 254 – 363 | Interdomain BBy similarityAdd BLAST | 110 | |
Regioni | 293 – 312 | DisorderedSequence analysisAdd BLAST | 20 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Repeat, SH2 domainPhylogenomic databases
eggNOGi | ENOG502QT06, Eukaryota |
InParanoidi | Q00655 |
OrthoDBi | 796831at2759 |
Family and domain databases
CDDi | cd09938, SH2_N-SH2_Zap70_Syk_like, 1 hit |
Gene3Di | 1.10.930.10, 1 hit 3.30.505.10, 2 hits |
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR023420, Kinase_SYK/ZAP-70_inter-SH2_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR001245, Ser-Thr/Tyr_kinase_cat_dom IPR000980, SH2 IPR036860, SH2_dom_sf IPR035838, SYK/ZAP-70_N_SH2 IPR008266, Tyr_kinase_AS IPR020635, Tyr_kinase_cat_dom IPR012234, Tyr_kinase_non-rcpt_SYK/ZAP70 |
Pfami | View protein in Pfam PF07714, PK_Tyr_Ser-Thr, 1 hit PF00017, SH2, 2 hits |
PIRSFi | PIRSF000604, TyrPK_SYK, 1 hit |
PRINTSi | PR00401, SH2DOMAIN PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00252, SH2, 2 hits SM00219, TyrKc, 1 hit |
SUPFAMi | SSF55550, SSF55550, 2 hits SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00109, PROTEIN_KINASE_TYR, 1 hit PS50001, SH2, 2 hits |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MADSANHLPF FFGQITREEA EDYLVQGGMS DGLYLLRQSR NYLGGFALSV
60 70 80 90 100
AYDRKAHHYT IERELNGTYA ISGGRTHGSP AELCHYHSQE LDGLVCLLKN
110 120 130 140 150
PFNRPPGVQP KTGPFEDLKE NLIREYVKQT WNLQGQALEQ AIISQKPQLE
160 170 180 190 200
KLIATTAHEK MPWFHGKISR DESEQIVLIG SKTNGKFLIR ARDNGSYALG
210 220 230 240 250
LLHEGKVLHY RIDKDKTGKL SIPGGKNFDT LWQLVEHYSY KSDGLLRVLT
260 270 280 290 300
VPCQKIGGQT GNDSFRPQLP SAHPATWSAG GIISRIKSYS FPKPGHRKAS
310 320 330 340 350
SPQGNRPESL VSYNPYESDR GPWANEREAQ REALPMDTEV YESPYADPEE
360 370 380 390 400
IRPKEVYLDR KLLTLEDKEL GSGNFGTVKK GYYQMKKVVK TVAVKILKNE
410 420 430 440 450
ANDPALKDEL LAEANVMQQL DNPYIVRMIG ICEAESWMLV MEMAELGPLN
460 470 480 490 500
KYLQQNRHVK DKNIIELVHQ VSMGMKYLEE CNFVHRDLAA RNVLLVTQHY
510 520 530 540 550
AKISDFGLSK ALRADENYYK AQTHGKWPVK WYAPECINYY KFSSKSDVWS
560 570 580 590 600
FGVLMWEAFS YGQKPYRGMK GSEVSAMLEK GERMGCPPGC PREMYELMTL
610 620
CWTYDVENRP GFVAVELRLR NYYYDVVN
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M73237 mRNA Translation: AAA31112.1 |
PIRi | A40802 |
RefSeqi | NP_001098422.1, NM_001104952.1 |
Genome annotation databases
GeneIDi | 100125540 |
KEGGi | ssc:100125540 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M73237 mRNA Translation: AAA31112.1 |
PIRi | A40802 |
RefSeqi | NP_001098422.1, NM_001104952.1 |
3D structure databases
SMRi | Q00655 |
ModBasei | Search... |
Protein-protein interaction databases
IntActi | Q00655, 1 interactor |
MINTi | Q00655 |
STRINGi | 9823.ENSSSCP00000010237 |
PTM databases
iPTMneti | Q00655 |
Proteomic databases
PaxDbi | Q00655 |
PRIDEi | Q00655 |
Genome annotation databases
GeneIDi | 100125540 |
KEGGi | ssc:100125540 |
Organism-specific databases
CTDi | 6850 |
Phylogenomic databases
eggNOGi | ENOG502QT06, Eukaryota |
InParanoidi | Q00655 |
OrthoDBi | 796831at2759 |
Enzyme and pathway databases
BRENDAi | 2.7.10.2, 6170 |
Family and domain databases
CDDi | cd09938, SH2_N-SH2_Zap70_Syk_like, 1 hit |
Gene3Di | 1.10.930.10, 1 hit 3.30.505.10, 2 hits |
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR023420, Kinase_SYK/ZAP-70_inter-SH2_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR001245, Ser-Thr/Tyr_kinase_cat_dom IPR000980, SH2 IPR036860, SH2_dom_sf IPR035838, SYK/ZAP-70_N_SH2 IPR008266, Tyr_kinase_AS IPR020635, Tyr_kinase_cat_dom IPR012234, Tyr_kinase_non-rcpt_SYK/ZAP70 |
Pfami | View protein in Pfam PF07714, PK_Tyr_Ser-Thr, 1 hit PF00017, SH2, 2 hits |
PIRSFi | PIRSF000604, TyrPK_SYK, 1 hit |
PRINTSi | PR00401, SH2DOMAIN PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00252, SH2, 2 hits SM00219, TyrKc, 1 hit |
SUPFAMi | SSF55550, SSF55550, 2 hits SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00109, PROTEIN_KINASE_TYR, 1 hit PS50001, SH2, 2 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | KSYK_PIG | |
Accessioni | Q00655Primary (citable) accession number: Q00655 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1993 |
Last sequence update: | April 1, 1993 | |
Last modified: | February 23, 2022 | |
This is version 165 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families