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Protein

Tyrosine-protein kinase SYK

Gene

SYK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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. 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 similarity6 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Activity regulationi

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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei402ATPPROSITE-ProRule annotation1
Active sitei494Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi377 – 385ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
Biological processAdaptive immunity, Angiogenesis, Host-virus interaction, Immunity, Innate immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-114604 GPVI-mediated activation cascade
R-HSA-2029481 FCGR activation
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-2029485 Role of phospholipids in phagocytosis
R-HSA-2424491 DAP12 signaling
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-354192 Integrin alphaIIb beta3 signaling
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-5621480 Dectin-2 family
R-HSA-9020558 Interleukin-2 signaling
R-HSA-912631 Regulation of signaling by CBL
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
SignaLinkiP43405
SIGNORiP43405

Protein family/group databases

MoonDBiP43405 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase SYK (EC:2.7.10.2)
Alternative name(s):
Spleen tyrosine kinase
p72-Syk
Gene namesi
Name:SYK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000165025.14
HGNCiHGNC:11491 SYK
MIMi600085 gene
neXtProtiNX_P43405

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi297S → A: Abolishes YWHAG binding. 1 Publication1
Mutagenesisi630Y → F: Loss of interaction with BLNK. 1 Publication1

Organism-specific databases

DisGeNETi6850
OpenTargetsiENSG00000165025
PharmGKBiPA36273

Chemistry databases

ChEMBLiCHEMBL2599
DrugBankiDB08846 Ellagic Acid
DB02010 Staurosporine
GuidetoPHARMACOLOGYi2230

Polymorphism and mutation databases

BioMutaiSYK
DMDMi1174527

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000881651 – 635Tyrosine-protein kinase SYKAdd BLAST635

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei28PhosphotyrosineCombined sources1 Publication1
Modified residuei44Phosphoserine1 Publication1
Modified residuei47Phosphotyrosine1 Publication1
Modified residuei131Phosphotyrosine1 Publication1
Modified residuei202Phosphoserine1 Publication1
Modified residuei256Phosphothreonine1 Publication1
Modified residuei295Phosphoserine1 Publication1
Modified residuei296Phosphotyrosine1 Publication1
Modified residuei297Phosphoserine1 Publication1
Modified residuei316Phosphoserine1 Publication1
Modified residuei317Phosphothreonine1 Publication1
Modified residuei319Phosphoserine1 Publication1
Modified residuei323Phosphotyrosine; by LYNCombined sources1 Publication1
Modified residuei345Phosphothreonine1 Publication1
Modified residuei348Phosphotyrosine1 Publication1
Modified residuei350Phosphoserine1 Publication1
Modified residuei352Phosphotyrosine1 Publication1
Modified residuei364Phosphotyrosine1 Publication1
Modified residuei379Phosphoserine1 Publication1
Modified residuei384Phosphothreonine1 Publication1
Modified residuei484Phosphotyrosine1 Publication1
Modified residuei507Phosphotyrosine1 Publication1
Modified residuei525Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei526Phosphotyrosine1 Publication1
Modified residuei530Phosphothreonine1 Publication1
Modified residuei546PhosphotyrosineBy similarity1
Modified residuei579Phosphoserine1 Publication1
Modified residuei582Phosphothreonine1 Publication1
Modified residuei629Phosphotyrosine1 Publication1
Modified residuei630Phosphotyrosine2 Publications1
Modified residuei631Phosphotyrosine1 Publication1

Post-translational modificationi

Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation.By similarity
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). 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.By similarity3 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP43405
MaxQBiP43405
PaxDbiP43405
PeptideAtlasiP43405
PRIDEiP43405
ProteomicsDBi55634
55635 [P43405-2]

PTM databases

iPTMnetiP43405
PhosphoSitePlusiP43405

Expressioni

Tissue specificityi

Widely expressed in hematopoietic cells (at protein level). Within the B-cells compartment it is for instance expressed for pro-B-cells to plasma cells.1 Publication

Gene expression databases

BgeeiENSG00000165025 Expressed in 185 organ(s), highest expression level in leukocyte
CleanExiHS_SYK
ExpressionAtlasiP43405 baseline and differential
GenevisibleiP43405 HS

Organism-specific databases

HPAiCAB007773
HPA001384

Interactioni

Subunit structurei

Interacts with LYN; phosphorylates SYK (By similarity). 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 with FCRL3 (PubMed:19843936, PubMed:11162587). 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. 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. Interacts with BLNK (via SH2 domain). Interacts (via the second SH2 domain) with USP25 (via C-terminus); phosphorylates USP25 and regulates USP25 intracellular levels. Interacts (via SH2 domains) with CLEC1B (dimer). Interacts with CLEC7A; participates in leukocyte activation in presence of fungal pathogens. Interacts (phosphorylated) with SLA; may regulate SYK through CBL recruitment. Interacts with YWHAG; attenuates BCR-induced membrane translocation and activation of SYK. Interacts (via SH2 domains) with GCSAM; the interaction increases after B-cell receptor stimulation, resulting in enhanced SYK autophosphorylation and activity. Interacts with TNS2; leading to the phosphorylation of SYK (PubMed:22019427). Interacts with FLNA (via filamin repeat 5); docks SYK to the plasma membrane (PubMed:20713593). Interacts with 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, leading to a reduction of the inflammasome activity (By similarity). Interacts (via SH2 domains) with CEACAM20 (phosphorylated form); the interaction further enhances CEACAM20 phosphorylation (By similarity).By similarity17 Publications
(Microbial infection) Interacts with Epstein-Barr virus LMP2A.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112717, 111 interactors
CORUMiP43405
DIPiDIP-253N
ELMiP43405
IntActiP43405, 46 interactors
MINTiP43405
STRINGi9606.ENSP00000364898

Chemistry databases

BindingDBiP43405

Structurei

Secondary structure

1635
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP43405
SMRiP43405
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP43405

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini15 – 107SH2 1PROSITE-ProRule annotationAdd BLAST93
Domaini168 – 259SH2 2PROSITE-ProRule annotationAdd BLAST92
Domaini371 – 631Protein kinasePROSITE-ProRule annotationAdd BLAST261

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni108 – 167Interdomain AAdd BLAST60
Regioni260 – 370Interdomain BAdd BLAST111

Domaini

The SH2 domains mediate the interaction of SYK with the phosphorylated ITAM domains of transmembrane proteins. Some proteins like CLEC1B have a partial ITAM domain (also called hemITAM) containing a single YxxL motif. The interaction with SYK requires CLEC1B homodimerization.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiENOG410IH0T Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118799
HOGENOMiHOG000113264
HOVERGENiHBG001540
InParanoidiP43405
KOiK05855
OMAiTFNPYEP
OrthoDBiEOG091G07KU
PhylomeDBiP43405
TreeFamiTF351629

Family and domain databases

CDDicd09938 SH2_N-SH2_Zap70_Syk_like, 1 hit
Gene3Di1.10.930.10, 1 hit
3.30.505.10, 2 hits
InterProiView 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
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 2 hits
PIRSFiPIRSF000604 TyrPK_SYK, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 2 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF55550 SSF55550, 2 hits
SSF56112 SSF56112, 1 hit
PROSITEiView 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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform Long (identifier: P43405-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MASSGMADSA NHLPFFFGNI TREEAEDYLV QGGMSDGLYL LRQSRNYLGG
60 70 80 90 100
FALSVAHGRK AHHYTIEREL NGTYAIAGGR THASPADLCH YHSQESDGLV
110 120 130 140 150
CLLKKPFNRP QGVQPKTGPF EDLKENLIRE YVKQTWNLQG QALEQAIISQ
160 170 180 190 200
KPQLEKLIAT TAHEKMPWFH GKISREESEQ IVLIGSKTNG KFLIRARDNN
210 220 230 240 250
GSYALCLLHE GKVLHYRIDK DKTGKLSIPE GKKFDTLWQL VEHYSYKADG
260 270 280 290 300
LLRVLTVPCQ KIGTQGNVNF GGRPQLPGSH PATWSAGGII SRIKSYSFPK
310 320 330 340 350
PGHRKSSPAQ GNRQESTVSF NPYEPELAPW AADKGPQREA LPMDTEVYES
360 370 380 390 400
PYADPEEIRP KEVYLDRKLL TLEDKELGSG NFGTVKKGYY QMKKVVKTVA
410 420 430 440 450
VKILKNEAND PALKDELLAE ANVMQQLDNP YIVRMIGICE AESWMLVMEM
460 470 480 490 500
AELGPLNKYL QQNRHVKDKN IIELVHQVSM GMKYLEESNF VHRDLAARNV
510 520 530 540 550
LLVTQHYAKI SDFGLSKALR ADENYYKAQT HGKWPVKWYA PECINYYKFS
560 570 580 590 600
SKSDVWSFGV LMWEAFSYGQ KPYRGMKGSE VTAMLEKGER MGCPAGCPRE
610 620 630
MYDLMNLCWT YDVENRPGFA AVELRLRNYY YDVVN
Length:635
Mass (Da):72,066
Last modified:November 1, 1995 - v1
Checksum:iEAA6BDE65881FC68
GO
Isoform Short (identifier: P43405-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     283-305: Missing.

Show »
Length:612
Mass (Da):69,510
Checksum:i1D4FD24C6C9F5C53
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti119P → A in CAA51970 (PubMed:8168854).Curated1
Sequence conflicti250G → P in CAA51970 (PubMed:8168854).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03383845R → H. Corresponds to variant dbSNP:rs16906862Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005010283 – 305Missing in isoform Short. 1 PublicationAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z29630 mRNA Translation: CAA82737.1
L28824 mRNA Translation: AAA36526.1
AL354862 Genomic DNA No translation available.
BC001645 mRNA Translation: AAH01645.1
BC011399 mRNA Translation: AAH11399.1
BC002962 mRNA Translation: AAH02962.1
X73568 mRNA Translation: CAA51970.1
CCDSiCCDS47992.1 [P43405-2]
CCDS6688.1 [P43405-1]
PIRiA53596
RefSeqiNP_001128524.1, NM_001135052.3 [P43405-2]
NP_001167638.1, NM_001174167.2 [P43405-1]
NP_001167639.1, NM_001174168.2 [P43405-2]
NP_003168.2, NM_003177.6 [P43405-1]
XP_005252204.1, XM_005252147.3 [P43405-1]
XP_011517248.1, XM_011518946.2 [P43405-1]
UniGeneiHs.371720

Genome annotation databases

EnsembliENST00000375746; ENSP00000364898; ENSG00000165025 [P43405-1]
ENST00000375747; ENSP00000364899; ENSG00000165025 [P43405-2]
ENST00000375751; ENSP00000364904; ENSG00000165025 [P43405-2]
ENST00000375754; ENSP00000364907; ENSG00000165025 [P43405-1]
GeneIDi6850
KEGGihsa:6850
UCSCiuc004aqz.4 human [P43405-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z29630 mRNA Translation: CAA82737.1
L28824 mRNA Translation: AAA36526.1
AL354862 Genomic DNA No translation available.
BC001645 mRNA Translation: AAH01645.1
BC011399 mRNA Translation: AAH11399.1
BC002962 mRNA Translation: AAH02962.1
X73568 mRNA Translation: CAA51970.1
CCDSiCCDS47992.1 [P43405-2]
CCDS6688.1 [P43405-1]
PIRiA53596
RefSeqiNP_001128524.1, NM_001135052.3 [P43405-2]
NP_001167638.1, NM_001174167.2 [P43405-1]
NP_001167639.1, NM_001174168.2 [P43405-2]
NP_003168.2, NM_003177.6 [P43405-1]
XP_005252204.1, XM_005252147.3 [P43405-1]
XP_011517248.1, XM_011518946.2 [P43405-1]
UniGeneiHs.371720

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A81X-ray3.00A/C/E/G/I/K9-262[»]
1CSYNMR-A163-265[»]
1CSZNMR-A163-265[»]
1XBAX-ray2.00A356-635[»]
1XBBX-ray1.57A356-635[»]
1XBCX-ray2.00A356-635[»]
3BUWX-ray1.45A/C317-329[»]
3EMGX-ray2.60A349-635[»]
3FQEX-ray2.50A356-635[»]
3FQHX-ray2.26A/B356-635[»]
3FQSX-ray2.10A356-635[»]
3SRVX-ray1.95A/B360-635[»]
3TUBX-ray2.23A343-635[»]
3TUCX-ray2.10A343-635[»]
3TUDX-ray2.33A343-635[»]
3VF8X-ray2.08A343-635[»]
3VF9X-ray2.30A343-635[»]
4DFLX-ray1.98A363-635[»]
4DFNX-ray2.48A363-635[»]
4F4PX-ray2.37A365-635[»]
4FL1X-ray1.79A356-635[»]
4FL2X-ray2.19A1-635[»]
4FL3X-ray1.90A1-635[»]
4FYNX-ray2.32A356-635[»]
4FYOX-ray1.40A356-635[»]
4FZ6X-ray1.85A356-635[»]
4FZ7X-ray1.75A356-635[»]
4GFGX-ray2.35A356-635[»]
4I0RX-ray2.10A356-635[»]
4I0SX-ray1.98A356-635[»]
4I0TX-ray1.70A356-635[»]
4PUZX-ray2.08A/B356-635[»]
4PV0X-ray2.00A363-635[»]
4PX6X-ray1.60A356-635[»]
4RSSX-ray1.83A356-635[»]
4RX7X-ray1.80A356-635[»]
4RX8X-ray1.59A356-635[»]
4RX9X-ray1.75A356-635[»]
4WNMX-ray2.50A343-635[»]
4XG2X-ray2.21A356-635[»]
4XG3X-ray2.30A/B356-635[»]
4XG4X-ray2.30A356-635[»]
4XG6X-ray2.40A356-635[»]
4XG7X-ray1.76A356-635[»]
4XG8X-ray2.40A/C356-635[»]
4XG9X-ray2.91A/B356-635[»]
4YJOX-ray1.60A355-635[»]
4YJPX-ray1.83A355-635[»]
4YJQX-ray1.34A355-635[»]
4YJRX-ray1.32A355-635[»]
4YJSX-ray2.22A355-635[»]
4YJTX-ray1.52A355-635[»]
4YJUX-ray1.67A355-635[»]
4YJVX-ray1.65A355-635[»]
5C26X-ray1.95A343-635[»]
5C27X-ray2.15A343-635[»]
5CXHX-ray1.90A356-635[»]
5CXZX-ray1.70A356-635[»]
5CY3X-ray1.76A356-635[»]
5GHVX-ray2.80A/B356-635[»]
5LMAX-ray1.43A360-635[»]
5LMBX-ray1.95A/B360-635[»]
5T68X-ray2.93A/B356-635[»]
5TIUX-ray1.49A356-635[»]
5TR6X-ray1.93A356-635[»]
5TT7X-ray1.77A356-635[»]
5Y5TX-ray1.80A356-635[»]
5Y5UX-ray2.14A/B356-635[»]
ProteinModelPortaliP43405
SMRiP43405
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112717, 111 interactors
CORUMiP43405
DIPiDIP-253N
ELMiP43405
IntActiP43405, 46 interactors
MINTiP43405
STRINGi9606.ENSP00000364898

Chemistry databases

BindingDBiP43405
ChEMBLiCHEMBL2599
DrugBankiDB08846 Ellagic Acid
DB02010 Staurosporine
GuidetoPHARMACOLOGYi2230

Protein family/group databases

MoonDBiP43405 Predicted

PTM databases

iPTMnetiP43405
PhosphoSitePlusiP43405

Polymorphism and mutation databases

BioMutaiSYK
DMDMi1174527

Proteomic databases

EPDiP43405
MaxQBiP43405
PaxDbiP43405
PeptideAtlasiP43405
PRIDEiP43405
ProteomicsDBi55634
55635 [P43405-2]

Protocols and materials databases

DNASUi6850
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375746; ENSP00000364898; ENSG00000165025 [P43405-1]
ENST00000375747; ENSP00000364899; ENSG00000165025 [P43405-2]
ENST00000375751; ENSP00000364904; ENSG00000165025 [P43405-2]
ENST00000375754; ENSP00000364907; ENSG00000165025 [P43405-1]
GeneIDi6850
KEGGihsa:6850
UCSCiuc004aqz.4 human [P43405-1]

Organism-specific databases

CTDi6850
DisGeNETi6850
EuPathDBiHostDB:ENSG00000165025.14
GeneCardsiSYK
HGNCiHGNC:11491 SYK
HPAiCAB007773
HPA001384
MIMi600085 gene
neXtProtiNX_P43405
OpenTargetsiENSG00000165025
PharmGKBiPA36273
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IH0T Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118799
HOGENOMiHOG000113264
HOVERGENiHBG001540
InParanoidiP43405
KOiK05855
OMAiTFNPYEP
OrthoDBiEOG091G07KU
PhylomeDBiP43405
TreeFamiTF351629

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-114604 GPVI-mediated activation cascade
R-HSA-2029481 FCGR activation
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-2029485 Role of phospholipids in phagocytosis
R-HSA-2424491 DAP12 signaling
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-354192 Integrin alphaIIb beta3 signaling
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-5621480 Dectin-2 family
R-HSA-9020558 Interleukin-2 signaling
R-HSA-912631 Regulation of signaling by CBL
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
SignaLinkiP43405
SIGNORiP43405

Miscellaneous databases

ChiTaRSiSYK human
EvolutionaryTraceiP43405
GeneWikiiSyk
GenomeRNAii6850
PROiPR:P43405
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165025 Expressed in 185 organ(s), highest expression level in leukocyte
CleanExiHS_SYK
ExpressionAtlasiP43405 baseline and differential
GenevisibleiP43405 HS

Family and domain databases

CDDicd09938 SH2_N-SH2_Zap70_Syk_like, 1 hit
Gene3Di1.10.930.10, 1 hit
3.30.505.10, 2 hits
InterProiView 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
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 2 hits
PIRSFiPIRSF000604 TyrPK_SYK, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 2 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF55550 SSF55550, 2 hits
SSF56112 SSF56112, 1 hit
PROSITEiView 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
ProtoNetiSearch...

Entry informationi

Entry nameiKSYK_HUMAN
AccessioniPrimary (citable) accession number: P43405
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 7, 2018
This is version 215 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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