Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Tyrosine-protein kinase SYK  

UniProtKB / Swiss-Prot ID :  KSYK_HUMAN

Gene Name (Synonyms) : 
SYK  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cell membrane (Probable). Cytoplasm, cytosol (Probable). 

Protein 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. Beside 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. 

Protein Sequence MASSGMADSANHLPFFFGNITREEAEDYLVQGGMSDGLYLLRQSRNYLGGFALSVAHGRKAHHYTIEREL...
Predicted Secondary Structure CCCCCCCCCHHHCCCCCCCCCHHHHHHHHHCCCCCCCCEEEECCCCCCCCEEEEEEECCEEEEEEEEECC...
Protein Variant
LocationDescription
45R -> H (in dbSNP:rs16906862). VAR_033838
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
28PhosphotyrosineEAEDYLVQG
HHHHHHHCC
10.57Phosphositeplus
Link
28Phosphotyrosine.EAEDYLVQG
HHHHHHHCC
10.57UniProtKB
Link
44Phosphoserine.LLRQSRNYL
EEECCCCCC
18.96UniProtKB
Link
47PhosphotyrosineQSRNYLGGF
CCCCCCCCE
12.96Phosphositeplus
Link
47Phosphotyrosine.QSRNYLGGF
CCCCCCCCE
12.96UniProtKB
Link
74PhosphotyrosineLNGTYAIAG
CCCCEEEEC
9.45Phosphositeplus
Link
131Phosphotyrosine (LYN)LIREYVKQT
HCCCCCCCE
11.78HPRD
Link
131Phosphotyrosine (SYK)LIREYVKQT
HCCCCCCCE
11.78HPRD
Link
131Phosphotyrosine.LIREYVKQT
HCCCCCCCE
11.78UniProtKB
Link
202Phosphoserine.DNNGSYALC
CCCCCEEEE
14.89UniProtKB
Link
203PhosphotyrosineNNGSYALCL
CCCCEEEEE
12.65Phosphositeplus
Link
244PhosphotyrosineLVEHYSYKA
HHHHHEECC
10.53Phosphositeplus
Link
256Phosphothreonine.LRVLTVPCQ
CEEEEEHHC
21.39UniProtKB
Link
295PhosphoserineSRIKSYSFP
CCCCCCCCC
24.52Phosphositeplus
Link-
295Phosphoserine.SRIKSYSFP
CCCCCCCCC
24.52UniProtKB
Link-
296PhosphotyrosineRIKSYSFPK
CCCCCCCCC
14.88HPRD
Link-
296PhosphotyrosineRIKSYSFPK
CCCCCCCCC
14.88PhosphoELM
Link-
296PhosphotyrosineRIKSYSFPK
CCCCCCCCC
14.88Phosphositeplus
Link-
296Phosphotyrosine.RIKSYSFPK
CCCCCCCCC
14.88UniProtKB
Link-
297PhosphoserineIKSYSFPKP
CCCCCCCCC
42.01HPRD
Link-
297PhosphoserineIKSYSFPKP
CCCCCCCCC
42.01PhosphoELM
Link-
297PhosphoserineIKSYSFPKP
CCCCCCCCC
42.01Phosphositeplus
Link-
297PhosphoserineIKSYSFPKP
CCCCCCCCC
42.01SysPTM
Link-
297Phosphoserine.IKSYSFPKP
CCCCCCCCC
42.01UniProtKB
Link-
316Phosphoserine.NRQESTVSF
CCCCCCCCC
26.27UniProtKB
Link-
317Phosphothreonine.RQESTVSFN
CCCCCCCCC
21.29UniProtKB
Link-
319PhosphoserineESTVSFNPY
CCCCCCCCC
21.28Phosphositeplus
Link-
319Phosphoserine.ESTVSFNPY
CCCCCCCCC
21.28UniProtKB
Link-
323PhosphotyrosineSFNPYEPEL
CCCCCCCCC
45.26PhosphoELM
Link-
323PhosphotyrosineSFNPYEPEL
CCCCCCCCC
45.26Phosphositeplus
Link-
323Phosphotyrosine (SYK)SFNPYEPEL
CCCCCCCCC
45.26HPRD
Link-
323Phosphotyrosine; by LYN.SFNPYEPEL
CCCCCCCCC
45.26UniProtKB
Link-
345PhosphothreonineLPMDTEVYE
CCCCCCCCC
22.54Phosphositeplus
Link-
345Phosphothreonine.LPMDTEVYE
CCCCCCCCC
22.54UniProtKB
Link-
348PhosphotyrosineDTEVYESPY
CCCCCCCCC
12.40Phosphositeplus
Link-
348Phosphotyrosine (SYK)DTEVYESPY
CCCCCCCCC
12.40HPRD
Link-
348Phosphotyrosine (SYK)DTEVYESPY
CCCCCCCCC
12.40PhosphoELM
Link-
348Phosphotyrosine.DTEVYESPY
CCCCCCCCC
12.40UniProtKB
Link-
350PhosphoserineEVYESPYAD
CCCCCCCCC
12.91Phosphositeplus
Link-
350Phosphoserine.EVYESPYAD
CCCCCCCCC
12.91UniProtKB
Link-
352PhosphotyrosineYESPYADPE
CCCCCCCCC
32.68Phosphositeplus
Link-
352Phosphotyrosine (SYK)YESPYADPE
CCCCCCCCC
32.68HPRD
Link-
352Phosphotyrosine (SYK)YESPYADPE
CCCCCCCCC
32.68PhosphoELM
Link-
352Phosphotyrosine.YESPYADPE
CCCCCCCCC
32.68UniProtKB
Link-
364Phosphotyrosine.PKEVYLDRK
CCCEEECCC
12.18UniProtKB
Link-
379Phosphoserine.KELGSGNFG
EEEEECCCC
43.09UniProtKB
Link-
384Phosphothreonine.GNFGTVKKG
CCCCEEEEE
25.64UniProtKB
Link-
484Phosphotyrosine.MGMKYLEES
HHHHHHHHC
15.51UniProtKB
Link-
507Phosphotyrosine.VTQHYAKIS
CCCCEEEEE
10.36UniProtKB
Link-
517Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)FGLSKALRA
CCEEEEECC
57.38Phosphositeplus
Link-
525PhosphotyrosineADENYYKAQ
CCCCEEEEE
12.33Phosphositeplus
Link-
525Phosphotyrosine (SYK)ADENYYKAQ
CCCCEEEEE
12.33HPRD
Link-
525Phosphotyrosine (SYK)ADENYYKAQ
CCCCEEEEE
12.33PhosphoELM
Link-
525Phosphotyrosine; by autocatalysis.ADENYYKAQ
CCCCEEEEE
12.33UniProtKB
Link-
526PhosphotyrosineDENYYKAQT
CCCEEEEEE
16.07Phosphositeplus
Link-
526Phosphotyrosine (SYK)DENYYKAQT
CCCEEEEEE
16.07HPRD
Link-
526Phosphotyrosine (SYK)DENYYKAQT
CCCEEEEEE
16.07PhosphoELM
Link-
526Phosphotyrosine.DENYYKAQT
CCCEEEEEE
16.07UniProtKB
Link-
530Phosphothreonine.YKAQTHGKW
EEEEEECCC
37.14UniProtKB
Link-
568PhosphotyrosineEAFSYGQKP
HHHHCCCCC
19.68HPRD
Link-
568PhosphotyrosineEAFSYGQKP
HHHHCCCCC
19.68Phosphositeplus
Link-
579Phosphoserine.GMKGSEVTA
CCCHHHHHH
24.31UniProtKB
Link-
582Phosphothreonine.GSEVTAMLE
HHHHHHHHH
11.42UniProtKB
Link-
629Phosphotyrosine.RLRNYYYDV
HHHHHHHHC
9.29UniProtKB
Link-
630Phosphotyrosine.LRNYYYDVV
HHHHHHHCC
9.20UniProtKB
Link-
631Phosphotyrosine.RNYYYDVVN
HHHHHHCCC
7.60UniProtKB
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
P85B_HUMANphysical interactionMINT-56749MINT15536084
EGFR_HUMANphysical interactionMINT-74759MINT16273093
EGFR_HUMANphysical interactionMINT-74760MINT16273093
EGFR_HUMANphysical interactionMINT-74761MINT16273093
ERBB2_HUMANphysical interactionMINT-74758MINT16273093
ERBB2_HUMANphysical interactionMINT-74765MINT16273093
ERBB2_HUMANphysical interactionMINT-74766MINT16273093
ERBB2_HUMANphysical interactionMINT-74767MINT16273093
ERBB2_HUMANphysical interactionMINT-74768MINT16273093
LCK_HUMANphysical interactionMINT-16945MINT8621719
LYN_HUMANphysical interactionMINT-16052MINT11536198
ERBB3_HUMANphysical interactionMINT-74770MINT16273093
ERBB3_HUMANphysical interactionMINT-74771MINT16273093
ERBB3_HUMANphysical interactionMINT-74772MINT16273093
ERBB3_HUMANphysical interactionMINT-74773MINT16273093
ERBB3_HUMANphysical interactionMINT-74774MINT16273093
ERBB3_HUMANphysical interactionMINT-74775MINT16273093
CBL_HUMANphysical interactionMINT-17273MINT8621719
CBL_HUMANphosphorylation reactionMINT-50715MINT15556646
CBL_HUMANphosphorylation reactionMINT-50719MINT15556646
P85A_HUMANphysical interactionMINT-56733MINT15536084
P85A_HUMANphysical interactionMINT-56736MINT15536084
ERBB4_HUMANphysical interactionMINT-74776MINT16273093
LYN_HUMANphysical interactionDIP:739EDIP7831290
KS6A2_HUMANphysical interactionDIP:97EDIP9218456
FCERG_HUMANphysical interactionEBI-515302
intact9280292
OBF1_HUMANcolocalizationEBI-943776
intact16713566
ITB2_HUMANphysical interactionEBI-300190
intact12885943
STAT3_HUMANin vivoHPRD:02514HPRD10825200
CD19_HUMANin vivoHPRD:02514HPRD9120258
CD22_HUMANin vitroHPRD:02514HPRD8627166
B3AT_HUMANin vitro
in vivo
HPRD:02514HPRD1998697
2065070
10942405
16118313
CD79A_HUMANin vitro
in vivo
HPRD:02514HPRD7500027
GRB2_HUMANin vitro
in vivo
HPRD:02514HPRD11964172
EPOR_HUMANin vitro
in vivo
HPRD:02514HPRD9852052
FYN_HUMANin vitro
in vivo
HPRD:02514HPRD9535867
CSF3R_HUMANin vitroHPRD:02514HPRD8197119
FCGR1_HUMANin vivoHPRD:02514HPRD11141335
FCG2A_HUMANin vitro
in vivo
HPRD:02514HPRD8756631
9295288
9280292
FCERB_HUMANin vitro
in vivo
HPRD:02514HPRD8071371
FCERG_HUMANin vitro
in vivo
HPRD:02514HPRD8071371
JAK1_HUMANin vitroHPRD:02514HPRD10825200
PLCG1_HUMANin vitro
in vivo
HPRD:02514HPRD8885868
8657103
1689310
7682059
15144186
SRC8_HUMANin vivoHPRD:02514HPRD8636079
VAV_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:02514HPRD8986718
SYUA_HUMANin vitro
in vivo
HPRD:02514HPRD12096713
11744621
11162638
FGR_HUMANin vitro
in vivo
HPRD:02514HPRD11672534
LCK_HUMANin vivoHPRD:02514HPRD7539035
8798764
CBL_HUMANin vitro
in vivo
HPRD:02514HPRD8621719
11133830
9857068
10540342
PTN6_HUMANin vivoHPRD:02514HPRD10072516
11356834
KPCA_HUMANin vitroHPRD:02514HPRD12881490
TBA4A_HUMANin vitroHPRD:02514HPRD8617742
ITB2_HUMANin vivoHPRD:02514HPRD12885943
BTK_HUMANin vitro
in vivo
HPRD:02514HPRD11226282
11598012
8629002
8630736
SRC_HUMANin vivoHPRD:02514HPRD7513017
KSYK_HUMANin vitro
in vivo
HPRD:02514HPRD11356834
9698567
8657103
9857068
9820500
SHC1_HUMANin vivoHPRD:02514HPRD10482988
9710204
9388490
9096689
HCLS1_HUMANin vitroHPRD:02514HPRD9104825
M4K1_HUMANin vitroHPRD:02514HPRD11514608
3BP2_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:02514HPRD9846481
11390470
12709437
TYOBP_HUMANin vitro
in vivo
HPRD:02514HPRD9490415
DBNL_HUMANin vivoHPRD:02514HPRD9891087
I15RA_HUMANin vitroHPRD:02514HPRD11714793
PLCG2_HUMANin vitroHPRD:02514HPRD12470302
12771181
10933389
VAV2_HUMANin vitroHPRD:02514HPRD15345594
KS6A1_HUMANin vitroHPRD:02514HPRD9218456
MK03_HUMANin vitroHPRD:02514HPRD9218456
TLR4_HUMANin vivoHPRD:02514HPRD14699155
CBLB_HUMANin vitroHPRD:02514HPRD10022120
12771181
KPCD1_HUMANin vitro
in vivo
HPRD:02514HPRD8885868
LAX1_HUMANin vivoHPRD:02514HPRD12359715
DUS3_HUMANin vitro
in vivo
HPRD:02514HPRD12447358
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Disease Reference
Kegg disease
There are no disease associations of PTM sites.
Drug Reference
Kegg drug
D09347 Fostamatinib (USAN)
D09348 Fostamatinib disodium (USAN)
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"Profiling of tyrosine phosphorylation pathways in human cells usingmass spectrometry.";
Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T.,Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.;
Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-348 AND TYR-352, ANDMASS SPECTROMETRY.
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer.";
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
Cell 131:1190-1203(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-296; TYR-323; TYR-348;TYR-352 AND TYR-526, AND MASS SPECTROMETRY.
"Multiple reaction monitoring for robust quantitative proteomicanalysis of cellular signaling networks.";
Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M.;
Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-323, AND MASSSPECTROMETRY.
"The kinase Syk as an adaptor controlling sustained calcium signallingand B-cell development.";
Kulathu Y., Hobeika E., Turchinovich G., Reth M.;
EMBO J. 27:1333-1344(2008).
Cited for: INTERACTION WITH BLNK, ENZYME REGULATION, MUTAGENESIS OF TYR-630, ANDPHOSPHORYLATION AT TYR-630.
"Phosphoproteome of resting human platelets.";
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,Schuetz C., Walter U., Gambaryan S., Sickmann A.;
J. Proteome Res. 7:526-534(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-297, AND MASSSPECTROMETRY.
"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-295; TYR-296; SER-319;TYR-323 AND TYR-352, AND MASS SPECTROMETRY.
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions.";
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.;
Sci. Signal. 2:RA46-RA46(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-28, AND MASSSPECTROMETRY.
"Complex phosphorylation dynamics control the composition of the Sykinteractome in B cells.";
Bohnenberger H., Oellerich T., Engelke M., Hsiao H.H., Urlaub H.,Wienands J.;
Eur. J. Immunol. 41:1550-1562(2011).
Cited for: PHOSPHORYLATION AT TYR-28; SER-44; TYR-47; TYR-131; SER-202; THR-256;SER-295; TYR-296; SER-297; SER-316; THR-317; SER-319; TYR-323;THR-345; TYR-348; SER-350; TYR-352; TYR-364; SER-379; THR-384;TYR-484; TYR-507; TYR-525; TYR-526; THR-530; SER-579; THR-582;TYR-629; TYR-630 AND TYR-631, INTERACTION WITH YWHAG, AND MUTAGENESISOF SER-297.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures