CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007675
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Tyrosine-protein kinase SYK 
Protein Synonyms/Alias
 Spleen tyrosine kinase; p72-Syk 
Gene Name
 SYK 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
517ISDFGLSKALRADENubiquitination[1, 2, 3]
587EVTAMLEKGERMGCPubiquitination[2]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 15 107 SH2 1.
 DOMAIN 168 259 SH2 2.
 DOMAIN 371 631 Protein kinase.
 NP_BIND 377 385 ATP (By similarity).
 REGION 108 167 Interdomain A.
 REGION 260 370 Interdomain B.
 ACT_SITE 494 494 Proton acceptor (By similarity).
 BINDING 402 402 ATP (By similarity).
 MOD_RES 28 28 Phosphotyrosine.
 MOD_RES 44 44 Phosphoserine.
 MOD_RES 47 47 Phosphotyrosine.
 MOD_RES 131 131 Phosphotyrosine.
 MOD_RES 202 202 Phosphoserine.
 MOD_RES 256 256 Phosphothreonine.
 MOD_RES 295 295 Phosphoserine.
 MOD_RES 296 296 Phosphotyrosine.
 MOD_RES 297 297 Phosphoserine.
 MOD_RES 316 316 Phosphoserine.
 MOD_RES 317 317 Phosphothreonine.
 MOD_RES 319 319 Phosphoserine.
 MOD_RES 323 323 Phosphotyrosine; by LYN.
 MOD_RES 345 345 Phosphothreonine.
 MOD_RES 348 348 Phosphotyrosine.
 MOD_RES 350 350 Phosphoserine.
 MOD_RES 352 352 Phosphotyrosine.
 MOD_RES 364 364 Phosphotyrosine.
 MOD_RES 379 379 Phosphoserine.
 MOD_RES 384 384 Phosphothreonine.
 MOD_RES 484 484 Phosphotyrosine.
 MOD_RES 507 507 Phosphotyrosine.
 MOD_RES 525 525 Phosphotyrosine; by autocatalysis.
 MOD_RES 526 526 Phosphotyrosine.
 MOD_RES 530 530 Phosphothreonine.
 MOD_RES 546 546 Phosphotyrosine (By similarity).
 MOD_RES 579 579 Phosphoserine.
 MOD_RES 582 582 Phosphothreonine.
 MOD_RES 629 629 Phosphotyrosine.
 MOD_RES 630 630 Phosphotyrosine.
 MOD_RES 631 631 Phosphotyrosine.  
Keyword
 3D-structure; Adaptive immunity; Alternative splicing; Angiogenesis; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Host-virus interaction; Immunity; Innate immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Repeat; SH2 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 635 AA 
Protein Sequence
MASSGMADSA NHLPFFFGNI TREEAEDYLV QGGMSDGLYL LRQSRNYLGG FALSVAHGRK 60
AHHYTIEREL NGTYAIAGGR THASPADLCH YHSQESDGLV CLLKKPFNRP QGVQPKTGPF 120
EDLKENLIRE YVKQTWNLQG QALEQAIISQ KPQLEKLIAT TAHEKMPWFH GKISREESEQ 180
IVLIGSKTNG KFLIRARDNN GSYALCLLHE GKVLHYRIDK DKTGKLSIPE GKKFDTLWQL 240
VEHYSYKADG LLRVLTVPCQ KIGTQGNVNF GGRPQLPGSH PATWSAGGII SRIKSYSFPK 300
PGHRKSSPAQ GNRQESTVSF NPYEPELAPW AADKGPQREA LPMDTEVYES PYADPEEIRP 360
KEVYLDRKLL TLEDKELGSG NFGTVKKGYY QMKKVVKTVA VKILKNEAND PALKDELLAE 420
ANVMQQLDNP YIVRMIGICE AESWMLVMEM AELGPLNKYL QQNRHVKDKN IIELVHQVSM 480
GMKYLEESNF VHRDLAARNV LLVTQHYAKI SDFGLSKALR ADENYYKAQT HGKWPVKWYA 540
PECINYYKFS SKSDVWSFGV LMWEAFSYGQ KPYRGMKGSE VTAMLEKGER MGCPAGCPRE 600
MYDLMNLCWT YDVENRPGFA AVELRLRNYY YDVVN 635 
Gene Ontology
 GO:0019815; C:B cell receptor complex; IEA:Compara.
 GO:0005829; C:cytosol; IC:UniProtKB.
 GO:0032009; C:early phagosome; ISS:UniProtKB.
 GO:0042101; C:T cell receptor complex; IDA:MGI.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
 GO:0004716; F:receptor signaling protein tyrosine kinase activity; IEA:Compara.
 GO:0007257; P:activation of JUN kinase activity; IEA:Compara.
 GO:0002250; P:adaptive immune response; ISS:UniProtKB.
 GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
 GO:0050853; P:B cell receptor signaling pathway; ISS:UniProtKB.
 GO:0043366; P:beta selection; IEA:Compara.
 GO:0048514; P:blood vessel morphogenesis; ISS:UniProtKB.
 GO:0008283; P:cell proliferation; TAS:ProtInc.
 GO:0071226; P:cellular response to molecule of fungal origin; ISS:UniProtKB.
 GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
 GO:0007167; P:enzyme linked receptor protein signaling pathway; IEA:Compara.
 GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
 GO:0045087; P:innate immune response; ISS:UniProtKB.
 GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB.
 GO:0007159; P:leukocyte cell-cell adhesion; IDA:UniProtKB.
 GO:0019370; P:leukotriene biosynthetic process; IEA:Compara.
 GO:0001945; P:lymph vessel development; ISS:UniProtKB.
 GO:0002281; P:macrophage activation involved in immune response; ISS:UniProtKB.
 GO:0002283; P:neutrophil activation involved in immune response; ISS:UniProtKB.
 GO:0030593; P:neutrophil chemotaxis; IDA:UniProtKB.
 GO:0009887; P:organ morphogenesis; TAS:ProtInc.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IEA:Compara.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0046638; P:positive regulation of alpha-beta T cell differentiation; IEA:Compara.
 GO:0046641; P:positive regulation of alpha-beta T cell proliferation; IEA:Compara.
 GO:0045579; P:positive regulation of B cell differentiation; IEA:Compara.
 GO:0045780; P:positive regulation of bone resorption; ISS:UniProtKB.
 GO:0050850; P:positive regulation of calcium-mediated signaling; IEA:Compara.
 GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
 GO:0050715; P:positive regulation of cytokine secretion; IEA:Compara.
 GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IEA:Compara.
 GO:0045425; P:positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process; IEA:Compara.
 GO:0045401; P:positive regulation of interleukin-3 biosynthetic process; IEA:Compara.
 GO:0043306; P:positive regulation of mast cell degranulation; IEA:Compara.
 GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Compara.
 GO:0046777; P:protein autophosphorylation; IEA:Compara.
 GO:0090237; P:regulation of arachidonic acid secretion; ISS:UniProtKB.
 GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
 GO:0043313; P:regulation of neutrophil degranulation; ISS:UniProtKB.
 GO:0050764; P:regulation of phagocytosis; ISS:UniProtKB.
 GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB.
 GO:0032928; P:regulation of superoxide anion generation; ISS:UniProtKB.
 GO:0002554; P:serotonin secretion by platelet; ISS:UniProtKB.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR023420; Kinase_SYK/ZAP-70_inter-SH2.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR000980; SH2.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom.
 IPR012234; Tyr_kinase_non-rcpt_SYK/ZAP70. 
Pfam
 PF07714; Pkinase_Tyr
 PF00017; SH2 
SMART
 SM00252; SH2
 SM00219; TyrKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS50001; SH2 
PRINTS
 PR00401; SH2DOMAIN.
 PR00109; TYRKINASE.