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Q00655 (KSYK_PIG) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase SYK

EC=2.7.10.2
Alternative name(s):
Spleen tyrosine kinase
Gene names
Name:SYK
OrganismSus scrofa (Pig) [Reference proteome]
Taxonomic identifier9823 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus

Protein attributes

Sequence length628 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.3 Ref.4 Ref.5

Catalytic activity

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

Enzyme 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 By similarity. May also be negatively regulated by PTPN6 through dephosphorylation By similarity. Downstream signaling adapters and intermediates like BLNK or RHOH may mediate positive and/or negative feedback regulation By similarity. Negatively regulated by CBL and CBLB through ubiquitination and probable degradation By similarity. Phosphorylates SH3BP2 which in turn may regulate SYK through LYN. Ref.5 Ref.6

Subunit structure

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 with FCRL3 By similarity. Interacts (via SH2 domains) with FCER1G (via ITAM domain); activates SYK and mediates neutrophils and macrophages integrin-mediated activation 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. Ref.2 Ref.3

Subcellular location

72 kDa tyrosine-protein kinase SYK: Cell membrane Probable. Cytoplasmcytosol. Note: Mainly associated with membranes.

40 kDa tyrosine-protein kinase SYK: Cell membrane Probable. Cytoplasmcytosol. Note: Equally distributed between membranes and cytosol.

Tissue specificity

Spleen and with lesser amounts in thymus.

Domain

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 By similarity.

Post-translational modification

Autophosphorylated. Phosphorylated on tyrosine residues by LYN following receptors engagement. Phosphorylation on Tyr-316 creates a binding site for CBL, an adapter protein that serves as a negative regulator of BCR-stimulated calcium ion signaling. Phosphorylation at Tyr-341 creates a binding site for VAV1 By similarity. Phosphorylation on Tyr-341 and Tyr-345 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-290 is very common, it peaks 5 minutes after BCR stimulation, and creates a binding site for YWHAG By similarity. Phosphorylation at Tyr-623 creates a binding site for BLNK By similarity. Dephosphorylated by PTPN6 By similarity. Ref.2 Ref.3

Shows high susceptibility to proteolysis.

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

Sequence similarities

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

Contains 1 protein kinase domain.

Contains 2 SH2 domains.

Ontologies

Keywords
   Biological processAdaptive immunity
Angiogenesis
Immunity
Innate immunity
   Cellular componentCell membrane
Cytoplasm
Membrane
   DomainRepeat
SH2 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processB cell receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

adaptive immune response

Inferred from sequence or structural similarity. Source: UniProtKB

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

blood vessel morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to molecule of fungal origin

Inferred from sequence or structural similarity. Source: UniProtKB

defense response to bacterium

Inferred from sequence or structural similarity. Source: UniProtKB

innate immune response

Inferred from sequence or structural similarity. Source: UniProtKB

integrin-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

leukocyte activation involved in immune response

Inferred from sequence or structural similarity. Source: UniProtKB

leukocyte cell-cell adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

lymph vessel development

Inferred from sequence or structural similarity. Source: UniProtKB

macrophage activation involved in immune response

Inferred from sequence or structural similarity. Source: UniProtKB

neutrophil activation involved in immune response

Inferred from sequence or structural similarity. Source: UniProtKB

neutrophil chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: GOC

positive regulation of bone resorption

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell adhesion mediated by integrin

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of arachidonic acid secretion

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of neutrophil degranulation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of phagocytosis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of platelet activation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of platelet aggregation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of superoxide anion generation

Inferred from sequence or structural similarity. Source: UniProtKB

serotonin secretion by platelet

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

early phagosome

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 62862872 kDa tyrosine-protein kinase SYK
PRO_0000024468
Chain313 – 62831640 kDa tyrosine-protein kinase SYK
PRO_0000024469

Regions

Domain10 – 10293SH2 1
Domain163 – 25391SH2 2
Domain364 – 624261Protein kinase
Nucleotide binding370 – 3789ATP By similarity
Region103 – 16260Interdomain A By similarity
Region254 – 363110Interdomain B By similarity

Sites

Active site4871Proton acceptor By similarity
Binding site3951ATP By similarity

Amino acid modifications

Modified residue231Phosphotyrosine By similarity
Modified residue391Phosphoserine By similarity
Modified residue421Phosphotyrosine By similarity
Modified residue1261Phosphotyrosine By similarity
Modified residue1961Phosphoserine By similarity
Modified residue2501Phosphothreonine By similarity
Modified residue2881Phosphoserine By similarity
Modified residue2891Phosphotyrosine By similarity
Modified residue2901Phosphoserine By similarity
Modified residue3091Phosphoserine By similarity
Modified residue3121Phosphoserine By similarity
Modified residue3161Phosphotyrosine; by LYN By similarity
Modified residue3381Phosphothreonine By similarity
Modified residue3411Phosphotyrosine Ref.3
Modified residue3431Phosphoserine By similarity
Modified residue3451Phosphotyrosine By similarity
Modified residue3571Phosphotyrosine By similarity
Modified residue3721Phosphoserine By similarity
Modified residue3771Phosphothreonine By similarity
Modified residue4771Phosphotyrosine By similarity
Modified residue5001Phosphotyrosine By similarity
Modified residue5181Phosphotyrosine; by autocatalysis By similarity
Modified residue5191Phosphotyrosine By similarity
Modified residue5231Phosphothreonine By similarity
Modified residue5391Phosphotyrosine By similarity
Modified residue5721Phosphoserine By similarity
Modified residue6221Phosphotyrosine By similarity
Modified residue6231Phosphotyrosine By similarity
Modified residue6241Phosphotyrosine By similarity

Experimental info

Mutagenesis3411Y → F: Alters interaction with VAV1. Ref.3
Mutagenesis3451Y → F: Moderately alters interaction with VAV1. Ref.3
Mutagenesis3951K → R: Loss of kinase activity. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Q00655 [UniParc].

Last modified April 1, 1993. Version 1.
Checksum: D7C0CEF7EBBEBC1E

FASTA62871,620
        10         20         30         40         50         60 
MADSANHLPF FFGQITREEA EDYLVQGGMS DGLYLLRQSR NYLGGFALSV AYDRKAHHYT 

        70         80         90        100        110        120 
IERELNGTYA ISGGRTHGSP AELCHYHSQE LDGLVCLLKN PFNRPPGVQP KTGPFEDLKE 

       130        140        150        160        170        180 
NLIREYVKQT WNLQGQALEQ AIISQKPQLE KLIATTAHEK MPWFHGKISR DESEQIVLIG 

       190        200        210        220        230        240 
SKTNGKFLIR ARDNGSYALG LLHEGKVLHY RIDKDKTGKL SIPGGKNFDT LWQLVEHYSY 

       250        260        270        280        290        300 
KSDGLLRVLT VPCQKIGGQT GNDSFRPQLP SAHPATWSAG GIISRIKSYS FPKPGHRKAS 

       310        320        330        340        350        360 
SPQGNRPESL VSYNPYESDR GPWANEREAQ REALPMDTEV YESPYADPEE IRPKEVYLDR 

       370        380        390        400        410        420 
KLLTLEDKEL GSGNFGTVKK GYYQMKKVVK TVAVKILKNE ANDPALKDEL LAEANVMQQL 

       430        440        450        460        470        480 
DNPYIVRMIG ICEAESWMLV MEMAELGPLN KYLQQNRHVK DKNIIELVHQ VSMGMKYLEE 

       490        500        510        520        530        540 
CNFVHRDLAA RNVLLVTQHY AKISDFGLSK ALRADENYYK AQTHGKWPVK WYAPECINYY 

       550        560        570        580        590        600 
KFSSKSDVWS FGVLMWEAFS YGQKPYRGMK GSEVSAMLEK GERMGCPPGC PREMYELMTL 

       610        620 
CWTYDVENRP GFVAVELRLR NYYYDVVN 

« Hide

References

[1]"Molecular cloning of a porcine gene syk that encodes a 72-kDa protein-tyrosine kinase showing high susceptibility to proteolysis."
Taniguchi T., Kobayashi T., Kondo J., Takahashi K., Nakamura H., Suzuki J., Nagai K., Yamada T., Nakamura S., Yamamura H.
J. Biol. Chem. 266:15790-15796(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 313-333; 346-354 AND 369-379.
Tissue: Spleen.
[2]"Syk activation by the Src-family tyrosine kinase in the B cell receptor signaling."
Kurosaki T., Takata M., Yamanashi Y., Inazu T., Taniguchi T., Yamamoto T., Yamamura H.
J. Exp. Med. 179:1725-1729(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY LYN, INTERACTION WITH LYN, AUTOPHOSPHORYLATION.
[3]"Functional and physical interactions of Syk family kinases with the Vav proto-oncogene product."
Deckert M., Tartare-Deckert S., Couture C., Mustelin T., Altman A.
Immunity 5:591-604(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TRANSCRIPTION REGULATION, INTERACTION WITH VAV1, MUTAGENESIS OF TYR-341 AND TYR-345, PHOSPHORYLATION AT TYR-341.
[4]"BLNK mediates Syk-dependent Btk activation."
Baba Y., Hashimoto S., Matsushita M., Watanabe D., Kishimoto T., Kurosaki T., Tsukada S.
Proc. Natl. Acad. Sci. U.S.A. 98:2582-2586(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BTK.
[5]"Adaptor protein 3BP2 is a potential ligand of Src homology 2 and 3 domains of Lyn protein-tyrosine kinase."
Maeno K., Sada K., Kyo S., Miah S.M., Kawauchi-Kamata K., Qu X., Shi Y., Yamamura H.
J. Biol. Chem. 278:24912-24920(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF SH3BP2, MUTAGENESIS OF LYS-395, ENZYME REGULATION.
[6]"Interdomain A is crucial for ITAM-dependent and -independent regulation of Syk."
Adachi T., Wienands J., Tsubata T., Kurosaki T.
Biochem. Biophys. Res. Commun. 364:111-117(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M73237 mRNA. Translation: AAA31112.1.
PIRA40802.
RefSeqNP_001098422.1. NM_001104952.1.
UniGeneSsc.55112.

3D structure databases

ProteinModelPortalQ00655.
SMRQ00655. Positions 4-256, 356-628.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ00655. 1 interaction.
MINTMINT-6622752.
STRING9823.ENSSSCP00000010237.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100125540.
KEGGssc:100125540.

Organism-specific databases

CTD6850.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000113264.
HOVERGENHBG001540.
KOK05855.

Enzyme and pathway databases

BRENDA2.7.10.2. 6170.
ReactomeREACT_85674. Hemostasis.

Family and domain databases

Gene3D1.10.930.10. 1 hit.
3.30.505.10. 2 hits.
InterProIPR011009. Kinase-like_dom.
IPR023420. Kinase_SYK/ZAP-70_inter-SH2.
IPR000719. Prot_kinase_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.
[Graphical view]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 2 hits.
[Graphical view]
PIRSFPIRSF000604. TyrPK_SYK. 1 hit.
PRINTSPR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTSM00252. SH2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF55550. SSF55550. 3 hits.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 2 hits.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameKSYK_PIG
AccessionPrimary (citable) accession number: Q00655
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: April 16, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families