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P48025 (KSYK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·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
Synonyms:ptk72, Sykb
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length629 AA.
Sequence statusComplete.
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.7 Ref.8 Ref.10 Ref.12 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.22 Ref.23 Ref.24 Ref.25

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. 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. Negatively regulated by CBL and CBLB through ubiquitination and probable degradation. Phosphorylates SH3BP2 which in turn may regulate SYK through LYN By similarity. Ref.11 Ref.23

Subunit structure

Interacts with LYN; phosphorylates SYK. Interacts with RHOH (phosphorylated); regulates mast cells activation. Interacts with NFAM1 (phosphorylated); probably involved in BCR signaling. Interacts with VAV1 (via SH2 domain); phosphorylates VAV1 upon BCR activation By similarity. Interacts with GAB2 (phosphorylated); probably involved in IgE Fc receptor signaling. Interacts (via its SH2 domains) with CD79A (via its phosphorylated ITAM domain); the interaction stimulates SYK autophosphorylation and activation. Interacts with FCRL3 By similarity. Interacts (via SH2 domains) with FCER1G (via ITAM domain); activates SYK and mediates neutrophils and macrophages integrin-mediated activation. Interacts with ITGB2 and FGR; involved in ITGB2 downstream signaling. 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. Interacts with MSN and SELPLG; mediates the selectin-dependent activation of SYK by SELPLG By similarity. Interacts with BLNK (via SH2 domain). 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. 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.5 Ref.8 Ref.13 Ref.15 Ref.17 Ref.18 Ref.21 Ref.23

Subcellular location

Cell membrane Probable. Cytoplasmcytosol Probable. Cytoplasmic vesiclephagosome Ref.15.

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-317 creates a binding site for CBL, an adapter protein that serves as a negative regulator of BCR-stimulated calcium ion signaling. Phosphorylation at Tyr-342 creates a binding site for VAV1 By similarity. Phosphorylation on Tyr-342 and Tyr-346 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-291 is very common, it peaks 5 minutes after BCR stimulation, and creates a binding site for YWHAG By similarity. Phosphorylation at Tyr-624 creates a binding site for BLNK By similarity. Dephosphorylated by PTPN6 By similarity. Ref.4 Ref.8 Ref.9

Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation. Ref.11

Disruption phenotype

Embryos display severe systemic hemorrhage and mice are not viable dying perinatally. While T-cells development is not affected, the development of B-cells is impaired most probably at the pro-B to pre-B transition and mice lack mature B-cells. Ref.1 Ref.6

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
Cytoplasmic vesicle
Membrane
   DomainRepeat
SH2 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell receptor signaling pathway

Inferred from direct assay PubMed 7499277PubMed 8626447. Source: MGI

G-protein coupled receptor signaling pathway

Traceable author statement PubMed 11676469. Source: MGI

activation of JUN kinase activity

Inferred from mutant phenotype PubMed 9000133. Source: MGI

activation of MAPK activity

Inferred from direct assay PubMed 8626447. Source: MGI

adaptive immune response

Inferred from sequence or structural similarity. Source: UniProtKB

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

beta selection

Inferred from genetic interaction PubMed 9275205. Source: MGI

blood vessel morphogenesis

Inferred from mutant phenotype Ref.12. Source: UniProtKB

cell surface receptor signaling pathway

Inferred from direct assay PubMed 9099676. Source: MGI

cellular response to molecule of fungal origin

Inferred from mutant phenotype Ref.15. Source: UniProtKB

defense response to bacterium

Inferred from mutant phenotype Ref.22. Source: UniProtKB

enzyme linked receptor protein signaling pathway

Inferred from direct assay PubMed 7744830. Source: MGI

innate immune response

Inferred from mutant phenotype Ref.15. Source: UniProtKB

integrin-mediated signaling pathway

Inferred from mutant phenotype Ref.10Ref.18. Source: UniProtKB

intracellular signal transduction

Inferred from direct assay PubMed 8626447. Source: MGI

leukocyte activation involved in immune response

Inferred from mutant phenotype Ref.15. Source: UniProtKB

leukocyte cell-cell adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

leukotriene biosynthetic process

Inferred from mutant phenotype PubMed 9000133. Source: MGI

lymph vessel development

Inferred from mutant phenotype Ref.12. Source: UniProtKB

macrophage activation involved in immune response

Inferred from mutant phenotype Ref.18. Source: UniProtKB

neutrophil activation involved in immune response

Inferred from mutant phenotype Ref.18. Source: UniProtKB

neutrophil chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from mutant phenotype Ref.17. Source: UniProtKB

positive regulation of B cell differentiation

Inferred from mutant phenotype Ref.1Ref.6. Source: MGI

positive regulation of alpha-beta T cell differentiation

Inferred from genetic interaction PubMed 9275205. Source: MGI

positive regulation of alpha-beta T cell proliferation

Inferred from genetic interaction PubMed 9275205. Source: MGI

positive regulation of bone resorption

Inferred from mutant phenotype Ref.19. Source: UniProtKB

positive regulation of calcium-mediated signaling

Inferred from mutant phenotype PubMed 9000133. Source: MGI

positive regulation of cell adhesion mediated by integrin

Inferred from mutant phenotype Ref.10. Source: UniProtKB

positive regulation of cytokine secretion

Inferred from genetic interaction PubMed 19770268. Source: MGI

positive regulation of gamma-delta T cell differentiation

Inferred from mutant phenotype Ref.1PubMed 8790395. Source: MGI

positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process

Inferred from mutant phenotype PubMed 9000133. Source: MGI

positive regulation of interleukin-3 biosynthetic process

Inferred from mutant phenotype PubMed 9000133. Source: MGI

positive regulation of mast cell degranulation

Inferred from mutant phenotype PubMed 9000133. Source: MGI

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from mutant phenotype PubMed 9000133. Source: MGI

protein autophosphorylation

Inferred from direct assay PubMed 8626447PubMed 8798454PubMed 9099676. Source: MGI

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of ERK1 and ERK2 cascade

Inferred from mutant phenotype Ref.22. Source: UniProtKB

regulation of arachidonic acid secretion

Inferred from mutant phenotype Ref.7. Source: UniProtKB

regulation of neutrophil degranulation

Inferred from mutant phenotype Ref.22. Source: UniProtKB

regulation of phagocytosis

Inferred from mutant phenotype Ref.22. Source: UniProtKB

regulation of platelet activation

Inferred from mutant phenotype Ref.7. Source: UniProtKB

regulation of platelet aggregation

Inferred from mutant phenotype Ref.7. Source: UniProtKB

regulation of superoxide anion generation

Inferred from mutant phenotype Ref.22. Source: UniProtKB

serotonin secretion

Inferred from mutant phenotype PubMed 9000133. Source: MGI

serotonin secretion by platelet

Inferred from mutant phenotype Ref.7. Source: UniProtKB

   Cellular_componentB cell receptor complex

Inferred from direct assay PubMed 8626447. Source: MGI

T cell receptor complex

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

early phagosome

Inferred from direct assay Ref.15. Source: UniProtKB

protein complex

Inferred from direct assay PubMed 22451653. Source: MGI

   Molecular_functionATP binding

Inferred from direct assay PubMed 8798454. Source: MGI

non-membrane spanning protein tyrosine kinase activity

Inferred from direct assay PubMed 8626447. Source: MGI

protein binding

Inferred from physical interaction Ref.15Ref.17Ref.18Ref.23. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.8. Source: UniProtKB

protein tyrosine kinase activity

Inferred from mutant phenotype Ref.17. Source: UniProtKB

receptor signaling protein tyrosine kinase activity

Inferred from direct assay PubMed 8626447. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PLCG1P084874EBI-300116,EBI-8013886From a different organism.
Pou2af1Q646932EBI-300116,EBI-943530

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 629629Tyrosine-protein kinase SYK
PRO_0000088166

Regions

Domain14 – 10693SH2 1
Domain167 – 25892SH2 2
Domain365 – 625261Protein kinase
Nucleotide binding371 – 3799ATP By similarity
Region107 – 16660Interdomain A
Region259 – 364106Interdomain B

Sites

Active site4881Proton acceptor By similarity
Binding site3961ATP By similarity

Amino acid modifications

Modified residue271Phosphotyrosine By similarity
Modified residue431Phosphoserine By similarity
Modified residue461Phosphotyrosine By similarity
Modified residue1301Phosphotyrosine By similarity
Modified residue2011Phosphoserine By similarity
Modified residue2551Phosphothreonine By similarity
Modified residue2891Phosphoserine By similarity
Modified residue2901Phosphotyrosine By similarity
Modified residue2911Phosphoserine By similarity
Modified residue3101Phosphoserine Ref.20
Modified residue3111Phosphothreonine By similarity
Modified residue3131Phosphoserine Ref.20
Modified residue3171Phosphotyrosine; by LYN Ref.9 Ref.20
Modified residue3391Phosphothreonine By similarity
Modified residue3421Phosphotyrosine Ref.8 Ref.9 Ref.20
Modified residue3441Phosphoserine By similarity
Modified residue3461Phosphotyrosine Ref.9 Ref.20
Modified residue3581Phosphotyrosine By similarity
Modified residue3731Phosphoserine By similarity
Modified residue3781Phosphothreonine By similarity
Modified residue4781Phosphotyrosine By similarity
Modified residue5011Phosphotyrosine By similarity
Modified residue5191Phosphotyrosine; by autocatalysis Ref.8 Ref.20
Modified residue5201Phosphotyrosine Ref.8 Ref.20
Modified residue5241Phosphothreonine By similarity
Modified residue5401Phosphotyrosine Ref.20
Modified residue5731Phosphoserine By similarity
Modified residue5761Phosphothreonine By similarity
Modified residue6231Phosphotyrosine Ref.20
Modified residue6241Phosphotyrosine Ref.20
Modified residue6251Phosphotyrosine By similarity

Experimental info

Mutagenesis411R → A: Loss of interaction with FCER1G and TYROBP; when associated with A-194. Ref.18
Mutagenesis1941R → A: Loss of interaction with FCER1G and TYROBP; when associated with A-41. Ref.18
Sequence conflict3261Missing in CAA90034. Ref.2
Sequence conflict446 – 4472EL → DV in CAA90034. Ref.2

Secondary structure

... 629
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P48025 [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: 2F98D21601F8224E

FASTA62971,376
        10         20         30         40         50         60 
MAGSAVDSAN HLTYFFGNIT REEAEDYLVQ GGMTDGLYLL RQSRNYLGGF ALSVAHNRKA 

        70         80         90        100        110        120 
HHYTIERELN GTYAISGGRA HASPADLCHY HSQEPDGLIC LLKKPFNRPP GVQPKTGPFE 

       130        140        150        160        170        180 
DLKENLIREY VKQTWNLQGQ ALEQAIISQK PQLEKLIATT AHEKMPWFHG NISRDESEQT 

       190        200        210        220        230        240 
VLIGSKTNGK FLIRARDNSG SYALCLLHEG KVLHYRIDRD KTGKLSIPEG KKFDTLWQLV 

       250        260        270        280        290        300 
EHYSYKPDGL LRVLTVPCQK IGAQMGHPGS PNAHPVTWSP GGIISRIKSY SFPKPGHKKP 

       310        320        330        340        350        360 
APPQGSRPES TVSFNPYEPT GGPWGPDRGL QREALPMDTE VYESPYADPE EIRPKEVYLD 

       370        380        390        400        410        420 
RSLLTLEDNE LGSGNFGTVK KGYYQMKKVV KTVAVKILKN EANDPALKDE LLAEANVMQQ 

       430        440        450        460        470        480 
LDNPYIVRMI GICEAESWML VMEMAELGPL NKYLQQNRHI KDKNIIELVH QVSMGMKYLE 

       490        500        510        520        530        540 
ESNFVHRDLA ARNVLLVTQH YAKISDFGLS KALRADENYY KAQTHGKWPV KWYAPECINY 

       550        560        570        580        590        600 
YKFSSKSDVW SFGVLMWEAF SYGQKPYRGM KGSEVTAMLE KGERMGCPAG CPREMYDLMN 

       610        620 
LCWTYDVENR PGFTAVELRL RNYYYDVVN 

« Hide

References

« Hide 'large scale' references
[1]"Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk."
Turner M., Mee P.J., Costello P.S., Williams O., Price A.A., Duddy L.P., Furlong M.T., Geahlen R.L., Tybulewicz V.L.
Nature 378:298-302(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], DISRUPTION PHENOTYPE.
[2]"Molecular characterization of the murine syk protein tyrosine kinase cDNA, transcripts and protein."
Flueck M., Zuercher G., Andres A., Ziemiecki A.
Biochem. Biophys. Res. Commun. 213:273-281(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Spleen.
[3]Richards J.D., Gold M.R., Hourihane S.L., Defranco A.L., Matsuuchi L.
Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"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.
[5]"Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation motif binding and autophosphorylation."
Rowley R.B., Burkhardt A.L., Chao H.-G., Matsueda G.R., Bolen J.B.
J. Biol. Chem. 270:11590-11594(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CD79A.
[6]"Syk tyrosine kinase required for mouse viability and B-cell development."
Cheng A.M., Rowley B., Pao W., Hayday A., Bolen J.B., Pawson T.
Nature 378:303-306(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[7]"The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen."
Poole A., Gibbins J.M., Turner M., van Vugt M.J., van de Winkel J.G., Saito T., Tybulewicz V.L., Watson S.P.
EMBO J. 16:2333-2341(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIVATION OF PLATELETS BY COLLAGEN, FUNCTION IN PLCG2 PHOSPHORYLATION.
[8]"Inhibition of beta 2 integrin receptor and Syk kinase signaling in monocytes by the Src family kinase Fgr."
Vines C.M., Potter J.W., Xu Y., Geahlen R.L., Costello P.S., Tybulewicz V.L., Lowell C.A., Chang P.W., Gresham H.D., Willman C.L.
Immunity 15:507-519(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INTEGRIN SIGNALING, PHOSPHORYLATION AT TYR-342; TYR-519 AND TYR-520, INTERACTION WITH ITGB2 AND FGR.
[9]"Regulation of signaling in B cells through the phosphorylation of Syk on linker region tyrosines. A mechanism for negative signaling by the Lyn tyrosine kinase."
Hong J.J., Yankee T.M., Harrison M.L., Geahlen R.L.
J. Biol. Chem. 277:31703-31714(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-317; TYR-342 AND TYR-346.
[10]"Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton."
Obergfell A., Eto K., Mocsai A., Buensuceso C., Moores S.L., Brugge J.S., Lowell C.A., Shattil S.J.
J. Cell Biol. 157:265-275(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INTEGRIN-MEDIATED PLATELET ADHESION.
[11]"Cbl-b negatively regulates B cell antigen receptor signaling in mature B cells through ubiquitination of the tyrosine kinase Syk."
Sohn H.W., Gu H., Pierce S.K.
J. Exp. Med. 197:1511-1524(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY CBLB, ENZYME REGULATION.
[12]"Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk."
Abtahian F., Guerriero A., Sebzda E., Lu M.M., Zhou R., Mocsai A., Myers E.E., Huang B., Jackson D.G., Ferrari V.A., Tybulewicz V., Lowell C.A., Lepore J.J., Koretzky G.A., Kahn M.L.
Science 299:247-251(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN VASCULAR DEVELOPMENT.
[13]"NFAM1, an immunoreceptor tyrosine-based activation motif-bearing molecule that regulates B cell development and signaling."
Ohtsuka M., Arase H., Takeuchi A., Yamasaki S., Shiina R., Suenaga T., Sakurai D., Yokosuka T., Arase N., Iwashima M., Kitamura T., Moriya H., Saito T.
Proc. Natl. Acad. Sci. U.S.A. 101:8126-8131(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NFAM1.
[14]"Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production."
Underhill D.M., Rossnagle E., Lowell C.A., Simmons R.M.
Blood 106:2543-2550(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ROS PRODUCTION, FUNCTION IN RESPONSE TO FUNGAL PATHOGEN.
[15]"Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins."
Rogers N.C., Slack E.C., Edwards A.D., Nolte M.A., Schulz O., Schweighoffer E., Williams D.L., Gordon S., Tybulewicz V.L., Brown G.D., Reis e Sousa C.
Immunity 22:507-517(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN RESPONSE TO FUNGAL PATHOGEN, INTERACTION WITH CLEC7A, SUBCELLULAR LOCATION.
[16]"A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2."
Suzuki-Inoue K., Fuller G.L.J., Garcia A., Eble J.A., Poehlmann S., Inoue O., Gartner T.K., Hughan S.C., Pearce A.C., Laing G.D., Theakston R.D.G., Schweighoffer E., Zitzmann N., Morita T., Tybulewicz V.L.J., Ozaki Y., Watson S.P.
Blood 107:542-549(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIVATION OF PLATELETS BY CLEC1B.
[17]"Scaffolding adapter Grb2-associated binder 2 requires Syk to transmit signals from FcepsilonRI."
Yu M., Lowell C.A., Neel B.G., Gu H.
J. Immunol. 176:2421-2429(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GAB2.
[18]"Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs."
Mocsai A., Abram C.L., Jakus Z., Hu Y., Lanier L.L., Lowell C.A.
Nat. Immunol. 7:1326-1333(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INTEGRIN-MEDIATED NEUTROPHIL ACTIVATION, INTERACTION WITH FCER1G AND TYROBP, MUTAGENESIS OF ARG-41 AND ARG-194.
[19]"Syk, c-Src, the alphavbeta3 integrin, and ITAM immunoreceptors, in concert, regulate osteoclastic bone resorption."
Zou W., Kitaura H., Reeve J., Long F., Tybulewicz V.L., Shattil S.J., Ginsberg M.H., Ross F.P., Teitelbaum S.L.
J. Cell Biol. 176:877-888(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN OSTEOCLASTIC BONE RESORPTION.
[20]"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310; SER-313; TYR-317; TYR-342; TYR-346; TYR-519; TYR-520; TYR-540; TYR-623 AND TYR-624, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Mast cell.
[21]"The kinase Syk as an adaptor controlling sustained calcium signalling and B-cell development."
Kulathu Y., Hobeika E., Turchinovich G., Reth M.
EMBO J. 27:1333-1344(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BLNK.
[22]"Neutrophil-specific deletion of Syk kinase results in reduced host defense to bacterial infection."
Van Ziffle J.A., Lowell C.A.
Blood 114:4871-4882(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN RESPONSE TO BACTERIA.
[23]"RhoH plays critical roles in Fc epsilon RI-dependent signal transduction in mast cells."
Oda H., Fujimoto M., Patrick M.S., Chida D., Sato Y., Azuma Y., Aoki H., Abe T., Suzuki H., Shirai M.
J. Immunol. 182:957-962(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MAST CELL ACTIVATION, INTERACTION WITH RHOH, ENZYME REGULATION.
[24]"Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence."
Gross O., Poeck H., Bscheider M., Dostert C., Hannesschlaeger N., Endres S., Hartmann G., Tardivel A., Schweighoffer E., Tybulewicz V., Mocsai A., Tschopp J., Ruland J.
Nature 459:433-436(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN RESPONSE TO FUNGAL PATHOGEN, FUNCTION IN INFLAMMASOME ACTIVATION, FUNCTION IN REGULATION OF TRANSCRIPTION.
[25]"Identification of a dendritic cell receptor that couples sensing of necrosis to immunity."
Sancho D., Joffre O.P., Keller A.M., Rogers N.C., Martinez D., Hernanz-Falcon P., Rosewell I., Reis e Sousa C.
Nature 458:899-903(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN IMMUNE SYSTEM STIMULATION BY CELL NECROSIS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U25685 mRNA. Translation: AAA87462.1.
Z49877 mRNA. Translation: CAA90034.1.
U36776 mRNA. Translation: AAA79996.1.
CCDSCCDS26517.1.
PIRI48781.
RefSeqNP_001185906.1. NM_001198977.1.
NP_035648.2. NM_011518.2.
XP_006516958.1. XM_006516895.1.
UniGeneMm.375031.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2LCTNMR-B338-350[»]
2MC1NMR-B338-350[»]
ProteinModelPortalP48025.
SMRP48025. Positions 7-629.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid203599. 11 interactions.
DIPDIP-32621N.
IntActP48025. 9 interactions.
MINTMINT-1209968.

PTM databases

PhosphoSiteP48025.

Proteomic databases

MaxQBP48025.
PaxDbP48025.
PRIDEP48025.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000055087; ENSMUSP00000060828; ENSMUSG00000021457.
ENSMUST00000120135; ENSMUSP00000113852; ENSMUSG00000021457.
GeneID20963.
KEGGmmu:20963.
UCSCuc007qmz.1. mouse.

Organism-specific databases

CTD6850.
MGIMGI:99515. Syk.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000113264.
HOVERGENHBG001540.
InParanoidP48025.
KOK05855.
OMAKGYYQMK.
OrthoDBEOG7MWGWD.
PhylomeDBP48025.
TreeFamTF351629.

Enzyme and pathway databases

BRENDA2.7.10.2. 3474.
ReactomeREACT_224553. Hemostasis.

Gene expression databases

ArrayExpressP48025.
BgeeP48025.
CleanExMM_SYK.
GenevestigatorP48025.

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. 2 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...

Other

ChiTaRSSYK. mouse.
NextBio299918.
PROP48025.
SOURCESearch...

Entry information

Entry nameKSYK_MOUSE
AccessionPrimary (citable) accession number: P48025
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 146 of the entry and version 2 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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot