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P43405 (KSYK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 167. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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
p72-Syk
Gene names
Name:SYK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length635 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.8 Ref.9 Ref.14 Ref.15 Ref.17 Ref.24

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. 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.10 Ref.11 Ref.18 Ref.19

Subunit structure

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. 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. 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 with Epstein-Barr virus LMP2A. Interacts (via SH2 domains) with GCSAM; the interaction increases after B-cell receptor stimulation, resulting in enhanced SYK autophosphorylation and activity. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.15 Ref.16 Ref.18 Ref.23 Ref.24 Ref.26 Ref.27

Subcellular location

Cell membrane Probable. Cytoplasmcytosol Probable.

Tissue specificity

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. Ref.2

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. Ref.29

Post-translational modification

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. Ref.2 Ref.11 Ref.18 Ref.26

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
Host-virus interaction
Immunity
Innate immunity
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   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 sequence or structural similarity. Source: UniProtKB

Fc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

Fc-gamma receptor signaling pathway involved in phagocytosis

Traceable author statement. Source: Reactome

activation of JUN kinase activity

Inferred from electronic annotation. Source: Ensembl

adaptive immune response

Inferred from sequence or structural similarity. Source: UniProtKB

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

beta selection

Inferred from electronic annotation. Source: Ensembl

blood coagulation

Traceable author statement. Source: Reactome

blood vessel morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cell proliferation

Traceable author statement PubMed 10963601. Source: ProtInc

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

enzyme linked receptor protein signaling pathway

Inferred from electronic annotation. Source: Ensembl

innate immune response

Inferred from sequence or structural similarity. Source: UniProtKB

integrin-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

leukocyte activation involved in immune response

Inferred from sequence or structural similarity. Source: UniProtKB

leukocyte cell-cell adhesion

Inferred from direct assay PubMed 12885943. Source: UniProtKB

leukotriene biosynthetic process

Inferred from electronic annotation. Source: Ensembl

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 direct assay PubMed 12885943. Source: UniProtKB

organ morphogenesis

Traceable author statement PubMed 7477352. Source: ProtInc

platelet activation

Traceable author statement. Source: Reactome

positive regulation of B cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of alpha-beta T cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of alpha-beta T cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of bone resorption

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of calcium-mediated signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell adhesion mediated by integrin

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cytokine secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of gamma-delta T cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-3 biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of mast cell degranulation

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

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

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentB cell receptor complex

Inferred from electronic annotation. Source: Ensembl

T cell receptor complex

Inferred from direct assay PubMed 8176201. Source: MGI

cytosol

Inferred by curator Ref.2. Source: UniProtKB

early phagosome

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

integrin binding

Inferred from physical interaction PubMed 12885943. Source: UniProtKB

non-membrane spanning protein tyrosine kinase activity

Inferred from direct assay Ref.2. Source: UniProtKB

protein kinase activity

Non-traceable author statement PubMed 12885943. Source: UniProtKB

protein tyrosine kinase activity

Inferred from experiment. Source: Reactome

receptor signaling protein tyrosine kinase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: P43405-1)

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.
Isoform Short (identifier: P43405-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 635635Tyrosine-protein kinase SYK
PRO_0000088165

Regions

Domain15 – 10793SH2 1
Domain168 – 25992SH2 2
Domain371 – 631261Protein kinase
Nucleotide binding377 – 3859ATP By similarity
Region108 – 16760Interdomain A
Region260 – 370111Interdomain B

Sites

Active site4941Proton acceptor By similarity
Binding site4021ATP By similarity

Amino acid modifications

Modified residue281Phosphotyrosine Ref.22 Ref.26
Modified residue441Phosphoserine Ref.26
Modified residue471Phosphotyrosine Ref.26
Modified residue1311Phosphotyrosine Ref.26
Modified residue2021Phosphoserine Ref.26
Modified residue2561Phosphothreonine Ref.26
Modified residue2951Phosphoserine Ref.26
Modified residue2961Phosphotyrosine Ref.26
Modified residue2971Phosphoserine Ref.26
Modified residue3161Phosphoserine Ref.26
Modified residue3171Phosphothreonine Ref.26
Modified residue3191Phosphoserine Ref.26
Modified residue3231Phosphotyrosine; by LYN Ref.21 Ref.26
Modified residue3451Phosphothreonine Ref.26
Modified residue3481Phosphotyrosine Ref.26
Modified residue3501Phosphoserine Ref.26
Modified residue3521Phosphotyrosine Ref.26
Modified residue3641Phosphotyrosine Ref.26
Modified residue3791Phosphoserine Ref.26
Modified residue3841Phosphothreonine Ref.26
Modified residue4841Phosphotyrosine Ref.26
Modified residue5071Phosphotyrosine Ref.26
Modified residue5251Phosphotyrosine; by autocatalysis Ref.26
Modified residue5261Phosphotyrosine Ref.26
Modified residue5301Phosphothreonine Ref.26
Modified residue5461Phosphotyrosine By similarity
Modified residue5791Phosphoserine Ref.26
Modified residue5821Phosphothreonine Ref.26
Modified residue6291Phosphotyrosine Ref.26
Modified residue6301Phosphotyrosine Ref.18 Ref.26
Modified residue6311Phosphotyrosine Ref.26

Natural variations

Alternative sequence283 – 30523Missing in isoform Short.
VSP_005010
Natural variant451R → H.
Corresponds to variant rs16906862 [ dbSNP | Ensembl ].
VAR_033838

Experimental info

Mutagenesis2971S → A: Abolishes YWHAG binding. Ref.26
Mutagenesis6301Y → F: Loss of interaction with BLNK. Ref.18
Sequence conflict1191P → A in CAA51970. Ref.5
Sequence conflict2501G → P in CAA51970. Ref.5

Secondary structure

.................................................................................................... 635
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: EAA6BDE65881FC68

FASTA63572,066
        10         20         30         40         50         60 
MASSGMADSA NHLPFFFGNI TREEAEDYLV QGGMSDGLYL LRQSRNYLGG FALSVAHGRK 

        70         80         90        100        110        120 
AHHYTIEREL NGTYAIAGGR THASPADLCH YHSQESDGLV CLLKKPFNRP QGVQPKTGPF 

       130        140        150        160        170        180 
EDLKENLIRE YVKQTWNLQG QALEQAIISQ KPQLEKLIAT TAHEKMPWFH GKISREESEQ 

       190        200        210        220        230        240 
IVLIGSKTNG KFLIRARDNN GSYALCLLHE GKVLHYRIDK DKTGKLSIPE GKKFDTLWQL 

       250        260        270        280        290        300 
VEHYSYKADG LLRVLTVPCQ KIGTQGNVNF GGRPQLPGSH PATWSAGGII SRIKSYSFPK 

       310        320        330        340        350        360 
PGHRKSSPAQ GNRQESTVSF NPYEPELAPW AADKGPQREA LPMDTEVYES PYADPEEIRP 

       370        380        390        400        410        420 
KEVYLDRKLL TLEDKELGSG NFGTVKKGYY QMKKVVKTVA VKILKNEAND PALKDELLAE 

       430        440        450        460        470        480 
ANVMQQLDNP YIVRMIGICE AESWMLVMEM AELGPLNKYL QQNRHVKDKN IIELVHQVSM 

       490        500        510        520        530        540 
GMKYLEESNF VHRDLAARNV LLVTQHYAKI SDFGLSKALR ADENYYKAQT HGKWPVKWYA 

       550        560        570        580        590        600 
PECINYYKFS SKSDVWSFGV LMWEAFSYGQ KPYRGMKGSE VTAMLEKGER MGCPAGCPRE 

       610        620        630 
MYDLMNLCWT YDVENRPGFA AVELRLRNYY YDVVN 

« Hide

Isoform Short [UniParc].

Checksum: 1D4FD24C6C9F5C53
Show »

FASTA61269,510

References

« Hide 'large scale' references
[1]"Cloning of the cDNA for the deleted syk kinase homologous to ZAP-70 from human basophilic leukemia cell line (KU812)."
Yagi S., Suzuki K., Hasegawa A., Okumura K., Ra C.
Biochem. Biophys. Res. Commun. 200:28-34(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Molecular cloning of human Syk. A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex."
Law C.-L., Sidorenko S.P., Chandran K.A., Draves K.E., Chan A.C., Weiss A., Edelhoff S., Disteche C.M., Clark E.A.
J. Biol. Chem. 269:12310-12319(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AUTOPHOSPHORYLATION.
[3]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND SHORT).
Tissue: Eye and Lymph.
[5]"Molecular cloning of the human homologue to the pig protein-tyrosine kinase syk."
Mueller B., Cooper L., Terhorst C.
Immunogenetics 39:359-362(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-635.
Tissue: Tonsil.
[6]"Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases."
Miller C.L., Burkhardt A.L., Lee J.H., Stealey B., Longnecker R., Bolen J.B., Kieff E.
Immunity 2:155-166(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EPSTEIN-BARR VIRUS LMP2A.
[7]"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: INTERACTION WITH VAV1.
[8]"Phospholipase C-gamma1 interacts with conserved phosphotyrosyl residues in the linker region of Syk and is a substrate for Syk."
Law C.L., Chandran K.A., Sidorenko S.P., Clark E.A.
Mol. Cell. Biol. 16:1305-1315(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PLCG1, INTERACTION WITH PLCG1.
[9]"Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk tyrosine kinases."
Deckert M., Elly C., Altman A., Liu Y.C.
J. Biol. Chem. 273:8867-8874(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CBL, INTERACTION WITH CBL.
[10]"Cbl-mediated negative regulation of the Syk tyrosine kinase. A critical role for Cbl phosphotyrosine-binding domain binding to Syk phosphotyrosine 323."
Lupher M.L. Jr., Rao N., Lill N.L., Andoniou C.E., Miyake S., Clark E.A., Druker B., Band H.
J. Biol. Chem. 273:35273-35281(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, INTERACTION WITH CBL.
[11]"Dephosphorylation of ZAP-70 and inhibition of T cell activation by activated SHP1."
Brockdorff J., Williams S., Couture C., Mustelin T.
Eur. J. Immunol. 29:2539-2550(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN6, ENZYME REGULATION.
[12]"SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling."
Tang J., Sawasdikosol S., Chang J.-H., Burakoff S.J.
Proc. Natl. Acad. Sci. U.S.A. 96:9775-9780(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLA.
[13]"Molecular cloning and characterization of SPAP1, an inhibitory receptor."
Xu M.-J., Zhao R., Zhao Z.J.
Biochem. Biophys. Res. Commun. 280:768-775(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FCRL3.
[14]"BLNK: molecular scaffolding through 'cis'-mediated organization of signaling proteins."
Chiu C.W., Dalton M., Ishiai M., Kurosaki T., Chan A.C.
EMBO J. 21:6461-6472(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN B-CELL RECEPTOR SIGNALING PATHWAY, FUNCTION IN PHOSPHORYLATION OF BLNK.
[15]"ITAM-based interaction of ERM proteins with Syk mediates signaling by the leukocyte adhesion receptor PSGL-1."
Urzainqui A., Serrador J.M., Viedma F., Yanez-Mo M., Rodriguez A., Corbi A.L., Alonso-Lebrero J.L., Luque A., Deckert M., Vazquez J., Sanchez-Madrid F.
Immunity 17:401-412(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL ADHESION, INTERACTION WITH SELPLG AND MSN.
[16]"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: INTERACTION WITH ITGB3.
[17]"Association of the Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) with the p85 subunit of phosphoinositide 3-kinase."
Shim E.K., Moon C.S., Lee G.Y., Ha Y.J., Chae S.K., Lee J.R.
FEBS Lett. 575:35-40(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF LCP2.
[18]"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, ENZYME REGULATION, MUTAGENESIS OF TYR-630, PHOSPHORYLATION AT TYR-630.
[19]"Molecular mechanism of the Syk activation switch."
Tsang E., Giannetti A.M., Shaw D., Dinh M., Tse J.K., Gandhi S., Ho H., Wang S., Papp E., Bradshaw J.M.
J. Biol. Chem. 283:32650-32659(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[20]"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) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[21]"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) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-323, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals 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) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-28, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[23]"CLEC-2 activates Syk through dimerization."
Hughes C.E., Pollitt A.Y., Mori J., Eble J.A., Tomlinson M.G., Hartwig J.H., O'Callaghan C.A., Fuetterer K., Watson S.P.
Blood 115:2947-2955(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CLEC1B.
[24]"Functional interaction between the ubiquitin-specific protease 25 and the SYK tyrosine kinase."
Cholay M., Reverdy C., Benarous R., Colland F., Daviet L.
Exp. Cell Res. 316:667-675(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH USP25, FUNCTION.
[25]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]"Complex phosphorylation dynamics control the composition of the Syk interactome in B cells."
Bohnenberger H., Oellerich T., Engelke M., Hsiao H.H., Urlaub H., Wienands J.
Eur. J. Immunol. 41:1550-1562(2011) [PubMed] [Europe PMC] [Abstract]
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, MUTAGENESIS OF SER-297.
Tissue: B-cell.
[27]"Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation."
Romero-Camarero I., Jiang X., Natkunam Y., Lu X., Vicente-Duenas C., Gonzalez-Herrero I., Flores T., Garcia J.L., McNamara G., Kunder C., Zhao S., Segura V., Fontan L., Martinez-Climent J.A., Garcia-Criado F.J., Theis J.D., Dogan A., Campos-Sanchez E. expand/collapse author list , Green M.R., Alizadeh A.A., Cobaleda C., Sanchez-Garcia I., Lossos I.S.
Nat. Commun. 4:1338-1338(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GCSAM.
[28]"Solution structure of the C-terminal SH2 domain of the human tyrosine kinase Syk complexed with a phosphotyrosine pentapeptide."
Narula S.S., Yuan R.W., Adams S.E., Green O.M., Green J., Philips T.B., Zydowsky L.D., Botfield M.C., Hatada M., Laird E.R., Zoller M.J., Karas J.L., Dalgarno D.C.
Structure 3:1061-1073(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 163-265.
[29]"Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide."
Fuetterer K., Wong J., Grucza R.A., Chan A.C., Waksman G.
J. Mol. Biol. 281:523-537(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF SH2 DOMAINS IN COMPLEX WITH CD3E PHOSPHORYLATED ITAM DOMAIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA53596.
RefSeqNP_001128524.1. NM_001135052.2.
NP_001167638.1. NM_001174167.1.
NP_001167639.1. NM_001174168.1.
NP_003168.2. NM_003177.5.
XP_005252204.1. XM_005252147.2.
UniGeneHs.371720.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP43405.
SMRP43405. Positions 9-635.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112717. 95 interactions.
DIPDIP-253N.
IntActP43405. 30 interactions.
MINTMINT-148486.
STRING9606.ENSP00000364898.

Chemistry

BindingDBP43405.
ChEMBLCHEMBL2599.
GuidetoPHARMACOLOGY2230.

PTM databases

PhosphoSiteP43405.

Polymorphism databases

DMDM1174527.

Proteomic databases

PaxDbP43405.
PeptideAtlasP43405.
PRIDEP43405.

Protocols and materials databases

DNASU6850.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000375746; ENSP00000364898; ENSG00000165025. [P43405-1]
ENST00000375747; ENSP00000364899; ENSG00000165025. [P43405-2]
ENST00000375751; ENSP00000364904; ENSG00000165025. [P43405-2]
ENST00000375754; ENSP00000364907; ENSG00000165025. [P43405-1]
GeneID6850.
KEGGhsa:6850.
UCSCuc004aqz.3. human. [P43405-1]
uc004ara.3. human. [P43405-2]

Organism-specific databases

CTD6850.
GeneCardsGC09P093564.
HGNCHGNC:11491. SYK.
HPACAB007773.
HPA001384.
MIM600085. gene.
neXtProtNX_P43405.
PharmGKBPA36273.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000113264.
HOVERGENHBG001540.
InParanoidP43405.
KOK05855.
OMAKGYYQMK.
OrthoDBEOG7MWGWD.
PhylomeDBP43405.
TreeFamTF351629.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkP43405.

Gene expression databases

BgeeP43405.
CleanExHS_SYK.
GenevestigatorP43405.

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

EvolutionaryTraceP43405.
GeneWikiSyk.
GenomeRNAi6850.
NextBio26739.
PROP43405.
SOURCESearch...

Entry information

Entry nameKSYK_HUMAN
AccessionPrimary (citable) accession number: P43405
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: April 16, 2014
This is version 167 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

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

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM