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Q00655

- KSYK_PIG

UniProt

Q00655 - KSYK_PIG

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Protein

Tyrosine-protein kinase SYK

Gene

SYK

Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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. In addition to 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.3 Publications

Catalytic activityi

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

Enzyme regulationi

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.By similarity2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei395 – 3951ATPPROSITE-ProRule annotation
Active sitei487 – 4871Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi370 – 3789ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  1. adaptive immune response Source: UniProtKB
  2. angiogenesis Source: UniProtKB-KW
  3. B cell receptor signaling pathway Source: UniProtKB
  4. blood vessel morphogenesis Source: UniProtKB
  5. cellular response to molecule of fungal origin Source: UniProtKB
  6. defense response to bacterium Source: UniProtKB
  7. innate immune response Source: UniProtKB
  8. integrin-mediated signaling pathway Source: UniProtKB
  9. intracellular signal transduction Source: InterPro
  10. leukocyte activation involved in immune response Source: UniProtKB
  11. leukocyte cell-cell adhesion Source: UniProtKB
  12. lymph vessel development Source: UniProtKB
  13. macrophage activation involved in immune response Source: UniProtKB
  14. neutrophil activation involved in immune response Source: UniProtKB
  15. neutrophil chemotaxis Source: UniProtKB
  16. peptidyl-tyrosine phosphorylation Source: GOC
  17. positive regulation of bone resorption Source: UniProtKB
  18. positive regulation of cell adhesion mediated by integrin Source: UniProtKB
  19. protein phosphorylation Source: UniProtKB
  20. regulation of arachidonic acid secretion Source: UniProtKB
  21. regulation of ERK1 and ERK2 cascade Source: UniProtKB
  22. regulation of neutrophil degranulation Source: UniProtKB
  23. regulation of phagocytosis Source: UniProtKB
  24. regulation of platelet activation Source: UniProtKB
  25. regulation of platelet aggregation Source: UniProtKB
  26. regulation of superoxide anion generation Source: UniProtKB
  27. serotonin secretion by platelet Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Adaptive immunity, Angiogenesis, Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 6170.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase SYK (EC:2.7.10.2)
Alternative name(s):
Spleen tyrosine kinase
Cleaved into the following 2 chains:
Gene namesi
Name:SYK
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
ProteomesiUP000008227: Unplaced

Subcellular locationi

Chain 72 kDa tyrosine-protein kinase SYK : Cell membrane Curated. Cytoplasmcytosol
Note: Mainly associated with membranes.
Chain 40 kDa tyrosine-protein kinase SYK : Cell membrane Curated. Cytoplasmcytosol
Note: Equally distributed between membranes and cytosol.

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. early phagosome Source: UniProtKB
  3. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi341 – 3411Y → F: Alters interaction with VAV1. 1 Publication
Mutagenesisi345 – 3451Y → F: Moderately alters interaction with VAV1. 1 Publication
Mutagenesisi395 – 3951K → R: Loss of kinase activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 62862872 kDa tyrosine-protein kinase SYKPRO_0000024468Add
BLAST
Chaini313 – 62831640 kDa tyrosine-protein kinase SYKPRO_0000024469Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei23 – 231PhosphotyrosineBy similarity
Modified residuei39 – 391PhosphoserineBy similarity
Modified residuei42 – 421PhosphotyrosineBy similarity
Modified residuei126 – 1261PhosphotyrosineBy similarity
Modified residuei196 – 1961PhosphoserineBy similarity
Modified residuei250 – 2501PhosphothreonineBy similarity
Modified residuei288 – 2881PhosphoserineBy similarity
Modified residuei289 – 2891PhosphotyrosineBy similarity
Modified residuei290 – 2901PhosphoserineBy similarity
Modified residuei309 – 3091PhosphoserineBy similarity
Modified residuei312 – 3121PhosphoserineBy similarity
Modified residuei316 – 3161Phosphotyrosine; by LYNBy similarity
Modified residuei338 – 3381PhosphothreonineBy similarity
Modified residuei341 – 3411Phosphotyrosine1 Publication
Modified residuei343 – 3431PhosphoserineBy similarity
Modified residuei345 – 3451PhosphotyrosineBy similarity
Modified residuei357 – 3571PhosphotyrosineBy similarity
Modified residuei372 – 3721PhosphoserineBy similarity
Modified residuei377 – 3771PhosphothreonineBy similarity
Modified residuei477 – 4771PhosphotyrosineBy similarity
Modified residuei500 – 5001PhosphotyrosineBy similarity
Modified residuei518 – 5181Phosphotyrosine; by autocatalysisBy similarity
Modified residuei519 – 5191PhosphotyrosineBy similarity
Modified residuei523 – 5231PhosphothreonineBy similarity
Modified residuei539 – 5391PhosphotyrosineBy similarity
Modified residuei572 – 5721PhosphoserineBy similarity
Modified residuei622 – 6221PhosphotyrosineBy similarity
Modified residuei623 – 6231PhosphotyrosineBy similarity
Modified residuei624 – 6241PhosphotyrosineBy similarity

Post-translational modificationi

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).By similarity
Shows high susceptibility to proteolysis.
Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Expressioni

Tissue specificityi

Spleen and with lesser amounts in thymus.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

IntActiQ00655. 1 interaction.
MINTiMINT-6622752.
STRINGi9823.ENSSSCP00000010237.

Structurei

3D structure databases

ProteinModelPortaliQ00655.
SMRiQ00655. Positions 4-256, 356-628.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini10 – 10293SH2 1PROSITE-ProRule annotationAdd
BLAST
Domaini163 – 25391SH2 2PROSITE-ProRule annotationAdd
BLAST
Domaini364 – 624261Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni103 – 16260Interdomain ABy similarityAdd
BLAST
Regioni254 – 363110Interdomain BBy similarityAdd
BLAST

Domaini

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).By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 2 SH2 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000113264.
HOVERGENiHBG001540.
InParanoidiQ00655.
KOiK05855.

Family and domain databases

Gene3Di1.10.930.10. 1 hit.
3.30.505.10. 2 hits.
InterProiIPR011009. 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]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 2 hits.
[Graphical view]
PIRSFiPIRSF000604. TyrPK_SYK. 1 hit.
PRINTSiPR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 3 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q00655-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MADSANHLPF FFGQITREEA EDYLVQGGMS DGLYLLRQSR NYLGGFALSV
60 70 80 90 100
AYDRKAHHYT IERELNGTYA ISGGRTHGSP AELCHYHSQE LDGLVCLLKN
110 120 130 140 150
PFNRPPGVQP KTGPFEDLKE NLIREYVKQT WNLQGQALEQ AIISQKPQLE
160 170 180 190 200
KLIATTAHEK MPWFHGKISR DESEQIVLIG SKTNGKFLIR ARDNGSYALG
210 220 230 240 250
LLHEGKVLHY RIDKDKTGKL SIPGGKNFDT LWQLVEHYSY KSDGLLRVLT
260 270 280 290 300
VPCQKIGGQT GNDSFRPQLP SAHPATWSAG GIISRIKSYS FPKPGHRKAS
310 320 330 340 350
SPQGNRPESL VSYNPYESDR GPWANEREAQ REALPMDTEV YESPYADPEE
360 370 380 390 400
IRPKEVYLDR KLLTLEDKEL GSGNFGTVKK GYYQMKKVVK TVAVKILKNE
410 420 430 440 450
ANDPALKDEL LAEANVMQQL DNPYIVRMIG ICEAESWMLV MEMAELGPLN
460 470 480 490 500
KYLQQNRHVK DKNIIELVHQ VSMGMKYLEE CNFVHRDLAA RNVLLVTQHY
510 520 530 540 550
AKISDFGLSK ALRADENYYK AQTHGKWPVK WYAPECINYY KFSSKSDVWS
560 570 580 590 600
FGVLMWEAFS YGQKPYRGMK GSEVSAMLEK GERMGCPPGC PREMYELMTL
610 620
CWTYDVENRP GFVAVELRLR NYYYDVVN
Length:628
Mass (Da):71,620
Last modified:April 1, 1993 - v1
Checksum:iD7C0CEF7EBBEBC1E
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M73237 mRNA. Translation: AAA31112.1.
PIRiA40802.
RefSeqiNP_001098422.1. NM_001104952.1.
UniGeneiSsc.55112.

Genome annotation databases

GeneIDi100125540.
KEGGissc:100125540.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M73237 mRNA. Translation: AAA31112.1 .
PIRi A40802.
RefSeqi NP_001098422.1. NM_001104952.1.
UniGenei Ssc.55112.

3D structure databases

ProteinModelPortali Q00655.
SMRi Q00655. Positions 4-256, 356-628.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q00655. 1 interaction.
MINTi MINT-6622752.
STRINGi 9823.ENSSSCP00000010237.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 100125540.
KEGGi ssc:100125540.

Organism-specific databases

CTDi 6850.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000113264.
HOVERGENi HBG001540.
InParanoidi Q00655.
KOi K05855.

Enzyme and pathway databases

BRENDAi 2.7.10.2. 6170.

Family and domain databases

Gene3Di 1.10.930.10. 1 hit.
3.30.505.10. 2 hits.
InterProi IPR011009. 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 ]
Pfami PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 2 hits.
[Graphical view ]
PIRSFi PIRSF000604. TyrPK_SYK. 1 hit.
PRINTSi PR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTi SM00252. SH2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF55550. SSF55550. 3 hits.
SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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. 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.

Entry informationi

Entry nameiKSYK_PIG
AccessioniPrimary (citable) accession number: Q00655
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: October 29, 2014
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3