Q64725 · KSYK_RAT

  • Protein
    Tyrosine-protein kinase SYK
  • Gene
    Syk
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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 DEPTOR, 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 also plays 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. Required for the stimulation of neutrophil phagocytosis by IL15 (By similarity).
Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity).
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. Also plays 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. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity).

Catalytic activity

Activity 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 (By similarity).
Phosphorylates SH3BP2 which in turn may regulate SYK through LYN (By similarity).

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site371-379ATP (UniProtKB | ChEBI)
Binding site396ATP (UniProtKB | ChEBI)
Active site488Proton acceptor

GO annotations

AspectTerm
Cellular ComponentB cell receptor complex
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentearly phagosome
Cellular Componentnucleus
Cellular Componentplasma membrane
Cellular Componentprotein-containing complex
Cellular ComponentT cell receptor complex
Molecular FunctionATP binding
Molecular Functionintegrin binding
Molecular Functioninterleukin-15 receptor binding
Molecular Functionkinase activity
Molecular Functionnon-membrane spanning protein tyrosine kinase activity
Molecular Functionphosphatase binding
Molecular Functionphospholipase binding
Molecular Functionphosphotyrosine residue binding
Molecular Functionprotein domain specific binding
Molecular Functionprotein kinase activity
Molecular Functionprotein kinase binding
Molecular Functionprotein serine/threonine kinase activity
Molecular Functionprotein tyrosine kinase activity
Molecular Functionscaffold protein binding
Molecular FunctionSH2 domain binding
Molecular Functionsignaling receptor binding
Molecular FunctionToll-like receptor binding
Molecular Functionubiquitin protein ligase binding
Biological Processadaptive immune response
Biological Processangiogenesis
Biological ProcessB cell differentiation
Biological ProcessB cell receptor signaling pathway
Biological Processbeta selection
Biological Processblood vessel morphogenesis
Biological Processcalcium-mediated signaling
Biological Processcell activation
Biological Processcell differentiation
Biological Processcell surface receptor protein tyrosine kinase signaling pathway
Biological Processcell surface receptor signaling pathway
Biological Processcellular response to lectin
Biological Processcellular response to lipid
Biological Processcellular response to low-density lipoprotein particle stimulus
Biological Processcellular response to molecule of fungal origin
Biological Processcollagen-activated tyrosine kinase receptor signaling pathway
Biological Processdefense response to bacterium
Biological Processenzyme-linked receptor protein signaling pathway
Biological Processestablishment of localization in cell
Biological Processgamma-delta T cell differentiation
Biological Processinnate immune response
Biological Processintegrin-mediated signaling pathway
Biological Processinterleukin-3-mediated signaling pathway
Biological Processintracellular signal transduction
Biological Processleukocyte activation involved in immune response
Biological Processleukocyte cell-cell adhesion
Biological Processleukotriene biosynthetic process
Biological Processlymph vessel development
Biological Processmacrophage activation involved in immune response
Biological Processmast cell degranulation
Biological Processneutrophil activation involved in immune response
Biological Processneutrophil chemotaxis
Biological Processpeptidyl-tyrosine phosphorylation
Biological Processpositive regulation of alpha-beta T cell differentiation
Biological Processpositive regulation of alpha-beta T cell proliferation
Biological Processpositive regulation of B cell differentiation
Biological Processpositive regulation of bone resorption
Biological Processpositive regulation of calcium-mediated signaling
Biological Processpositive regulation of cell adhesion mediated by integrin
Biological Processpositive regulation of cold-induced thermogenesis
Biological Processpositive regulation of cytokine production
Biological Processpositive regulation of gamma-delta T cell differentiation
Biological Processpositive regulation of granulocyte macrophage colony-stimulating factor production
Biological Processpositive regulation of interleukin-10 production
Biological Processpositive regulation of interleukin-12 production
Biological Processpositive regulation of interleukin-3 production
Biological Processpositive regulation of interleukin-4 production
Biological Processpositive regulation of interleukin-6 production
Biological Processpositive regulation of interleukin-8 production
Biological Processpositive regulation of killing of cells of another organism
Biological Processpositive regulation of MAPK cascade
Biological Processpositive regulation of mast cell cytokine production
Biological Processpositive regulation of mast cell degranulation
Biological Processpositive regulation of monocyte chemotactic protein-1 production
Biological Processpositive regulation of peptidyl-tyrosine phosphorylation
Biological Processpositive regulation of protein-containing complex assembly
Biological Processpositive regulation of receptor internalization
Biological Processpositive regulation of superoxide anion generation
Biological Processpositive regulation of TORC1 signaling
Biological Processpositive regulation of tumor necrosis factor production
Biological Processpositive regulation of type I interferon production
Biological Processprotein import into nucleus
Biological Processreceptor internalization
Biological Processregulation of arachidonic acid secretion
Biological Processregulation of ERK1 and ERK2 cascade
Biological Processregulation of immune response
Biological Processregulation of neutrophil degranulation
Biological Processregulation of phagocytosis
Biological Processregulation of platelet activation
Biological Processregulation of platelet aggregation
Biological Processregulation of superoxide anion generation
Biological Processregulation of tumor necrosis factor-mediated signaling pathway
Biological Processserotonin secretion
Biological Processserotonin secretion by platelet
Biological Processstimulatory C-type lectin receptor signaling pathway

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Tyrosine-protein kinase SYK
  • EC number
  • Alternative names
    • Spleen tyrosine kinase
    • p72Syk

Gene names

    • Name
      Syk

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    Q64725

Proteomes

Organism-specific databases

Phenotypes & Variants

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00000881671-629Tyrosine-protein kinase SYK
Modified residue27Phosphotyrosine
Modified residue43Phosphoserine
Modified residue46Phosphotyrosine
Modified residue130Phosphotyrosine
Modified residue201Phosphoserine
Modified residue255Phosphothreonine
Modified residue270Phosphoserine
Modified residue289Phosphoserine
Modified residue290Phosphotyrosine
Modified residue291Phosphoserine
Modified residue310Phosphoserine
Modified residue311Phosphothreonine
Modified residue313Phosphoserine
Modified residue317Phosphotyrosine; by LYN
Modified residue339Phosphothreonine
Modified residue342Phosphotyrosine
Modified residue344Phosphoserine
Modified residue346Phosphotyrosine
Modified residue358Phosphotyrosine
Modified residue373Phosphoserine
Modified residue378Phosphothreonine
Modified residue478Phosphotyrosine
Modified residue501Phosphotyrosine
Modified residue519Phosphotyrosine; by autocatalysis
Modified residue520Phosphotyrosine
Modified residue524Phosphothreonine
Modified residue540Phosphotyrosine
Modified residue573Phosphoserine
Modified residue576Phosphothreonine
Modified residue623Phosphotyrosine
Modified residue624Phosphotyrosine
Modified residue625Phosphotyrosine

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 (By similarity).
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).
Phosphorylated on tyrosine residues in response to IL15 (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).
Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation.

Keywords

Proteomic databases

PTM databases

Interaction

Subunit

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. 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 (via SH2 domains) with FCER1G (via ITAM domain); activates SYK and mediates neutrophils and macrophages integrin-mediated activation. Interaction with FCER1G in basophils triggers IL3-induced IL4 production (By similarity).
Interacts with ITGB2 and FGR; involved in ITGB2 downstream signaling. 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. 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 (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).
Interacts with TNS2; leading to the phosphorylation of SYK (By similarity).
Interacts with FLNA (via filamin repeat 5); docks SYK to the plasma membrane (By similarity).
Interacts with CEACAM1; lipopolysaccharide activated neutrophils induce phosphorylation of SYK resulting in the formation of a complex including TLR4, phosphorylated form of SYK and CEACAM1, which in turn, recruits PTPN6 that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, leading to a reduction of the inflammasome activity (By similarity).
Interacts (via SH2 domains) with CEACAM20 (phosphorylated form); the interaction further enhances CEACAM20 phosphorylation (By similarity).
Interacts with IL15RA (By similarity).

Protein-protein interaction databases

Chemistry

Structure

Family & Domains

Features

Showing features for domain, region.

TypeIDPosition(s)Description
Domain14-106SH2 1
Region107-166Interdomain A
Domain167-258SH2 2
Region259-364Interdomain B
Region289-330Disordered
Domain365-625Protein kinase

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).

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

Q64725-1

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.

  • Name
    SykB
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    629
  • Mass (Da)
    71,529
  • Last updated
    1996-11-01 v1
  • Checksum
    81169A643EC6A6FE
MAGNAVDNANHLTYFFGNITREEAEDYLVQGGMTDGLYLLRQSRNYLGGFALSVAHNRKAHHYTIERELNGTYAISGGRAHASPADLCHYHSQEPEGLVCLLKKPFNRPPGVQPKTGPFEDLKENLIREYVKQTWNLQGQALEQAIISQKPQLEKLIATTAHEKMPWFHGNISRDESEQTVLIGSKTNGKFLIRARDNNGSFALCLLHEGKVLHYRIDRDKTGKLSIPEGKKFDTLWQLVEHYSYKPDGLLRVLTVPCQKIGVQMGHPGSSNAHPVTWSPGGIISRIKSYSFPKPGHKKPPPPQGSRPESTVSFNPYEPTGGAWGPDRGLQREALPMDTEVYESPYADPEEIRPKEVYLDRKLLTLEDNELGSGNFGTVKKGYYQMKKVVKTVAVKILKNEANDPALKDELLAEANVMQQLDNPYIVRMIGICEAESWMLVMEMAAWGPLNKYLQQNRHIKDKNIIELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADENYYKAQTHGKWPVKWYAPECINYFKFSSKSDVWSFGVLMWEAFSYGQKPYRGMKGSEVTAMLEKGERMGCPPGCPREMYDLMFLCWTYDVENRPGFAAVELRLRNYYYDVVN

Q64725-2

  • Name
    SykA
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
D3ZH44D3ZH44_RATSyk606
G3V7N4G3V7N4_RATSyk629

Features

Showing features for alternative sequence.

TypeIDPosition(s)Description
Alternative sequenceVSP_005011277-299in isoform SykA

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U21684
EMBL· GenBank· DDBJ
AAA75167.1
EMBL· GenBank· DDBJ
mRNA
U21683
EMBL· GenBank· DDBJ
AAA75166.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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