P48025

SS
Gene name
Syk (ptk72, Sykb)
Protein name
Tyrosine-protein kinase SYK
Names
Spleen tyrosine kinase
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:20963
EC number
2.7.10.2: Protein-tyrosine kinases
Protein Class

Descriptions

Syk is non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Upon BCR crosslinking, Syk is recruited via its tandem SH2 domain to tyrosine-phosphorylated Ig-α/Ig-β constituting components of BCR, and intimately cooperates with the signaling subunits of the BCR and plays a central role in the amplification and diversification of BCR signals. Syk has two linkers called interdomains that regulate conformations of SYK: interdomain A (SH2-SH2), interdomain B (SH2-Protein Kinase). The interdomain interaction of A and B maintains the kinase domain inactive.

Autoinhibitory domains (AIDs)

107-166 (Interdomain A) SS

Target domain

365-525 (Protein kinase domain)

Relief mechanism

Partner binding, PTM

Assay

259-364 (Interdomain B) SS

Target domain

365-525 (Protein kinase domain)

Relief mechanism

Partner binding, PTM

Assay

Accessory elements

505-531 (Activation loop from InterPro)

Target domain

365-625 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

3 structures for P48025

Entry ID Method Resolution Chain Position Source
2LCT NMR - B 338-350 PDB
2MC1 NMR - B 338-350 PDB
AF-P48025-F1 Predicted AlphaFoldDB

2 variants for P48025

Variant ID(s) Position Change Description Diseaes Association Provenance
rs238633155 362 S>N No Ensembl
rs6363905 482 S>C No Ensembl

No associated diseases with P48025

8 regional properties for P48025

Type Name Position InterPro Accession
domain Protein kinase domain 365 - 625 IPR000719
domain SH2 domain 12 - 106 IPR000980-1
domain SH2 domain 165 - 258 IPR000980-2
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 369 - 617 IPR001245
active_site Tyrosine-protein kinase, active site 484 - 496 IPR008266
binding_site Protein kinase, ATP binding site 371 - 396 IPR017441
domain Tyrosine-protein kinase, catalytic domain 365 - 620 IPR020635
domain SYK/ZAP-70, N-terminal SH2 domain 12 - 115 IPR035838

Functions

Description
EC Number 2.7.10.2 Protein-tyrosine kinases
Subcellular Localization
  • Cell membrane
  • Cytoplasm, cytosol
  • Cytoplasmic vesicle, phagosome
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

8 GO annotations of cellular component

Name Definition
B cell receptor complex An immunoglobulin complex that is present in the plasma membrane of B cells and that in its canonical form is composed of two identical immunoglobulin heavy chains and two identical immunoglobulin light chains and a signaling subunit, a heterodimer of the Ig-alpha and Ig-beta proteins.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
early phagosome A membrane-bounded intracellular vesicle as initially formed upon the ingestion of particulate material by phagocytosis.
extrinsic component of cytoplasmic side of plasma membrane The component of a plasma membrane consisting of gene products and protein complexes that are loosely bound to its cytoplasmic surface, but not integrated into the hydrophobic region.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
protein-containing complex A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.
T cell receptor complex A protein complex that contains a disulfide-linked heterodimer of T cell receptor (TCR) chains, which are members of the immunoglobulin superfamily, and mediates antigen recognition, ultimately resulting in T cell activation. The TCR heterodimer is associated with the CD3 complex, which consists of the nonpolymorphic polypeptides gamma, delta, epsilon, zeta, and, in some cases, eta (an RNA splice variant of zeta) or Fc epsilon chains.

18 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
integrin binding Binding to an integrin.
interleukin-15 receptor binding Binding to an interleukin-15 receptor.
non-membrane spanning protein tyrosine kinase activity Catalysis of the reaction: ATP + protein L-tyrosine = ADP + protein L-tyrosine phosphate by a non-membrane spanning protein.
phosphatase binding Binding to a phosphatase.
phospholipase binding Binding to a phospholipase.
phosphotyrosine residue binding Binding to a phosphorylated tyrosine residue within a protein.
protein domain specific binding Binding to a specific domain of a protein.
protein kinase activity Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP.
protein kinase binding Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein serine/threonine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
protein tyrosine kinase activity Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
scaffold protein binding Binding to a scaffold protein. Scaffold proteins are crucial regulators of many key signaling pathways. Although not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes.
SH2 domain binding Binding to a SH2 domain (Src homology 2) of a protein, a protein domain of about 100 amino-acid residues and belonging to the alpha + beta domain class.
signaling receptor binding Binding to one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.
Toll-like receptor binding Binding to a Toll-like protein, a pattern recognition receptor that binds pattern motifs from a variety of microbial sources to initiate an innate immune response.
ubiquitin protein ligase binding Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.

75 GO annotations of biological process

Name Definition
adaptive immune response An immune response mediated by cells expressing specific receptors for antigen produced through a somatic diversification process, and allowing for an enhanced secondary response to subsequent exposures to the same antigen (immunological memory).
angiogenesis Blood vessel formation when new vessels emerge from the proliferation of pre-existing blood vessels.
B cell receptor signaling pathway The series of molecular signals initiated by the cross-linking of an antigen receptor on a B cell.
beta selection The process in which successful recombination of a T cell receptor beta chain into a translatable protein coding sequence leads to rescue from apoptosis and subsequent proliferation of an immature T cell.
blood vessel morphogenesis The process in which the anatomical structures of blood vessels are generated and organized. The blood vessel is the vasculature carrying blood.
cell activation A change in the morphology or behavior of a cell resulting from exposure to an activating factor such as a cellular or soluble ligand.
cell differentiation The process in which relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organism's life history. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
cell surface receptor signaling pathway The series of molecular signals initiated by activation of a receptor on the surface of a cell. The pathway begins with binding of an extracellular ligand to a cell surface receptor, or for receptors that signal in the absence of a ligand, by ligand-withdrawal or the activity of a constitutively active receptor. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
cellular response to lectin Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lectin stimulus. A lectin is a carbohydrate-binding protein, highly specific for binding sugar moieties.
cellular response to lipid Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipid stimulus.
cellular response to low-density lipoprotein particle stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a low-density lipoprotein particle stimulus.
cellular response to molecule of fungal origin Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus by molecules of fungal origin such as chito-octamer oligosaccharide.
collagen-activated tyrosine kinase receptor signaling pathway The series of molecular signals initiated by collagen binding to its receptor on the surface of a target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.
defense response to bacterium Reactions triggered in response to the presence of a bacterium that act to protect the cell or organism.
enzyme linked receptor protein signaling pathway The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell, where the receptor possesses catalytic activity or is closely associated with an enzyme such as a protein kinase, and ending with the regulation of a downstream cellular process, e.g. transcription.
G protein-coupled receptor signaling pathway The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
integrin-mediated signaling pathway The series of molecular signals initiated by an extracellular ligand binding to an integrin on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
interleukin-3-mediated signaling pathway The series of molecular signals initiated by interleukin-3 binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
leukocyte activation involved in immune response A change in morphology and behavior of a leukocyte resulting from exposure to a specific antigen, mitogen, cytokine, cellular ligand, or soluble factor, leading to the initiation or perpetuation of an immune response.
leukocyte cell-cell adhesion The attachment of a leukocyte to another cell via adhesion molecules.
leukotriene biosynthetic process The chemical reactions and pathways resulting in the formation of leukotriene, a pharmacologically active substance derived from a polyunsaturated fatty acid, such as arachidonic acid.
lymph vessel development The process whose specific outcome is the progression of a lymph vessel over time, from its formation to the mature structure.
macrophage activation involved in immune response A change in morphology and behavior of a macrophage resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor, leading to the initiation or perpetuation of an immune response.
neutrophil activation involved in immune response The change in morphology and behavior of a neutrophil resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor, leading to the initiation or perpetuation of an immune response.
neutrophil chemotaxis The directed movement of a neutrophil cell, the most numerous polymorphonuclear leukocyte found in the blood, in response to an external stimulus, usually an infection or wounding.
peptidyl-serine phosphorylation The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
peptidyl-tyrosine phosphorylation The phosphorylation of peptidyl-tyrosine to form peptidyl-O4'-phospho-L-tyrosine.
positive regulation of alpha-beta T cell differentiation Any process that activates or increases the frequency, rate or extent of alpha-beta T cell differentiation.
positive regulation of alpha-beta T cell proliferation Any process that activates or increases the frequency, rate or extent of alpha-beta T cell proliferation.
positive regulation of B cell differentiation Any process that activates or increases the frequency, rate or extent of B cell differentiation.
positive regulation of bone resorption Any process that activates or increases the frequency, rate or extent of bone resorption.
positive regulation of calcium-mediated signaling Any process that activates or increases the frequency, rate or extent of calcium-mediated signaling.
positive regulation of cell adhesion mediated by integrin Any process that activates or increases the frequency, rate, or extent of cell adhesion mediated by integrin.
positive regulation of cold-induced thermogenesis Any process that activates or increases the frequency, rate or extent of cold-induced thermogenesis.
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Any process that activates or increases the activity of a cysteine-type endopeptidase involved in the apoptotic process.
positive regulation of cytokine production Any process that activates or increases the frequency, rate or extent of production of a cytokine.
positive regulation of gamma-delta T cell differentiation Any process that activates or increases the frequency, rate or extent of gamma-delta T cell differentiation.
positive regulation of granulocyte macrophage colony-stimulating factor production Any process that activates or increases the frequency, rate, or extent of granulocyte macrophage colony-stimulating factor production.
positive regulation of interleukin-10 production Any process that activates or increases the frequency, rate, or extent of interleukin-10 production.
positive regulation of interleukin-12 production Any process that activates or increases the frequency, rate, or extent of interleukin-12 production.
positive regulation of interleukin-3 production Any process that activates or increases the frequency, rate, or extent of interleukin-3 production.
positive regulation of interleukin-4 production Any process that activates or increases the frequency, rate, or extent of interleukin-4 production.
positive regulation of interleukin-6 production Any process that activates or increases the frequency, rate, or extent of interleukin-6 production.
positive regulation of interleukin-8 production Any process that activates or increases the frequency, rate, or extent of interleukin-8 production.
positive regulation of JUN kinase activity Any process that activates or increases the frequency, rate or extent of JUN kinase activity.
positive regulation of killing of cells of other organism Any process that activates or increases the frequency, rate or extent of the killing by an organism of cells in another organism.
positive regulation of MAPK cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the MAPK cascade.
positive regulation of mast cell degranulation Any process that activates or increases the frequency, rate or extent of mast cell degranulation.
positive regulation of monocyte chemotactic protein-1 production Any process that activates or increases the frequency, rate, or extent of production of monocyte chemotactic protein-1.
positive regulation of peptidyl-tyrosine phosphorylation Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-tyrosine.
positive regulation of protein-containing complex assembly Any process that activates or increases the frequency, rate or extent of protein complex assembly.
positive regulation of receptor internalization Any process that activates or increases the frequency, rate or extent of receptor internalization.
positive regulation of superoxide anion generation Any process that activates or increases the frequency, rate or extent of enzymatic generation of superoxide by a cell.
positive regulation of tumor necrosis factor production Any process that activates or increases the frequency, rate or extent of tumor necrosis factor production.
positive regulation of type I interferon production Any process that activates or increases the frequency, rate, or extent of type I interferon production. Type I interferons include the interferon-alpha, beta, delta, episilon, zeta, kappa, tau, and omega gene families.
protein autophosphorylation The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation).
protein import into nucleus The directed movement of a protein from the cytoplasm to the nucleus.
protein phosphorylation The process of introducing a phosphate group on to a protein.
receptor internalization A receptor-mediated endocytosis process that results in the movement of receptors from the plasma membrane to the inside of the cell. The process begins when cell surface receptors are monoubiquitinated following ligand-induced activation. Receptors are subsequently taken up into endocytic vesicles from where they are either targeted to the lysosome or vacuole for degradation or recycled back to the plasma membrane.
regulation of arachidonic acid secretion Any process that modulates the rate, frequency, or extent of arachidonic acid secretion, the controlled release of arachidonic acid from a cell or a tissue.
regulation of DNA-binding transcription factor activity Any process that modulates the frequency, rate or extent of the activity of a transcription factor, any factor involved in the initiation or regulation of transcription.
regulation of ERK1 and ERK2 cascade Any process that modulates the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
regulation of immune response Any process that modulates the frequency, rate or extent of the immune response, the immunological reaction of an organism to an immunogenic stimulus.
regulation of neutrophil degranulation Any process that modulates the frequency, rate, or extent of neutrophil degranulation.
regulation of phagocytosis Any process that modulates the frequency, rate or extent of phagocytosis, the process in which phagocytes engulf external particulate material.
regulation of platelet activation Any process that modulates the rate or frequency of platelet activation. Platelet activation is a series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue.
regulation of platelet aggregation Any process that modulates the rate, frequency or extent of platelet aggregation. Platelet aggregation is the adhesion of one platelet to one or more other platelets via adhesion molecules.
regulation of superoxide anion generation Any process that modulates the frequency, rate or extent of enzymatic generation of superoxide by a cell.
regulation of tumor necrosis factor-mediated signaling pathway Any process that modulates the rate or extent of the tumor necrosis factor-mediated signaling pathway. The tumor necrosis factor-mediated signaling pathway is the series of molecular signals generated as a consequence of tumor necrosis factor binding to a cell surface receptor.
serotonin secretion The regulated release of serotonin by a cell. Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine synthesised in serotonergic neurons in the central nervous system, enterochromaffin cells in the gastrointestinal tract and some immune system cells.
serotonin secretion by platelet The regulated release of serotonin by a platelet or group of platelets.
stimulatory C-type lectin receptor signaling pathway The series of molecular signals initiated by the binding of C-type lectin to its receptor on the surface of a target cell, and resulting in cellular activation.
transmembrane receptor protein tyrosine kinase signaling pathway The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.

36 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
F1N9Y5 SYK Tyrosine-protein kinase SYK Gallus gallus (Chicken) SS
P43403 ZAP70 Tyrosine-protein kinase ZAP-70 Homo sapiens (Human) EV
P43405 SYK Tyrosine-protein kinase SYK Homo sapiens (Human) EV
P16277 Blk Tyrosine-protein kinase Blk Mus musculus (Mouse) SS
Q64434 Ptk6 Protein-tyrosine kinase 6 Mus musculus (Mouse) SS
P05480 Src Proto-oncogene tyrosine-protein kinase Src Mus musculus (Mouse) EV
P14234 Fgr Tyrosine-protein kinase Fgr Mus musculus (Mouse) SS
P35991 Btk Tyrosine-protein kinase BTK Mus musculus (Mouse) EV
P41241 Csk Tyrosine-protein kinase CSK Mus musculus (Mouse) EV
P06240 Lck Proto-oncogene tyrosine-protein kinase LCK Mus musculus (Mouse) SS
Q04736 Yes1 Tyrosine-protein kinase Yes Mus musculus (Mouse) SS
Q03526 Itk Tyrosine-protein kinase ITK/TSK Mus musculus (Mouse) SS
Q922K9 Frk Tyrosine-protein kinase FRK Mus musculus (Mouse) SS
P43404 Zap70 Tyrosine-protein kinase ZAP-70 Mus musculus (Mouse) SS
P25911 Lyn Tyrosine-protein kinase Lyn Mus musculus (Mouse) EV
P39688 Fyn Tyrosine-protein kinase Fyn Mus musculus (Mouse) SS
P08103 Hck Tyrosine-protein kinase HCK Mus musculus (Mouse) SS
P24604 Tec Tyrosine-protein kinase Tec Mus musculus (Mouse) SS
P41242 Matk Megakaryocyte-associated tyrosine-protein kinase Mus musculus (Mouse) SS
Q9QVP9 Ptk2b Protein-tyrosine kinase 2-beta Mus musculus (Mouse) PR
P34152 Ptk2 Focal adhesion kinase 1 Mus musculus (Mouse) SS
Q99ML2 Tnk1 Non-receptor tyrosine-protein kinase TNK1 Mus musculus (Mouse) PR
O54967 Tnk2 Activated CDC42 kinase 1 Mus musculus (Mouse) SS
P70451 Fer Tyrosine-protein kinase Fer Mus musculus (Mouse) PR
Q6J9G1 Styk1 Tyrosine-protein kinase STYK1 Mus musculus (Mouse) PR
P00520 Abl1 Tyrosine-protein kinase ABL1 Mus musculus (Mouse) EV
Q62270 Srms Tyrosine-protein kinase Srms Mus musculus (Mouse) SS
Q4JIM5 Abl2 Tyrosine-protein kinase ABL2 Mus musculus (Mouse) SS
Q00655 SYK Tyrosine-protein kinase SYK Sus scrofa (Pig) SS
Q64725 Syk Tyrosine-protein kinase SYK Rattus norvegicus (Rat) SS
Q9SYA0 At1g61500 G-type lectin S-receptor-like serine/threonine-protein kinase At1g61500 Arabidopsis thaliana (Mouse-ear cress) SS
Q9FG33 LECRKS5 Probable L-type lectin-domain containing receptor kinase S.5 Arabidopsis thaliana (Mouse-ear cress) PR
Q2MHE4 HT1 Serine/threonine/tyrosine-protein kinase HT1 Arabidopsis thaliana (Mouse-ear cress) PR
O22558 STY8 Serine/threonine-protein kinase STY8 Arabidopsis thaliana (Mouse-ear cress) PR
Q8RWL6 STY17 Serine/threonine-protein kinase STY17 Arabidopsis thaliana (Mouse-ear cress) PR
F4JTP5 STY46 Serine/threonine-protein kinase STY46 Arabidopsis thaliana (Mouse-ear cress) PR
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