Tyrosine-protein kinase SYK (SYK)
The protein contains 635 amino acids for an estimated molecular weight of 72066 Da.
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 r (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs16906862 |
Biological Process
Activation of JUN kinase activity
Adaptive immune response
Angiogenesis
Animal organ morphogenesis
B cell receptor signaling pathway
Beta selection
Blood coagulation
Blood vessel morphogenesis
Cell differentiation
Cell population proliferation
Cellular response to low-density lipoprotein particle stimulus
Cellular response to molecule of fungal origin
Collagen-activated tyrosine kinase receptor signaling pathway
Cytokine-mediated signaling pathway
Defense response to bacterium
Fc-epsilon receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
Inflammatory response
Innate immune response
Integrin-mediated signaling pathway
Interleukin-2-mediated signaling pathway
Interleukin-3-mediated signaling pathway
Intracellular signal transduction
Leukocyte activation involved in immune response
Leukocyte cell-cell adhesion
Leukotriene biosynthetic process
Lymph vessel development
Macrophage activation involved in immune response
Negative regulation of inflammatory response to antigenic stimulus
Neutrophil activation involved in immune response
Neutrophil chemotaxis
Obsolete transcription factor import into nucleus
Peptidyl-serine phosphorylation
Peptidyl-tyrosine autophosphorylation
Peptidyl-tyrosine phosphorylation
Platelet activation
Positive regulation of alpha-beta T cell differentiation
Positive regulation of alpha-beta T cell proliferation
Positive regulation of B cell differentiation
Positive regulation of bone resorption
Positive regulation of calcium-mediated signaling
Positive regulation of cell adhesion mediated by integrin
Positive regulation of cold-induced thermogenesis
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
Positive regulation of cytokine secretion
Positive regulation of gamma-delta T cell differentiation
Positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process
Positive regulation of granulocyte macrophage colony-stimulating factor production
Positive regulation of interleukin-10 biosynthetic process
Positive regulation of interleukin-10 production
Positive regulation of interleukin-12 biosynthetic process
Positive regulation of interleukin-12 production
Positive regulation of interleukin-3 biosynthetic process
Positive regulation of interleukin-3 production
Positive regulation of interleukin-4 production
Positive regulation of interleukin-6 biosynthetic process
Positive regulation of interleukin-6 production
Positive regulation of interleukin-8 biosynthetic process
Positive regulation of interleukin-8 production
Positive regulation of killing of cells of other organism
Positive regulation of mast cell degranulation
Positive regulation of monocyte chemotactic protein-1 production
Positive regulation of peptidyl-tyrosine autophosphorylation
Positive regulation of peptidyl-tyrosine phosphorylation
Positive regulation of protein-containing complex assembly
Positive regulation of receptor internalization
Positive regulation of superoxide anion generation
Positive regulation of tumor necrosis factor biosynthetic process
Positive regulation of tumor necrosis factor production
Positive regulation of type I interferon production
Protein autophosphorylation
Protein import into nucleus
Protein phosphorylation
Receptor internalization
Regulation of arachidonic acid secretion
Regulation of cell population proliferation
Regulation of DNA-binding transcription factor activity
Regulation of ERK1 and ERK2 cascade
Regulation of neutrophil degranulation
Regulation of phagocytosis
Regulation of platelet activation
Regulation of platelet aggregation
Regulation of superoxide anion generation
Regulation of tumor necrosis factor-mediated signaling pathway
Serotonin secretion by platelet
Stimulatory C-type lectin receptor signaling pathway
Transmembrane receptor protein tyrosine kinase signaling pathway
Viral process
Cellular Component
B cell receptor complex
Cytoplasm
Cytosol
Early phagosome
Extrinsic component of cytoplasmic side of plasma membrane
Nucleus
Plasma membrane
Protein complex
Protein-containing complex
T cell receptor complex
Molecular Function
ATP binding
Integrin binding
Interleukin-15 receptor binding
Non-membrane spanning protein tyrosine kinase activity
Obsolete signal transducer, downstream of receptor, with protein tyrosine kinase activity
Phosphatase binding
Phosphotyrosine residue binding
Protein kinase activity
Protein kinase binding
Protein serine/threonine kinase activity
Protein tyrosine kinase activity
Scaffold protein binding
SH2 domain binding
Signaling receptor binding
Toll-like receptor binding
Transmembrane receptor protein tyrosine kinase activity
The reference OMIM entry for this protein is 600085
Protein-tyrosine kinase syk; syk
Spleen tyrosine kinase
CLONING
The pig protein-tyrosine kinase SYK, with a relative molecular mass of 72,000, was first described as a protein predominantly expressed in the spleen and thymus (Zioncheck et al., 1988). The nucleotide and deduced amino acid sequence indicated that SYK is a member of the family of nonreceptor type kinases (Taniguchi et al., 1991). Muller et al. (1994) cloned the human homolog. They found an open reading frame of 1,890 bp encoding a protein of 630 amino acids, in comparison with the pig SYK of 628 amino acids. In the human protein, the N-terminal SH2 domain spans amino acids 10-102, the C-terminal SH2 domain spans amino acids 163-254, and the kinase domain includes amino acids 366-621. On the amino acid level, the overall similarity between human and pig SYK is 93%. The similarity was highest in the kinase domain.GENE FUNCTION
Toyabe et al. (2001) determined that a subpopulation of T cells can express high levels of SYK and partially compensate for loss of T-cell functions in patients with deficiency of ZAP70 (176947). SYK is a protein-tyrosine kinase that is widely expressed in hematopoietic cells. It is involved in coupling activated immunoreceptors to downstream signaling events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis. SYK expression has been reported in cell lines of epithelial origin. Coopman et al. (2000) showed that SYK is commonly expressed in normal human breast tissue, benign breast lesions, and low-tumorigenic breast cancer cell lines. SYK mRNA and protein, however, are low or undetectable in invasive breast carcinoma tissue and cell lines. Transfection of wildtype SYK into an SYK-negative breast cancer cell line markedly inhibited its tumor growth and metastasis formation in athymic mice. Conversely, overexpression of a kinase-deficient SYK in an SYK-positive breast cancer cell line significantly increased its tumor incidence and growth. Suppression of tumor growth by the reintroduction of SYK appeared to be the result of aberrant mitosis and cytokinesis. Coopman et al. (2000) proposed that SYK is a potent modulator of epithelial cell growth and a potential tumor suppressor in human breast carcinomas. Inatome et al. (2001) found increased expression of SYK in human umbilical vein epithelial cells (HUVEC) during cell growth and in response to serum following serum deprivation. A porcine kinase-minus mutant of SYK, carrying a point mutation in the ATP-binding site, suppressed proliferation and survival when transfected into HUVEC cells. Overexpression of the kinase-minus mutant suppressed ERK (EPHB2; 600997) activation in these cells, whereas overexpression of the wildtype porcine SYK induced ERK activation. Inatome et al. (2001) suggested that SYK has a role in endothelial cell growth and survival as well as in the ERK signaling pathway. Using flow cytometric, Western blot, and RT-PCR analyses, Siegel et al. (2006) showed that mice lacking Ocab (POU2AF1; 601206) had an altered distribution of bone marrow B cells and compromised pre-B cell receptor differentiation and signaling. Quantitative PCR and immunoblot analysis revealed reduced Syk expression in Ocab -/- cells. Immunofluorescence and immunoprecipitation analysis showed that Syk and Ocab colocalized in cytoplasm and interacted directly. Siegel et al. (2006) suggested that, together with dysregulation of other OCAB target genes, altered regulation of SYK may help explain the magnitu ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600085 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed