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SYK (spleen tyrosine kinase)

Written2002-02Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated2016-03Barnabas Nyesiga, Anette Gjörloff Wingren
Department of Biomedical Science, Health and Society, Malmö University, Malmö, Sweden. anette.gjorloff-wingren@mah.se

(Note : for Links provided by Atlas : click)

Identity

Other namesp72-Syk
HGNC (Hugo) SYK
LocusID (NCBI) 6850
Atlas_Id 394
Location 9q22.2
Location_base_pair Starts at 93563962 and ends at 93660842 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  Figure 1. Mapping of SYK gene on chromosome 9q22.2 (from GeneCards Syk gene).
Fusion genes
(updated 2016)
DNMT3B (20q11.21) / SYK (9q22.2)ETV6 (12p13.2) / SYK (9q22.2)ITK (5q33.3) / SYK (9q22.2)
SYK (9q22.2) / ETV6 (12p13.2)SYK (9q22.2) / ITK (5q33.3)SYK (9q22.2) / SYK (9q22.2)

DNA/RNA

Description The spleen tyrosine kinase (SYK) gene encodes a member of the family of non-receptor type Tyr protein kinases (http://www.genecards.org/cgi-bin/carddisp.pl?gene=SYK). The cDNA clone encoding porcine SYK was identified by Taniguchi et al (Taniguchi 1991; Yamada 1993), and thereafter the SYK cDNA for mouse and human, respectively, was cloned (Hutchcroft 1991; Hutchcroft 1992; Müller 1994; Ku 1994). Initially, a smaller porcine SYK protein product was purified and was found to be proteolytically cleaved from the mature SYK protein (Kobayashi 1990). The PTK72 was at the same time found to be identical with the cloned SYK (LePrince 1993; Law 1994).
Transcription The transcript encodes 635 amino acids with a mass of 72,066 Da. Two isoforms have been described, isoform long (L) and isoform short (S) (http://www.uniprot.org/uniprot/P43405): Isoform 1 (full-length); Isoform 2 (283-305 missing)

Protein

Description SYK is a 72 kDa non-receptor type protein tyrosine kinase (PTK) that contains two SRC homology 2 (SH2) domains, interdomains A and B, and a C-terminal kinase domain (Fig. 2). SYK was initially shown to be expressed in lymphocytes and associated with the IgM and IgD receptor complexes in B cells (Taniguchi 1991; Hutchcroft 1992). The requirement for Src-PTKs associated with the B cell receptor (BCR) for phosphorylation of SYK was investigated early, and was shown to enhance the activity of SYK (Kurosaki 1994).
The PTK ZAP70 was cloned in T lymphocytes and shown to be homologous to SYK (Chan 1992). An alternatively spliced form of SYK also exists, missing 23 amino acids from interdomain A (Sada 2001). The topology of the N-terminal part of SYK is similar to its counterpart ZAP70 as revealed by the crystal structure (Narula 1995; Hatada 1995). In 1998, Fütterer et al presented the crystal structure of the tandem SH2 domain of SYK complexed with a dually phosphorylated ITAM peptide (Fütterer 1998). The tandem SH2 domains selectively bind to diphosphorylated immunoreceptor tyrosine based activating motifs (ITAM) of the cytoplasmic region of the BCR (Sada 2001). The crystal structure of a full-length version of ZAP70 has given a greater understanding of the activation process for both SYK and Zap-70 (Deindl 2007).
Atwell et al determined the structure of the unphosphorylated form of the SYK kinase catalytic domain (SYK-KD) in order to understand the molecular mechanism responsible for its enzymatic activity (Atwell 2004). The SYK kinase domain has a subdomain structure composed of a largely β-sheet N-terminal lobe, a largely α–helical C-terminal lobe, with the active site being sandwiched between the two lobes. The N-terminal lobe consists of a five-stranded β -sheet plus a single α –helix. The larger C-terminal lobe is predominantly α –helical with three short β -strands: one at the hinge region and two between the activation loop and the main body of the C-lobe. From the structure of the SYK kinase domain it was deduced that the SYK catalytic activity does not require activation loop phosphorylation.
SYK have multiple sites of phosphorylation which both regulate activity and serve as docking motifs for other proteins (Sada 2001). Phosphorylation sites include Tyr-348 and Tyr-352 within the SH2-linker region (Brdicka 2005), Tyr-525 and Tyr-526 within the activation loop of the kinase domain (Zhang 2000), Tyr-630 in the C terminus of SYK, and others (Kulathu 2008; Tsang 2008; and reviewed by Sada 2001). In B cells, the phosphorylation of two tyrosines within the ITAM leads to the physical recruitment of SYK to the site of the clustered receptor in an interaction mediated by its tandem pair of SH2 domains (reviewed in Geahlen 2009). Shortly following BCR engagement, SYK that has been recruited to the receptor becomes phosphorylated on multiple tyrosines through both autophosphorylation and phosphorylation by Lyn.
 
  Figure 2. Schematic structure of spleen tyrosine kinase (SYK) protein (adopted from Pamuk et al 2010). The protein includes two tandem SH2 domains and a tyrosine kinase domain. Between the two SH2 domains is interdomain A while interdomain B is located between the tyrosine kinase domain and C-terminal domain. ITAM, immunoreceptor tyrosine-based activation motif; SH2, Src homology 2.
Expression SYK expression in hematopoietic cells has been extensively determined by studying SYK as an effector of BCR signalling. Turner and co-workers found that after BCR activation, SYK-dependent signaling pathways regulate the clonal expansion, differentiation, or apoptosis of B cells (Turner 2000). Most of the cells of the hematopoietic system express SYK, but the PTK is also expressed at lower levels in some epithelial cells, fibroblasts, hepatocytes, vascular smooth muscle cells, endothelial cells and neuronal cells where it mediates various responses including adipogenesis, cell division, tumor suppression, ERK activation and neuronal differentiation (Turner 2000; Yanagi 2001; Zhou 2006; Tohyama 2009; Geahlen 2009; Mócsai 2010; Krisenko 2015).
In hepatocytes, after the use of the SYK-selective inhibitor piceatannol, it was indicated that SYK is necessary for mitogen activated protein kinase (MAPK) activation by G-protein coupled receptors in this cell type (Tsuchida 2000). Additionally, SYK expression has also been observed in normal human breast tissue, benign lesions and low-tumourigenic breast cancer cell lines (Coopman 2000).
Localisation SYK is an intracellular PTK, known to function at the plasma membrane, where the receptors to which it is recruited are located (Zhou 2006). In lymphoid and epithelial cells, SYK has been found to reside in both the nucleus and cytoplasm (Ma 2001; Wang 2003; Wang 2004). The expression and localization of SYK in the nucleus of breast cancer cells have been correlated with the repression of invasive tumor growth (Wang 2003).
Function The SYK protein is known to have an important role in adaptive immune receptor signalling with recent reports indicating its mediation of other diverse biological functions, including cellular adhesion, innate immune recognition, osteoclast maturation, platelet activation and vascular development (Mócsai 2010). The protein is also involved in coupling activated immunoreceptors to downstream signaling events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis.
SYK plays a critical role in the transition of pro-B cells into pre-B cells (Turner 1995). SYK is greatly involved in signal transduction initiated by the classic immunoreceptors, including BCRs, Fc receptors, and the activating natural killer receptors (Tohyama 2009; Berton 2005; Crowley 1997). SYK is associated mainly with ITAM dependent pathways and affects early development and activation of various cells including B cells, mast cell degranulation, neutrophil and macrophage phagocytosis, as well as platelet activation (Zhou 2006; Tohyama 2009; Mócsai 2010). SYK-mediated phosphorylation of various adaptor proteins leads to the activation of downstream pathways that execute phagocytosis. SYK is important in complement-mediated phagocytosis resulting from the binding of C3bi-coated particles to complement receptor 3 (Tohyama 2009; Tohyama 2006). SYK is known to play a major role in the development of signal transduction events initiated after high-affinity IgE receptor (FCER1A) aggregation (Wong 2004; Matsubara 2006), mast cell activation, degranulation, and cytokine production (Matsubara 2006; Masuda 2008). It is anticipated that SYK activation coupled with platelet activation and aggregation may assist in lymphatic vessel development and their separation from blood vessels (Mócsai 2010, Turner 1995). SYK is claimed to have a role in osteoclast differentiation and osteoclast function (Tohyama 2009, Mócsai 2010). SYK has been found to have a major role in pre T-cell receptor (TCR) signalling. This is known to occur during the transition from the double negative 3 (DN3) to the DN4 stage of early thymocyte development (Palacios 2007). In vivo studies have shown that SYK is required for firm leukocyte adhesion to inflamed endothelium (Frommhold 2007) and development of vasculopathy reaction (Hirahashi 2006). The innate immune system uses pattern recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMPs) and activate immune responses. SYK has been found to be a key component of these pathways and increased evidence points to the involvement of SYK-coupled PRRs in innate recognition of bacteria, with CLEC7A, CLEC6A and CLEC4E all implicated in sensing of mycobacterial PAMPs (Geijtenbeek 2009). SYK is presumably also involved in signalling PRR-mediated recognition of certain viruses.
The role of ZAP70 in B cells have been investigated, but is poorly understood possibly due to the functional redundancy between SYK and ZAP70 (Fallah-Arani 2008). Toyabe et al displayed the ability of a T cell subpopulation to express high levels of SYK and partially compensate for loss of T-cell functions in patients with deficiency of ZAP70 (Toyabe 2001).
Homology Both ZAP-70 and SYK are dependent upon a Src-family protein tyrosine kinase for association with the phosphorylated zeta-chain. Thus, the differential expression of these kinases suggests the possibility of different roles for ZAP70 and SYK in TCR signaling and thymic development (Palacios 2007). Activation of PTKs is an important mechanism in the transduction of signals from multi-subunit immunoreceptors, including the B and T cell receptors for antigen and the widely distributed receptors for the Fc portion of immunoglobulins (Paolini 2001). ZAP70 is expressed in T cells, natural killer cells and thymocytes, whereas SYK is present in all hematopoietic cells. Both ZAP70 and SYK are reported to be activated after TCR stimulation. Nonetheless, ZAP70 activation is known to require presence of Lck or another associated Src family PTK, while SYK is independent of Lck to undergo phosphorylation (Chan 1994, Couture 1994, Kolanus 1993). Regardless of its presence in all thymocyte subsets, SYK expression is downregulated three- to fourfold in peripheral T cells and, contrary to ZAP70, SYK expression is 12- to 15-fold higher in peripheral B cells compared to peripheral T cells (Chan 1994).
Another study showed functional homology in antigen receptor signaling by demonstrating that expression of ZAP70 in SYK-B cells reconstitutes BCR function (Kong 1995). Another feature that distinguish ZAP70 from SYK is its greater dependency on Src kinases for activation and its ability to phosphorylate and promote the auto-activation of the downstream MAPK p38 (reviewed in Au-Yeung 2009).

Mutations

Note The development of B cells proceeds through a well-characterized set of stages defined by the extent of antigen receptor rearrangement and the expression of particular cell surface markers. When mice deficient for recombination-activating gene 1 (RAG1) were reconstituted with fetal liver from SYK-deficient embryos, the pool of pre-B cells formed was reduced. This suggests that SYK is required for the proper signalling from the pre-BCR to generate or maintain the pool of pre-B cells. Indeed, it has been shown that SYK is an essential transducer of BCR signals required for the transition of immature into recirculating B cells (Turner 2000). Moreover, SYK-deficient mice die due to embryonic and perinatal death (Turner 1995; Cheng 1995).
Epigenetics SYK can also be inactivated by epigenetic modifications (i.e. hypermethylation)

Implicated in

Entity t(5;9)(q33;q22)
Disease found in Peripheral T-cell lymphoma (Streubel et al. 2006).
Hybrid/Mutated Gene N-terminal ITK (bp 1-577) fused in frame with C-terminal SYK cDNA
  
Entity t(9;12)(q22;p12)
Disease found in a case of myelodysplastic syndrome (Kuno et al. 2001).
Oncogenesis ETV6-SYK is constituvely tyrosine phosphorylated
  
Entity Breast cancer
Note SYK mRNA and protein expression in a panel of well-characterized breast cancer cell lines, normal mammary gland tissue, and a normal breast epithelial cell line has been investigated by Coopman et al (Coopman 2000). They readily detected SYK expression in normal mammary tissue and epithelium, as well as in non-invasive breast carcinoma cell lines. SYK expression was however observed to be reduced or absent in the invasive breast tumor cell lines. Hypermethylation of the SYK locus during breast cancer progression was found to cause a loss of SYK protein expression in highly invasive and metastatic human mammary carcinomas (Coopman 2000,Yuan 2001). Moreover, Wang et al have shown that full-length SYK can enter the nucleus and thereby suppress invasion (Wang 2003). The sequences confined to a region of the SYK molecule near the junction of the linker B and catalytic domain were determined to be responsible for its distribution between the nucleus and cytoplasm (Zhou 2006). It was further demonstrated that the distribution of SYK between the nucleus and cytoplasm was regulated by signals sent downstream from the activated BCR and require the receptor-mediated activation of protein kinase C (PKC) and the induction of new protein synthesis.
  
Entity Colon carcinoma
Note Expression of the SYK gene in human colon carcinoma cells is known to be suppressed in a p53-dependent manner, an indication that loss of p53 function during tumorigenesis can lead to deregulation of SYK activity (Okamura 1999). As reviewed recently by Krisenko et al,the levels of SYK mRNA in many cancerous tissues, including colon, are higher than in normal corresponding tissue (Krisenko 2015).
  
Entity Gastric cancer
Note An inverse correlation between nuclear SYK and lymph node metastasis was observed in gastric cancer patients (Wang 2004).
  
Entity Ovarian cancer
Note Ovarian tumors of low malignant grade have low levels of SYK compared to aggressive grades, which have the highest levels (Prinos 2011). Interestingly, when SYK expression was silenced, anchorage-independent growth was inhibited, and apoptosis was induced in SYK-expressing ovarian cancer cells.
  
Entity Lung cancer
Note Primary tumors of small cell lung cancer (SCLC) was examined and found to express higher levels of SYK compared to normal alveolar epithelium (reviewed by Krisenko 2015).
  
Entity Chronic lymphocytic leukemia (CLL)
Note Both SYK and ZAP70 are present in CLL in B cells and may compete in facilitating BCR signaling (reviewed in Au-Yeung 2009). CLL fall into two classes, an indolent milder form and an aggressive form that is particularly dependent on SYK activity for survival (Buchner 2009).
  
Entity Diffuse large B-cell lymphoma (DLBCL)
Note DLBCL can exhibit tonic or chronic signaling from the BCR that results in constitutive phosphorylation of SYK on activation loop tyrosines (Chen 2008). In a study from 2011 by Cheng et al, 44% of DLBCL samples showed elevated levels of phosphorylated SYK (Cheng 2011).
  
Entity Follicular lymphoma (FL)
Note Constitutive activation of SYK has been reported in FL, were primary cells are hyperresponsive to BCR engagement as compared to nonmalignant B cells (Leseux 2006; Irish 2006).
  
Entity Mantle cell lymphoma (MCL)
Note Constitutive activation of SYK has been reported in MCL as well, with a frequent overexpression of SYK due to gene amplification in both cell lines and primary tumors (Rinaldi 2006).
  
Entity Marginal zone lymphoma (MZL)
Note Ruiz-Ballesteros reported upregulation of SYK in splenic MZL, potentially due to downregulation of microRNAs predicted to modulate SYK gene transcription (Ruiz-Ballesteros 2005).
  
Entity B cell acute lymphocytic leukemia (B-ALL)
Note B-ALL cells are derived from pro-B cells that lack pre-BCR or BCR complexes, but still these cells have elevated levels of constitutively active phosphorylated SYK (Perova 2014).
  
Entity Rheumatoid arthritis (RA)
Note It is likely that SYK is widely expressed in a range of haemopoietic cell lineages in RA synovium. Inhibition of Syk suppresses both inflammation and bone erosion in animal models of RA (Singh Najjar 2014). Indeed, Syk has been shown to be necessary for emerging pathology in several animal models of arthritis.
  

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PMID 19290920
 
Syk tyrosine kinase required for mouse viability and B-cell development
Cheng AM, Rowley B, Pao W, Hayday A, Bolen JB, Pawson T
Nature 1995 Nov 16;378(6554):303-6
PMID 7477353
 
Identification of seven genes regulated by wild-type p53 in a colon cancer cell line carrying a well-controlled wild-type p53 expression system
Okamura S, Ng CC, Koyama K, Takei Y, Arakawa H, Monden M, Nakamura Y
Oncol Res 1999;11(6):281-5
PMID 10691030
 
Alternative splicing of SYK regulates mitosis and cell survival
Prinos P, Garneau D, Lucier JF, Gendron D, Couture S, Boivin M, Brosseau JP, Lapointe E, Thibault P, Durand M, Tremblay K, Gervais-Bird J, Nwilati H, Klinck R, Chabot B, Perreault JP, Wellinger RJ, Elela SA
Nat Struct Mol Biol 2011 Jun;18(6):673-9
PMID 21552259
 
Novel insights into the mechanism of decreased expression of type X collagen in human mesenchymal stem cells from patients with osteoarthritis cultured on nitrogen-rich plasma polymers: implication of cyclooxygenase-1
Petit A, Wang HT, Girard-Lauriault PL, Wertheimer MR, Antoniou J, Mwale F
J Biomed Mater Res A 2010 Sep 1;94(3):744-50
PMID 20225218
 
ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia
Chen L, Huynh L, Apgar J, Tang L, Rassenti L, Weiss A, Kipps TJ
Blood 2008 Mar 1;111(5):2685-92
PMID 18048647
 
SYK inhibition and response prediction in diffuse large B-cell lymphoma
Cheng S, Coffey G, Zhang XH, Shaknovich R, Song Z, Lu P, Pandey A, Melnick AM, Sinha U, Wang YL
Blood 2011 Dec 8;118(24):6342-52
PMID 22025527
 
Syk-dependent mTOR activation in follicular lymphoma cells
Leseux L, Hamdi SM, Al Saati T, Capilla F, Recher C, Laurent G, Bezombes C
Blood 2006 Dec 15;108(13):4156-62
PMID 16912221
 
Altered B-cell receptor signaling kinetics distinguish human follicular lymphoma B cells from tumor-infiltrating nonmalignant B cells
Irish JM, Czerwinski DK, Nolan GP, Levy R
Blood 2006 Nov 1;108(9):3135-42
PMID 16835385
 
Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma
Rinaldi A, Kwee I, Taborelli M, Largo C, Uccella S, Martin V, Poretti G, Gaidano G, Calabrese G, Martinelli G, Baldini L, Pruneri G, Capella C, Zucca E, Cotter FE, Cigudosa JC, Catapano CV, Tibiletti MG, Bertoni F
Br J Haematol 2006 Feb;132(3):303-16
PMID 16409295
 
Splenic marginal zone lymphoma: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis
Ruiz-Ballesteros E, Mollejo M, Rodriguez A, Camacho FI, Algara P, Martinez N, Pollán M, Sanchez-Aguilera A, Menarguez J, Campo E, Martinez P, Mateo M, Piris MA
Blood 2005 Sep 1;106(5):1831-8
PMID 15914563
 
Therapeutic potential of spleen tyrosine kinase inhibition for treating high-risk precursor B cell acute lymphoblastic leukemia
Perova T, Grandal I, Nutter LM, Papp E, Matei IR, Beyene J, Kowalski PE, Hitzler JK, Minden MD, Guidos CJ, Danska JS
Sci Transl Med 2014 May 14;6(236):236ra62
PMID 24828076
 
Inhibition of spleen tyrosine kinase in the treatment of rheumatoid arthritis
Nijjar JS, Tindell A, McInnes IB, Siebert S
Rheumatology (Oxford) 2013 Sep;52(9):1556-62
PMID 23861534
 

Citation

This paper should be referenced as such :
Nyesiga B, Gjörloff Wingren A
SYK (spleen tyrosine kinase);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/SYKID394.html
History of this paper:
Huret, JL. SYK (spleen tyrosine kinase). Atlas Genet Cytogenet Oncol Haematol. 2002;6(2):124-124.
http://documents.irevues.inist.fr/bitstream/handle/2042/37844/02-2002-SYKID394.pdf


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  t(5;9)(q33;q22) ITK/SYK
t(9;12)(q22;p12) ETV6/SYK

External links

Nomenclature
HGNC (Hugo)SYK   11491
Cards
AtlasSYKID394
Entrez_Gene (NCBI)SYK  6850  spleen tyrosine kinase
GeneCards (Weizmann)SYK
Ensembl hg19 (Hinxton)ENSG00000165025 [Gene_View]  chr9:93563962-93660842 [Contig_View]  SYK [Vega]
Ensembl hg38 (Hinxton)ENSG00000165025 [Gene_View]  chr9:93563962-93660842 [Contig_View]  SYK [Vega]
ICGC DataPortalENSG00000165025
TCGA cBioPortalSYK
AceView (NCBI)SYK
Genatlas (Paris)SYK
WikiGenes6850
SOURCE (Princeton)SYK
Genomic and cartography
GoldenPath hg19 (UCSC)SYK  -     chr9:93563962-93660842 +  9q22   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)SYK  -     9q22   [Description]    (hg38-Dec_2013)
EnsemblSYK - 9q22 [CytoView hg19]  SYK - 9q22 [CytoView hg38]
Mapping of homologs : NCBISYK [Mapview hg19]  SYK [Mapview hg38]
OMIM600085   
Gene and transcription
Genbank (Entrez)AJ420449 AK057772 AK075020 AK094808 AK290927
RefSeq transcript (Entrez)NM_001135052 NM_001174167 NM_001174168 NM_003177
RefSeq genomic (Entrez)NC_000009 NC_018920 NG_017046 NT_008470 NW_004929366
Consensus coding sequences : CCDS (NCBI)SYK
Cluster EST : UnigeneHs.371720 [ NCBI ]
CGAP (NCI)Hs.371720
Alternative Splicing GalleryENSG00000165025
Gene ExpressionSYK [ NCBI-GEO ]   SYK [ EBI - ARRAY_EXPRESS ]   SYK [ SEEK ]   SYK [ MEM ]
Gene Expression Viewer (FireBrowse)SYK [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6850
GTEX Portal (Tissue expression)SYK
Protein : pattern, domain, 3D structure
UniProt/SwissProtP43405 (Uniprot)
NextProtP43405  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP43405
Splice isoforms : SwissVarP43405 (Swissvar)
Catalytic activity : Enzyme2.7.10.2 [ Enzyme-Expasy ]   2.7.10.22.7.10.2 [ IntEnz-EBI ]   2.7.10.2 [ BRENDA ]   2.7.10.2 [ KEGG ]   
PhosPhoSitePlusP43405
Domaine pattern : Prosite (Expaxy)PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_TYR (PS00109)    SH2 (PS50001)   
Domains : Interpro (EBI)Kinase-like_dom    Kinase_SYK/ZAP-70_inter-SH2    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser-Thr/Tyr_kinase_cat_dom    SH2    Tyr_kinase_AS    Tyr_kinase_cat_dom    Tyr_kinase_non-rcpt_SYK/ZAP70   
Domain families : Pfam (Sanger)Pkinase_Tyr (PF07714)    SH2 (PF00017)   
Domain families : Pfam (NCBI)pfam07714    pfam00017   
Domain families : Smart (EMBL)SH2 (SM00252)  TyrKc (SM00219)  
DMDM Disease mutations6850
Blocks (Seattle)SYK
PDB (SRS)1A81    1CSY    1CSZ    1XBA    1XBB    1XBC    3BUW    3EMG    3FQE    3FQH    3FQS    3SRV    3TUB    3TUC    3TUD    3VF8    3VF9    4DFL    4DFN    4F4P    4FL1    4FL2    4FL3    4FYN    4FYO    4FZ6    4FZ7    4GFG    4I0R    4I0S    4I0T    4PUZ    4PV0    4PX6    4RSS    4RX7    4RX8    4RX9    4WNM    4XG2    4XG3    4XG4    4XG5    4XG6    4XG7    4XG8    4XG9    4YJO    4YJP    4YJQ    4YJR    4YJS    4YJT    4YJU    4YJV    5C26    5C27    5CXH    5CXZ    5CY3   
PDB (PDBSum)1A81    1CSY    1CSZ    1XBA    1XBB    1XBC    3BUW    3EMG    3FQE    3FQH    3FQS    3SRV    3TUB    3TUC    3TUD    3VF8    3VF9    4DFL    4DFN    4F4P    4FL1    4FL2    4FL3    4FYN    4FYO    4FZ6    4FZ7    4GFG    4I0R    4I0S    4I0T    4PUZ    4PV0    4PX6    4RSS    4RX7    4RX8    4RX9    4WNM    4XG2    4XG3    4XG4    4XG5    4XG6    4XG7    4XG8    4XG9    4YJO    4YJP    4YJQ    4YJR    4YJS    4YJT    4YJU    4YJV    5C26    5C27    5CXH    5CXZ    5CY3   
PDB (IMB)1A81    1CSY    1CSZ    1XBA    1XBB    1XBC    3BUW    3EMG    3FQE    3FQH    3FQS    3SRV    3TUB    3TUC    3TUD    3VF8    3VF9    4DFL    4DFN    4F4P    4FL1    4FL2    4FL3    4FYN    4FYO    4FZ6    4FZ7    4GFG    4I0R    4I0S    4I0T    4PUZ    4PV0    4PX6    4RSS    4RX7    4RX8    4RX9    4WNM    4XG2    4XG3    4XG4    4XG5    4XG6    4XG7    4XG8    4XG9    4YJO    4YJP    4YJQ    4YJR    4YJS    4YJT    4YJU    4YJV    5C26    5C27    5CXH    5CXZ    5CY3   
PDB (RSDB)1A81    1CSY    1CSZ    1XBA    1XBB    1XBC    3BUW    3EMG    3FQE    3FQH    3FQS    3SRV    3TUB    3TUC    3TUD    3VF8    3VF9    4DFL    4DFN    4F4P    4FL1    4FL2    4FL3    4FYN    4FYO    4FZ6    4FZ7    4GFG    4I0R    4I0S    4I0T    4PUZ    4PV0    4PX6    4RSS    4RX7    4RX8    4RX9    4WNM    4XG2    4XG3    4XG4    4XG5    4XG6    4XG7    4XG8    4XG9    4YJO    4YJP    4YJQ    4YJR    4YJS    4YJT    4YJU    4YJV    5C26    5C27    5CXH    5CXZ    5CY3   
Structural Biology KnowledgeBase1A81    1CSY    1CSZ    1XBA    1XBB    1XBC    3BUW    3EMG    3FQE    3FQH    3FQS    3SRV    3TUB    3TUC    3TUD    3VF8    3VF9    4DFL    4DFN    4F4P    4FL1    4FL2    4FL3    4FYN    4FYO    4FZ6    4FZ7    4GFG    4I0R    4I0S    4I0T    4PUZ    4PV0    4PX6    4RSS    4RX7    4RX8    4RX9    4WNM    4XG2    4XG3    4XG4    4XG5    4XG6    4XG7    4XG8    4XG9    4YJO    4YJP    4YJQ    4YJR    4YJS    4YJT    4YJU    4YJV    5C26    5C27    5CXH    5CXZ    5CY3   
SCOP (Structural Classification of Proteins)1A81    1CSY    1CSZ    1XBA    1XBB    1XBC    3BUW    3EMG    3FQE    3FQH    3FQS    3SRV    3TUB    3TUC    3TUD    3VF8    3VF9    4DFL    4DFN    4F4P    4FL1    4FL2    4FL3    4FYN    4FYO    4FZ6    4FZ7    4GFG    4I0R    4I0S    4I0T    4PUZ    4PV0    4PX6    4RSS    4RX7    4RX8    4RX9    4WNM    4XG2    4XG3    4XG4    4XG5    4XG6    4XG7    4XG8    4XG9    4YJO    4YJP    4YJQ    4YJR    4YJS    4YJT    4YJU    4YJV    5C26    5C27    5CXH    5CXZ    5CY3   
CATH (Classification of proteins structures)1A81    1CSY    1CSZ    1XBA    1XBB    1XBC    3BUW    3EMG    3FQE    3FQH    3FQS    3SRV    3TUB    3TUC    3TUD    3VF8    3VF9    4DFL    4DFN    4F4P    4FL1    4FL2    4FL3    4FYN    4FYO    4FZ6    4FZ7    4GFG    4I0R    4I0S    4I0T    4PUZ    4PV0    4PX6    4RSS    4RX7    4RX8    4RX9    4WNM    4XG2    4XG3    4XG4    4XG5    4XG6    4XG7    4XG8    4XG9    4YJO    4YJP    4YJQ    4YJR    4YJS    4YJT    4YJU    4YJV    5C26    5C27    5CXH    5CXZ    5CY3   
SuperfamilyP43405
Human Protein AtlasENSG00000165025
Peptide AtlasP43405
HPRD02514
IPIIPI00018597   IPI00218278   IPI00930553   
Protein Interaction databases
DIP (DOE-UCLA)P43405
IntAct (EBI)P43405
FunCoupENSG00000165025
BioGRIDSYK
STRING (EMBL)SYK
ZODIACSYK
Ontologies - Pathways
QuickGOP43405
Ontology : AmiGOangiogenesis  lymph vessel development  positive regulation of receptor internalization  stimulatory C-type lectin receptor signaling pathway  adaptive immune response  adaptive immune response  macrophage activation involved in immune response  macrophage activation involved in immune response  neutrophil activation involved in immune response  neutrophil activation involved in immune response  leukocyte activation involved in immune response  serotonin secretion by platelet  protein kinase activity  protein kinase activity  protein serine/threonine kinase activity  protein tyrosine kinase activity  protein tyrosine kinase activity  non-membrane spanning protein tyrosine kinase activity  non-membrane spanning protein tyrosine kinase activity  receptor signaling protein tyrosine kinase activity  integrin binding  protein binding  ATP binding  nucleus  cytoplasm  cytosol  cytosol  plasma membrane  protein phosphorylation  protein phosphorylation  inflammatory response  leukocyte cell-cell adhesion  transmembrane receptor protein tyrosine kinase signaling pathway  integrin-mediated signaling pathway  integrin-mediated signaling pathway  activation of JUN kinase activity  cell proliferation  organ morphogenesis  regulation of platelet activation  regulation of tumor necrosis factor-mediated signaling pathway  viral process  peptidyl-serine phosphorylation  leukotriene biosynthetic process  B cell receptor complex  protein kinase binding  platelet activation  neutrophil chemotaxis  extrinsic component of cytoplasmic side of plasma membrane  receptor internalization  early phagosome  positive regulation of type I interferon production  regulation of superoxide anion generation  positive regulation of cell adhesion mediated by integrin  positive regulation of cell adhesion mediated by integrin  peptidyl-tyrosine autophosphorylation  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  T cell receptor complex  defense response to bacterium  transcription factor import into nucleus  protein complex  positive regulation of mast cell degranulation  regulation of neutrophil degranulation  beta selection  innate immune response  innate immune response  positive regulation of interleukin-3 biosynthetic process  positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process  positive regulation of B cell differentiation  positive regulation of gamma-delta T cell differentiation  positive regulation of bone resorption  positive regulation of alpha-beta T cell differentiation  positive regulation of alpha-beta T cell proliferation  blood vessel morphogenesis  positive regulation of cytokine secretion  positive regulation of peptidyl-tyrosine phosphorylation  regulation of phagocytosis  positive regulation of calcium-mediated signaling  B cell receptor signaling pathway  B cell receptor signaling pathway  regulation of sequence-specific DNA binding transcription factor activity  regulation of ERK1 and ERK2 cascade  cellular response to molecule of fungal origin  cellular response to low-density lipoprotein particle stimulus  regulation of arachidonic acid secretion  regulation of platelet aggregation  regulation of platelet aggregation  
Ontology : EGO-EBIangiogenesis  lymph vessel development  positive regulation of receptor internalization  stimulatory C-type lectin receptor signaling pathway  adaptive immune response  adaptive immune response  macrophage activation involved in immune response  macrophage activation involved in immune response  neutrophil activation involved in immune response  neutrophil activation involved in immune response  leukocyte activation involved in immune response  serotonin secretion by platelet  protein kinase activity  protein kinase activity  protein serine/threonine kinase activity  protein tyrosine kinase activity  protein tyrosine kinase activity  non-membrane spanning protein tyrosine kinase activity  non-membrane spanning protein tyrosine kinase activity  receptor signaling protein tyrosine kinase activity  integrin binding  protein binding  ATP binding  nucleus  cytoplasm  cytosol  cytosol  plasma membrane  protein phosphorylation  protein phosphorylation  inflammatory response  leukocyte cell-cell adhesion  transmembrane receptor protein tyrosine kinase signaling pathway  integrin-mediated signaling pathway  integrin-mediated signaling pathway  activation of JUN kinase activity  cell proliferation  organ morphogenesis  regulation of platelet activation  regulation of tumor necrosis factor-mediated signaling pathway  viral process  peptidyl-serine phosphorylation  leukotriene biosynthetic process  B cell receptor complex  protein kinase binding  platelet activation  neutrophil chemotaxis  extrinsic component of cytoplasmic side of plasma membrane  receptor internalization  early phagosome  positive regulation of type I interferon production  regulation of superoxide anion generation  positive regulation of cell adhesion mediated by integrin  positive regulation of cell adhesion mediated by integrin  peptidyl-tyrosine autophosphorylation  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  T cell receptor complex  defense response to bacterium  transcription factor import into nucleus  protein complex  positive regulation of mast cell degranulation  regulation of neutrophil degranulation  beta selection  innate immune response  innate immune response  positive regulation of interleukin-3 biosynthetic process  positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process  positive regulation of B cell differentiation  positive regulation of gamma-delta T cell differentiation  positive regulation of bone resorption  positive regulation of alpha-beta T cell differentiation  positive regulation of alpha-beta T cell proliferation  blood vessel morphogenesis  positive regulation of cytokine secretion  positive regulation of peptidyl-tyrosine phosphorylation  regulation of phagocytosis  positive regulation of calcium-mediated signaling  B cell receptor signaling pathway  B cell receptor signaling pathway  regulation of sequence-specific DNA binding transcription factor activity  regulation of ERK1 and ERK2 cascade  cellular response to molecule of fungal origin  cellular response to low-density lipoprotein particle stimulus  regulation of arachidonic acid secretion  regulation of platelet aggregation  regulation of platelet aggregation  
Pathways : BIOCARTARas-Independent pathway in NK cell-mediated cytotoxicity [Genes]    Aspirin Blocks Signaling Pathway Involved in Platelet Activation [Genes]    Fc Epsilon Receptor I Signaling in Mast Cells [Genes]    BCR Signaling Pathway [Genes]    IL 2 signaling pathway [Genes]    IL-2 Receptor Beta Chain in T cell Activation [Genes]   
Pathways : KEGGNF-kappa B signaling pathway    PI3K-Akt signaling pathway    Osteoclast differentiation    Natural killer cell mediated cytotoxicity    B cell receptor signaling pathway    Fc epsilon RI signaling pathway    Fc gamma R-mediated phagocytosis    Tuberculosis    Epstein-Barr virus infection    Viral carcinogenesis   
REACTOMEP43405 [protein]
REACTOME PathwaysR-HSA-5621480 Dectin-2 family [pathway]
REACTOME PathwaysR-HSA-5607764 CLEC7A (Dectin-1) signaling [pathway]
REACTOME PathwaysR-HSA-354192 Integrin alphaIIb beta3 signaling [pathway]
REACTOME PathwaysR-HSA-2871796 FCERI mediated MAPK activation [pathway]
REACTOME PathwaysR-HSA-2730905 Role of LAT2/NTAL/LAB on calcium mobilization [pathway]
REACTOME PathwaysR-HSA-2424491 DAP12 signaling [pathway]
REACTOME PathwaysR-HSA-912631 Regulation of signaling by CBL [pathway]
REACTOME PathwaysR-HSA-2454202 Fc epsilon receptor (FCERI) signaling [pathway]
REACTOME PathwaysR-HSA-2029485 Role of phospholipids in phagocytosis [pathway]
REACTOME PathwaysR-HSA-114604 GPVI-mediated activation cascade [pathway]
REACTOME PathwaysR-HSA-451927 Interleukin-2 signaling [pathway]
REACTOME PathwaysR-HSA-2871809 FCERI mediated Ca+2 mobilization [pathway]
REACTOME PathwaysR-HSA-2029481 FCGR activation [pathway]
REACTOME PathwaysR-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers [pathway]
REACTOME PathwaysR-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkSYK
Wikipedia pathwaysSYK
Orthology - Evolution
OrthoDB6850
GeneTree (enSembl)ENSG00000165025
Phylogenetic Trees/Animal Genes : TreeFamSYK
Homologs : HomoloGeneSYK
Homology/Alignments : Family Browser (UCSC)SYK
Gene fusions - Rearrangements
Fusion : MitelmanETV6/SYK [12p13.2/9q22.2]  [t(9;12)(q22;p13)]  
Fusion : MitelmanITK/SYK [5q33.3/9q22.2]  [t(5;9)(q33;q22)]  
Fusion : TICdbETV6 [12p13.2]  -  SYK [9q22.2]
Fusion : TICdbITK [5q33.3]  -  SYK [9q22.2]
Polymorphisms : SNP, variants
NCBI Variation ViewerSYK [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SYK
dbVarSYK
ClinVarSYK
1000_GenomesSYK 
Exome Variant ServerSYK
ExAC (Exome Aggregation Consortium)SYK (select the gene name)
Genetic variants : HAPMAP6850
Genomic Variants (DGV)SYK [DGVbeta]
Mutations
ICGC Data PortalSYK 
TCGA Data PortalSYK 
Broad Tumor PortalSYK
OASIS PortalSYK [ Somatic mutations - Copy number]
Cancer Gene: CensusSYK 
Somatic Mutations in Cancer : COSMICSYK 
intOGen PortalSYK
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SYK
DgiDB (Drug Gene Interaction Database)SYK
DoCM (Curated mutations)SYK (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SYK (select a term)
intoGenSYK
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)9:93563962-93660842  ENSG00000165025
CONAN: Copy Number AnalysisSYK 
Mutations and Diseases : HGMDSYK
OMIM600085   
MedgenSYK
Genetic Testing Registry SYK
NextProtP43405 [Medical]
TSGene6850
GENETestsSYK
Huge Navigator SYK [HugePedia]
snp3D : Map Gene to Disease6850
BioCentury BCIQSYK
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6850
Chemical/Pharm GKB GenePA36273
Clinical trialSYK
Miscellaneous
canSAR (ICR)SYK (select the gene name)
Probes
Litterature
PubMed435 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSYK
EVEXSYK
GoPubMedSYK
iHOPSYK
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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