Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

SYK

contributors: mct/npt - updated : 03-03-2016

HGNC name	spleen tyrosine kinase
HGNC id	11491

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

text	alternative splice variant in breast cancer (PMID: 12907655)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003177 14 - 5079 NP_003168 72 635 - 2009 187158 NM_001135052 13 - 5010 NP_001128524 69.4 612 - 2009 187158 NM_001174168 - - 4927 NP_001167639 - 612 - 2009 187158 NM_001174167 - - 5072 NP_001167638 72 635 - 2009 187158

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth tongue     moderately Endocrine parathyroid       highly Lymphoid/Immune lymph node       highly   spleen           thymus           tonsils       highly Reproductive female system breast mammary gland   highly Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     predominantly Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic megakaryocyte Homo sapiens Blood/Hematopoietic platelet Homo sapiens Lymphoid/Immune B cell Lymphoid/Immune T cell

cell lineage	myeloid cells
cell lines
fluid/secretion	blood, lymph

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an N-terminal pair of Src homology 2 (SH2)2 domains
	an inter-SH2 linker
	an SH2-domain-kinase linker
	and a C-terminal kinase domain
	multiple sites of phosphorylation which both regulate activity and serve as docking motifs for other proteins

mono polymer

complex

HOMOLOGY

interspecies	ortholog to rattus Syk (92.5pc)
	ortholog to murine Syk (93pc)

Homologene

FAMILY	protein kinase superfamily
	Tyr protein kinase family
	SYK/ZAP-70 subfamily

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
text	intracellular signaling cascade

basic FUNCTION	tyrosine kinase that functions immediately downstream of antigen receptors in immune cells including B lymphocytes, mast cells, and macrophages
	coupling activated immunoreceptors to downstream signaling events
	mediates LPS-induced tyrosine phosphorylation of BCAP in a manner similar to BCR signaling
	coupling the B cell antigen receptor (BCR) to the mobilization of calcium ion either through a phosphoinositide 3-kinase-dependent pathway, when not phosphorylated on tyrosines of the linker region, or through a phospholipase C-gamma-dependent pathway, when phosphorylated on Tyr-342 and Tyr-346
	potential modulator of cell growth
	regulating blood and vascular separation (through hematopoietic signaling pathway)
	involved in signal transduction in a variety of cell types
	acting as a positive effector of BCR-stimulated responses
	having a crucial role in adaptive immune receptor signalling
	also mediates other, unexpectedly diverse biological functions, including cellular adhesion, innate immune recognition, osteoclast maturation, platelet activation and vascular development
	required for FCER1A signalling in mast cells and FCGR signalling in neutrophils and macrophages
	dual-specificity kinase that self-regulates the signal output from the B-cell antigen receptor
	requirement for SYK in migration and polarization of naive recirculating B cells by interaction with SWAP70
	CLEC1B acts as a SYK-coupled C-type lectin receptors (CLR) able to modulate TLR signaling and inflammatory responses
	with CLEC1B, are essential for development in the megakaryocytic/platelet lineage
	plays a key role in TLR4-mediated macrophage responses to host-generated ligands, with subsequent activation of an AP-1 transcription program
	SYK plays an indispensable role in nuclear localization of native IKZF1
	ZAP70 inhibits SYK-mediated osteoclast function
	regulator of immune cell function, plays an increasingly recognized role in tumorigenesis as a promoter of cell survival in both hematological and nonhematological malignancies
	differential requirements of ZAP70 and SYK during thymic development, peripheral homeostasis as well as effector functions of CD4 and CD8 T cells (PMUID: 26187144)

CELLULAR PROCESS	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

development

text	organ morphogenesis

PATHWAY

metabolism

signaling

signal transduction

	integrin-mediated signaling pathway
	pathway of SYK regulation by PRKCB in human platelets
	SYK/SHC1 pathway that regulates the plasma membrane levels of CFTR channels, contributing to a better understanding of how CFTR-mediated chloride secretion is regulated
	SIGLEC15-TYROBP-SYK-signaling cascade plays a critical role in functional osteoclast formation

a component	T cell receptor complex
	key component of a signaling network of proteins
	ITK-SYK exists in the active conformation state and is therefore capable of signaling without SRC family kinases or stimulation of the T cell receptor

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP

protein	activating BTK (BLNK dependent), phosphorylating BLNK
	LCP2(interaction required to regulate separation of blood and lymphatic vascular networks)
	can bind a variety of differently spaced ITAM motifs within the cell
	CBL and SLA when it is phosphorylated (interaction with SLA may link it to CBL, leading to its destruction)
	phosphorylated NFAM1
	TYROBP and TREM2, with SYK are required for the cytokine-induced formation of giant cells
	overexpression of TRAIP sensitizes cells to TNF-induced apoptosis, an effect that can be reversed by the coexpression of SYK
	association of SYK to IL4R is of biological significance and IL4R is a new candidate to be added to the few cytokine receptor components which associate with SYK
	interaction between SYK and the ubiquitin-specific protease 25 (USP25)
	CLEC1B activates platelets through SRC and SYK tyrosine kinases, leading to tyrosine phosphorylation of downstream adapter proteins and effector enzymes, including PLCG2
	interacting with UBASH3B in platelets (able to associate with SYK and dephosphorylate it)
	BCAR1 is a physiological substrate of SYK
	KAT2A binds to the 5prime proximal regions of SYK and BTK genes, suggesting that gene expressions of SYK and BTK are regulated by KAT2A
	stimulates likely angiogenesis via transactivation of the EGF receptor, which promotes the phosphorylation of FLT1 and activation of SYK independent of VEGFA expression
	new role for THBS1 and CD36 in the activation of the KDR signaling pathway that requires SYK
	regulation of CFTR by SYK, a recognized controller of inflammation
	CLEC1B signals through a pathway that is critically dependent on the tyrosine kinase SYK
	SELPLG/ERM-binding sequence plays a critical role in recruiting leukocytes on selectins and in activating the MAPK pathway
	SELPLG/ERM-binding sequence is involved in ERK phosphorylation but is dispensable for SYK activation
	SYK is a partner and posttranslational regulator of IKZF1
	LCP2 is critical for ITK-SYK activation and is particularly required for the ITK-SYK-dependent phosphorylation of SYK activation loop tyrosines
	role for PRKCB as a negative regulator of SYK tyrosine phosphorylation downstream of GP6
	binds robustly to nucleolin and phosphorylates it on tyrosine, enhancing its ability to bind the BCL2L1 mRNA
	SYK negatively regulates TLR4-mediated production of IFNB1 and IL10 and promotes inflammatory responses in dendritic cells through divergent regulation of downstream PI3K-AKT1 and NFKB1 signaling pathways
	UBASH3B suppresses activation of SYK through the GP6 platelet receptor for collagen by dephosphorylating Tyr(P)346, a regulatory site of SYK
	BCNP1 promotes BCR signaling by modulating the phosphorylation of BLNK, SYK, and PLCG2

cell & other	Epstein-Barr virus LMP2A
	leukocyte adhesion

REGULATION

activated by	a mechanism of switch-like activation (explain how SYK is both rapidly activated after receptor binding but also sustains activity over time to facilitate longer term changes in gene expression)
	by C-type lectins and integrins

inhibited by

dephosphorylation of phospho-Tyr58 (likely promote the down-regulation of SYk activation and suppression of mast cell responses)

Other	differential phosphorylation of Syk can determine the pathway by which BCR is coupled to the regulation of intracellular calcium ion
	ubiquitinated by CBLB after BCR activation promoting proteasomal degradation
	phosphorylation on Tyr-323 creates a binding site for c-Cbl, an adapter protein that serves as a negative regulator of BCR-stimulated calcium ion signaling
	phosphorylation on Tyr-348 and Tyr-352 enhances the phosphorylation and activation of phospholipase C-gamma and the early phase of calcium ion mobilization via a phosphoinositide 3-kinase-independent pathway
	kinase activity is equivalently increased by phosphorylation, ITAM binding, or both stimuli together
	autophosphorylated

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         absent in invasive breast carcinoma tumoral       gain of function in 44p100 primary diffuse large B-cell lymphoma tissues ( constitutional         loss of Syk kinase-mediated integrin signaling impairs leukocyte activation, leading to reduced host defense responses

Susceptibility

Variant & Polymorphism

Candidate gene	may act as potential therapeutic target for the treatment of breast cancer
	SYK inhibition could be beneficial for treatment of disorders including rheumatoid arthritis, allergic rhinitis, and asthma
Marker
Therapy target
	System Type Disorder Pubmed cancer hemopathy   SYK kinase inhibition is suggested as a powerful tool for the therapy of different pathologies cancer hemopathy   SYK inhibition as a potentially useful therapy for diffuse large B-cell lymphoma

ANIMAL & CELL MODELS