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FLASH GENE

Symbol

ITK

contributors: mct/npt/pgu - updated : 01-03-2013

HGNC name	IL2-inducible T-cell kinase
HGNC id	6171

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 intestine small intestine     lowly   pharynx       lowly Endocrine thyroid       lowly Lymphoid/Immune spleen       lowly   thymus       predominantly Homo sapiens Adult Respiratory respiratory tract trachea     lowly

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune activated B lymphocyte Lymphoid/Immune T cell Homo sapiens Adult

cell lineage	hematopoietic
cell lines
fluid/secretion	blood

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an intracellular tyrosine kinase with SH2, SH3 domains
	a Bruton's tyrosine kinase (Btk)-type zinc finger
	three aromatic AAs, termed the FYF motif, located in the inner walls of the phospholipid-binding pocket of the ITK PH domain, are conserved in the PH domains of all Tec kinases
	a zinc binding regions within its Tec homology domain to interacting with GNA13

HOMOLOGY

interspecies	homolog to rattus Itk (94.52 pc)
	homolog to murine Itk (94.35 pc)

Homologene

FAMILY	protein kinase superfamily
	Tyr protein kinase family
	TEC subfamily

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic

basic FUNCTION	tyrosine kinase
	involved in regulating antigen receptor induced serum response factor (SRF) activation
	critical role for ITK and TXK in conventional CD8(+) T cell development in the thymus
	ITK and TXK are required for efficient positive selection of conventional CD4+ and CD8+ T cells in the thymus
	important role for ITK and TXK in the development of conventional as opposed to innate CD4(+) and CD8(+) T cells
	play critical roles in helping shape immune responses via their effects on the differentiation and function of distinct cytokine-producing, effector T-cell populations
	serves as a modulator, or rheostat, critically fine-tuning the T cell response
	required for efficient replication of influenza virus in infected T-cells
	Tec-family kinase that regulates the spatiotemporal organization of components of T cell signaling pathways and CDC42-dependent actin polymerization
	ITK signaling promotes IRF4 up-regulation following CD8(+) T-cell activation and that this signaling pathway normally suppresses EOMES expression, thereby regulating the differentiation pathway of CD8(+) T cells
	critical for the recruitment of the kinase to the plasma membrane and its co-localization with the TCR-CD3 molecular complex
	catalyzes phosphorylation on tyrosine residues within a number of its natural substrates, including the well-characterized gamma783 of PLCG1
	involved in T-cell proliferation and differentiation
	important for the activation of T cells via the T cell Receptor (TCR)

CELLULAR PROCESS	cell life, differentiation
	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

immunity/defense

PATHWAY

metabolism

signaling

signal transduction

	possible cross talk between ITK and G-protein signaling downstream of the TCR
	ITK signaling is required to prevent the expansion of gammadelta NKT cells in the adult thymus, to block their emigration, and to promote terminal NKT cell maturation

a component

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	metal binding, nucleotide,
	Zinc
	ATP

protein	ongoing physical interaction between LCP2 and ITK is required to maintain ITK in an active conformation
	SH2D2A is required for tyrosine phosphorylation of the LCK substrate ITK
	ITK-LCP2 interaction in cytokine production
	controlled the central localization of DEF6, which may contribute to the activation of CDC42 at the center of the interface (PMId: 21971040)
	plays a domineering role in the T-cell development, differentiation and production of pro-inflammatory cytokines such as IL2, IL4, IL5, IL10, IL13 and IL17
	modulates T-cell signaling by activating PLCG1 and regulating the extent of Ca2+ flux
	both interacts with DEF6 and phosphorylates DEF6 at tyrosine residues Tyr(210) and Tyr(222)
	IRF4 is transiently up-regulated during thymic development as cells undergo positive selection and ITK is required for optimal IRF4 expression
	ITK signaling promotes IRF4 up-regulation following CD8+ T-cell activation and this signaling pathway normally suppresses EOMES expression, thereby regulating the differentiation pathway of CD8+ T cells
	a specific docking interaction between the kinase domain of ITK and the C-terminal Src homology 2 (SH2C) domain of PLCG1 that promotes substrate specificity for this enzyme/substrate pair
	LCP2 is critical for ITK-SYK activation and is particularly required for the ITK-SYK-dependent phosphorylation of SYK activation loop tyrosines
	ITK interacts with GNA13 during TCR triggering

cell & other

REGULATION

induced by

interleukin-2 inducible

repressed by

intermolecular clustering and disruption of this clustering leads to increased ITK kinase activity following TCR stimulation

Other

regulated by the peptidyl prolyl cis-trans isomerase PPIB

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology inflammatory   inhibitors of ITK are potential therapeutic candidates for the treatment of various inflammatory disease

ANIMAL & CELL MODELS