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FLASH GENE

Symbol

BTK

contributors: mct/pgu - updated : 08-06-2017

HGNC name	Bruton agammaglobulinemia tyrosine kinase
HGNC id	1133

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	AGMX1 agammaglobulinemia 1, Bruton type IGHD3 agammaglobulinemia and isolated growth hormone deficiency
Location	Xq22.1      Physical location : 100.604.434 - 100.641.212
Synonym name	B cell progenitor tyrosine kinase
	dominant-negative kinase-deficient Brutons tyrosine kinase
	tyrosine-protein kinase BTK
Synonym symbol(s)	ATK, BPK, SRCR, IMD1, XLA, PSCTK1, MGC126261, MGC126262
EC.number	2.7.10.2

DNA

TYPE	functioning gene
STRUCTURE	41.35 kb     19 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000061 19 - 2611 NP_000052 - 659 - 2001 11226282 NM_001287344 19 - 2767 NP_001274273 - 693 - 2001 11226282 NM_001287345 17 - 2248 NP_001274274 - 483 - 2001 11226282

EXPRESSION

Type

widely

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 Lymphoid/Immune lymph node       highly   spleen       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic mature hematopoietic Homo sapiens Blood/Hematopoietic progenitor cell Homo sapiens Lymphoid/Immune lymphocyte

cell lineage
cell lines
fluid/secretion	blood

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a Pleckstrin homology (PH) domain, which is responsible for plasma membrane targeting
	adjacent Tec homology domains in addition to the Src homology domains SH3, SH2, SH1 (SRC family, Tec subfamily)

HOMOLOGY

Homologene

FAMILY	protein kinase superfamily
	Tec family of protein tyrosine kinases
	TEC subfamily
	SRC family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,vesicle
	intracellular,nucleus
text	is a nucleocytoplasmic protein

basic FUNCTION	non receptor tyrosine kinase
	coupling activated immunoreceptors to downstream signaling events
	playing crucial roles in the differentiation and activation of B and myeloid cells
	having negative regulatory functions in dendritic cells, mediated mainly through autocrine secretion of IL10 and subsequent activation of STAT3
	required for NFkappaB activation, participating in the pathway to increased phosphorylation of RELA on serine 536 activated by TLR8 and TLR9
	is required for the initial loss of tolerance to DNA and the subsequent production of pathogenic autoantibodies once tolerance is breached
	plays a central role in signal transduction pathways regulating survival, activation, proliferation, and differentiation of B-lineage lymphoid cells
	BTK signaling is crucial for optimal actin cytoskeletal organization and lacunar resorption in isolated osteoclasts
	essential for B cell development and function and also appears to be important for myeloid cells
	important regulator of neutrophilic granulocyte maturation and function
	positive regulator in the ITAM-mediated TREM1/TYROBP pathway, suggesting its implication in inflammatory processes
	is essential for B-lymphocyte development
	is not only critical for B cell development and differentiation but is also involved in the regulation of Toll-like receptor-triggered innate response of macrophages
	is required for activation of NK cells, thus providing insight into the physiological significance of BTK in the regulation of immune cell functions and innate inflammatory response
	BTK-induced activating phosphorylation is critical for the optimal transcription factor function of IKZF1 (
	BTK regulates dendritic cell responses upon TLR9 engagement in terms of activation, cytokine production, and STAT1/3 upregulation
	not only plays a fundamental role in the regulation of BCR signalling, but may also mediate crosstalk with cytokine signalling pathways through regulation of IL21-induced phosphorylation of STAT1 in the nuclei of human B cells
	BTK is an essential component of the NLRP3 inflammasome, in which BTK physically interacts with ASC and NLRP3
	mediates B cell signaling and is also present in innate immune cells but not T cells
	contributions of BTK to immune tolerance
	is a cytoplasmic protein tyrosine kinase with a fundamental role in B-lymphocyte development and activation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

text	B cell ontogeny

PATHWAY

metabolism

signaling

a component

BTK PH domain forms a homodimer and each molecule binds phosphatidylinositol in the binding pocket

INTERACTION

DNA

RNA

small molecule

protein	directly interacts with a nuclear component of Wnt-beta-catenin signaling, CDC73
	ARID3A transiently interacts with sumoylation enzymes, blocks calcium flux and phosphorylation of BTK and GTF2II and is then discharged from lipid rafts as a Sumo-I-modified form
	KAT2A binds to the 5prime proximal regions of SYK and BTK genes, suggesting that gene expressions of SYK and BTK are regulated by KAT2A
	ANKRD54 is the first protein identified that specifically influences the nucleocytoplasmic shuttling of BTK and TXK and belongs to a rare group of known proteins carrying out this activity in a CRM1-dependent manner
	BTK is a partner and posttranslational regulator of IKAROS, a zinc finger-containing DNA-binding protein that plays a pivotal role in immune homeostasis
	BTK is an important player for TLR9 but not TLR7 signaling in human Plasmacytoid dendritic cells (PDCs)
	BTK was involved in close contact with Tyr86 and Tyr106 of MAL whereas PKRKCD may phosphorylate Tyr106 only
	BTK physically interacts with PYCARD and NLRP3, and is essential for NLRP3 inflammasome activation
	nucleocytoplasmic shuttling of BTK is specifically modulated by the Ankyrin Repeat Domain 54 (ANKRD54) protein and the interaction is known to be exclusively SH3-dependent

cell & other

REGULATION

activated by

LYN (partly),SYK (modulated by BLNK)

ASSOCIATED DISORDERS

corresponding disease(s)

AGMX1 , IGHD3

related resource

Bruton Agammaglobulinemia - BTK base

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in chronic lymphocytic leukemia

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	represents a useful marker to identify B cell non-Hodgkin lymphomas
Therapy target
	System Type Disorder Pubmed cancer hemopathy   promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765 cardiovascular atheroma   could be a potent therapeutic target in ischaemic stroke cancer hemopathy   is a therapeutic target in acute myeloid leukemia

ANIMAL & CELL MODELS