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FLASH GENE
Symbol BTK contributors: mct/pgu - updated : 08-06-2017
HGNC name Bruton agammaglobulinemia tyrosine kinase
HGNC id 1133
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
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
19 - 2611 - 659 - 2001 11226282
19 - 2767 - 693 - 2001 11226282
17 - 2248 - 483 - 2001 11226282
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunelymph node   highly
 spleen   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Lymphoid    
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticmature hematopoietic Homo sapiens
Blood/Hematopoieticprogenitor cell Homo sapiens
Lymphoid/Immunelymphocyte
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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    cancerhemopathy 
    promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765
    cardiovascularatheroma 
    could be a potent therapeutic target in ischaemic stroke
    cancerhemopathy 
    is a therapeutic target in acute myeloid leukemia
    ANIMAL & CELL MODELS