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Symbol BTK contributors: mct/pgu - updated : 08-06-2017
HGNC name Bruton agammaglobulinemia tyrosine kinase
HGNC id 1133
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
    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
    Physical map
    LOC392507 X similar to HSPC129 protein LOC158656 Xq22.1 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) PCDH19 Xq13.3 protocadherin 19 TNMD Xq21.33-q23 protocadherin 19 TM4SF6 Xq22 transmembrane 4 superfamily member 6 SRPUL Xq21.33-q23 sushi-repeat protein SYTL4 Xq21.33 synaptotagmin-like 4 (granuphilin-a) LOC392508 X similar to Double-strand-break repair protein rad21 homolog (hHR21) (Nuclear matrix protein 1) (NXP-1) (SCC1 homolog) CSTF2 Xq22.2-q22.3 cleavage stimulation factor, 3' pre-RNA, subunit 2, 64kDa NOX1 Xq22 NADPH oxidase 1 LOC389877 X similar to Heterogeneous nuclear ribonucleoprotein A1 (Helix-destabilizing protein) (Single-strand binding protein) (hnRNP core protein A1) (HDP-1) (Topoisomerase-inhibitor suppressed) LOC347424 Xq22.1 similar to TGF beta-inducible nuclear protein 1 (Hairy cell leukemia protein 1) (HUSSY-29) LOC286453 Xq22.1 similar to dJ341D10.1 (novel protein) LOC392509 X similar to hypothetical protein DKFZp761H079 isoform 1 FLJ12687 Xq22.1 hypothetical protein FLJ12687 FLJ14084 Xq22.1 hypothetical protein FLJ14084 FSHPRH1 Xq22 FSH primary response (LRPR1 homolog, rat) 1 LOC392510 X similar to 14-3-3 protein tau (14-3-3 protein theta) DRP2 Xq22 dystrophin related protein 2 TAF7L Xq22.1 TAF7-like RNA polymerase II, TATA box binding protein (TBP)-associated factor, 50kDa TIMM8A Xq22.1 translocase of inner mitochondrial membrane 8 homolog A (yeast) BTK Xq22.1-q22.2 Bruton agammaglobulinemia tyrosine kinase RPL36A Xq26.3-q27.3 ribosomal protein L36a GLA Xq22.11 galactosidase, alpha HNRPH2 Xq21.3-q22 heterogeneous nuclear ribonucleoprotein H2 (H') LOC389878 X LOC389878 MGC40053 Xq22.1 hypothetical protein MGC40053 LOC158948 Xq22.1 protein kinase C, iota pseudogene ALEX1 Xq21.33-q22.2 protein kinase C, iota pseudogene FLJ20811 Xq21.33-q22.3 hypothetical protein FLJ20811 ALEX3 Xq21.33-q22.2 ALEX3 protein ALEX2 Xq21.33-q22.2 ALEX2 protein GKP6 Xq22-q23 glycerol kinase pseudogene 6 NXF5 Xq22 nuclear RNA export factor 5 KIAA1789 Xq21 KIAA1789 protein my048 Xq22.1-q22.3 my048 protein LOC158931 Xq22.1 similar to hypothetical protein MGC15737 LOC340542 Xq22.1 hypothetical protein LOC340542 NXF2 Xq22-q23 nuclear RNA export factor 2 TMSNB Xq21.33-q22.3 thymosin, beta, identified in neuroblastoma cells LOC139707 Xq22.1 similar to checkpoint suppressor 1 NXF4 Xq22 nuclear RNA export factor 4 FLJ12969 Xq22.1-q22.3 hypothetical protein FLJ12969 GASP Xq22.1 G protein-coupled receptor-associated sorting protein
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 - 2611 - 659 - 2001 11226282
    19 - 2767 - 693 - 2001 11226282
    17 - 2248 - 483 - 2001 11226282
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
     spleen   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmature hematopoietic Homo sapiens
    Blood/Hematopoieticprogenitor cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
  • 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)
  • protein kinase superfamily
  • Tec family of protein tyrosine kinases
  • TEC subfamily
  • SRC family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
  • 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
    text B cell ontogeny
    a component BTK PH domain forms a homodimer and each molecule binds phosphatidylinositol in the binding pocket
    small molecule
  • 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
    activated by LYN (partly),SYK (modulated by BLNK)
    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
    Variant & Polymorphism
    Candidate gene
  • represents a useful marker to identify B cell non-Hodgkin lymphomas
  • Therapy target
    promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765
    could be a potent therapeutic target in ischaemic stroke
    is a therapeutic target in acute myeloid leukemia