Bruton'S Tyrosine Kinase (Btk)

AGMX1; AT; ATK; BPK; IMD1; PSCTK1; XLA; Bruton Agammaglobulinemia Tyrosine Kinase; B-cell progenitor kinase

SPN	U926
HGNC	1133
MGI	88216
PubMed	21422473
RGD	1359683
UniProt	Q06187
Wiki	BTK

Bruton's tyrosine kinase (or Btk) is a type of kinase enzyme implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). Patients with XLA have normal pre-B cell populations in their bone marrow but these cells fail to mature and enter the circulation. The BTK gene is located on the X chromosome. At least 400 mutations of the BTK gene have been identified. Btk contains a PH domain which binds Phosphatidylinositol (3,4,5)-trisphosphate (PIP3). PIP3 binding induces Btk to phosphorylate phospholipase C, which in turn hydrolyzes PIP₂, a phosphatidylinositol, into two second messagers, inositol triphosphate (IP3) and diacylglycerol(DAG), which then go on to modulate the activity of downstream proteins during B-cell signalling.

Reference

"The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases."
Nature 361:226-233(1993) [PubMed] [Europe PMC] [Abstract]

Erratum
Nature 364:362-362(1993)

"Genomic organization and structure of Bruton agammaglobulinemia tyrosine kinase: localization of mutations associated with varied clinical presentations and course in X chromosome-linked agammaglobulinemia."
Proc. Natl. Acad. Sci. U.S.A. 91:9062-9066(1994) [PubMed] [Europe PMC] [Abstract]

"The genomic structure of human BTK, the defective gene in X-linked agammaglobulinemia."
Immunogenetics 40:319-324(1994) [PubMed] [Europe PMC] [Abstract]

"Genomic organization of the Btk gene and exon scanning for mutations in patients with X-linked agammaglobulinemia."
Hum. Mol. Genet. 3:1743-1749(1994) [PubMed] [Europe PMC] [Abstract]

"Sixty-nine kilobases of contiguous human genomic sequence containing the alpha-galactosidase A and Bruton's tyrosine kinase loci."
Mamm. Genome 6:334-338(1995) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence of the human X chromosome."
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

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Cell 72:279-290(1993) [PubMed] [Europe PMC] [Abstract]

, Submitted (NOV-2005) to UniProtKB

"Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases."
Biochim. Biophys. Acta 1645:123-132(2003) [PubMed] [Europe PMC] [Abstract]

"An exon-skipping mutation in the btk gene of a patient with X-linked agammaglobulinemia and isolated growth hormone deficiency."
FEBS Lett. 346:165-170(1994) [PubMed] [Europe PMC] [Abstract]

"Tec homology (TH) adjacent to the PH domain."
FEBS Lett. 350:263-265(1994) [PubMed] [Europe PMC] [Abstract]

"Regulation of Btk function by a major autophosphorylation site within the SH3 domain."
Immunity 4:515-525(1996) [PubMed] [Europe PMC] [Abstract]

"BAP-135, a target for Bruton's tyrosine kinase in response to B cell receptor engagement."
Proc. Natl. Acad. Sci. U.S.A. 94:604-609(1997) [PubMed] [Europe PMC] [Abstract]

"Identification and characterization of a novel SH3-domain binding protein, Sab, which preferentially associates with Bruton's tyrosine kinase (Btk)."
Biochem. Biophys. Res. Commun. 245:337-343(1998) [PubMed] [Europe PMC] [Abstract]

"Phosphatidylinositol 3-kinase-dependent membrane association of the Bruton's tyrosine kinase pleckstrin homology domain visualized in single living cells."
J. Biol. Chem. 274:10983-10989(1999) [PubMed] [Europe PMC] [Abstract]

"Bruton's tyrosine kinase activity is negatively regulated by Sab, the Btk-SH3 domain-binding protein."
Proc. Natl. Acad. Sci. U.S.A. 96:6341-6346(1999) [PubMed] [Europe PMC] [Abstract]

"Redistribution of Bruton's tyrosine kinase by activation of phosphatidylinositol 3-kinase and Rho-family GTPases."
Eur. J. Immunol. 30:145-154(2000) [PubMed] [Europe PMC] [Abstract]

"Nucleocytoplasmic shuttling of Bruton's tyrosine kinase."
J. Biol. Chem. 275:40614-40619(2000) [PubMed] [Europe PMC] [Abstract]

"PKCbeta modulates antigen receptor signaling via regulation of Btk membrane localization."
EMBO J. 20:5692-5702(2001) [PubMed] [Europe PMC] [Abstract]

"Tyrosine residues in phospholipase Cgamma 2 essential for the enzyme function in B-cell signaling."
J. Biol. Chem. 276:47982-47992(2001) [PubMed] [Europe PMC] [Abstract]

"Direct inhibition of Bruton's tyrosine kinase by IBtk, a Btk-binding protein."
Nat. Immunol. 2:939-946(2001) [PubMed] [Europe PMC] [Abstract]

"Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx."
J. Biol. Chem. 277:9351-9357(2002) [PubMed] [Europe PMC] [Abstract]

"A phosphorylation site in Bruton's tyrosine kinase selectively regulates B cell calcium signaling efficiency by altering phospholipase C-gamma activation."
Proc. Natl. Acad. Sci. U.S.A. 101:14180-14185(2004) [PubMed] [Europe PMC] [Abstract]

"Regulation of Bruton tyrosine kinase by the peptidylprolyl isomerase Pin1."
J. Biol. Chem. 281:18201-18207(2006) [PubMed] [Europe PMC] [Abstract]

"Bruton's tyrosine kinase is required for TLR2 and TLR4-induced TNF, but not IL-6, production."
J. Immunol. 176:3635-3641(2006) [PubMed] [Europe PMC] [Abstract]

"Induction of immunoglobulin heavy-chain transcription through the transcription factor Bright requires TFII-I."
Mol. Cell. Biol. 26:4758-4768(2006) [PubMed] [Europe PMC] [Abstract]

"Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation."
Nat. Immunol. 7:148-155(2006) [PubMed] [Europe PMC] [Abstract]

"Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine kinase."
J. Biol. Chem. 282:36953-36960(2007) [PubMed] [Europe PMC] [Abstract]

"Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening."
BMC Immunol. 10:53-53(2009) [PubMed] [Europe PMC] [Abstract]

"Bruton's tyrosine kinase (BTK) as a dual-function regulator of apoptosis."
Biochem. Pharmacol. 56:683-691(1998) [PubMed] [Europe PMC] [Abstract]

"Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain."
Immunol. Rev. 228:58-73(2009) [PubMed] [Europe PMC] [Abstract]

"Large-scale proteomics analysis of the human kinome."
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"A novel isoform of the B cell tyrosine kinase BTK protects breast cancer cells from apoptosis."
Genes Chromosomes Cancer 52:961-975(2013) [PubMed] [Europe PMC] [Abstract]

"Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia."
EMBO J. 16:3396-3404(1997) [PubMed] [Europe PMC] [Abstract]

"Solution structure of the SH3 domain from Bruton's tyrosine kinase."
Biochemistry 37:2912-2924(1998) [PubMed] [Europe PMC] [Abstract]

"Structure of the PH domain from Bruton's tyrosine kinase in complex with inositol 1,3,4,5-tetrakisphosphate."
Structure 7:449-460(1999) [PubMed] [Europe PMC] [Abstract]

"Solution structure of the human BTK SH3 domain complexed with a proline-rich peptide from p120cbl."
J. Biomol. NMR 16:303-312(2000) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of Bruton's tyrosine kinase domain suggests a novel pathway for activation and provides insights into the molecular basis of X-linked agammaglobulinemia."
J. Biol. Chem. 276:41435-41443(2001) [PubMed] [Europe PMC] [Abstract]

"Solution structure and phosphopeptide binding of the SH2 domain from the human Bruton's tyrosine kinase."
J. Biomol. NMR 36:73-78(2006) [PubMed] [Europe PMC] [Abstract]

"A novel, specific Btk inhibitor antagonizes BCR and Fc[gamma]R signaling and suppresses inflammatory arthritis."
Submitted (AUG-2010) to the PDB data bank

"Crystal structure of PH domain of Bruton's tyrosine kinase."
Submitted (MAY-2007) to the PDB data bank

"Structures of human Bruton's tyrosine kinase in active and inactive conformations suggest a mechanism of activation for TEC family kinases."
Protein Sci. 19:429-439(2010) [PubMed] [Europe PMC] [Abstract]

"A novel, specific BTK inhibitor antagonizes BCR and FcgR signaling and suppresses inflammatory arthritis."
Submitted (SEP-2010) to the PDB data bank

"Insights into the conformational flexibility of Bruton's tyrosine kinase from multiple ligand complex structures."
Protein Sci. 20:428-436(2011) [PubMed] [Europe PMC] [Abstract]

"BTKbase, mutation database for X-linked agammaglobulinemia (XLA)."
Nucleic Acids Res. 24:160-165(1996) [PubMed] [Europe PMC] [Abstract]

"BTKbase, mutation database for X-linked agammaglobulinemia (XLA)."
Nucleic Acids Res. 25:166-171(1997) [PubMed] [Europe PMC] [Abstract]

"Mutation detection in the X-linked agammaglobulinemia gene, BTK, using single strand conformation polymorphism analysis."
Hum. Mol. Genet. 3:79-83(1994) [PubMed] [Europe PMC] [Abstract]

"Mutation analysis of the Bruton's tyrosine kinase gene in X-linked agammaglobulinemia: identification of a mutation which affects the same codon as is altered in immunodeficient xid mice."
Hum. Mol. Genet. 3:161-166(1994) [PubMed] [Europe PMC] [Abstract]

"Screening of genomic DNA to identify mutations in the gene for Bruton's tyrosine kinase."
Hum. Mol. Genet. 3:1751-1756(1994) [PubMed] [Europe PMC] [Abstract]

"Unique mutations of Bruton's tyrosine kinase in fourteen unrelated X-linked agammaglobulinemia families."
Hum. Mol. Genet. 3:1899-1900(1994) [PubMed] [Europe PMC] [Abstract]

"Structural basis for chromosome X-linked agammaglobulinemia: a tyrosine kinase disease."
Proc. Natl. Acad. Sci. U.S.A. 91:12803-12807(1994) [PubMed] [Europe PMC] [Abstract]

"Structural basis for pleckstrin homology domain mutations in X-linked agammaglobulinemia."
Biochemistry 34:1475-1481(1995) [PubMed] [Europe PMC] [Abstract]

"DNA-based mutation analysis of Bruton's tyrosine kinase gene in patients with X-linked agammaglobulinaemia."
Hum. Mol. Genet. 4:51-58(1995) [PubMed] [Europe PMC] [Abstract]

"Identification of Btk mutations in 20 unrelated patients with X-linked agammaglobulinaemia (XLA)."
Hum. Mol. Genet. 4:693-700(1995) [PubMed] [Europe PMC] [Abstract]

"Mutation analysis in Bruton's tyrosine kinase, the X-linked agammaglobulinaemia gene, including identification of an insertional hotspot."
Hum. Mol. Genet. 4:755-757(1995) [PubMed] [Europe PMC] [Abstract]

"Improved oligonucleotide primer set for molecular diagnosis of X-linked agammaglobulinaemia: predominance of amino acid substitutions in the catalytic domain of Bruton's tyrosine kinase."
Hum. Mol. Genet. 4:2403-2405(1995) [PubMed] [Europe PMC] [Abstract]

"Characterization of germline mutations of the gene encoding Bruton's tyrosine kinase in families with X-linked agammaglobulinemia."
Hum. Mutat. 5:296-302(1995) [PubMed] [Europe PMC] [Abstract]

"A new point mutation involving a highly conserved leucine in the Btk SH2 domain in a family with X linked agammaglobulinaemia."
J. Med. Genet. 32:77-79(1995) [PubMed] [Europe PMC] [Abstract]

"Detection of a novel mutation in the SRC homology domain 2 (SH2) of Bruton's tyrosine kinase and direct female carrier evaluation in a family with X-linked agammaglobulinemia."
Am. J. Med. Genet. 63:318-322(1996) [PubMed] [Europe PMC] [Abstract]

"Identification of Bruton's tyrosine kinase (Btk) gene mutations and characterization of the derived proteins in 35 X-linked agammaglobulinemia families: a nationwide study of Btk deficiency in Japan."
Blood 88:561-573(1996) [PubMed] [Europe PMC] [Abstract]

"Mutations of the Btk gene in 12 unrelated families with X-linked agammaglobulinemia in Japan."
Hum. Genet. 97:424-430(1996) [PubMed] [Europe PMC] [Abstract]

"Missense mutations affecting a conserved cysteine pair in the TH domain of Btk."
FEBS Lett. 413:205-210(1997) [PubMed] [Europe PMC] [Abstract]

"Molecular and structural characterization of five novel mutations in the Bruton's tyrosine kinase gene from patients with X-linked agammaglobulinemia."
Mol. Med. 3:477-485(1997) [PubMed] [Europe PMC] [Abstract]

"Mutations in btk in patients with presumed X-linked agammaglobulinemia."
Am. J. Hum. Genet. 62:1034-1043(1998) [PubMed] [Europe PMC] [Abstract]

"Mutation screening of the BTK gene in 56 families with X-linked agammaglobulinemia (XLA): 47 unique mutations without correlation to clinical course."
Pediatrics 101:276-284(1998) [PubMed] [Europe PMC] [Abstract]

"Mutations of the human BTK gene coding for Bruton tyrosine kinase in X-linked agammaglobulinemia."
Hum. Mutat. 13:280-285(1999) [PubMed] [Europe PMC] [Abstract]

"Twin carriers of X-linked agammaglobulinemia (XLA) due to germline mutation in the Btk gene."
Am. J. Med. Genet. 90:229-232(2000) [PubMed] [Europe PMC] [Abstract]

"Identification of nine novel mutations in the Bruton's tyrosine kinase gene in X-linked agammaglobulinaemia patients."
Hum. Mutat. 15:117-117(2000) [PubMed] [Europe PMC] [Abstract]

"Patterns of somatic mutation in human cancer genomes."
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]