| Bruton agammaglobulinemia tyrosine kinase |

PH domain of Bruton's tyrosine kinase dimer with bound lipids. Blue plane shows hydrocarbon boundary of the lipid bilayer |
| Available structures |
| PDB |
1AWW, 1AWX, 1B55, 1BTK, 1BWN, 1K2P, 1QLY, 2GE9, 2Z0P, 3GEN, 3K54, 3OCS, 3OCT, 3P08, 3PIX, 3PIY, 3PIZ, 3PJ1, 3PJ2, 3PJ3 |
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| Identifiers |
| Symbols |
BTK; AGMX1; AT; ATK; BPK; IMD1; PSCTK1; XLA |
| External IDs |
OMIM: 300300 MGI: 88216 HomoloGene: 30953 GeneCards: BTK Gene |
| EC number |
2.7.10.2 |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
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| Entrez |
695 |
12229 |
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| Ensembl |
ENSG00000010671 |
ENSMUSG00000031264 |
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| UniProt |
Q06187 |
P35991 |
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| RefSeq (mRNA) |
NM_000061.2 |
NM_013482.2 |
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| RefSeq (protein) |
NP_000052.1 |
NP_038510.2 |
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| Location (UCSC) |
Chr X:
100.6 – 100.64 Mb |
Chr X:
131.08 – 131.12 Mb |
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| PubMed search |
[1] |
[2] |
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Bruton's tyrosine kinase (or Btk) is a type of kinase enzyme implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). Its exact mechanism of action remains unknown, but it plays a crucial role in B cell maturation as well as mast cell activation through the high-affinity IgE receptor. 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.[1] At least 400 mutations of the Btk gene have been identified.
Btk contains a PH domain that 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. Patients often have sinopulmonary infections beginning 6 months after birth (maternally derived antibodies offer some protection until that time).
Bruton's tyrosine kinase was discovered in 1993 and is named for Ogden Bruton, who first described XLA in 1952.[1]
[edit] Interactions
Bruton's tyrosine kinase has been shown to interact with GNAQ,[2] PLCG2,[3][4] Protein kinase D1,[5] B-cell linker,[3][6] SH3BP5,[7][8] Caveolin 1,[9] ARID3A[10] and GTF2I.[11][12][13]
[edit] See also
- Ibrutinib (PCI-32765), a selective Bruton's tyrosine kinase inhibitor
[edit] References
- ^ a b X-Linked Agammaglobulinemia Patient and Family Handbook for The Primary Immune Diseases. Third Edition. 2001. Published by the Immune Deficiency Foundation.
- ^ Ma, Y C; Huang X Y (Oct. 1998). "Identification of the binding site for Gqalpha on its effector Bruton's tyrosine kinase". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 95 (21): 12197–201. doi:10.1073/pnas.95.21.12197. ISSN 0027-8424. PMC 22808. PMID 9770463. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=22808.
- ^ a b Yasuda, Tomoharu; Tezuka Tohru, Maeda Akito, Inazu Tetsuya, Yamanashi Yuji, Gu Hua, Kurosaki Tomohiro, Yamamoto Tadashi (Jul. 2002). "Cbl-b positively regulates Btk-mediated activation of phospholipase C-gamma2 in B cells". J. Exp. Med. (United States) 196 (1): 51–63. doi:10.1084/jem.20020068. ISSN 0022-1007. PMC 2194016. PMID 12093870. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2194016.
- ^ Guo, B; Kato R M, Garcia-Lloret M, Wahl M I, Rawlings D J (Aug. 2000). "Engagement of the human pre-B cell receptor generates a lipid raft-dependent calcium signaling complex". Immunity (UNITED STATES) 13 (2): 243–53. doi:10.1016/S1074-7613(00)00024-8. ISSN 1074-7613. PMID 10981967.
- ^ Johannes, F J; Hausser A, Storz P, Truckenmüller L, Link G, Kawakami T, Pfizenmaier K (Nov. 1999). "Bruton's tyrosine kinase (Btk) associates with protein kinase C mu". FEBS Lett. (NETHERLANDS) 461 (1-2): 68–72. doi:10.1016/S0014-5793(99)01424-6. ISSN 0014-5793. PMID 10561498.
- ^ Hashimoto, S; Iwamatsu A, Ishiai M, Okawa K, Yamadori T, Matsushita M, Baba Y, Kishimoto T, Kurosaki T, Tsukada S (Oct. 1999). "Identification of the SH2 domain binding protein of Bruton's tyrosine kinase as BLNK--functional significance of Btk-SH2 domain in B-cell antigen receptor-coupled calcium signaling". Blood (UNITED STATES) 94 (7): 2357–64. ISSN 0006-4971. PMID 10498607.
- ^ Matsushita, M; Yamadori T, Kato S, Takemoto Y, Inazawa J, Baba Y, Hashimoto S, Sekine S, Arai S, Kunikata T, Kurimoto M, Kishimoto T, Tsukada S (Apr. 1998). "Identification and characterization of a novel SH3-domain binding protein, Sab, which preferentially associates with Bruton's tyrosine kinase (BtK)". Biochem. Biophys. Res. Commun. (UNITED STATES) 245 (2): 337–43. doi:10.1006/bbrc.1998.8420. ISSN 0006-291X. PMID 9571151.
- ^ Yamadori, T; Baba Y, Matsushita M, Hashimoto S, Kurosaki M, Kurosaki T, Kishimoto T, Tsukada S (May. 1999). "Bruton's tyrosine kinase activity is negatively regulated by Sab, the Btk-SH3 domain-binding protein". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 96 (11): 6341–6. doi:10.1073/pnas.96.11.6341. ISSN 0027-8424. PMC 26883. PMID 10339589. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=26883.
- ^ Vargas, Leonardo; Nore Beston F, Berglof Anna, Heinonen Juhana E, Mattsson Pekka T, Smith C I Edvard, Mohamed Abdalla J (Mar. 2002). "Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx". J. Biol. Chem. (United States) 277 (11): 9351–7. doi:10.1074/jbc.M108537200. ISSN 0021-9258. PMID 11751885.
- ^ Nixon, Jamee C; Rajaiya Jaya B, Ayers Neil, Evetts Seth, Webb Carol F (Mar. 2004). "The transcription factor, Bright, is not expressed in all human B lymphocyte subpopulations". Cell. Immunol. (United States) 228 (1): 42–53. doi:10.1016/j.cellimm.2004.03.004. ISSN 0008-8749. PMID 15203319.
- ^ Sacristán, Catarina; Tussié-Luna María Isabel, Logan Sheila M, Roy Ananda L (Feb. 2004). "Mechanism of Bruton's tyrosine kinase-mediated recruitment and regulation of TFII-I". J. Biol. Chem. (United States) 279 (8): 7147–58. doi:10.1074/jbc.M303724200. ISSN 0021-9258. PMID 14623887.
- ^ Novina, C D; Kumar S, Bajpai U, Cheriyath V, Zhang K, Pillai S, Wortis H H, Roy A L (Jul. 1999). "Regulation of nuclear localization and transcriptional activity of TFII-I by Bruton's tyrosine kinase". Mol. Cell. Biol. (UNITED STATES) 19 (7): 5014–24. ISSN 0270-7306. PMC 84330. PMID 10373551. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84330.
- ^ Yang, W; Desiderio S (Jan. 1997). "BAP-135, a target for Bruton's tyrosine kinase in response to B cell receptor engagement". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 94 (2): 604–9. doi:10.1073/pnas.94.2.604. ISSN 0027-8424. PMC 19560. PMID 9012831. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=19560.
[edit] External links
[edit] Further reading
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PDB gallery
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1aww: SH3 DOMAIN FROM BRUTON'S TYROSINE KINASE, NMR, 42 STRUCTURES
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1awx: SH3 DOMAIN FROM BRUTON'S TYROSINE KINASE, NMR, MINIMIZED AVERAGE STRUCTURE
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1b55: PH DOMAIN FROM BRUTON'S TYROSINE KINASE IN COMPLEX WITH INOSITOL 1,3,4,5-TETRAKISPHOSPHATE
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1btk: PH DOMAIN AND BTK MOTIF FROM BRUTON'S TYROSINE KINASE MUTANT R28C
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1bwn: PH DOMAIN AND BTK MOTIF FROM BRUTON'S TYROSINE KINASE MUTANT E41K IN COMPLEX WITH INS(1,3,4,5)P4
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1k2p: Crystal structure of Bruton's tyrosine kinase domain
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1qly: NMR STUDY OF THE SH3 DOMAIN FROM BRUTON'S TYROSINE KINASE, 20 STRUCTURES
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2ge9: Solution Structures of the SH2 domain of Bruton's Tyrosine Kinase
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