{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:50:05Z","timestamp":1790779805628,"version":"4.1.0"},"reference-count":84,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2005,2,5]],"date-time":"2005-02-05T00:00:00Z","timestamp":1107561600000},"content-version":"vor","delay-in-days":3049,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioEssays"],"published-print":{"date-parts":[[1996,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>X\u2010linked agammaglobulinemia is a heritable immunodeficiency disease caused by a differentiation abnormality, resulting in the virtual absence of B Iymphocytes and plasma cells. The affected gene encodes a cytoplasmic protein tyrosine kinase, Bruton's agammaglobulinemia tyrosine kinase, designated Btk. Btk and the other family members, Tec, Itk and Bmx, contain five regions, four of which are common structural and functional modules that are found in other signaling proteins. Mutations affect all domains of the gene, but amino acid substitutions seem to be confined to certain regions. More than 150 unique mutations have been identified and are collected in a mutation database, BTKbase. Here we discuss the three\u2010dimensional structural implications of such mutations and their putative functional role. Of special interest are mutations affecting the pleckstrin homology domain, as Btk is the only disease\u2010associated protein so far reported to carry mutations in this particular module.<\/jats:p>","DOI":"10.1002\/bies.950181009","type":"journal-article","created":{"date-parts":[[2005,2,25]],"date-time":"2005-02-25T07:43:20Z","timestamp":1109317400000},"page":"825-834","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["X\u2010linked agammaglobulinemia (XLA): A genetic tyrosine kinase (Btk) disease"],"prefix":"10.1002","volume":"18","author":[{"given":"Pekka T.","family":"Mattsson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauno","family":"Vihinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. I. Edvard","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,2,5]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.9.6.722"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198407263110406"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199508173330707"},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1542\/peds.18.1.109","article-title":"Disturbances in gamma globulin synthesis as \u2018experiments of nature\u2019","volume":"18","author":"Good R. A.","year":"1956","journal-title":"Pediatrics"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-198505000-00001"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60631-8"},{"key":"e_1_2_1_8_2","unstructured":"Smith C. I. E.andNotarangelo L. D.(1996). Molecular basis for X\u2010linked immunodeficiencies.Adv. Genet. (in press)."},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198608283150907"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/361226a0"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90667-F"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8332900"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8332901"},{"key":"e_1_2_1_14_2","first-page":"417","article-title":"Expression of a novel form of Tec kinase in hematopoietic cells and mapping of the gene to chromosome 5 near Kit","volume":"8","author":"Mano H.","year":"1993","journal-title":"Oncogene"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.23.11194"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.2.669"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1404"},{"key":"e_1_2_1_18_2","first-page":"3683","article-title":"BMX\/TXK, a novel cytoplasmic tyrosine kinases gene of the BTK\/ITK\/TEC family located in chromosome Xp22.2","volume":"9","author":"Tamagnone L.","year":"1994","journal-title":"Oncogene"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1994.tb00851.x"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)00783-7"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.6.897"},{"key":"e_1_2_1_22_2","article-title":"Identification of Rlk, a novel protein tyrosine kinase with predominant expression in the T cell lineage","volume":"270","author":"Hu Q.","year":"1995","journal-title":"J. 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