ID BTK_HUMAN Reviewed; 659 AA. AC Q06187; B2RAW1; Q32ML5; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 266. DE RecName: Full=Tyrosine-protein kinase BTK; DE EC=2.7.10.2 {ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:34554188}; DE AltName: Full=Agammaglobulinemia tyrosine kinase; DE Short=ATK; DE AltName: Full=B-cell progenitor kinase; DE Short=BPK; DE AltName: Full=Bruton tyrosine kinase; GN Name=BTK; Synonyms=AGMX1, ATK, BPK; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BTK-A). RX PubMed=8380905; DOI=10.1038/361226a0; RA Vetrie D., Vorechovsky I., Sideras P., Holland J., Davies A., Flinter F., RA Hammarstroem L., Kinnon C., Levinsky R.J., Bobrow M., Smith C.I.E., RA Bentley D.R.; RT "The gene involved in X-linked agammaglobulinaemia is a member of the src RT family of protein-tyrosine kinases."; RL Nature 361:226-233(1993). RN [2] RP ERRATUM OF PUBMED:8380905. RA Vetrie D., Vorechovsky I., Sideras P., Holland J., Davies A., Flinter F., RA Hammarstroem L., Kinnon C., Levinsky R.J., Bobrow M., Smith C.I.E., RA Bentley D.R.; RL Nature 364:362-362(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Blood; RX PubMed=8090769; DOI=10.1073/pnas.91.19.9062; RA Ohta Y., Haire R.N., Litman R.T., Fu S.M., Nelson R.P., Kratz J., RA Kornfeld S.J., la Morena M., Good R.A., Litman G.W.; RT "Genomic organization and structure of Bruton agammaglobulinemia tyrosine RT kinase: localization of mutations associated with varied clinical RT presentations and course in X chromosome-linked agammaglobulinemia."; RL Proc. Natl. Acad. Sci. U.S.A. 91:9062-9066(1994). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7927535; DOI=10.1007/bf01246672; RA Rohrer J., Parolini O., Belmont J.W., Conley M.E.; RT "The genomic structure of human BTK, the defective gene in X-linked RT agammaglobulinemia."; RL Immunogenetics 40:319-324(1994). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS XLA SER-334; ARG-506; RP GLN-520; TRP-562 AND LYS-630. RX PubMed=7880320; DOI=10.1093/hmg/3.10.1743; RA Hagemann T.L., Chen Y., Rosen F.S., Kwan S.-P.; RT "Genomic organization of the Btk gene and exon scanning for mutations in RT patients with X-linked agammaglobulinemia."; RL Hum. Mol. Genet. 3:1743-1749(1994). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7626884; DOI=10.1007/bf00364796; RA Oeltjen J.C., Liu X., Lu J., Allen R.C., Muzny D.M., Belmont J.W., RA Gibbs R.A.; RT "Sixty-nine kilobases of contiguous human genomic sequence containing the RT alpha-galactosidase A and Bruton's tyrosine kinase loci."; RL Mamm. Genome 6:334-338(1995). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BTK-A). RC TISSUE=Umbilical cord blood; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BTK-A). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE OF 1-442. RX PubMed=8425221; DOI=10.1016/0092-8674(93)90667-f; RA Tsukada S., Saffran D.C., Rawlings D.J., Parolini O., Allen R.C., RA Klisak I., Sparkes R.S., Kubagawa H., Mohandas T., Quan S., Belmont J.W., RA Cooper M.D., Conley M.E., Witte O.N.; RT "Deficient expression of a B cell cytoplasmic tyrosine kinase in human X- RT linked agammaglobulinemia."; RL Cell 72:279-290(1993). RN [11] RP PROTEIN SEQUENCE OF 2-12 AND 323-332, CLEAVAGE OF INITIATOR METHIONINE, RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Platelet; RA Bienvenut W.V., Claeys D.; RL Submitted (NOV-2005) to UniProtKB. RN [12] RP PROTEIN SEQUENCE OF 219-235, AND PHOSPHORYLATION AT TYR-223. RX PubMed=12573241; DOI=10.1016/s1570-9639(02)00524-1; RA Nore B.F., Mattsson P.T., Antonsson P., Backesjo C.-M., Westlund A., RA Lennartsson J., Hansson H., Low P., Ronnstrand L., Smith C.I.E.; RT "Identification of phosphorylation sites within the SH3 domains of Tec RT family tyrosine kinases."; RL Biochim. Biophys. Acta 1645:123-132(2003). RN [13] RP INVOLVEMENT IN IGHD3. RX PubMed=8013627; DOI=10.1016/0014-5793(94)00457-9; RA Duriez B., Duquesnoy P., Dastot F., Bougneres P., Amselem S., Goossens M.; RT "An exon-skipping mutation in the btk gene of a patient with X-linked RT agammaglobulinemia and isolated growth hormone deficiency."; RL FEBS Lett. 346:165-170(1994). RN [14] RP DOMAIN PH. RX PubMed=8070576; DOI=10.1016/0014-5793(94)00783-7; RA Vihinen M., Nilsson L., Smith C.I.; RT "Tec homology (TH) adjacent to the PH domain."; RL FEBS Lett. 350:263-265(1994). RN [15] RP PHOSPHORYLATION AT TYR-223 AND TYR-551, MUTAGENESIS OF TYR-223, AND RP ACTIVITY REGULATION. RX PubMed=8630736; DOI=10.1016/s1074-7613(00)80417-3; RA Park H., Wahl M.I., Afar D.E., Turck C.W., Rawlings D.J., Tam C., RA Scharenberg A.M., Kinet J.P., Witte O.N.; RT "Regulation of Btk function by a major autophosphorylation site within the RT SH3 domain."; RL Immunity 4:515-525(1996). RN [16] RP FUNCTION IN PHOSPHORYLATION OF GTF2I, PHOSPHORYLATION AT TYR-223 AND RP TYR-551, AND MUTAGENESIS OF GLU-41; PRO-189; TYR-223; TRP-251; ARG-307 AND RP TYR-551. RX PubMed=9012831; DOI=10.1073/pnas.94.2.604; RA Yang W., Desiderio S.; RT "BAP-135, a target for Bruton's tyrosine kinase in response to B cell RT receptor engagement."; RL Proc. Natl. Acad. Sci. U.S.A. 94:604-609(1997). RN [17] RP MUTAGENESIS OF 251-TRP-TRP-252, AND INTERACTION WITH SH3BP5. RX PubMed=9571151; DOI=10.1006/bbrc.1998.8420; RA Matsushita M., Yamadori T., Kato S., Takemoto Y., Inazawa J., Baba Y., RA Hashimoto S., Sekine S., Arai S., Kunikata T., Kurimoto M., Kishimoto T., RA Tsukada S.; RT "Identification and characterization of a novel SH3-domain binding protein, RT Sab, which preferentially associates with Bruton's tyrosine kinase (Btk)."; RL Biochem. Biophys. Res. Commun. 245:337-343(1998). RN [18] RP DOMAIN PH, AND SUBCELLULAR LOCATION. RX PubMed=10196179; DOI=10.1074/jbc.274.16.10983; RA Varnai P., Rother K.I., Balla T.; RT "Phosphatidylinositol 3-kinase-dependent membrane association of the RT Bruton's tyrosine kinase pleckstrin homology domain visualized in single RT living cells."; RL J. Biol. Chem. 274:10983-10989(1999). RN [19] RP INTERACTION WITH SH3BP5, AND ACTIVITY REGULATION. RX PubMed=10339589; DOI=10.1073/pnas.96.11.6341; RA Yamadori T., Baba Y., Mastushita M., Hashimoto S., Kurosaki M., RA Kurosaki T., Kishimoto T., Tsukada S.; RT "Bruton's tyrosine kinase activity is negatively regulated by Sab, the Btk- RT SH3 domain-binding protein."; RL Proc. Natl. Acad. Sci. U.S.A. 96:6341-6346(1999). RN [20] RP SUBCELLULAR LOCATION. RX PubMed=10602036; RX DOI=10.1002/1521-4141(200001)30:1<145::aid-immu145>3.0.co;2-0; RA Nore B.F., Vargas L., Mohamed A.J., Branden L.J., Backesjo C.M., RA Islam T.C., Mattsson P.T., Hultenby K., Christensson B., Smith C.I.; RT "Redistribution of Bruton's tyrosine kinase by activation of RT phosphatidylinositol 3-kinase and Rho-family GTPases."; RL Eur. J. Immunol. 30:145-154(2000). RN [21] RP SUBCELLULAR LOCATION. RX PubMed=11016936; DOI=10.1074/jbc.m006952200; RA Mohamed A.J., Vargas L., Nore B.F., Backesjo C.M., Christensson B., RA Smith C.I.; RT "Nucleocytoplasmic shuttling of Bruton's tyrosine kinase."; RL J. Biol. Chem. 275:40614-40619(2000). RN [22] RP PHOSPHORYLATION AT SER-180, AND ACTIVITY REGULATION. RX PubMed=11598012; DOI=10.1093/emboj/20.20.5692; RA Kang S.W., Wahl M.I., Chu J., Kitaura J., Kawakami Y., Kato R.M., RA Tabuchi R., Tarakhovsky A., Kawakami T., Turck C.W., Witte O.N., RA Rawlings D.J.; RT "PKCbeta modulates antigen receptor signaling via regulation of Btk RT membrane localization."; RL EMBO J. 20:5692-5702(2001). RN [23] RP FUNCTION IN PHOSPHORYLATION OF PLCG2, AND CATALYTIC ACTIVITY. RX PubMed=11606584; DOI=10.1074/jbc.m107577200; RA Rodriguez R., Matsuda M., Perisic O., Bravo J., Paul A., Jones N.P., RA Light Y., Swann K., Williams R.L., Katan M.; RT "Tyrosine residues in phospholipase Cgamma 2 essential for the enzyme RT function in B-cell signaling."; RL J. Biol. Chem. 276:47982-47992(2001). RN [24] RP INTERACTION WITH IBTK, AND ACTIVITY REGULATION. RX PubMed=11577348; DOI=10.1038/ni1001-939; RA Liu W., Quinto I., Chen X., Palmieri C., Rabin R.L., Schwartz O.M., RA Nelson D.L., Scala G.; RT "Direct inhibition of Bruton's tyrosine kinase by IBtk, a Btk-binding RT protein."; RL Nat. Immunol. 2:939-946(2001). RN [25] RP DOMAIN, INTERACTION WITH CAV1, SUBCELLULAR LOCATION, AND ACTIVITY RP REGULATION. RX PubMed=11751885; DOI=10.1074/jbc.m108537200; RA Vargas L., Nore B.F., Berglof A., Heinonen J.E., Mattsson P.T., Smith C.I., RA Mohamed A.J.; RT "Functional interaction of caveolin-1 with Bruton's tyrosine kinase and RT Bmx."; RL J. Biol. Chem. 277:9351-9357(2002). RN [26] RP PHOSPHORYLATION AT TYR-617 AND SER-623, AND MUTAGENESIS OF TYR-617. RX PubMed=15375214; DOI=10.1073/pnas.0405878101; RA Guo S., Ferl G.Z., Deora R., Riedinger M., Yin S., Kerwin J.L., Loo J.A., RA Witte O.N.; RT "A phosphorylation site in Bruton's tyrosine kinase selectively regulates B RT cell calcium signaling efficiency by altering phospholipase C-gamma RT activation."; RL Proc. Natl. Acad. Sci. U.S.A. 101:14180-14185(2004). RN [27] RP INTERACTION WITH PIN1, PHOSPHORYLATION AT SER-21 AND SER-115, AND ACTIVITY RP REGULATION. RX PubMed=16644721; DOI=10.1074/jbc.m603090200; RA Yu L., Mohamed A.J., Vargas L., Berglof A., Finn G., Lu K.P., Smith C.I.; RT "Regulation of Bruton tyrosine kinase by the peptidylprolyl isomerase RT Pin1."; RL J. Biol. Chem. 281:18201-18207(2006). RN [28] RP FUNCTION IN THE TLR PATHWAY. RX PubMed=16517732; DOI=10.4049/jimmunol.176.6.3635; RA Horwood N.J., Page T.H., McDaid J.P., Palmer C.D., Campbell J., Mahon T., RA Brennan F.M., Webster D., Foxwell B.M.; RT "Bruton's tyrosine kinase is required for TLR2 and TLR4-induced TNF, but RT not IL-6, production."; RL J. Immunol. 176:3635-3641(2006). RN [29] RP INTERACTION WITH GTF2I AND ARID3A, AND FUNCTION. RX PubMed=16738337; DOI=10.1128/mcb.02009-05; RA Rajaiya J., Nixon J.C., Ayers N., Desgranges Z.P., Roy A.L., Webb C.F.; RT "Induction of immunoglobulin heavy-chain transcription through the RT transcription factor Bright requires TFII-I."; RL Mol. Cell. Biol. 26:4758-4768(2006). RN [30] RP FUNCTION IN PHOSPHORYLATION OF TIRAP, AND ACTIVITY REGULATION. RX PubMed=16415872; DOI=10.1038/ni1299; RA Mansell A., Smith R., Doyle S.L., Gray P., Fenner J.E., Crack P.J., RA Nicholson S.E., Hilton D.J., O'Neill L.A., Hertzog P.J.; RT "Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor RT signaling by mediating Mal degradation."; RL Nat. Immunol. 7:148-155(2006). RN [31] RP FUNCTION, INTERACTION WITH TLR8 AND TLR9, ACTIVITY REGULATION, AND RP PHOSPHORYLATION AT TYR-223. RX PubMed=17932028; DOI=10.1074/jbc.m707682200; RA Doyle S.L., Jefferies C.A., Feighery C., O'Neill L.A.; RT "Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine RT kinase."; RL J. Biol. Chem. 282:36953-36960(2007). RN [32] RP INTERACTION WITH FASLG. RX PubMed=19807924; DOI=10.1186/1471-2172-10-53; RA Voss M., Lettau M., Janssen O.; RT "Identification of SH3 domain interaction partners of human FasL (CD178) by RT phage display screening."; RL BMC Immunol. 10:53-53(2009). RN [33] RP REVIEW ON FUNCTION IN REGULATION OF APOPTOSIS. RX PubMed=9751072; DOI=10.1016/s0006-2952(98)00122-1; RA Uckun F.M.; RT "Bruton's tyrosine kinase (BTK) as a dual-function regulator of RT apoptosis."; RL Biochem. Pharmacol. 56:683-691(1998). RN [34] RP REVIEW ON FUNCTION, AND REVIEW ON ACTIVITY REGULATION. RX PubMed=19290921; DOI=10.1111/j.1600-065x.2008.00741.x; RA Mohamed A.J., Yu L., Backesjo C.M., Vargas L., Faryal R., Aints A., RA Christensson B., Berglof A., Vihinen M., Nore B.F., Smith C.I.; RT "Bruton's tyrosine kinase (Btk): function, regulation, and transformation RT with special emphasis on the PH domain."; RL Immunol. Rev. 228:58-73(2009). RN [35] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55; THR-191; TYR-361 AND RP SER-659, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [36] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [37] RP ALTERNATIVE PROMOTER USAGE (ISOFORM BTK-C). RX PubMed=23913792; DOI=10.1002/gcc.22091; RA Eifert C., Wang X., Kokabee L., Kourtidis A., Jain R., Gerdes M.J., RA Conklin D.S.; RT "A novel isoform of the B cell tyrosine kinase BTK protects breast cancer RT cells from apoptosis."; RL Genes Chromosomes Cancer 52:961-975(2013). RN [38] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-191; TYR-223 AND SER-604, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [39] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [40] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=34554188; DOI=10.1084/jem.20201656; RA Bittner Z.A., Liu X., Mateo Tortola M., Tapia-Abellan A., Shankar S., RA Andreeva L., Mangan M., Spalinger M., Kalbacher H., Duewell P., Lovotti M., RA Bosch K., Dickhoefer S., Marcu A., Stevanovic S., Herster F., RA Cardona Gloria Y., Chang T.H., Bork F., Greve C.L., Loeffler M.W., RA Wolz O.O., Schilling N.A., Kuemmerle-Deschner J.B., Wagner S., Delor A., RA Grimbacher B., Hantschel O., Scharl M., Wu H., Latz E., Weber A.N.R.; RT "BTK operates a phospho-tyrosine switch to regulate NLRP3 inflammasome RT activity."; RL J. Exp. Med. 218:0-0(2021). RN [41] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 2-170 IN COMPLEX WITH ZINC, AND RP COFACTOR. RX PubMed=9218782; DOI=10.1093/emboj/16.12.3396; RA Hyvoenen M., Saraste M.; RT "Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: RT molecular explanations for X-linked agammaglobulinaemia."; RL EMBO J. 16:3396-3404(1997). RN [42] RP STRUCTURE BY NMR OF 212-275. RX PubMed=9485443; DOI=10.1021/bi972409f; RA Hansson H., Mattsson P.T., Allard P., Haapaniemi P., Vihinen M., RA Smith C.I.E., Haerd T.; RT "Solution structure of the SH3 domain from Bruton's tyrosine kinase."; RL Biochemistry 37:2912-2924(1998). RN [43] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-170 IN COMPLEX WITH RP INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE AND ZINC, DOMAIN PH, AND COFACTOR. RX PubMed=10196129; DOI=10.1016/s0969-2126(99)80057-4; RA Baraldi E., Carugo K.D., Hyvoenen M., Surdo P.L., Riley A.M., RA Potter B.V.L., O'Brien R., Ladbury J.E., Saraste M.; RT "Structure of the PH domain from Bruton's tyrosine kinase in complex with RT inositol 1,3,4,5-tetrakisphosphate."; RL Structure 7:449-460(1999). RN [44] RP STRUCTURE BY NMR OF 216-273. RX PubMed=10826882; DOI=10.1023/a:1008376624863; RA Tzeng S.R., Lou Y.C., Pai M.T., Jain M.L., Cheng J.W.; RT "Solution structure of the human BTK SH3 domain complexed with a proline- RT rich peptide from p120cbl."; RL J. Biomol. NMR 16:303-312(2000). RN [45] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 397-659. RX PubMed=11527964; DOI=10.1074/jbc.m104828200; RA Mao C., Zhou M., Uckun F.M.; RT "Crystal structure of Bruton's tyrosine kinase domain suggests a novel RT pathway for activation and provides insights into the molecular basis of X- RT linked agammaglobulinemia."; RL J. Biol. Chem. 276:41435-41443(2001). RN [46] RP STRUCTURE BY NMR OF 270-386. RX PubMed=16969585; DOI=10.1007/s10858-006-9064-3; RA Huang K.C., Cheng H.T., Pai M.T., Tzeng S.R., Cheng J.W.; RT "Solution structure and phosphopeptide binding of the SH2 domain from the RT human Bruton's tyrosine kinase."; RL J. Biomol. NMR 36:73-78(2006). RN [47] {ECO:0007744|PDB:3OCS, ECO:0007744|PDB:3OCT} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 393-656 IN COMPLEX WITH RP INHIBITOR. RA Di Paolo J.A., Huang T., Balazs M., Barbosa J., Barck K.H., Carano R.A.D., RA Darrow J., Davies D.R., DeForge L.E., Dennis G. Jr., Diehl L., Ferrando R.; RT "A novel, specific Btk inhibitor antagonizes BCR and Fc[gamma]R signaling RT and suppresses inflammatory arthritis."; RL Submitted (AUG-2010) to the PDB data bank. RN [48] {ECO:0007744|PDB:2Z0P} RP X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS) OF 2-170 IN COMPLEX WITH INHIBITOR RP AND ZINC, AND COFACTOR. RA Murayama K., Kato-Murayama M., Mishima C., Shirouzu M., Yokoyama S.; RT "Crystal structure of PH domain of Bruton's tyrosine kinase."; RL Submitted (MAY-2007) to the PDB data bank. RN [49] {ECO:0007744|PDB:3GEN, ECO:0007744|PDB:3K54} RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 382-659 IN COMPLEX WITH INHIBITOR RP DASATINIB. RX PubMed=20052711; DOI=10.1002/pro.321; RA Marcotte D.J., Liu Y.T., Arduini R.M., Hession C.A., Miatkowski K., RA Wildes C.P., Cullen P.F., Hong V., Hopkins B.T., Mertsching E., RA Jenkins T.J., Romanowski M.J., Baker D.P., Silvian L.F.; RT "Structures of human Bruton's tyrosine kinase in active and inactive RT conformations suggest a mechanism of activation for TEC family kinases."; RL Protein Sci. 19:429-439(2010). RN [50] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 393-659. RA Di Paolo J., Huang T., Balazs M., Barbosa J., Barck K.H., Bravo B., RA Carano R.A.D., Darrow J., Davies D.R., DeForge L.E., Diehl L., Ferrando R., RA Gallion S.L., Gianetti A.M., Gribling P., Hurez V., Hymowitz S.G., RA Jones R., Kropf J.E., Lee W.P., Maciejewski P.M., Mitchell S.A., Rong H., RA Staker B.L., Whitney J.A., Yeh S., Young W., Yu C., Zhang J., Reif K., RA Currie K.S.; RT "A novel, specific BTK inhibitor antagonizes BCR and FcgR signaling and RT suppresses inflammatory arthritis."; RL Submitted (SEP-2010) to the PDB data bank. RN [51] {ECO:0007744|PDB:3PIX, ECO:0007744|PDB:3PIY, ECO:0007744|PDB:3PIZ, ECO:0007744|PDB:3PJ1, ECO:0007744|PDB:3PJ2, ECO:0007744|PDB:3PJ3} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 387-659 IN COMPLEX WITH RP INHIBITOR. RX PubMed=21280133; DOI=10.1002/pro.575; RA Kuglstatter A., Wong A., Tsing S., Lee S.W., Lou Y., Villasenor A.G., RA Bradshaw J.M., Shaw D., Barnett J.W., Browner M.F.; RT "Insights into the conformational flexibility of Bruton's tyrosine kinase RT from multiple ligand complex structures."; RL Protein Sci. 20:428-436(2011). RN [52] RP REVIEW ON VARIANTS XLA. RX PubMed=8594569; DOI=10.1093/nar/24.1.160; RA Vihinen M., Iwata T., Kinnon C., Kwan S.-P., Ochs H.D., Vorechovsky I., RA Smith C.I.E.; RT "BTKbase, mutation database for X-linked agammaglobulinemia (XLA)."; RL Nucleic Acids Res. 24:160-165(1996). RN [53] RP REVIEW ON VARIANTS XLA. RX PubMed=9016530; DOI=10.1093/nar/25.1.166; RA Vihinen M., Belohradsky B.H., Haire R.N., Holinski-Feder E., Kwan S.-P., RA Lappalainen I., Lehvaeslaiho H., Lester T., Meindl A., Ochs H.D., RA Ollila J., Vorechovsky I., Weiss M., Smith C.I.E.; RT "BTKbase, mutation database for X-linked agammaglobulinemia (XLA)."; RL Nucleic Acids Res. 25:166-171(1997). RN [54] RP VARIANTS XLA TRP-288; GLY-307; ASP-607 AND SER-VAL-PHE-SER-SER-THR-ARG-103 RP INS. RX PubMed=8162056; DOI=10.1093/hmg/3.1.79; RA Bradley L.A.D., Sweatman A.K., Lovering R.C., Jones A.M., Morgan G., RA Levinsky R.J., Kinnon C.; RT "Mutation detection in the X-linked agammaglobulinemia gene, BTK, using RT single strand conformation polymorphism analysis."; RL Hum. Mol. Genet. 3:79-83(1994). RN [55] RP VARIANTS XLA HIS-28 AND TRP-288. RX PubMed=8162018; DOI=10.1093/hmg/3.1.161; RA de Weers M., Mensink R.G.J., Kraakman M.E.M., Schuurman R.K.B., RA Hendriks R.W.; RT "Mutation analysis of the Bruton's tyrosine kinase gene in X-linked RT agammaglobulinemia: identification of a mutation which affects the same RT codon as is altered in immunodeficient xid mice."; RL Hum. Mol. Genet. 3:161-166(1994). RN [56] RP VARIANTS XLA ASP-113; CYS-361; GLN-520; PRO-542; TRP-562; LYS-630 AND RP PRO-652. RX PubMed=7849697; DOI=10.1093/hmg/3.10.1751; RA Conley M.E., Fitch-Hilgenberg M.E., Cleveland J.L., Parolini O., Rohrer J.; RT "Screening of genomic DNA to identify mutations in the gene for Bruton's RT tyrosine kinase."; RL Hum. Mol. Genet. 3:1751-1756(1994). RN [57] RP VARIANTS XLA HIS-28; PRO-33; PRO-408; GLY-589; ASP-613 AND 260-GLN--GLU-280 RP DEL. RX PubMed=7849721; DOI=10.1093/hmg/3.10.1899; RA Zhu Q., Zhang M., Winkelstein J., Chen S.-H., Ochs H.D.; RT "Unique mutations of Bruton's tyrosine kinase in fourteen unrelated X- RT linked agammaglobulinemia families."; RL Hum. Mol. Genet. 3:1899-1900(1994). RN [58] RP VARIANTS XLA GLU-430; GLN-520; GLN-525; PRO-562; VAL-582; GLY-589; GLU-594 RP AND ASP-613. RX PubMed=7809124; DOI=10.1073/pnas.91.26.12803; RA Vihinen M., Vetrie D., Maniar H.S., Ochs H.D., Zhu Q., Vorechovsky I., RA Webster A.D.B., Notarangelo L.D., Nilsson L., Sowadski J.M., Smith C.I.E.; RT "Structural basis for chromosome X-linked agammaglobulinemia: a tyrosine RT kinase disease."; RL Proc. Natl. Acad. Sci. U.S.A. 91:12803-12807(1994). RN [59] RP VARIANT XLA PHE-64, AND CHARACTERIZATION OF OTHER XLA VARIANTS. RX PubMed=7849006; DOI=10.1021/bi00005a002; RA Vihinen M., Zvelebil J.J.M., Zhu Q., Brooimans R.A., Ochs H.D., RA Zegers B.J.M., Nilsson L., Waterfield M.D., Smith C.I.E.; RT "Structural basis for pleckstrin homology domain mutations in X-linked RT agammaglobulinemia."; RL Biochemistry 34:1475-1481(1995). RN [60] RP VARIANTS XLA SER-25; TRP-288; MET-370; VAL-509; PRO-525; LYS-526; TRP-562; RP VAL-582 AND ARG-594. RX PubMed=7711734; DOI=10.1093/hmg/4.1.51; RA Vorechovsky I., Vihinen M., de Saint Basile G., Honsova S., RA Hammarstroem L., Mueller S., Nilsson L., Fischer A., Smith C.I.E.; RT "DNA-based mutation analysis of Bruton's tyrosine kinase gene in patients RT with X-linked agammaglobulinaemia."; RL Hum. Mol. Genet. 4:51-58(1995). RN [61] RP VARIANTS XLA LYS-567; LEU-587 AND HIS-641. RX PubMed=7633420; DOI=10.1093/hmg/4.4.693; RA Jin H., Webster A.D.B., Vihinen M., Sideras P., Vorechovsky I., RA Hammarstroem L., Bernatowska-Matuszkiewicz E., Smith C.I.E., Bobrow M., RA Vetrie D.; RT "Identification of Btk mutations in 20 unrelated patients with X-linked RT agammaglobulinaemia (XLA)."; RL Hum. Mol. Genet. 4:693-700(1995). RN [62] RP VARIANTS XLA PRO-33; GLY-302 DEL; GLN-520 AND CYS-641. RX PubMed=7633429; DOI=10.1093/hmg/4.4.755; RA Gaspar H.B., Bradley L.A.D., Katz F., Lovering R.C., Roifman C.M., RA Morgan G., Levinsky R.J., Kinnon C.; RT "Mutation analysis in Bruton's tyrosine kinase, the X-linked RT agammaglobulinaemia gene, including identification of an insertional RT hotspot."; RL Hum. Mol. Genet. 4:755-757(1995). RN [63] RP VARIANTS XLA ASN-429 AND ARG-477. RX PubMed=8634718; DOI=10.1093/hmg/4.12.2403; RA Vorechovsky I., Luo L., de Saint Basile G., Hammarstroem L., RA Webster A.D.B., Smith C.I.E.; RT "Improved oligonucleotide primer set for molecular diagnosis of X-linked RT agammaglobulinaemia: predominance of amino acid substitutions in the RT catalytic domain of Bruton's tyrosine kinase."; RL Hum. Mol. Genet. 4:2403-2405(1995). RN [64] RP VARIANTS XLA GLU-302 AND ASP-476. RX PubMed=7627183; DOI=10.1002/humu.1380050405; RA Hagemann T.L., Rosen F.S., Kwan S.-P.; RT "Characterization of germline mutations of the gene encoding Bruton's RT tyrosine kinase in families with X-linked agammaglobulinemia."; RL Hum. Mutat. 5:296-302(1995). RN [65] RP VARIANT XLA PHE-358. RX PubMed=7897635; DOI=10.1136/jmg.32.1.77; RA Ohashi Y., Tsuchiya S., Konno T.; RT "A new point mutation involving a highly conserved leucine in the Btk SH2 RT domain in a family with X linked agammaglobulinaemia."; RL J. Med. Genet. 32:77-79(1995). RN [66] RP VARIANT XLA PRO-295. RX PubMed=8723128; RX DOI=10.1002/(sici)1096-8628(19960503)63:1<318::aid-ajmg53>3.0.co;2-n; RA Schuster V., Seidenspinner S., Kreth H.W.; RT "Detection of a novel mutation in the SRC homology domain 2 (SH2) of RT Bruton's tyrosine kinase and direct female carrier evaluation in a family RT with X-linked agammaglobulinemia."; RL Am. J. Med. Genet. 63:318-322(1996). RN [67] RP VARIANTS XLA ARG-12; PRO-28; GLU-302; TRP-502; HIS-521; TYR-633 AND RP SER-644. RX PubMed=8695804; RA Hashimoto S., Tsukada S., Matsushita M., Miyawaki T., Niida Y., Yachie A., RA Kobayashi S., Iwata T., Hayakawa H., Matsuoka H., Tsuge I., Yamadori T., RA Kunikata T., Arai S., Yoshizaki K., Taniguchi N., Kishimoto T.; RT "Identification of Bruton's tyrosine kinase (Btk) gene mutations and RT characterization of the derived proteins in 35 X-linked agammaglobulinemia RT families: a nationwide study of Btk deficiency in Japan."; RL Blood 88:561-573(1996). RN [68] RP VARIANTS XLA TRP-288; LYS-544 AND PRO-592. RX PubMed=8834236; DOI=10.1007/s004390050066; RA Kobayashi S., Iwata T., Saito M., Iwasaki R., Matsumoto H., Naritaka S., RA Kono Y., Hayashi Y.; RT "Mutations of the Btk gene in 12 unrelated families with X-linked RT agammaglobulinemia in Japan."; RL Hum. Genet. 97:424-430(1996). RN [69] RP VARIANTS XLA SER-154 AND ARG-155. RX PubMed=9280283; DOI=10.1016/s0014-5793(97)00912-5; RA Vihinen M., Nore B., Mattsson P.T., Backesj C.-M., Nars M., Koutaniemi S., RA Watanabe C., Lester T., Jones A.M., Ochs H.D., Smith C.I.E.; RT "Missense mutations affecting a conserved cysteine pair in the TH domain of RT Btk."; RL FEBS Lett. 413:205-210(1997). RN [70] RP VARIANTS XLA. RX PubMed=9260159; DOI=10.1007/bf03401694; RA Saha B.K., Curtis S.K., Vogler L.B., Vihinen M.; RT "Molecular and structural characterization of five novel mutations in the RT Bruton's tyrosine kinase gene from patients with X-linked RT agammaglobulinemia."; RL Mol. Med. 3:477-485(1997). RN [71] RP VARIANTS XLA GLN-288; THR-307; ARG-430; ASP-445; GLY-525; PHE-535; LEU-563 RP AND PRO-622. RX PubMed=9545398; DOI=10.1086/301828; RA Conley M.E., Mathias D., Treadaway J., Minegishi Y., Rohrer J.; RT "Mutations in btk in patients with presumed X-linked agammaglobulinemia."; RL Am. J. Hum. Genet. 62:1034-1043(1998). RN [72] RP VARIANTS XLA GLU-19; HIS-28; ASN-61; PRO-117; HIS-127; ARG-155; PRO-295; RP PHE-369; GLY-372; ARG-414; TYR-506; GLY-521; GLN-525; SER-559; TRP-562; RP GLU-594; THR-619; GLY-626 AND HIS-641. RX PubMed=9445504; DOI=10.1542/peds.101.2.276; RA Holinski-Feder E., Weiss M., Brandau O., Jedele K.B., Nore B., RA Baeckesjoe C.-M., Vihinen M., Hubbard S.R., Belohradsky B.H., Smith C.I.E., RA Meindl A.; RT "Mutation screening of the BTK gene in 56 families with X-linked RT agammaglobulinemia (XLA): 47 unique mutations without correlation to RT clinical course."; RL Pediatrics 101:276-284(1998). RN [73] RP VARIANTS XLA. RX PubMed=10220140; RX DOI=10.1002/(sici)1098-1004(1999)13:4<280::aid-humu3>3.0.co;2-l; RA Vihinen M., Kwan S.-P., Lester T., Ochs H.D., Resnick I., Vaeliaho J., RA Conley M.E., Smith C.I.E.; RT "Mutations of the human BTK gene coding for Bruton tyrosine kinase in X- RT linked agammaglobulinemia."; RL Hum. Mutat. 13:280-285(1999). RN [74] RP VARIANT XLA PRO-562. RX PubMed=10678660; RX DOI=10.1002/(sici)1096-8628(20000131)90:3<229::aid-ajmg8>3.0.co;2-q; RA Curtis S.K., Hebert M.D., Saha B.K.; RT "Twin carriers of X-linked agammaglobulinemia (XLA) due to germline RT mutation in the Btk gene."; RL Am. J. Med. Genet. 90:229-232(2000). RN [75] RP VARIANTS XLA SER-39; PRO-512; GLN-512; GLY-544; TYR-578 AND LYS-589. RX PubMed=10612838; RX DOI=10.1002/(sici)1098-1004(200001)15:1<117::aid-humu26>3.0.co;2-h; RA Orlandi P., Ritis K., Moschese V., Angelini F., Arvanitidis K., RA Speletas M., Sideras P., Plebani A., Rossi P.; RT "Identification of nine novel mutations in the Bruton's tyrosine kinase RT gene in X-linked agammaglobulinaemia patients."; RL Hum. Mutat. 15:117-117(2000). RN [76] RP VARIANTS [LARGE SCALE ANALYSIS] LYS-82 AND LYS-190. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [77] RP VARIANT SER-481, AND CHARACTERIZATION OF VARIANT SER-481. RX PubMed=24869598; DOI=10.1056/nejmoa1400029; RA Woyach J.A., Furman R.R., Liu T.M., Ozer H.G., Zapatka M., Ruppert A.S., RA Xue L., Li D.H., Steggerda S.M., Versele M., Dave S.S., Zhang J., RA Yilmaz A.S., Jaglowski S.M., Blum K.A., Lozanski A., Lozanski G., RA James D.F., Barrientos J.C., Lichter P., Stilgenbauer S., Buggy J.J., RA Chang B.Y., Johnson A.J., Byrd J.C.; RT "Resistance mechanisms for the Bruton's tyrosine kinase inhibitor RT ibrutinib."; RL N. Engl. J. Med. 370:2286-2294(2014). RN [78] RP CHARACTERIZATION OF VARIANT SER-481. RX PubMed=24869597; DOI=10.1056/nejmc1402716; RA Furman R.R., Cheng S., Lu P., Setty M., Perez A.R., Perez A.R., Guo A., RA Racchumi J., Xu G., Wu H., Ma J., Steggerda S.M., Coleman M., Leslie C., RA Wang Y.L.; RT "Ibrutinib resistance in chronic lymphocytic leukemia."; RL N. Engl. J. Med. 370:2352-2354(2014). RN [79] RP CHARACTERIZATION OF VARIANT SER-481. RX PubMed=25189416; DOI=10.1038/leu.2014.263; RA Cheng S., Guo A., Lu P., Ma J., Coleman M., Wang Y.L.; RT "Functional characterization of BTK(C481S) mutation that confers ibrutinib RT resistance: exploration of alternative kinase inhibitors."; RL Leukemia 29:895-900(2015). CC -!- FUNCTION: Non-receptor tyrosine kinase indispensable for B lymphocyte CC development, differentiation and signaling (PubMed:19290921). Binding CC of antigen to the B-cell antigen receptor (BCR) triggers signaling that CC ultimately leads to B-cell activation (PubMed:19290921). After BCR CC engagement and activation at the plasma membrane, phosphorylates PLCG2 CC at several sites, igniting the downstream signaling pathway through CC calcium mobilization, followed by activation of the protein kinase C CC (PKC) family members (PubMed:11606584). PLCG2 phosphorylation is CC performed in close cooperation with the adapter protein B-cell linker CC protein BLNK (PubMed:11606584). BTK acts as a platform to bring CC together a diverse array of signaling proteins and is implicated in CC cytokine receptor signaling pathways (PubMed:16517732, CC PubMed:17932028). Plays an important role in the function of immune CC cells of innate as well as adaptive immunity, as a component of the CC Toll-like receptors (TLR) pathway (PubMed:16517732). The TLR pathway CC acts as a primary surveillance system for the detection of pathogens CC and are crucial to the activation of host defense (PubMed:16517732). CC Especially, is a critical molecule in regulating TLR9 activation in CC splenic B-cells (PubMed:16517732, PubMed:17932028). Within the TLR CC pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP CC degradation (PubMed:16415872). BTK also plays a critical role in CC transcription regulation (PubMed:19290921). Induces the activity of NF- CC kappa-B, which is involved in regulating the expression of hundreds of CC genes (PubMed:19290921). BTK is involved on the signaling pathway CC linking TLR8 and TLR9 to NF-kappa-B (PubMed:19290921). Acts as an CC activator of NLRP3 inflammasome assembly by mediating phosphorylation CC of NLRP3 (PubMed:34554188). Transiently phosphorylates transcription CC factor GTF2I on tyrosine residues in response to BCR (PubMed:9012831). CC GTF2I then translocates to the nucleus to bind regulatory enhancer CC elements to modulate gene expression (PubMed:9012831). ARID3A and NFAT CC are other transcriptional target of BTK (PubMed:16738337). BTK is CC required for the formation of functional ARID3A DNA-binding complexes CC (PubMed:16738337). There is however no evidence that BTK itself binds CC directly to DNA (PubMed:16738337). BTK has a dual role in the CC regulation of apoptosis (PubMed:9751072). {ECO:0000269|PubMed:11606584, CC ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16517732, CC ECO:0000269|PubMed:16738337, ECO:0000269|PubMed:17932028, CC ECO:0000269|PubMed:34554188, ECO:0000269|PubMed:9012831, CC ECO:0000303|PubMed:19290921, ECO:0000303|PubMed:9751072}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, CC ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:34554188}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:10196129, ECO:0000269|PubMed:9218782, CC ECO:0000269|Ref.48}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:10196129, CC ECO:0000269|PubMed:9218782, ECO:0000269|Ref.48}; CC -!- ACTIVITY REGULATION: Activated by phosphorylation. In primary B CC lymphocytes, is almost always non-phosphorylated and is thus CC catalytically inactive. Stimulation of TLR8 and TLR9 causes BTK CC activation. As a negative feedback mechanism to fine-tune BCR CC signaling, activated PRKCB down-modulates BTK function via direct CC phosphorylation of BTK at Ser-180, resulting in translocation of BTK CC back to the cytoplasmic fraction. PIN1, SH3BP5, and IBTK were also CC identified as BTK activity inhibitors. Interaction with CAV1 leads to CC dramatic down-regulation of the kinase activity of BTK. LFM-13A is a CC specific inhibitor of BTK. Dasatinib, a cancer drug acting as a CC tyrosine kinase inhibitor, also blocks BTK activity. CC {ECO:0000269|PubMed:10339589, ECO:0000269|PubMed:11577348, CC ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:11751885, CC ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16644721, CC ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:8630736}. CC -!- SUBUNIT: Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, CC GAB2, TEC and BTK; complex formation increases in the presence of CC TNFSF11/RANKL (By similarity). Binds GTF2I through the PH domain. CC Interacts with SH3BP5 via the SH3 domain. Interacts with IBTK via its CC PH domain. Interacts with ARID3A, CAV1, FASLG, PIN1, TLR8 and TLR9. CC {ECO:0000250|UniProtKB:P35991, ECO:0000269|PubMed:10196129, CC ECO:0000269|PubMed:10339589, ECO:0000269|PubMed:11577348, CC ECO:0000269|PubMed:11751885, ECO:0000269|PubMed:16644721, CC ECO:0000269|PubMed:16738337, ECO:0000269|PubMed:17932028, CC ECO:0000269|PubMed:19807924, ECO:0000269|PubMed:20052711, CC ECO:0000269|PubMed:21280133, ECO:0000269|PubMed:9218782, CC ECO:0000269|PubMed:9571151, ECO:0000269|Ref.47, ECO:0000269|Ref.48}. CC -!- INTERACTION: CC Q06187; Q13444: ADAM15; NbExp=2; IntAct=EBI-624835, EBI-77818; CC Q06187; Q99856: ARID3A; NbExp=3; IntAct=EBI-624835, EBI-5458244; CC Q06187; Q8WV28: BLNK; NbExp=2; IntAct=EBI-624835, EBI-2623522; CC Q06187; Q06187: BTK; NbExp=2; IntAct=EBI-624835, EBI-624835; CC Q06187; P78347: GTF2I; NbExp=6; IntAct=EBI-624835, EBI-359622; CC Q06187; P08238: HSP90AB1; NbExp=2; IntAct=EBI-624835, EBI-352572; CC Q06187; P21145: MAL; NbExp=5; IntAct=EBI-624835, EBI-3932027; CC Q06187; P50222: MEOX2; NbExp=3; IntAct=EBI-624835, EBI-748397; CC Q06187; Q04759: PRKCQ; NbExp=2; IntAct=EBI-624835, EBI-374762; CC Q06187; O60239: SH3BP5; NbExp=4; IntAct=EBI-624835, EBI-624860; CC Q06187; P42768: WAS; NbExp=4; IntAct=EBI-624835, EBI-346375; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11016936}. Cell CC membrane {ECO:0000269|PubMed:10196179, ECO:0000269|PubMed:10602036}; CC Peripheral membrane protein {ECO:0000269|PubMed:10196179, CC ECO:0000269|PubMed:10602036}. Nucleus {ECO:0000269|PubMed:11016936}. CC Membrane raft {ECO:0000250|UniProtKB:P35991}. Note=In steady state, BTK CC is predominantly cytosolic. Following B-cell receptor (BCR) engagement CC by antigen, translocates to the plasma membrane through its PH domain. CC Plasma membrane localization is a critical step in the activation of CC BTK. A fraction of BTK also shuttles between the nucleus and the CC cytoplasm, and nuclear export is mediated by the nuclear export CC receptor CRM1. {ECO:0000303|PubMed:19290921}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage; Named isoforms=2; CC Name=BTK-A; CC IsoId=Q06187-1; Sequence=Displayed; CC Name=BTK-C; CC IsoId=Q06187-2; Sequence=VSP_053838; CC -!- TISSUE SPECIFICITY: Predominantly expressed in B-lymphocytes. CC -!- DOMAIN: The PH domain mediates the binding to inositol polyphosphate CC and phosphoinositides, leading to its targeting to the plasma membrane. CC It is extended in the BTK kinase family by a region designated the TH CC (Tec homology) domain, which consists of about 80 residues preceding CC the SH3 domain. {ECO:0000269|PubMed:10196129, CC ECO:0000269|PubMed:10196179, ECO:0000269|PubMed:11751885, CC ECO:0000269|PubMed:8070576}. CC -!- PTM: Following B-cell receptor (BCR) engagement, translocates to the CC plasma membrane where it gets phosphorylated at Tyr-551 by LYN and SYK. CC Phosphorylation at Tyr-551 is followed by autophosphorylation of Tyr- CC 223 which may create a docking site for a SH2 containing protein. CC Phosphorylation at Ser-180 by PRKCB, leads in translocation of BTK back CC to the cytoplasmic fraction. Phosphorylation at Ser-21 and Ser-115 CC creates a binding site for PIN1 at these Ser-Pro motifs, and promotes CC it's recruitment. {ECO:0000269|PubMed:11598012, CC ECO:0000269|PubMed:12573241, ECO:0000269|PubMed:15375214, CC ECO:0000269|PubMed:16644721, ECO:0000269|PubMed:17932028, CC ECO:0000269|PubMed:8630736, ECO:0000269|PubMed:9012831}. CC -!- DISEASE: X-linked agammaglobulinemia (XLA) [MIM:300755]: Humoral CC immunodeficiency disease which results in developmental defects in the CC maturation pathway of B-cells. Affected boys have normal levels of pre- CC B-cells in their bone marrow but virtually no circulating mature B- CC lymphocytes. This results in a lack of immunoglobulins of all classes CC and leads to recurrent bacterial infections like otitis, CC conjunctivitis, dermatitis, sinusitis in the first few years of life, CC or even some patients present overwhelming sepsis or meningitis, CC resulting in death in a few hours. Treatment in most cases is by CC infusion of intravenous immunoglobulin. {ECO:0000269|PubMed:10220140, CC ECO:0000269|PubMed:10612838, ECO:0000269|PubMed:10678660, CC ECO:0000269|PubMed:7627183, ECO:0000269|PubMed:7633420, CC ECO:0000269|PubMed:7633429, ECO:0000269|PubMed:7711734, CC ECO:0000269|PubMed:7809124, ECO:0000269|PubMed:7849006, CC ECO:0000269|PubMed:7849697, ECO:0000269|PubMed:7849721, CC ECO:0000269|PubMed:7880320, ECO:0000269|PubMed:7897635, CC ECO:0000269|PubMed:8013627, ECO:0000269|PubMed:8162018, CC ECO:0000269|PubMed:8162056, ECO:0000269|PubMed:8594569, CC ECO:0000269|PubMed:8634718, ECO:0000269|PubMed:8695804, CC ECO:0000269|PubMed:8723128, ECO:0000269|PubMed:8834236, CC ECO:0000269|PubMed:9016530, ECO:0000269|PubMed:9260159, CC ECO:0000269|PubMed:9280283, ECO:0000269|PubMed:9445504, CC ECO:0000269|PubMed:9545398}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Growth hormone deficiency, isolated, 3, with CC agammaglobulinemia (IGHD3) [MIM:307200]: An X-linked recessive disorder CC characterized by growth hormone deficiency, short stature, delayed bone CC age, agammaglobulinemia with markedly reduced numbers of B cells, and CC good response to treatment with growth hormone. CC {ECO:0000269|PubMed:8013627}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform BTK-C]: Produced by alternative promoter usage. CC Predominant form in many tumor cells where it may function as an anti- CC apoptotic cell survival factor. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. TEC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/851/BTK"; CC -!- WEB RESOURCE: Name=BTKbase; Note=BTK mutation db; CC URL="http://structure.bmc.lu.se/idbase/BTKbase/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X58957; CAA41728.1; -; mRNA. DR EMBL; U10087; AAB60639.1; -; Genomic_DNA. DR EMBL; U10084; AAB60639.1; JOINED; Genomic_DNA. DR EMBL; U10085; AAB60639.1; JOINED; Genomic_DNA. DR EMBL; U10086; AAB60639.1; JOINED; Genomic_DNA. DR EMBL; L31572; AAA61479.1; -; Genomic_DNA. DR EMBL; L31557; AAA61479.1; JOINED; Genomic_DNA. DR EMBL; L31558; AAA61479.1; JOINED; Genomic_DNA. DR EMBL; L31559; AAA61479.1; JOINED; Genomic_DNA. DR EMBL; L31561; AAA61479.1; JOINED; Genomic_DNA. DR EMBL; L31563; AAA61479.1; JOINED; Genomic_DNA. DR EMBL; L31564; AAA61479.1; JOINED; Genomic_DNA. DR EMBL; L31565; AAA61479.1; JOINED; Genomic_DNA. DR EMBL; L31566; AAA61479.1; JOINED; Genomic_DNA. DR EMBL; L31567; AAA61479.1; JOINED; Genomic_DNA. DR EMBL; L31568; AAA61479.1; JOINED; Genomic_DNA. DR EMBL; L31569; AAA61479.1; JOINED; Genomic_DNA. DR EMBL; L31570; AAA61479.1; JOINED; Genomic_DNA. DR EMBL; L31571; AAA61479.1; JOINED; Genomic_DNA. DR EMBL; U13433; AAC51347.1; -; Genomic_DNA. DR EMBL; U13410; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13412; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13413; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13414; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13415; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13416; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13417; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13422; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13423; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13424; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13425; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13427; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13428; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13429; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13430; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13431; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U13432; AAC51347.1; JOINED; Genomic_DNA. DR EMBL; U78027; AAB64205.1; -; Genomic_DNA. DR EMBL; AK314382; BAG37008.1; -; mRNA. DR EMBL; AL035422; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC109079; AAI09080.1; -; mRNA. DR EMBL; BC109080; AAI09081.1; -; mRNA. DR CCDS; CCDS14482.1; -. [Q06187-1] DR CCDS; CCDS76003.1; -. [Q06187-2] DR PIR; I37212; A45184. DR RefSeq; NP_000052.1; NM_000061.2. [Q06187-1] DR RefSeq; NP_001274273.1; NM_001287344.1. [Q06187-2] DR RefSeq; NP_001274274.1; NM_001287345.1. DR PDB; 1AWW; NMR; -; A=212-275. DR PDB; 1AWX; NMR; -; A=212-275. DR PDB; 1B55; X-ray; 2.40 A; A/B=2-170. DR PDB; 1BTK; X-ray; 1.60 A; A/B=2-170. DR PDB; 1BWN; X-ray; 2.10 A; A/B=2-170. DR PDB; 1K2P; X-ray; 2.10 A; A/B=397-659. DR PDB; 1QLY; NMR; -; A=216-273. DR PDB; 2GE9; NMR; -; A=270-387. DR PDB; 2Z0P; X-ray; 2.58 A; A/B/C/D=2-170. DR PDB; 3GEN; X-ray; 1.60 A; A=382-659. DR PDB; 3K54; X-ray; 1.94 A; A=382-659. DR PDB; 3OCS; X-ray; 1.80 A; A=393-656. DR PDB; 3OCT; X-ray; 1.95 A; A=393-656. DR PDB; 3P08; X-ray; 2.30 A; A/B=393-659. DR PDB; 3PIX; X-ray; 1.85 A; A=387-659. DR PDB; 3PIY; X-ray; 2.55 A; A=387-659. DR PDB; 3PIZ; X-ray; 2.21 A; A=387-659. DR PDB; 3PJ1; X-ray; 2.00 A; A=387-659. DR PDB; 3PJ2; X-ray; 1.75 A; A=387-659. DR PDB; 3PJ3; X-ray; 1.85 A; A=387-659. DR PDB; 4NWM; X-ray; 2.03 A; A/B=396-657. DR PDB; 4OT5; X-ray; 1.55 A; A=378-659. DR PDB; 4OT6; X-ray; 2.05 A; A=378-659. DR PDB; 4OTF; X-ray; 1.95 A; A=393-657. DR PDB; 4OTQ; X-ray; 1.55 A; A=378-659. DR PDB; 4OTR; X-ray; 1.95 A; A=378-659. DR PDB; 4RFY; X-ray; 1.70 A; A=378-659. DR PDB; 4RFZ; X-ray; 1.17 A; A=378-659. DR PDB; 4RG0; X-ray; 2.50 A; A=378-659. DR PDB; 4RX5; X-ray; 1.36 A; A=393-657. DR PDB; 4YHF; X-ray; 2.20 A; A/B=382-659. DR PDB; 4Z3V; X-ray; 1.60 A; A=382-659. DR PDB; 4ZLY; X-ray; 1.65 A; A=389-658. DR PDB; 4ZLZ; X-ray; 2.00 A; A=389-658. DR PDB; 5BPY; X-ray; 2.31 A; A/B=396-659. DR PDB; 5BQ0; X-ray; 1.57 A; A=382-659. DR PDB; 5FBN; X-ray; 1.80 A; C/D=389-659. DR PDB; 5FBO; X-ray; 1.89 A; A=389-659. DR PDB; 5J87; X-ray; 1.59 A; A/B/C/D=385-658. DR PDB; 5JRS; X-ray; 1.97 A; A/B=396-659. DR PDB; 5KUP; X-ray; 1.39 A; A=393-657. DR PDB; 5P9F; X-ray; 1.71 A; A=382-659. DR PDB; 5P9G; X-ray; 1.75 A; A=382-659. DR PDB; 5P9H; X-ray; 1.95 A; A=382-659. DR PDB; 5P9I; X-ray; 1.11 A; A=382-659. DR PDB; 5P9J; X-ray; 1.08 A; A=382-659. DR PDB; 5P9K; X-ray; 1.28 A; A=382-659. DR PDB; 5P9L; X-ray; 1.25 A; A=382-659. DR PDB; 5P9M; X-ray; 1.41 A; A=382-659. DR PDB; 5T18; X-ray; 1.50 A; A=396-659. DR PDB; 5U9D; X-ray; 1.33 A; A=389-659. DR PDB; 5VFI; X-ray; 1.59 A; A=389-659. DR PDB; 5VGO; X-ray; 1.62 A; A=393-657. DR PDB; 5XYZ; X-ray; 2.64 A; A/B=393-656. DR PDB; 5ZZ4; X-ray; 2.90 A; A/B/C/D/E/F=393-656. DR PDB; 6AUA; X-ray; 1.66 A; A=394-656. DR PDB; 6AUB; X-ray; 1.65 A; A=395-657. DR PDB; 6BIK; X-ray; 1.90 A; A=392-657. DR PDB; 6BKE; X-ray; 1.95 A; A=392-657. DR PDB; 6BKH; X-ray; 1.79 A; A=392-657. DR PDB; 6BKW; X-ray; 1.50 A; A=392-657. DR PDB; 6BLN; X-ray; 1.30 A; A=392-657. DR PDB; 6DI0; X-ray; 1.30 A; A=389-659. DR PDB; 6DI1; X-ray; 1.10 A; A=389-659. DR PDB; 6DI3; X-ray; 2.00 A; A=389-659. DR PDB; 6DI5; X-ray; 1.42 A; A=389-659. DR PDB; 6DI9; X-ray; 1.25 A; A=389-659. DR PDB; 6E4F; X-ray; 1.15 A; A=387-659. DR PDB; 6EP9; X-ray; 2.01 A; A=378-659. DR PDB; 6HRP; X-ray; 1.12 A; A=378-659. DR PDB; 6HRT; X-ray; 1.36 A; A=378-659. DR PDB; 6HTF; X-ray; 2.10 A; A=271-383. DR PDB; 6J6M; X-ray; 1.25 A; A=393-659. DR PDB; 6N9P; X-ray; 2.23 A; A=389-659. DR PDB; 6NFH; X-ray; 1.40 A; A=389-659. DR PDB; 6NFI; X-ray; 2.41 A; A=392-659. DR PDB; 6NZM; X-ray; 1.72 A; A/D=382-659. DR PDB; 6O8I; X-ray; 1.42 A; A=391-659. DR PDB; 6OMU; X-ray; 1.41 A; A=389-659. DR PDB; 6S90; X-ray; 1.82 A; A/B=393-658. DR PDB; 6TFP; X-ray; 2.00 A; A/B/C/D/E=385-659. DR PDB; 6TSE; X-ray; 1.41 A; A/B=2-170. DR PDB; 6TT2; X-ray; 1.36 A; A/B=2-170. DR PDB; 6TUH; X-ray; 2.25 A; A/B/C/D=2-170. DR PDB; 6TVN; X-ray; 2.31 A; A/B/C/D=2-170. DR PDB; 6VXQ; X-ray; 1.40 A; A=371-659. DR PDB; 6W06; X-ray; 1.55 A; A=371-659. DR PDB; 6W07; X-ray; 1.51 A; A=371-659. DR PDB; 6W7O; X-ray; 2.17 A; A/B=384-659. DR PDB; 6W8I; X-ray; 3.80 A; A/B/C=384-659. DR PDB; 6X3N; X-ray; 1.95 A; A=389-659. DR PDB; 6X3O; X-ray; 1.90 A; A/B=389-659. DR PDB; 6X3P; X-ray; 1.34 A; A=389-659. DR PDB; 6XE4; X-ray; 1.60 A; A=393-657. DR PDB; 6YYF; X-ray; 1.93 A; A/B=2-170. DR PDB; 6YYG; X-ray; 1.95 A; A/B/C/D=2-170. DR PDB; 6YYK; X-ray; 2.04 A; A/B=2-170. DR PDB; 7KXL; X-ray; 1.84 A; A=392-659. DR PDB; 7KXM; X-ray; 1.33 A; A=389-659. DR PDB; 7KXN; X-ray; 1.34 A; A=393-659. DR PDB; 7KXO; X-ray; 1.94 A; A=393-659. DR PDB; 7KXP; X-ray; 1.83 A; A=389-659. DR PDB; 7KXQ; X-ray; 1.38 A; A=390-659. DR PDB; 7L5O; X-ray; 1.21 A; A=389-659. DR PDB; 7L5P; X-ray; 2.14 A; A/B=389-659. DR PDB; 7LTY; X-ray; 1.69 A; A=393-659. DR PDB; 7LTZ; X-ray; 1.53 A; A=393-659. DR PDB; 7N4Q; X-ray; 1.50 A; A=391-659. DR PDB; 7N4R; X-ray; 1.62 A; A=391-659. DR PDB; 7N4S; X-ray; 2.05 A; A=391-659. DR PDB; 7N5O; X-ray; 1.25 A; A=382-659. DR PDB; 7N5R; X-ray; 1.55 A; A=382-659. DR PDB; 7N5X; X-ray; 1.60 A; A=382-659. DR PDB; 7N5Y; X-ray; 1.85 A; A=382-659. DR PDB; 7R60; X-ray; 1.94 A; A=389-659. DR PDB; 7R61; X-ray; 1.52 A; A=390-659. DR PDB; 7YC9; X-ray; 1.40 A; A=393-659. DR PDB; 8DSO; X-ray; 2.33 A; B=384-659. DR PDB; 8E2M; X-ray; 1.90 A; A=389-659. DR PDB; 8EJB; X-ray; 1.58 A; A=389-658. DR PDB; 8FLG; X-ray; 2.20 A; A=371-659. DR PDB; 8FLH; X-ray; 1.55 A; A=382-659. DR PDB; 8FLL; X-ray; 1.50 A; A=389-659. DR PDB; 8FLN; X-ray; 1.33 A; A=389-659. DR PDB; 8FLV; X-ray; 1.30 A; A=382-659. DR PDBsum; 1AWW; -. DR PDBsum; 1AWX; -. DR PDBsum; 1B55; -. DR PDBsum; 1BTK; -. DR PDBsum; 1BWN; -. DR PDBsum; 1K2P; -. DR PDBsum; 1QLY; -. DR PDBsum; 2GE9; -. DR PDBsum; 2Z0P; -. DR PDBsum; 3GEN; -. DR PDBsum; 3K54; -. DR PDBsum; 3OCS; -. DR PDBsum; 3OCT; -. DR PDBsum; 3P08; -. DR PDBsum; 3PIX; -. DR PDBsum; 3PIY; -. DR PDBsum; 3PIZ; -. DR PDBsum; 3PJ1; -. DR PDBsum; 3PJ2; -. DR PDBsum; 3PJ3; -. DR PDBsum; 4NWM; -. DR PDBsum; 4OT5; -. DR PDBsum; 4OT6; -. DR PDBsum; 4OTF; -. DR PDBsum; 4OTQ; -. DR PDBsum; 4OTR; -. DR PDBsum; 4RFY; -. DR PDBsum; 4RFZ; -. DR PDBsum; 4RG0; -. DR PDBsum; 4RX5; -. DR PDBsum; 4YHF; -. DR PDBsum; 4Z3V; -. DR PDBsum; 4ZLY; -. DR PDBsum; 4ZLZ; -. DR PDBsum; 5BPY; -. DR PDBsum; 5BQ0; -. DR PDBsum; 5FBN; -. DR PDBsum; 5FBO; -. DR PDBsum; 5J87; -. DR PDBsum; 5JRS; -. DR PDBsum; 5KUP; -. DR PDBsum; 5P9F; -. DR PDBsum; 5P9G; -. DR PDBsum; 5P9H; -. DR PDBsum; 5P9I; -. DR PDBsum; 5P9J; -. DR PDBsum; 5P9K; -. DR PDBsum; 5P9L; -. DR PDBsum; 5P9M; -. DR PDBsum; 5T18; -. DR PDBsum; 5U9D; -. DR PDBsum; 5VFI; -. DR PDBsum; 5VGO; -. DR PDBsum; 5XYZ; -. DR PDBsum; 5ZZ4; -. DR PDBsum; 6AUA; -. DR PDBsum; 6AUB; -. DR PDBsum; 6BIK; -. DR PDBsum; 6BKE; -. DR PDBsum; 6BKH; -. DR PDBsum; 6BKW; -. DR PDBsum; 6BLN; -. DR PDBsum; 6DI0; -. DR PDBsum; 6DI1; -. DR PDBsum; 6DI3; -. DR PDBsum; 6DI5; -. DR PDBsum; 6DI9; -. DR PDBsum; 6E4F; -. DR PDBsum; 6EP9; -. DR PDBsum; 6HRP; -. DR PDBsum; 6HRT; -. DR PDBsum; 6HTF; -. DR PDBsum; 6J6M; -. DR PDBsum; 6N9P; -. DR PDBsum; 6NFH; -. DR PDBsum; 6NFI; -. DR PDBsum; 6NZM; -. DR PDBsum; 6O8I; -. DR PDBsum; 6OMU; -. DR PDBsum; 6S90; -. DR PDBsum; 6TFP; -. DR PDBsum; 6TSE; -. DR PDBsum; 6TT2; -. DR PDBsum; 6TUH; -. DR PDBsum; 6TVN; -. DR PDBsum; 6VXQ; -. DR PDBsum; 6W06; -. DR PDBsum; 6W07; -. DR PDBsum; 6W7O; -. DR PDBsum; 6W8I; -. DR PDBsum; 6X3N; -. DR PDBsum; 6X3O; -. DR PDBsum; 6X3P; -. DR PDBsum; 6XE4; -. DR PDBsum; 6YYF; -. DR PDBsum; 6YYG; -. DR PDBsum; 6YYK; -. DR PDBsum; 7KXL; -. DR PDBsum; 7KXM; -. DR PDBsum; 7KXN; -. DR PDBsum; 7KXO; -. DR PDBsum; 7KXP; -. DR PDBsum; 7KXQ; -. DR PDBsum; 7L5O; -. DR PDBsum; 7L5P; -. DR PDBsum; 7LTY; -. DR PDBsum; 7LTZ; -. DR PDBsum; 7N4Q; -. DR PDBsum; 7N4R; -. DR PDBsum; 7N4S; -. DR PDBsum; 7N5O; -. DR PDBsum; 7N5R; -. DR PDBsum; 7N5X; -. DR PDBsum; 7N5Y; -. DR PDBsum; 7R60; -. DR PDBsum; 7R61; -. DR PDBsum; 7YC9; -. DR PDBsum; 8DSO; -. DR PDBsum; 8E2M; -. DR PDBsum; 8EJB; -. DR PDBsum; 8FLG; -. DR PDBsum; 8FLH; -. DR PDBsum; 8FLL; -. DR PDBsum; 8FLN; -. DR PDBsum; 8FLV; -. DR AlphaFoldDB; Q06187; -. DR BMRB; Q06187; -. DR SASBDB; Q06187; -. DR SMR; Q06187; -. DR BioGRID; 107160; 105. DR CORUM; Q06187; -. DR DIP; DIP-34071N; -. DR ELM; Q06187; -. DR IntAct; Q06187; 62. DR MINT; Q06187; -. DR STRING; 9606.ENSP00000483570; -. DR BindingDB; Q06187; -. DR ChEMBL; CHEMBL5251; -. DR DrugBank; DB15327; Abivertinib. DR DrugBank; DB11703; Acalabrutinib. DR DrugBank; DB15347; Branebrutinib. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB15170; Evobrutinib. DR DrugBank; DB14785; Fenebrutinib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB09053; Ibrutinib. DR DrugBank; DB01863; Inositol 1,3,4,5-Tetrakisphosphate. DR DrugBank; DB11764; Spebrutinib. DR DrugBank; DB15227; Tirabrutinib. DR DrugBank; DB16657; Vecabrutinib. DR DrugBank; DB05204; XL418. DR DrugBank; DB15035; Zanubrutinib. DR DrugCentral; Q06187; -. DR GuidetoPHARMACOLOGY; 1948; -. DR GlyGen; Q06187; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q06187; -. DR PhosphoSitePlus; Q06187; -. DR BioMuta; BTK; -. DR DMDM; 547759; -. DR CPTAC; CPTAC-2855; -. DR CPTAC; CPTAC-2856; -. DR EPD; Q06187; -. DR jPOST; Q06187; -. DR MassIVE; Q06187; -. DR MaxQB; Q06187; -. DR PaxDb; 9606-ENSP00000483570; -. DR PeptideAtlas; Q06187; -. DR ProteomicsDB; 58419; -. [Q06187-1] DR Pumba; Q06187; -. DR ABCD; Q06187; 7 sequenced antibodies. DR Antibodypedia; 699; 1510 antibodies from 47 providers. DR CPTC; Q06187; 1 antibody. DR DNASU; 695; -. DR Ensembl; ENST00000308731.8; ENSP00000308176.8; ENSG00000010671.18. [Q06187-1] DR Ensembl; ENST00000621635.4; ENSP00000483570.1; ENSG00000010671.18. [Q06187-2] DR Ensembl; ENST00000695614.1; ENSP00000512053.1; ENSG00000010671.18. [Q06187-1] DR Ensembl; ENST00000695615.1; ENSP00000512054.1; ENSG00000010671.18. [Q06187-1] DR GeneID; 695; -. DR KEGG; hsa:695; -. DR MANE-Select; ENST00000308731.8; ENSP00000308176.8; NM_000061.3; NP_000052.1. DR UCSC; uc004ehg.3; human. [Q06187-1] DR AGR; HGNC:1133; -. DR CTD; 695; -. DR DisGeNET; 695; -. DR GeneCards; BTK; -. DR GeneReviews; BTK; -. DR HGNC; HGNC:1133; BTK. DR HPA; ENSG00000010671; Tissue enhanced (bone marrow, lymphoid tissue). DR MalaCards; BTK; -. DR MIM; 300300; gene. DR MIM; 300755; phenotype. DR MIM; 307200; phenotype. DR neXtProt; NX_Q06187; -. DR OpenTargets; ENSG00000010671; -. DR Orphanet; 632; Short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia. DR Orphanet; 47; X-linked agammaglobulinemia. DR PharmGKB; PA25454; -. DR VEuPathDB; HostDB:ENSG00000010671; -. DR eggNOG; KOG0197; Eukaryota. DR GeneTree; ENSGT00940000158469; -. DR InParanoid; Q06187; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; Q06187; -. DR TreeFam; TF351634; -. DR BRENDA; 2.7.10.2; 2681. DR PathwayCommons; Q06187; -. DR Reactome; R-HSA-1236974; ER-Phagosome pathway. DR Reactome; R-HSA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane. DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation. DR Reactome; R-HSA-2424491; DAP12 signaling. DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR Reactome; R-HSA-416482; G alpha (12/13) signalling events. DR Reactome; R-HSA-5602498; MyD88 deficiency (TLR2/4). DR Reactome; R-HSA-5603041; IRAK4 deficiency (TLR2/4). DR Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs. DR Reactome; R-HSA-8964315; G beta:gamma signalling through BTK. DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR SignaLink; Q06187; -. DR SIGNOR; Q06187; -. DR BioGRID-ORCS; 695; 25 hits in 823 CRISPR screens. DR ChiTaRS; BTK; human. DR EvolutionaryTrace; Q06187; -. DR GeneWiki; Bruton%27s_tyrosine_kinase; -. DR GenomeRNAi; 695; -. DR Pharos; Q06187; Tclin. DR PRO; PR:Q06187; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q06187; Protein. DR Bgee; ENSG00000010671; Expressed in monocyte and 140 other cell types or tissues. DR ExpressionAtlas; Q06187; baseline and differential. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0045121; C:membrane raft; IDA:HGNC-UCL. DR GO; GO:0005634; C:nucleus; TAS:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0005524; F:ATP binding; TAS:HGNC-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:ARUK-UCL. DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB. DR GO; GO:0016004; F:phospholipase activator activity; IDA:ARUK-UCL. DR GO; GO:0043274; F:phospholipase binding; IPI:ARUK-UCL. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IBA:GO_Central. DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:ProtInc. DR GO; GO:0042113; P:B cell activation; TAS:UniProtKB. DR GO; GO:0002344; P:B cell affinity maturation; IEA:Ensembl. DR GO; GO:0050853; P:B cell receptor signaling pathway; IDA:ARUK-UCL. DR GO; GO:0019722; P:calcium-mediated signaling; TAS:HGNC-UCL. DR GO; GO:0048469; P:cell maturation; IEA:Ensembl. DR GO; GO:0098761; P:cellular response to interleukin-7; IEA:Ensembl. DR GO; GO:0071226; P:cellular response to molecule of fungal origin; IEA:Ensembl. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IEA:Ensembl. DR GO; GO:1990959; P:eosinophil homeostasis; IEA:Ensembl. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0002553; P:histamine secretion by mast cell; IEA:Ensembl. DR GO; GO:0045087; P:innate immune response; TAS:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IDA:ARUK-UCL. DR GO; GO:0007498; P:mesoderm development; TAS:ProtInc. DR GO; GO:0061516; P:monocyte proliferation; IEA:Ensembl. DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0030889; P:negative regulation of B cell proliferation; IEA:Ensembl. DR GO; GO:0032693; P:negative regulation of interleukin-10 production; IEA:Ensembl. DR GO; GO:0001780; P:neutrophil homeostasis; IEA:Ensembl. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:ARUK-UCL. DR GO; GO:0045579; P:positive regulation of B cell differentiation; TAS:UniProtKB. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl. DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IEA:Ensembl. DR GO; GO:0150153; P:positive regulation of interleukin-17A production; IEA:Ensembl. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:UniProtKB. DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; IDA:UniProtKB. DR GO; GO:0050766; P:positive regulation of phagocytosis; IEA:Ensembl. DR GO; GO:1901647; P:positive regulation of synoviocyte proliferation; IEA:Ensembl. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl. DR GO; GO:0001812; P:positive regulation of type I hypersensitivity; IEA:Ensembl. DR GO; GO:0001805; P:positive regulation of type III hypersensitivity; IEA:Ensembl. DR GO; GO:0006468; P:protein phosphorylation; TAS:HGNC-UCL. DR GO; GO:0030167; P:proteoglycan catabolic process; IEA:Ensembl. DR GO; GO:0002902; P:regulation of B cell apoptotic process; TAS:UniProtKB. DR GO; GO:0002721; P:regulation of B cell cytokine production; TAS:UniProtKB. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central. DR CDD; cd01238; PH_Btk; 1. DR CDD; cd05113; PTKc_Btk_Bmx; 1. DR CDD; cd10397; SH2_Tec_Btk; 1. DR CDD; cd11906; SH3_BTK; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR035574; BTK_SH3. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR001562; Znf_Btk_motif. DR PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1. DR PANTHER; PTHR24418:SF92; TYROSINE-PROTEIN KINASE BTK; 1. DR Pfam; PF00779; BTK; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF00017; SH2; 1. DR Pfam; PF00018; SH3_1; 1. DR PRINTS; PR00401; SH2DOMAIN. DR PRINTS; PR00452; SH3DOMAIN. DR PRINTS; PR00402; TECBTKDOMAIN. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00107; BTK; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00252; SH2; 1. DR SMART; SM00326; SH3; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50001; SH2; 1. DR PROSITE; PS50002; SH3; 1. DR PROSITE; PS51113; ZF_BTK; 1. DR Genevisible; Q06187; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Adaptive immunity; Alternative promoter usage; KW Apoptosis; ATP-binding; Cell membrane; Cytoplasm; KW Direct protein sequencing; Disease variant; Dwarfism; Immunity; KW Innate immunity; Kinase; Lipid-binding; Membrane; Metal-binding; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW SH2 domain; SH3 domain; Transcription; Transcription regulation; KW Transferase; Tyrosine-protein kinase; Zinc; Zinc-finger. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.11, ECO:0007744|PubMed:25944712" FT CHAIN 2..659 FT /note="Tyrosine-protein kinase BTK" FT /id="PRO_0000088065" FT DOMAIN 3..133 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 214..274 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 281..377 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 402..655 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT ZN_FING 135..171 FT /note="Btk-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432" FT REGION 12..24 FT /note="Inositol-(1,3,4,5)-tetrakisphosphate 1-binding" FT REGION 171..210 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 581..588 FT /note="CAV1-binding" FT ACT_SITE 521 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 26 FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate" FT /ligand_id="ChEBI:CHEBI:57895" FT /evidence="ECO:0000269|PubMed:10196129" FT BINDING 28 FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate" FT /ligand_id="ChEBI:CHEBI:57895" FT /evidence="ECO:0000269|PubMed:10196129" FT BINDING 39 FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate" FT /ligand_id="ChEBI:CHEBI:57895" FT /evidence="ECO:0000269|PubMed:10196129" FT BINDING 53 FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate" FT /ligand_id="ChEBI:CHEBI:57895" FT /evidence="ECO:0000269|PubMed:10196129" FT BINDING 143 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432, FT ECO:0000269|PubMed:10196129, ECO:0000269|PubMed:9218782, FT ECO:0000269|Ref.48" FT BINDING 154 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432, FT ECO:0000269|PubMed:10196129, ECO:0000269|PubMed:9218782, FT ECO:0000269|Ref.48" FT BINDING 155 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432, FT ECO:0000269|PubMed:10196129, ECO:0000269|PubMed:9218782, FT ECO:0000269|Ref.48" FT BINDING 165 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432, FT ECO:0000269|PubMed:10196129, ECO:0000269|PubMed:9218782, FT ECO:0000269|Ref.48" FT BINDING 408..416 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 430 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 474..477 FT /ligand="clofedanol" FT /ligand_id="ChEBI:CHEBI:187895" FT /ligand_note="inhibitor" FT /evidence="ECO:0000269|PubMed:21280133, FT ECO:0007744|PDB:3PIY" FT BINDING 474..477 FT /ligand="dasatinib" FT /ligand_id="ChEBI:CHEBI:190514" FT /ligand_note="inhibitor" FT /evidence="ECO:0000269|PubMed:20052711, FT ECO:0007744|PDB:3K54, ECO:0007744|PDB:3OCT" FT BINDING 542 FT /ligand="clofedanol" FT /ligand_id="ChEBI:CHEBI:187895" FT /ligand_note="inhibitor" FT /evidence="ECO:0000269|PubMed:21280133, FT ECO:0007744|PDB:3PIY" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.11, ECO:0007744|PubMed:25944712" FT MOD_RES 21 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:16644721" FT MOD_RES 40 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P35991" FT MOD_RES 55 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 115 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:16644721" FT MOD_RES 180 FT /note="Phosphoserine; by PKC/PRKCB" FT /evidence="ECO:0000269|PubMed:11598012" FT MOD_RES 191 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:23186163" FT MOD_RES 223 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12573241, FT ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:8630736, FT ECO:0000269|PubMed:9012831, ECO:0007744|PubMed:23186163" FT MOD_RES 344 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P35991" FT MOD_RES 361 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 551 FT /note="Phosphotyrosine; by LYN and SYK" FT /evidence="ECO:0000269|PubMed:8630736, FT ECO:0000269|PubMed:9012831" FT MOD_RES 604 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 617 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:15375214" FT MOD_RES 623 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15375214" FT MOD_RES 659 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT VAR_SEQ 1 FT /note="M -> MASWSIQQMVIGCPLCGRHCSGGEHTGELQKEEAM (in isoform FT BTK-C)" FT /evidence="ECO:0000305" FT /id="VSP_053838" FT VARIANT 11 FT /note="L -> P (in XLA; dbSNP:rs1603020228)" FT /id="VAR_006216" FT VARIANT 12 FT /note="K -> R (in XLA)" FT /evidence="ECO:0000269|PubMed:8695804" FT /id="VAR_006217" FT VARIANT 14 FT /note="S -> F (in XLA; dbSNP:rs1057520682)" FT /id="VAR_006218" FT VARIANT 19 FT /note="K -> E (in XLA)" FT /evidence="ECO:0000269|PubMed:9445504" FT /id="VAR_008291" FT VARIANT 25 FT /note="F -> S (in XLA)" FT /evidence="ECO:0000269|PubMed:7711734" FT /id="VAR_006219" FT VARIANT 27 FT /note="K -> R (in XLA)" FT /id="VAR_008292" FT VARIANT 28 FT /note="R -> C (in XLA; no effect on phosphorylation of FT GTF2I)" FT /id="VAR_008293" FT VARIANT 28 FT /note="R -> H (in XLA; moderate; dbSNP:rs128620185)" FT /evidence="ECO:0000269|PubMed:7849721, FT ECO:0000269|PubMed:8162018, ECO:0000269|PubMed:9445504" FT /id="VAR_006220" FT VARIANT 28 FT /note="R -> P (in XLA)" FT /evidence="ECO:0000269|PubMed:8695804" FT /id="VAR_006221" FT VARIANT 33 FT /note="T -> P (in XLA; severe; dbSNP:rs128620189)" FT /evidence="ECO:0000269|PubMed:7633429, FT ECO:0000269|PubMed:7849721" FT /id="VAR_006222" FT VARIANT 39 FT /note="Y -> S (in XLA)" FT /evidence="ECO:0000269|PubMed:10612838" FT /id="VAR_008960" FT VARIANT 40 FT /note="Y -> C (in XLA; dbSNP:rs1555980875)" FT /id="VAR_008294" FT VARIANT 40 FT /note="Y -> N (in XLA)" FT /id="VAR_008295" FT VARIANT 61 FT /note="I -> N (in XLA)" FT /evidence="ECO:0000269|PubMed:9445504" FT /id="VAR_008296" FT VARIANT 64 FT /note="V -> D (in XLA)" FT /id="VAR_008297" FT VARIANT 64 FT /note="V -> F (in XLA)" FT /evidence="ECO:0000269|PubMed:7849006" FT /id="VAR_006223" FT VARIANT 82 FT /note="R -> K (in dbSNP:rs56035945)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041676" FT VARIANT 103 FT /note="Q -> QSVFSSTR (in XLA)" FT /id="VAR_006224" FT VARIANT 113 FT /note="V -> D (in XLA; dbSNP:rs128621190)" FT /evidence="ECO:0000269|PubMed:7849697" FT /id="VAR_006225" FT VARIANT 115 FT /note="S -> F (in XLA)" FT /id="VAR_008298" FT VARIANT 117 FT /note="T -> P (in XLA)" FT /evidence="ECO:0000269|PubMed:9445504" FT /id="VAR_008299" FT VARIANT 127 FT /note="Q -> H (in XLA)" FT /evidence="ECO:0000269|PubMed:9445504" FT /id="VAR_008300" FT VARIANT 154 FT /note="C -> S (in XLA)" FT /evidence="ECO:0000269|PubMed:9280283" FT /id="VAR_008301" FT VARIANT 155 FT /note="C -> G (in XLA)" FT /id="VAR_008302" FT VARIANT 155 FT /note="C -> R (in XLA)" FT /evidence="ECO:0000269|PubMed:9280283, FT ECO:0000269|PubMed:9445504" FT /id="VAR_008303" FT VARIANT 184 FT /note="T -> P (in XLA)" FT /id="VAR_008304" FT VARIANT 190 FT /note="P -> K (in a lung large cell carcinoma sample; FT somatic mutation; requires 2 nucleotide substitutions)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041677" FT VARIANT 260..280 FT /note="Missing (in XLA; severe)" FT /evidence="ECO:0000269|PubMed:7849721" FT /id="VAR_006226" FT VARIANT 288 FT /note="R -> Q (in XLA; dbSNP:rs1555978277)" FT /evidence="ECO:0000269|PubMed:9545398" FT /id="VAR_008305" FT VARIANT 288 FT /note="R -> W (in XLA; dbSNP:rs128621194)" FT /evidence="ECO:0000269|PubMed:7711734, FT ECO:0000269|PubMed:8162018, ECO:0000269|PubMed:8162056, FT ECO:0000269|PubMed:8834236" FT /id="VAR_006227" FT VARIANT 295 FT /note="L -> P (in XLA)" FT /evidence="ECO:0000269|PubMed:8723128, FT ECO:0000269|PubMed:9445504" FT /id="VAR_006228" FT VARIANT 302 FT /note="G -> E (in XLA)" FT /evidence="ECO:0000269|PubMed:7627183, FT ECO:0000269|PubMed:8695804" FT /id="VAR_006230" FT VARIANT 302 FT /note="G -> R (in XLA)" FT /id="VAR_008306" FT VARIANT 302 FT /note="Missing (in XLA)" FT /evidence="ECO:0000269|PubMed:7633429" FT /id="VAR_006229" FT VARIANT 307 FT /note="R -> G (in XLA; loss of activity; FT dbSNP:rs128621195)" FT /evidence="ECO:0000269|PubMed:8162056" FT /id="VAR_006231" FT VARIANT 307 FT /note="R -> T (in XLA)" FT /evidence="ECO:0000269|PubMed:9545398" FT /id="VAR_008307" FT VARIANT 308 FT /note="D -> E (in XLA)" FT /id="VAR_008308" FT VARIANT 319 FT /note="V -> A (in XLA; moderate)" FT /id="VAR_008309" FT VARIANT 334 FT /note="Y -> S (in XLA; dbSNP:rs128621196)" FT /evidence="ECO:0000269|PubMed:7880320" FT /id="VAR_006232" FT VARIANT 358 FT /note="L -> F (in XLA)" FT /evidence="ECO:0000269|PubMed:7897635" FT /id="VAR_006233" FT VARIANT 361 FT /note="Y -> C (in XLA; mild; dbSNP:rs28935478)" FT /evidence="ECO:0000269|PubMed:7849697" FT /id="VAR_006234" FT VARIANT 362 FT /note="H -> Q (in XLA)" FT /id="VAR_006235" FT VARIANT 364 FT /note="H -> P (in XLA)" FT /id="VAR_006236" FT VARIANT 365 FT /note="N -> Y (in XLA)" FT /id="VAR_006237" FT VARIANT 366 FT /note="S -> F (in XLA)" FT /id="VAR_008310" FT VARIANT 369 FT /note="L -> F (in XLA)" FT /evidence="ECO:0000269|PubMed:9445504" FT /id="VAR_008311" FT VARIANT 370 FT /note="I -> M (in XLA)" FT /evidence="ECO:0000269|PubMed:7711734" FT /id="VAR_006238" FT VARIANT 372 FT /note="R -> G (in XLA)" FT /evidence="ECO:0000269|PubMed:9445504" FT /id="VAR_008312" FT VARIANT 408 FT /note="L -> P (in XLA; moderate; dbSNP:rs128621198)" FT /evidence="ECO:0000269|PubMed:7849721" FT /id="VAR_006239" FT VARIANT 414 FT /note="G -> R (in XLA)" FT /evidence="ECO:0000269|PubMed:9445504" FT /id="VAR_008313" FT VARIANT 418 FT /note="Y -> H (in XLA; dbSNP:rs144079566)" FT /id="VAR_006240" FT VARIANT 429 FT /note="I -> N (in XLA)" FT /evidence="ECO:0000269|PubMed:8634718" FT /id="VAR_006241" FT VARIANT 430 FT /note="K -> E (in XLA; loss of phosphorylation of GTF2I; FT dbSNP:rs128620184)" FT /evidence="ECO:0000269|PubMed:7809124" FT /id="VAR_006242" FT VARIANT 430 FT /note="K -> R (in XLA)" FT /evidence="ECO:0000269|PubMed:9545398" FT /id="VAR_008314" FT VARIANT 445 FT /note="E -> D (in XLA)" FT /evidence="ECO:0000269|PubMed:9545398" FT /id="VAR_008315" FT VARIANT 462 FT /note="G -> D (in XLA)" FT /id="VAR_008316" FT VARIANT 462 FT /note="G -> V (in XLA)" FT /id="VAR_008317" FT VARIANT 476 FT /note="Y -> D (in XLA)" FT /evidence="ECO:0000269|PubMed:7627183" FT /id="VAR_006243" FT VARIANT 477 FT /note="M -> R (in XLA)" FT /evidence="ECO:0000269|PubMed:8634718" FT /id="VAR_006244" FT VARIANT 481 FT /note="C -> S (found in patients with chronic lymphocytic FT leukemia; uncertain significance; results in resistance to FT ibrutinib therapy; results in a protein that is reversibly FT inhibited by ibrutinib; disrupts the covalent binding FT between the enzyme and ibrutinib; dbSNP:rs1057519825 and FT dbSNP:rs1057519826)" FT /evidence="ECO:0000269|PubMed:24869597, FT ECO:0000269|PubMed:24869598, ECO:0000269|PubMed:25189416" FT /id="VAR_074309" FT VARIANT 502 FT /note="C -> F (in XLA)" FT /id="VAR_006245" FT VARIANT 502 FT /note="C -> W (in XLA; dbSNP:rs41310709)" FT /evidence="ECO:0000269|PubMed:8695804" FT /id="VAR_006246" FT VARIANT 506 FT /note="C -> R (in XLA; dbSNP:rs128621200)" FT /evidence="ECO:0000269|PubMed:7880320" FT /id="VAR_006247" FT VARIANT 506 FT /note="C -> Y (in XLA)" FT /evidence="ECO:0000269|PubMed:9445504" FT /id="VAR_006248" FT VARIANT 508 FT /note="A -> D (in XLA)" FT /id="VAR_008318" FT VARIANT 509 FT /note="M -> I (in XLA)" FT /id="VAR_008319" FT VARIANT 509 FT /note="M -> V (in XLA)" FT /evidence="ECO:0000269|PubMed:7711734" FT /id="VAR_006249" FT VARIANT 512 FT /note="L -> P (in XLA)" FT /evidence="ECO:0000269|PubMed:10612838" FT /id="VAR_008961" FT VARIANT 512 FT /note="L -> Q (in XLA)" FT /evidence="ECO:0000269|PubMed:10612838" FT /id="VAR_008962" FT VARIANT 518 FT /note="L -> R (in XLA)" FT /id="VAR_008320" FT VARIANT 520 FT /note="R -> Q (in XLA; severe; prevents activation due to FT absence of contact between the catalytic loop and the FT regulatory phosphorylated residue; dbSNP:rs128621202)" FT /evidence="ECO:0000269|PubMed:7633429, FT ECO:0000269|PubMed:7809124, ECO:0000269|PubMed:7849697, FT ECO:0000269|PubMed:7880320" FT /id="VAR_006251" FT VARIANT 521 FT /note="D -> G (in XLA)" FT /evidence="ECO:0000269|PubMed:9445504" FT /id="VAR_008321" FT VARIANT 521 FT /note="D -> H (in XLA; severe)" FT /evidence="ECO:0000269|PubMed:8695804" FT /id="VAR_006252" FT VARIANT 521 FT /note="D -> N (in XLA; severe)" FT /id="VAR_006253" FT VARIANT 523 FT /note="A -> E (in XLA)" FT /id="VAR_008322" FT VARIANT 525 FT /note="R -> G (in XLA; dbSNP:rs886041149)" FT /evidence="ECO:0000269|PubMed:9545398" FT /id="VAR_008323" FT VARIANT 525 FT /note="R -> P (in XLA)" FT /evidence="ECO:0000269|PubMed:7711734" FT /id="VAR_006254" FT VARIANT 525 FT /note="R -> Q (in XLA; severe; disturbs ATP-binding; FT dbSNP:rs128620183)" FT /evidence="ECO:0000269|PubMed:7809124, FT ECO:0000269|PubMed:9445504" FT /id="VAR_006255" FT VARIANT 526 FT /note="N -> K (in XLA; dbSNP:rs1569291237)" FT /evidence="ECO:0000269|PubMed:7711734" FT /id="VAR_006256" FT VARIANT 535 FT /note="V -> F (in XLA)" FT /evidence="ECO:0000269|PubMed:9545398" FT /id="VAR_008324" FT VARIANT 542 FT /note="L -> P (in XLA; growth hormone deficiency; FT dbSNP:rs128621203)" FT /evidence="ECO:0000269|PubMed:7849697" FT /id="VAR_006257" FT VARIANT 544 FT /note="R -> G (in XLA)" FT /evidence="ECO:0000269|PubMed:10612838" FT /id="VAR_008963" FT VARIANT 544 FT /note="R -> K (in XLA)" FT /evidence="ECO:0000269|PubMed:8834236" FT /id="VAR_006258" FT VARIANT 559 FT /note="F -> S (in XLA)" FT /evidence="ECO:0000269|PubMed:9445504" FT /id="VAR_008325" FT VARIANT 562 FT /note="R -> P (in XLA; dbSNP:rs104894770)" FT /evidence="ECO:0000269|PubMed:10678660, FT ECO:0000269|PubMed:7809124" FT /id="VAR_006259" FT VARIANT 562 FT /note="R -> W (in XLA; dbSNP:rs128621204)" FT /evidence="ECO:0000269|PubMed:7711734, FT ECO:0000269|PubMed:7849697, ECO:0000269|PubMed:7880320, FT ECO:0000269|PubMed:9445504" FT /id="VAR_006260" FT VARIANT 563 FT /note="W -> L (in XLA; dbSNP:rs1555977474)" FT /evidence="ECO:0000269|PubMed:9545398" FT /id="VAR_008326" FT VARIANT 567 FT /note="E -> K (in XLA; severe)" FT /evidence="ECO:0000269|PubMed:7633420" FT /id="VAR_006261" FT VARIANT 578 FT /note="S -> Y (in XLA)" FT /evidence="ECO:0000269|PubMed:10612838" FT /id="VAR_008964" FT VARIANT 581 FT /note="W -> R (in XLA; dbSNP:rs128621205)" FT /id="VAR_006262" FT VARIANT 582 FT /note="A -> V (in XLA)" FT /evidence="ECO:0000269|PubMed:7711734, FT ECO:0000269|PubMed:7809124" FT /id="VAR_006263" FT VARIANT 583 FT /note="F -> S (in XLA)" FT /id="VAR_008327" FT VARIANT 587 FT /note="M -> L (in XLA; mild; dbSNP:rs1603001822)" FT /evidence="ECO:0000269|PubMed:7633420" FT /id="VAR_006264" FT VARIANT 589 FT /note="E -> D (in XLA)" FT /id="VAR_008328" FT VARIANT 589 FT /note="E -> G (in XLA; moderate; interferes with substrate FT binding; dbSNP:rs128621206)" FT /evidence="ECO:0000269|PubMed:7809124, FT ECO:0000269|PubMed:7849721" FT /id="VAR_006265" FT VARIANT 589 FT /note="E -> K (in XLA)" FT /evidence="ECO:0000269|PubMed:10612838" FT /id="VAR_008965" FT VARIANT 592 FT /note="S -> P (in XLA; dbSNP:rs1603001783)" FT /evidence="ECO:0000269|PubMed:8834236" FT /id="VAR_006267" FT VARIANT 594 FT /note="G -> E (in XLA; mild; interferes with substrate FT binding)" FT /evidence="ECO:0000269|PubMed:7809124, FT ECO:0000269|PubMed:9445504" FT /id="VAR_006268" FT VARIANT 594 FT /note="G -> R (in XLA; dbSNP:rs1555977339)" FT /evidence="ECO:0000269|PubMed:7711734" FT /id="VAR_006269" FT VARIANT 598 FT /note="Y -> C (in XLA)" FT /id="VAR_006270" FT VARIANT 607 FT /note="A -> D (in XLA; mild; dbSNP:rs128621208)" FT /evidence="ECO:0000269|PubMed:8162056" FT /id="VAR_006271" FT VARIANT 613 FT /note="G -> D (in XLA; mild; interferes with substrate FT binding and/or domain interactions; dbSNP:rs128621209)" FT /evidence="ECO:0000269|PubMed:7809124, FT ECO:0000269|PubMed:7849721" FT /id="VAR_006272" FT VARIANT 619 FT /note="P -> A (in XLA)" FT /id="VAR_008330" FT VARIANT 619 FT /note="P -> S (in XLA)" FT /id="VAR_006273" FT VARIANT 619 FT /note="P -> T (in XLA)" FT /evidence="ECO:0000269|PubMed:9445504" FT /id="VAR_008331" FT VARIANT 622 FT /note="A -> P (in XLA)" FT /evidence="ECO:0000269|PubMed:9545398" FT /id="VAR_008332" FT VARIANT 626 FT /note="V -> G (in XLA)" FT /evidence="ECO:0000269|PubMed:9445504" FT /id="VAR_008333" FT VARIANT 630 FT /note="M -> I" FT /id="VAR_006274" FT VARIANT 630 FT /note="M -> K (in XLA; dbSNP:rs128621210)" FT /evidence="ECO:0000269|PubMed:7849697, FT ECO:0000269|PubMed:7880320" FT /id="VAR_006275" FT VARIANT 630 FT /note="M -> T (in XLA)" FT /id="VAR_008334" FT VARIANT 633 FT /note="C -> Y (in XLA)" FT /evidence="ECO:0000269|PubMed:8695804" FT /id="VAR_006276" FT VARIANT 641 FT /note="R -> C (in XLA)" FT /evidence="ECO:0000269|PubMed:7633429" FT /id="VAR_006277" FT VARIANT 641 FT /note="R -> H (in XLA; severe)" FT /evidence="ECO:0000269|PubMed:7633420, FT ECO:0000269|PubMed:9445504" FT /id="VAR_006278" FT VARIANT 644 FT /note="F -> L (in XLA)" FT /id="VAR_008335" FT VARIANT 644 FT /note="F -> S (in XLA)" FT /evidence="ECO:0000269|PubMed:8695804" FT /id="VAR_006279" FT VARIANT 647 FT /note="L -> P (in XLA)" FT /id="VAR_006280" FT VARIANT 652 FT /note="L -> P (in XLA; dbSNP:rs128622212)" FT /evidence="ECO:0000269|PubMed:7849697" FT /id="VAR_006281" FT MUTAGEN 41 FT /note="E->K: No effect on phosphorylation of GTF2I." FT /evidence="ECO:0000269|PubMed:9012831" FT MUTAGEN 189 FT /note="P->A: No effect on phosphorylation of GTF2I." FT /evidence="ECO:0000269|PubMed:9012831" FT MUTAGEN 223 FT /note="Y->F: Loss of phosphorylation of GTF2I." FT /evidence="ECO:0000269|PubMed:8630736, FT ECO:0000269|PubMed:9012831" FT MUTAGEN 251..252 FT /note="WW->LL: Large decrease in binding by SH3BP5." FT /evidence="ECO:0000269|PubMed:9571151" FT MUTAGEN 251 FT /note="W->L: No effect on phosphorylation of GTF2I." FT /evidence="ECO:0000269|PubMed:9012831" FT MUTAGEN 307 FT /note="R->K: Loss of phosphorylation of GTF2I." FT /evidence="ECO:0000269|PubMed:9012831" FT MUTAGEN 551 FT /note="Y->F: Loss of phosphorylation of GTF2I." FT /evidence="ECO:0000269|PubMed:9012831" FT MUTAGEN 617 FT /note="Y->E: Defective in mediating calcium response." FT /evidence="ECO:0000269|PubMed:15375214" FT CONFLICT 253 FT /note="R -> K (in Ref. 7; BAG37008)" FT /evidence="ECO:0000305" FT STRAND 5..13 FT /evidence="ECO:0007829|PDB:6TT2" FT STRAND 15..17 FT /evidence="ECO:0007829|PDB:6TUH" FT STRAND 19..21 FT /evidence="ECO:0007829|PDB:6TUH" FT STRAND 25..32 FT /evidence="ECO:0007829|PDB:6TT2" FT STRAND 34..43 FT /evidence="ECO:0007829|PDB:6TT2" FT TURN 44..47 FT /evidence="ECO:0007829|PDB:6TT2" FT STRAND 48..57 FT /evidence="ECO:0007829|PDB:6TT2" FT HELIX 58..60 FT /evidence="ECO:0007829|PDB:6TT2" FT STRAND 63..66 FT /evidence="ECO:0007829|PDB:6TT2" FT HELIX 75..77 FT /evidence="ECO:0007829|PDB:6TT2" FT STRAND 82..85 FT /evidence="ECO:0007829|PDB:6YYG" FT HELIX 93..96 FT /evidence="ECO:0007829|PDB:6TT2" FT STRAND 100..106 FT /evidence="ECO:0007829|PDB:6TT2" FT STRAND 109..117 FT /evidence="ECO:0007829|PDB:6TT2" FT HELIX 118..132 FT /evidence="ECO:0007829|PDB:6TT2" FT STRAND 140..142 FT /evidence="ECO:0007829|PDB:6TT2" FT STRAND 149..152 FT /evidence="ECO:0007829|PDB:2Z0P" FT TURN 153..155 FT /evidence="ECO:0007829|PDB:6TT2" FT STRAND 165..167 FT /evidence="ECO:0007829|PDB:6TT2" FT TURN 212..215 FT /evidence="ECO:0007829|PDB:1AWX" FT STRAND 218..223 FT /evidence="ECO:0007829|PDB:1AWW" FT STRAND 228..232 FT /evidence="ECO:0007829|PDB:1AWW" FT STRAND 240..242 FT /evidence="ECO:0007829|PDB:1AWW" FT STRAND 248..252 FT /evidence="ECO:0007829|PDB:1AWW" FT TURN 257..259 FT /evidence="ECO:0007829|PDB:1QLY" FT STRAND 261..265 FT /evidence="ECO:0007829|PDB:1AWX" FT TURN 266..268 FT /evidence="ECO:0007829|PDB:1AWW" FT STRAND 279..282 FT /evidence="ECO:0007829|PDB:2GE9" FT HELIX 288..298 FT /evidence="ECO:0007829|PDB:6HTF" FT STRAND 303..308 FT /evidence="ECO:0007829|PDB:6HTF" FT STRAND 310..313 FT /evidence="ECO:0007829|PDB:6HTF" FT STRAND 315..321 FT /evidence="ECO:0007829|PDB:6HTF" FT STRAND 330..335 FT /evidence="ECO:0007829|PDB:6HTF" FT STRAND 337..339 FT /evidence="ECO:0007829|PDB:2GE9" FT TURN 340..342 FT /evidence="ECO:0007829|PDB:2GE9" FT STRAND 344..347 FT /evidence="ECO:0007829|PDB:6HTF" FT STRAND 352..354 FT /evidence="ECO:0007829|PDB:6HTF" FT HELIX 355..362 FT /evidence="ECO:0007829|PDB:6HTF" FT STRAND 369..371 FT /evidence="ECO:0007829|PDB:6HTF" FT STRAND 373..376 FT /evidence="ECO:0007829|PDB:2GE9" FT HELIX 393..395 FT /evidence="ECO:0007829|PDB:6O8I" FT HELIX 399..401 FT /evidence="ECO:0007829|PDB:5P9J" FT STRAND 402..410 FT /evidence="ECO:0007829|PDB:5P9J" FT STRAND 412..414 FT /evidence="ECO:0007829|PDB:6W7O" FT STRAND 415..421 FT /evidence="ECO:0007829|PDB:5P9J" FT TURN 422..424 FT /evidence="ECO:0007829|PDB:5P9J" FT STRAND 425..431 FT /evidence="ECO:0007829|PDB:5P9J" FT TURN 434..436 FT /evidence="ECO:0007829|PDB:5FBO" FT HELIX 439..450 FT /evidence="ECO:0007829|PDB:5P9J" FT STRAND 460..464 FT /evidence="ECO:0007829|PDB:5P9J" FT STRAND 466..469 FT /evidence="ECO:0007829|PDB:5P9J" FT STRAND 471..474 FT /evidence="ECO:0007829|PDB:5P9J" FT HELIX 482..487 FT /evidence="ECO:0007829|PDB:5P9J" FT HELIX 489..491 FT /evidence="ECO:0007829|PDB:5P9J" FT HELIX 495..514 FT /evidence="ECO:0007829|PDB:5P9J" FT TURN 524..526 FT /evidence="ECO:0007829|PDB:5P9J" FT STRAND 527..529 FT /evidence="ECO:0007829|PDB:6DI1" FT STRAND 535..537 FT /evidence="ECO:0007829|PDB:5P9J" FT HELIX 542..545 FT /evidence="ECO:0007829|PDB:5P9J" FT HELIX 549..551 FT /evidence="ECO:0007829|PDB:5P9J" FT STRAND 556..559 FT /evidence="ECO:0007829|PDB:6NFH" FT HELIX 561..563 FT /evidence="ECO:0007829|PDB:5P9J" FT HELIX 566..571 FT /evidence="ECO:0007829|PDB:5P9J" FT HELIX 576..591 FT /evidence="ECO:0007829|PDB:5P9J" FT TURN 592..594 FT /evidence="ECO:0007829|PDB:5P9J" FT TURN 597..600 FT /evidence="ECO:0007829|PDB:5P9J" FT HELIX 603..611 FT /evidence="ECO:0007829|PDB:5P9J" FT HELIX 624..632 FT /evidence="ECO:0007829|PDB:5P9J" FT HELIX 638..640 FT /evidence="ECO:0007829|PDB:5P9J" FT HELIX 644..657 FT /evidence="ECO:0007829|PDB:5P9J" SQ SEQUENCE 659 AA; 76281 MW; DF06B5D1FEC257CC CRC64; MAAVILESIF LKRSQQKKKT SPLNFKKRLF LLTVHKLSYY EYDFERGRRG SKKGSIDVEK ITCVETVVPE KNPPPERQIP RRGEESSEME QISIIERFPY PFQVVYDEGP LYVFSPTEEL RKRWIHQLKN VIRYNSDLVQ KYHPCFWIDG QYLCCSQTAK NAMGCQILEN RNGSLKPGSS HRKTKKPLPP TPEEDQILKK PLPPEPAAAP VSTSELKKVV ALYDYMPMNA NDLQLRKGDE YFILEESNLP WWRARDKNGQ EGYIPSNYVT EAEDSIEMYE WYSKHMTRSQ AEQLLKQEGK EGGFIVRDSS KAGKYTVSVF AKSTGDPQGV IRHYVVCSTP QSQYYLAEKH LFSTIPELIN YHQHNSAGLI SRLKYPVSQQ NKNAPSTAGL GYGSWEIDPK DLTFLKELGT GQFGVVKYGK WRGQYDVAIK MIKEGSMSED EFIEEAKVMM NLSHEKLVQL YGVCTKQRPI FIITEYMANG CLLNYLREMR HRFQTQQLLE MCKDVCEAME YLESKQFLHR DLAARNCLVN DQGVVKVSDF GLSRYVLDDE YTSSVGSKFP VRWSPPEVLM YSKFSSKSDI WAFGVLMWEI YSLGKMPYER FTNSETAEHI AQGLRLYRPH LASEKVYTIM YSCWHEKADE RPTFKILLSN ILDVMDEES //