BTK_HUMAN
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 03-AUG-2022, entry version 257.
DE RecName: Full=Tyrosine-protein kinase BTK;
DE EC=2.7.10.2;
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.
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 X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 2-170 IN COMPLEX WITH ZINC.
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 [41]
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 [42]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-170 IN COMPLEX WITH
RP INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE AND ZINC, AND DOMAIN PH.
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 [43]
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 [44]
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 [45]
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 [46] {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 [47] {ECO:0007744|PDB:2Z0P}
RP X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS) OF 2-170 IN COMPLEX WITH INHIBITOR
RP AND ZINC.
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 [48] {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 [49]
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 [50] {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 [51]
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 [52]
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 [53]
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 [54]
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 [55]
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 [56]
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 [57]
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 [58]
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 [59]
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 [60]
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 [61]
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 [62]
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 [63]
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 [64]
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 [65]
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 [66]
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 [67]
RP VARIANTS XLA TRP-288; LYS-544 AND PRO-592.
RX PubMed=8834236; DOI=10.1007/bf02267060;
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 [68]
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 [69]
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 [70]
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 [71]
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 [72]
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 [73]
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 [74]
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 [75]
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 [76]
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 [77]
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 [78]
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. Binding of antigen to the
CC B-cell antigen receptor (BCR) triggers signaling that ultimately leads
CC to B-cell activation. After BCR engagement and activation at the plasma
CC membrane, phosphorylates PLCG2 at several sites, igniting the
CC downstream signaling pathway through calcium mobilization, followed by
CC activation of the protein kinase C (PKC) family members. PLCG2
CC phosphorylation is performed in close cooperation with the adapter
CC protein B-cell linker protein BLNK. BTK acts as a platform to bring
CC together a diverse array of signaling proteins and is implicated in
CC cytokine receptor signaling pathways. Plays an important role in the
CC function of immune cells of innate as well as adaptive immunity, as a
CC component of the Toll-like receptors (TLR) pathway. 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. Especially, is a
CC critical molecule in regulating TLR9 activation in splenic B-cells.
CC Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which
CC leads to TIRAP degradation. BTK also plays a critical role in
CC transcription regulation. Induces the activity of NF-kappa-B, which is
CC involved in regulating the expression of hundreds of genes. BTK is
CC involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B.
CC Transiently phosphorylates transcription factor GTF2I on tyrosine
CC residues in response to BCR. GTF2I then translocates to the nucleus to
CC bind regulatory enhancer elements to modulate gene expression. ARID3A
CC and NFAT are other transcriptional target of BTK. BTK is required for
CC the formation of functional ARID3A DNA-binding complexes. There is
CC however no evidence that BTK itself binds directly to DNA. BTK has a
CC dual role in the regulation of apoptosis. {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:9012831}.
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 -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 1 zinc ion per subunit.;
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: Binds GTF2I through the PH domain. Interacts with SH3BP5 via
CC the SH3 domain. Interacts with IBTK via its PH domain. Interacts with
CC ARID3A, CAV1, FASLG, PIN1, TLR8 and TLR9. {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.46, ECO:0000269|Ref.47}.
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. Cell membrane; Peripheral membrane
CC protein. Nucleus. Note=In steady state, BTK is predominantly cytosolic.
CC Following B-cell receptor (BCR) engagement by antigen, translocates to
CC the plasma membrane through its PH domain. Plasma membrane localization
CC is a critical step in the activation of BTK. A fraction of BTK also
CC shuttles between the nucleus and the cytoplasm, and nuclear export is
CC mediated by the nuclear export receptor CRM1.
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="http://atlasgeneticsoncology.org/Genes/BTKID851chXq22.html";
CC -!- WEB RESOURCE: Name=BTKbase; Note=BTK mutation db;
CC URL="http://structure.bmc.lu.se/idbase/BTKbase/";
CC ---------------------------------------------------------------------------
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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; 7LTY; X-ray; 1.69 A; A=393-659.
DR PDB; 7LTZ; X-ray; 1.53 A; A=393-659.
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 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; 7LTY; -.
DR PDBsum; 7LTZ; -.
DR PDBsum; 7N5O; -.
DR PDBsum; 7N5R; -.
DR PDBsum; 7N5X; -.
DR PDBsum; 7N5Y; -.
DR PDBsum; 7R60; -.
DR PDBsum; 7R61; -.
DR AlphaFoldDB; Q06187; -.
DR BMRB; Q06187; -.
DR SASBDB; Q06187; -.
DR SMR; Q06187; -.
DR BioGRID; 107160; 102.
DR CORUM; Q06187; -.
DR DIP; DIP-34071N; -.
DR ELM; Q06187; -.
DR IntAct; Q06187; 60.
DR MINT; Q06187; -.
DR STRING; 9606.ENSP00000483570; -.
DR BindingDB; Q06187; -.
DR ChEMBL; CHEMBL5251; -.
DR DrugBank; DB15327; Abivertinib.
DR DrugBank; DB11703; Acalabrutinib.
DR DrugBank; DB01254; Dasatinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB09053; Ibrutinib.
DR DrugBank; DB01863; Inositol 1,3,4,5-Tetrakisphosphate.
DR DrugBank; DB16657; Vecabrutinib.
DR DrugBank; DB05204; XL418.
DR DrugBank; DB15035; Zanubrutinib.
DR DrugCentral; Q06187; -.
DR GuidetoPHARMACOLOGY; 1948; -.
DR iPTMnet; Q06187; -.
DR PhosphoSitePlus; Q06187; -.
DR BioMuta; BTK; -.
DR DMDM; 547759; -.
DR EPD; Q06187; -.
DR jPOST; Q06187; -.
DR MassIVE; Q06187; -.
DR MaxQB; Q06187; -.
DR PaxDb; Q06187; -.
DR PeptideAtlas; Q06187; -.
DR PRIDE; Q06187; -.
DR ProteomicsDB; 58419; -. [Q06187-1]
DR ABCD; Q06187; 7 sequenced antibodies.
DR Antibodypedia; 699; 1331 antibodies from 47 providers.
DR CPTC; Q06187; 1 antibody.
DR DNASU; 695; -.
DR Ensembl; ENST00000308731.8; ENSP00000308176.8; ENSG00000010671.17. [Q06187-1]
DR Ensembl; ENST00000621635.4; ENSP00000483570.1; ENSG00000010671.17. [Q06187-2]
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 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; 1047190at2759; -.
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-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR SignaLink; Q06187; -.
DR SIGNOR; Q06187; -.
DR BioGRID-ORCS; 695; 17 hits in 740 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 138 other tissues.
DR ExpressionAtlas; Q06187; baseline and differential.
DR Genevisible; Q06187; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
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:UniProtKB.
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; EXP:Reactome.
DR GO; GO:0002250; P:adaptive immune response; TAS:UniProtKB.
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:0007249; P:I-kappaB kinase/NF-kappaB signaling; 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:0038083; P:peptidyl-tyrosine autophosphorylation; 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: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 CDD; cd11906; SH3_BTK; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 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 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; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 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.
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.47"
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.47"
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.47"
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.47"
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; unknown pathological significance; results in
FT resistance to ibrutinib therapy; results in a protein that
FT is reversibly inhibited by ibrutinib; disrupts the covalent
FT binding between the enzyme and ibrutinib;
FT dbSNP:rs1057519825 and 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
