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Tyrosine-protein kinase BTK (EC 2.7.10.2) (Agammaglobulinemia tyrosine kinase) (ATK) (B-cell progenitor kinase) (BPK) (Bruton tyrosine kinase)

 BTK_HUMAN               Reviewed;         659 AA.
Q06187; B2RAW1; Q32ML5;
01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
23-JAN-2007, sequence version 3.
27-SEP-2017, entry version 220.
RecName: Full=Tyrosine-protein kinase BTK;
EC=2.7.10.2;
AltName: Full=Agammaglobulinemia tyrosine kinase;
Short=ATK;
AltName: Full=B-cell progenitor kinase;
Short=BPK;
AltName: Full=Bruton tyrosine kinase;
Name=BTK; Synonyms=AGMX1, ATK, BPK;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BTK-A).
PubMed=8380905; DOI=10.1038/361226a0;
Vetrie D., Vorechovsky I., Sideras P., Holland J., Davies A.,
Flinter F., Hammarstroem L., Kinnon C., Levinsky R.J., Bobrow M.,
Smith C.I.E., Bentley D.R.;
"The gene involved in X-linked agammaglobulinaemia is a member of the
src family of protein-tyrosine kinases.";
Nature 361:226-233(1993).
[2]
ERRATUM.
Vetrie D., Vorechovsky I., Sideras P., Holland J., Davies A.,
Flinter F., Hammarstroem L., Kinnon C., Levinsky R.J., Bobrow M.,
Smith C.I.E., Bentley D.R.;
Nature 364:362-362(1993).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
TISSUE=Blood;
PubMed=8090769; DOI=10.1073/pnas.91.19.9062;
Ohta Y., Haire R.N., Litman R.T., Fu S.M., Nelson R.P., Kratz J.,
Kornfeld S.J., la Morena M., Good R.A., Litman G.W.;
"Genomic organization and structure of Bruton agammaglobulinemia
tyrosine kinase: localization of mutations associated with varied
clinical presentations and course in X chromosome-linked
agammaglobulinemia.";
Proc. Natl. Acad. Sci. U.S.A. 91:9062-9066(1994).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=7927535; DOI=10.1007/BF01246672;
Rohrer J., Parolini O., Belmont J.W., Conley M.E.;
"The genomic structure of human BTK, the defective gene in X-linked
agammaglobulinemia.";
Immunogenetics 40:319-324(1994).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS XLA SER-334; ARG-506;
GLN-520; TRP-562 AND LYS-630.
PubMed=7880320; DOI=10.1093/hmg/3.10.1743;
Hagemann T.L., Chen Y., Rosen F.S., Kwan S.-P.;
"Genomic organization of the Btk gene and exon scanning for mutations
in patients with X-linked agammaglobulinemia.";
Hum. Mol. Genet. 3:1743-1749(1994).
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=7626884; DOI=10.1007/BF00364796;
Oeltjen J.C., Liu X., Lu J., Allen R.C., Muzny D.M., Belmont J.W.,
Gibbs R.A.;
"Sixty-nine kilobases of contiguous human genomic sequence containing
the alpha-galactosidase A and Bruton's tyrosine kinase loci.";
Mamm. Genome 6:334-338(1995).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BTK-A).
TISSUE=Umbilical cord blood;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15772651; DOI=10.1038/nature03440;
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence of the human X chromosome.";
Nature 434:325-337(2005).
[9]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BTK-A).
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[10]
NUCLEOTIDE SEQUENCE OF 1-442.
PubMed=8425221; DOI=10.1016/0092-8674(93)90667-F;
Tsukada S., Saffran D.C., Rawlings D.J., Parolini O., Allen R.C.,
Klisak I., Sparkes R.S., Kubagawa H., Mohandas T., Quan S.,
Belmont J.W., Cooper M.D., Conley M.E., Witte O.N.;
"Deficient expression of a B cell cytoplasmic tyrosine kinase in human
X-linked agammaglobulinemia.";
Cell 72:279-290(1993).
[11]
PROTEIN SEQUENCE OF 2-12 AND 323-332, CLEAVAGE OF INITIATOR
METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS
SPECTROMETRY.
TISSUE=Platelet;
Bienvenut W.V., Claeys D.;
Submitted (NOV-2005) to UniProtKB.
[12]
PROTEIN SEQUENCE OF 219-235, AND PHOSPHORYLATION AT TYR-223.
PubMed=12573241; DOI=10.1016/S1570-9639(02)00524-1;
Nore B.F., Mattsson P.T., Antonsson P., Backesjo C.-M., Westlund A.,
Lennartsson J., Hansson H., Low P., Ronnstrand L., Smith C.I.E.;
"Identification of phosphorylation sites within the SH3 domains of Tec
family tyrosine kinases.";
Biochim. Biophys. Acta 1645:123-132(2003).
[13]
INVOLVEMENT IN XLA-IGHD.
PubMed=8013627; DOI=10.1016/0014-5793(94)00457-9;
Duriez B., Duquesnoy P., Dastot F., Bougneres P., Amselem S.,
Goossens M.;
"An exon-skipping mutation in the btk gene of a patient with X-linked
agammaglobulinemia and isolated growth hormone deficiency.";
FEBS Lett. 346:165-170(1994).
[14]
DOMAIN PH.
PubMed=8070576; DOI=10.1016/0014-5793(94)00783-7;
Vihinen M., Nilsson L., Smith C.I.;
"Tec homology (TH) adjacent to the PH domain.";
FEBS Lett. 350:263-265(1994).
[15]
PHOSPHORYLATION AT TYR-223 AND TYR-551, MUTAGENESIS OF TYR-223, AND
ENZYME REGULATION.
PubMed=8630736; DOI=10.1016/S1074-7613(00)80417-3;
Park H., Wahl M.I., Afar D.E., Turck C.W., Rawlings D.J., Tam C.,
Scharenberg A.M., Kinet J.P., Witte O.N.;
"Regulation of Btk function by a major autophosphorylation site within
the SH3 domain.";
Immunity 4:515-525(1996).
[16]
FUNCTION IN PHOSPHORYLATION OF GTF2I, PHOSPHORYLATION AT TYR-223 AND
TYR-551, AND MUTAGENESIS OF GLU-41; PRO-189; TYR-223; TRP-251; ARG-307
AND TYR-551.
PubMed=9012831; DOI=10.1073/pnas.94.2.604;
Yang W., Desiderio S.;
"BAP-135, a target for Bruton's tyrosine kinase in response to B cell
receptor engagement.";
Proc. Natl. Acad. Sci. U.S.A. 94:604-609(1997).
[17]
MUTAGENESIS OF 251-TRP-TRP-252, AND INTERACTION WITH SH3BP5.
PubMed=9571151; DOI=10.1006/bbrc.1998.8420;
Matsushita M., Yamadori T., Kato S., Takemoto Y., Inazawa J., Baba Y.,
Hashimoto S., Sekine S., Arai S., Kunikata T., Kurimoto M.,
Kishimoto T., Tsukada S.;
"Identification and characterization of a novel SH3-domain binding
protein, Sab, which preferentially associates with Bruton's tyrosine
kinase (Btk).";
Biochem. Biophys. Res. Commun. 245:337-343(1998).
[18]
DOMAIN PH, AND SUBCELLULAR LOCATION.
PubMed=10196179; DOI=10.1074/jbc.274.16.10983;
Varnai P., Rother K.I., Balla T.;
"Phosphatidylinositol 3-kinase-dependent membrane association of the
Bruton's tyrosine kinase pleckstrin homology domain visualized in
single living cells.";
J. Biol. Chem. 274:10983-10989(1999).
[19]
INTERACTION WITH SH3BP5, AND ENZYME REGULATION.
PubMed=10339589; DOI=10.1073/pnas.96.11.6341;
Yamadori T., Baba Y., Mastushita M., Hashimoto S., Kurosaki M.,
Kurosaki T., Kishimoto T., Tsukada S.;
"Bruton's tyrosine kinase activity is negatively regulated by Sab, the
Btk-SH3 domain-binding protein.";
Proc. Natl. Acad. Sci. U.S.A. 96:6341-6346(1999).
[20]
SUBCELLULAR LOCATION.
PubMed=10602036;
DOI=10.1002/1521-4141(200001)30:1<145::AID-IMMU145>3.0.CO;2-0;
Nore B.F., Vargas L., Mohamed A.J., Branden L.J., Backesjo C.M.,
Islam T.C., Mattsson P.T., Hultenby K., Christensson B., Smith C.I.;
"Redistribution of Bruton's tyrosine kinase by activation of
phosphatidylinositol 3-kinase and Rho-family GTPases.";
Eur. J. Immunol. 30:145-154(2000).
[21]
SUBCELLULAR LOCATION.
PubMed=11016936; DOI=10.1074/jbc.M006952200;
Mohamed A.J., Vargas L., Nore B.F., Backesjo C.M., Christensson B.,
Smith C.I.;
"Nucleocytoplasmic shuttling of Bruton's tyrosine kinase.";
J. Biol. Chem. 275:40614-40619(2000).
[22]
PHOSPHORYLATION AT SER-180, AND ENZYME REGULATION.
PubMed=11598012; DOI=10.1093/emboj/20.20.5692;
Kang S.W., Wahl M.I., Chu J., Kitaura J., Kawakami Y., Kato R.M.,
Tabuchi R., Tarakhovsky A., Kawakami T., Turck C.W., Witte O.N.,
Rawlings D.J.;
"PKCbeta modulates antigen receptor signaling via regulation of Btk
membrane localization.";
EMBO J. 20:5692-5702(2001).
[23]
FUNCTION IN PHOSPHORYLATION OF PLCG2.
PubMed=11606584; DOI=10.1074/jbc.M107577200;
Rodriguez R., Matsuda M., Perisic O., Bravo J., Paul A., Jones N.P.,
Light Y., Swann K., Williams R.L., Katan M.;
"Tyrosine residues in phospholipase Cgamma 2 essential for the enzyme
function in B-cell signaling.";
J. Biol. Chem. 276:47982-47992(2001).
[24]
INTERACTION WITH IBTK, AND ENZYME REGULATION.
PubMed=11577348; DOI=10.1038/ni1001-939;
Liu W., Quinto I., Chen X., Palmieri C., Rabin R.L., Schwartz O.M.,
Nelson D.L., Scala G.;
"Direct inhibition of Bruton's tyrosine kinase by IBtk, a Btk-binding
protein.";
Nat. Immunol. 2:939-946(2001).
[25]
DOMAIN, INTERACTION WITH CAV1, SUBCELLULAR LOCATION, AND ENZYME
REGULATION.
PubMed=11751885; DOI=10.1074/jbc.M108537200;
Vargas L., Nore B.F., Berglof A., Heinonen J.E., Mattsson P.T.,
Smith C.I., Mohamed A.J.;
"Functional interaction of caveolin-1 with Bruton's tyrosine kinase
and Bmx.";
J. Biol. Chem. 277:9351-9357(2002).
[26]
PHOSPHORYLATION AT TYR-617 AND SER-623, AND MUTAGENESIS OF TYR-617.
PubMed=15375214; DOI=10.1073/pnas.0405878101;
Guo S., Ferl G.Z., Deora R., Riedinger M., Yin S., Kerwin J.L.,
Loo J.A., Witte O.N.;
"A phosphorylation site in Bruton's tyrosine kinase selectively
regulates B cell calcium signaling efficiency by altering
phospholipase C-gamma activation.";
Proc. Natl. Acad. Sci. U.S.A. 101:14180-14185(2004).
[27]
INTERACTION WITH PIN1, PHOSPHORYLATION AT SER-21 AND SER-115, AND
ENZYME REGULATION.
PubMed=16644721; DOI=10.1074/jbc.M603090200;
Yu L., Mohamed A.J., Vargas L., Berglof A., Finn G., Lu K.P.,
Smith C.I.;
"Regulation of Bruton tyrosine kinase by the peptidylprolyl isomerase
Pin1.";
J. Biol. Chem. 281:18201-18207(2006).
[28]
FUNCTION IN THE TLR PATHWAY.
PubMed=16517732; DOI=10.4049/jimmunol.176.6.3635;
Horwood N.J., Page T.H., McDaid J.P., Palmer C.D., Campbell J.,
Mahon T., Brennan F.M., Webster D., Foxwell B.M.;
"Bruton's tyrosine kinase is required for TLR2 and TLR4-induced TNF,
but not IL-6, production.";
J. Immunol. 176:3635-3641(2006).
[29]
INTERACTION WITH GTF2I AND ARID3A, AND FUNCTION.
PubMed=16738337; DOI=10.1128/MCB.02009-05;
Rajaiya J., Nixon J.C., Ayers N., Desgranges Z.P., Roy A.L.,
Webb C.F.;
"Induction of immunoglobulin heavy-chain transcription through the
transcription factor Bright requires TFII-I.";
Mol. Cell. Biol. 26:4758-4768(2006).
[30]
FUNCTION IN PHOSPHORYLATION OF TIRAP, AND ENZYME REGULATION.
PubMed=16415872; DOI=10.1038/ni1299;
Mansell A., Smith R., Doyle S.L., Gray P., Fenner J.E., Crack P.J.,
Nicholson S.E., Hilton D.J., O'Neill L.A., Hertzog P.J.;
"Suppressor of cytokine signaling 1 negatively regulates Toll-like
receptor signaling by mediating Mal degradation.";
Nat. Immunol. 7:148-155(2006).
[31]
FUNCTION, INTERACTION WITH TLR8 AND TLR9, ENZYME REGULATION, AND
PHOSPHORYLATION AT TYR-223.
PubMed=17932028; DOI=10.1074/jbc.M707682200;
Doyle S.L., Jefferies C.A., Feighery C., O'Neill L.A.;
"Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine
kinase.";
J. Biol. Chem. 282:36953-36960(2007).
[32]
INTERACTION WITH FASLG.
PubMed=19807924; DOI=10.1186/1471-2172-10-53;
Voss M., Lettau M., Janssen O.;
"Identification of SH3 domain interaction partners of human FasL
(CD178) by phage display screening.";
BMC Immunol. 10:53-53(2009).
[33]
REVIEW ON FUNCTION IN REGULATION OF APOPTOSIS.
PubMed=9751072; DOI=10.1016/S0006-2952(98)00122-1;
Uckun F.M.;
"Bruton's tyrosine kinase (BTK) as a dual-function regulator of
apoptosis.";
Biochem. Pharmacol. 56:683-691(1998).
[34]
REVIEW ON FUNCTION, AND REVIEW ON ENZYME REGULATION.
PubMed=19290921; DOI=10.1111/j.1600-065X.2008.00741.x;
Mohamed A.J., Yu L., Backesjo C.M., Vargas L., Faryal R., Aints A.,
Christensson B., Berglof A., Vihinen M., Nore B.F., Smith C.I.;
"Bruton's tyrosine kinase (Btk): function, regulation, and
transformation with special emphasis on the PH domain.";
Immunol. Rev. 228:58-73(2009).
[35]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55; THR-191; TYR-361 AND
SER-659, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].
PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
Mann M., Daub H.;
"Large-scale proteomics analysis of the human kinome.";
Mol. Cell. Proteomics 8:1751-1764(2009).
[36]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[37]
ALTERNATIVE PROMOTER USAGE (ISOFORM BTK-C).
PubMed=23913792; DOI=10.1002/gcc.22091;
Eifert C., Wang X., Kokabee L., Kourtidis A., Jain R., Gerdes M.J.,
Conklin D.S.;
"A novel isoform of the B cell tyrosine kinase BTK protects breast
cancer cells from apoptosis.";
Genes Chromosomes Cancer 52:961-975(2013).
[38]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-191; TYR-223 AND
SER-604, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].
TISSUE=Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[39]
ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=25944712; DOI=10.1002/pmic.201400617;
Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M.,
Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
"N-terminome analysis of the human mitochondrial proteome.";
Proteomics 15:2519-2524(2015).
[40]
X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 2-170 IN COMPLEX WITH ZINC.
PubMed=9218782; DOI=10.1093/emboj/16.12.3396;
Hyvoenen M., Saraste M.;
"Structure of the PH domain and Btk motif from Bruton's tyrosine
kinase: molecular explanations for X-linked agammaglobulinaemia.";
EMBO J. 16:3396-3404(1997).
[41]
STRUCTURE BY NMR OF 212-275.
PubMed=9485443; DOI=10.1021/bi972409f;
Hansson H., Mattsson P.T., Allard P., Haapaniemi P., Vihinen M.,
Smith C.I.E., Haerd T.;
"Solution structure of the SH3 domain from Bruton's tyrosine kinase.";
Biochemistry 37:2912-2924(1998).
[42]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-170 IN COMPLEX WITH
INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE AND ZINC, AND DOMAIN PH.
PubMed=10196129; DOI=10.1016/S0969-2126(99)80057-4;
Baraldi E., Carugo K.D., Hyvoenen M., Surdo P.L., Riley A.M.,
Potter B.V.L., O'Brien R., Ladbury J.E., Saraste M.;
"Structure of the PH domain from Bruton's tyrosine kinase in complex
with inositol 1,3,4,5-tetrakisphosphate.";
Structure 7:449-460(1999).
[43]
STRUCTURE BY NMR OF 216-273.
PubMed=10826882; DOI=10.1023/A:1008376624863;
Tzeng S.R., Lou Y.C., Pai M.T., Jain M.L., Cheng J.W.;
"Solution structure of the human BTK SH3 domain complexed with a
proline-rich peptide from p120cbl.";
J. Biomol. NMR 16:303-312(2000).
[44]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 397-659.
PubMed=11527964; DOI=10.1074/jbc.M104828200;
Mao C., Zhou M., Uckun F.M.;
"Crystal structure of Bruton's tyrosine kinase domain suggests a novel
pathway for activation and provides insights into the molecular basis
of X-linked agammaglobulinemia.";
J. Biol. Chem. 276:41435-41443(2001).
[45]
STRUCTURE BY NMR OF 270-386.
PubMed=16969585; DOI=10.1007/s10858-006-9064-3;
Huang K.C., Cheng H.T., Pai M.T., Tzeng S.R., Cheng J.W.;
"Solution structure and phosphopeptide binding of the SH2 domain from
the human Bruton's tyrosine kinase.";
J. Biomol. NMR 36:73-78(2006).
[46]
X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 393-656 IN COMPLEX WITH
INHIBITOR.
Di Paolo J.A., Huang T., Balazs M., Barbosa J., Barck K.H.,
Carano R.A.D., Darrow J., Davies D.R., DeForge L.E., Dennis G. Jr.,
Diehl L., Ferrando R.;
"A novel, specific Btk inhibitor antagonizes BCR and Fc[gamma]R
signaling and suppresses inflammatory arthritis.";
Submitted (AUG-2010) to the PDB data bank.
[47]
X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS) OF 2-170 IN COMPLEX WITH
INHIBITOR AND ZINC.
Murayama K., Kato-Murayama M., Mishima C., Shirouzu M., Yokoyama S.;
"Crystal structure of PH domain of Bruton's tyrosine kinase.";
Submitted (MAY-2007) to the PDB data bank.
[48]
X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 382-659 IN COMPLEX WITH
INHIBITOR DASATINIB.
PubMed=20052711; DOI=10.1002/pro.321;
Marcotte D.J., Liu Y.T., Arduini R.M., Hession C.A., Miatkowski K.,
Wildes C.P., Cullen P.F., Hong V., Hopkins B.T., Mertsching E.,
Jenkins T.J., Romanowski M.J., Baker D.P., Silvian L.F.;
"Structures of human Bruton's tyrosine kinase in active and inactive
conformations suggest a mechanism of activation for TEC family
kinases.";
Protein Sci. 19:429-439(2010).
[49]
X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 393-659.
Di Paolo J., Huang T., Balazs M., Barbosa J., Barck K.H., Bravo B.,
Carano R.A.D., Darrow J., Davies D.R., DeForge L.E., Diehl L.,
Ferrando R., Gallion S.L., Gianetti A.M., Gribling P., Hurez V.,
Hymowitz S.G., Jones R., Kropf J.E., Lee W.P., Maciejewski P.M.,
Mitchell S.A., Rong H., Staker B.L., Whitney J.A., Yeh S., Young W.,
Yu C., Zhang J., Reif K., Currie K.S.;
"A novel, specific BTK inhibitor antagonizes BCR and FcgR signaling
and suppresses inflammatory arthritis.";
Submitted (SEP-2010) to the PDB data bank.
[50]
X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 387-659 IN COMPLEX WITH
INHIBITOR.
PubMed=21280133; DOI=10.1002/pro.575;
Kuglstatter A., Wong A., Tsing S., Lee S.W., Lou Y., Villasenor A.G.,
Bradshaw J.M., Shaw D., Barnett J.W., Browner M.F.;
"Insights into the conformational flexibility of Bruton's tyrosine
kinase from multiple ligand complex structures.";
Protein Sci. 20:428-436(2011).
[51]
REVIEW ON VARIANTS XLA.
PubMed=8594569; DOI=10.1093/nar/24.1.160;
Vihinen M., Iwata T., Kinnon C., Kwan S.-P., Ochs H.D.,
Vorechovsky I., Smith C.I.E.;
"BTKbase, mutation database for X-linked agammaglobulinemia (XLA).";
Nucleic Acids Res. 24:160-165(1996).
[52]
REVIEW ON VARIANTS XLA.
PubMed=9016530; DOI=10.1093/nar/25.1.166;
Vihinen M., Belohradsky B.H., Haire R.N., Holinski-Feder E.,
Kwan S.-P., Lappalainen I., Lehvaeslaiho H., Lester T., Meindl A.,
Ochs H.D., Ollila J., Vorechovsky I., Weiss M., Smith C.I.E.;
"BTKbase, mutation database for X-linked agammaglobulinemia (XLA).";
Nucleic Acids Res. 25:166-171(1997).
[53]
VARIANTS XLA TRP-288; GLY-307; ASP-607 AND
SER-VAL-PHE-SER-SER-THR-ARG-103 INS.
PubMed=8162056; DOI=10.1093/hmg/3.1.79;
Bradley L.A.D., Sweatman A.K., Lovering R.C., Jones A.M., Morgan G.,
Levinsky R.J., Kinnon C.;
"Mutation detection in the X-linked agammaglobulinemia gene, BTK,
using single strand conformation polymorphism analysis.";
Hum. Mol. Genet. 3:79-83(1994).
[54]
VARIANTS XLA HIS-28 AND TRP-288.
PubMed=8162018; DOI=10.1093/hmg/3.1.161;
de Weers M., Mensink R.G.J., Kraakman M.E.M., Schuurman R.K.B.,
Hendriks R.W.;
"Mutation analysis of the Bruton's tyrosine kinase gene in X-linked
agammaglobulinemia: identification of a mutation which affects the
same codon as is altered in immunodeficient xid mice.";
Hum. Mol. Genet. 3:161-166(1994).
[55]
VARIANTS XLA ASP-113; CYS-361; GLN-520; PRO-542; TRP-562; LYS-630 AND
PRO-652.
PubMed=7849697; DOI=10.1093/hmg/3.10.1751;
Conley M.E., Fitch-Hilgenberg M.E., Cleveland J.L., Parolini O.,
Rohrer J.;
"Screening of genomic DNA to identify mutations in the gene for
Bruton's tyrosine kinase.";
Hum. Mol. Genet. 3:1751-1756(1994).
[56]
VARIANTS XLA HIS-28; PRO-33; PRO-408; GLY-589; ASP-613 AND
260-GLN--GLU-280 DEL.
PubMed=7849721; DOI=10.1093/hmg/3.10.1899;
Zhu Q., Zhang M., Winkelstein J., Chen S.-H., Ochs H.D.;
"Unique mutations of Bruton's tyrosine kinase in fourteen unrelated X-
linked agammaglobulinemia families.";
Hum. Mol. Genet. 3:1899-1900(1994).
[57]
VARIANTS XLA GLU-430; GLN-520; GLN-525; PRO-562; VAL-582; GLY-589;
GLU-594 AND ASP-613.
PubMed=7809124; DOI=10.1073/pnas.91.26.12803;
Vihinen M., Vetrie D., Maniar H.S., Ochs H.D., Zhu Q., Vorechovsky I.,
Webster A.D.B., Notarangelo L.D., Nilsson L., Sowadski J.M.,
Smith C.I.E.;
"Structural basis for chromosome X-linked agammaglobulinemia: a
tyrosine kinase disease.";
Proc. Natl. Acad. Sci. U.S.A. 91:12803-12807(1994).
[58]
VARIANT XLA PHE-64, AND CHARACTERIZATION OF OTHER XLA VARIANTS.
PubMed=7849006; DOI=10.1021/bi00005a002;
Vihinen M., Zvelebil J.J.M., Zhu Q., Brooimans R.A., Ochs H.D.,
Zegers B.J.M., Nilsson L., Waterfield M.D., Smith C.I.E.;
"Structural basis for pleckstrin homology domain mutations in X-linked
agammaglobulinemia.";
Biochemistry 34:1475-1481(1995).
[59]
VARIANTS XLA SER-25; TRP-288; MET-370; VAL-509; PRO-525; LYS-526;
TRP-562; VAL-582 AND ARG-594.
PubMed=7711734; DOI=10.1093/hmg/4.1.51;
Vorechovsky I., Vihinen M., de Saint Basile G., Honsova S.,
Hammarstroem L., Mueller S., Nilsson L., Fischer A., Smith C.I.E.;
"DNA-based mutation analysis of Bruton's tyrosine kinase gene in
patients with X-linked agammaglobulinaemia.";
Hum. Mol. Genet. 4:51-58(1995).
[60]
VARIANTS XLA LYS-567; LEU-587 AND HIS-641.
PubMed=7633420; DOI=10.1093/hmg/4.4.693;
Jin H., Webster A.D.B., Vihinen M., Sideras P., Vorechovsky I.,
Hammarstroem L., Bernatowska-Matuszkiewicz E., Smith C.I.E.,
Bobrow M., Vetrie D.;
"Identification of Btk mutations in 20 unrelated patients with X-
linked agammaglobulinaemia (XLA).";
Hum. Mol. Genet. 4:693-700(1995).
[61]
VARIANTS XLA PRO-33; GLY-302 DEL; GLN-520 AND CYS-641.
PubMed=7633429; DOI=10.1093/hmg/4.4.755;
Gaspar H.B., Bradley L.A.D., Katz F., Lovering R.C., Roifman C.M.,
Morgan G., Levinsky R.J., Kinnon C.;
"Mutation analysis in Bruton's tyrosine kinase, the X-linked
agammaglobulinaemia gene, including identification of an insertional
hotspot.";
Hum. Mol. Genet. 4:755-757(1995).
[62]
VARIANTS XLA ASN-429 AND ARG-477.
PubMed=8634718; DOI=10.1093/hmg/4.12.2403;
Vorechovsky I., Luo L., de Saint Basile G., Hammarstroem L.,
Webster A.D.B., Smith C.I.E.;
"Improved oligonucleotide primer set for molecular diagnosis of X-
linked agammaglobulinaemia: predominance of amino acid substitutions
in the catalytic domain of Bruton's tyrosine kinase.";
Hum. Mol. Genet. 4:2403-2405(1995).
[63]
VARIANTS XLA GLU-302 AND ASP-476.
PubMed=7627183; DOI=10.1002/humu.1380050405;
Hagemann T.L., Rosen F.S., Kwan S.-P.;
"Characterization of germline mutations of the gene encoding Bruton's
tyrosine kinase in families with X-linked agammaglobulinemia.";
Hum. Mutat. 5:296-302(1995).
[64]
VARIANT XLA PHE-358.
PubMed=7897635; DOI=10.1136/jmg.32.1.77;
Ohashi Y., Tsuchiya S., Konno T.;
"A new point mutation involving a highly conserved leucine in the Btk
SH2 domain in a family with X linked agammaglobulinaemia.";
J. Med. Genet. 32:77-79(1995).
[65]
VARIANT XLA PRO-295.
PubMed=8723128;
DOI=10.1002/(SICI)1096-8628(19960503)63:1<318::AID-AJMG53>3.0.CO;2-N;
Schuster V., Seidenspinner S., Kreth H.W.;
"Detection of a novel mutation in the SRC homology domain 2 (SH2) of
Bruton's tyrosine kinase and direct female carrier evaluation in a
family with X-linked agammaglobulinemia.";
Am. J. Med. Genet. 63:318-322(1996).
[66]
VARIANTS XLA ARG-12; PRO-28; GLU-302; TRP-502; HIS-521; TYR-633 AND
SER-644.
PubMed=8695804;
Hashimoto S., Tsukada S., Matsushita M., Miyawaki T., Niida Y.,
Yachie A., Kobayashi S., Iwata T., Hayakawa H., Matsuoka H., Tsuge I.,
Yamadori T., Kunikata T., Arai S., Yoshizaki K., Taniguchi N.,
Kishimoto T.;
"Identification of Bruton's tyrosine kinase (Btk) gene mutations and
characterization of the derived proteins in 35 X-linked
agammaglobulinemia families: a nationwide study of Btk deficiency in
Japan.";
Blood 88:561-573(1996).
[67]
VARIANTS XLA TRP-288; LYS-544 AND PRO-592.
PubMed=8834236; DOI=10.1007/BF02267060;
Kobayashi S., Iwata T., Saito M., Iwasaki R., Matsumoto H.,
Naritaka S., Kono Y., Hayashi Y.;
"Mutations of the Btk gene in 12 unrelated families with X-linked
agammaglobulinemia in Japan.";
Hum. Genet. 97:424-430(1996).
[68]
VARIANTS XLA SER-154 AND ARG-155.
PubMed=9280283; DOI=10.1016/S0014-5793(97)00912-5;
Vihinen M., Nore B., Mattsson P.T., Backesj C.-M., Nars M.,
Koutaniemi S., Watanabe C., Lester T., Jones A.M., Ochs H.D.,
Smith C.I.E.;
"Missense mutations affecting a conserved cysteine pair in the TH
domain of Btk.";
FEBS Lett. 413:205-210(1997).
[69]
VARIANTS XLA.
PubMed=9260159;
Saha B.K., Curtis S.K., Vogler L.B., Vihinen M.;
"Molecular and structural characterization of five novel mutations in
the Bruton's tyrosine kinase gene from patients with X-linked
agammaglobulinemia.";
Mol. Med. 3:477-485(1997).
[70]
VARIANTS XLA GLN-288; THR-307; ARG-430; ASP-445; GLY-525; PHE-535;
LEU-563 AND PRO-622.
PubMed=9545398; DOI=10.1086/301828;
Conley M.E., Mathias D., Treadaway J., Minegishi Y., Rohrer J.;
"Mutations in btk in patients with presumed X-linked
agammaglobulinemia.";
Am. J. Hum. Genet. 62:1034-1043(1998).
[71]
VARIANTS XLA GLU-19; HIS-28; ASN-61; PRO-117; HIS-127; ARG-155;
PRO-295; PHE-369; GLY-372; ARG-414; TYR-506; GLY-521; GLN-525;
SER-559; TRP-562; GLU-594; THR-619; GLY-626 AND HIS-641.
PubMed=9445504; DOI=10.1542/peds.101.2.276;
Holinski-Feder E., Weiss M., Brandau O., Jedele K.B., Nore B.,
Baeckesjoe C.-M., Vihinen M., Hubbard S.R., Belohradsky B.H.,
Smith C.I.E., Meindl A.;
"Mutation screening of the BTK gene in 56 families with X-linked
agammaglobulinemia (XLA): 47 unique mutations without correlation to
clinical course.";
Pediatrics 101:276-284(1998).
[72]
VARIANTS XLA.
PubMed=10220140;
DOI=10.1002/(SICI)1098-1004(1999)13:4<280::AID-HUMU3>3.0.CO;2-L;
Vihinen M., Kwan S.-P., Lester T., Ochs H.D., Resnick I., Vaeliaho J.,
Conley M.E., Smith C.I.E.;
"Mutations of the human BTK gene coding for Bruton tyrosine kinase in
X-linked agammaglobulinemia.";
Hum. Mutat. 13:280-285(1999).
[73]
VARIANT XLA PRO-562.
PubMed=10678660;
DOI=10.1002/(SICI)1096-8628(20000131)90:3<229::AID-AJMG8>3.0.CO;2-Q;
Curtis S.K., Hebert M.D., Saha B.K.;
"Twin carriers of X-linked agammaglobulinemia (XLA) due to germline
mutation in the Btk gene.";
Am. J. Med. Genet. 90:229-232(2000).
[74]
VARIANTS XLA SER-39; PRO-512; GLN-512; GLY-544; TYR-578 AND LYS-589.
PubMed=10612838;
DOI=10.1002/(SICI)1098-1004(200001)15:1<117::AID-HUMU26>3.0.CO;2-H;
Orlandi P., Ritis K., Moschese V., Angelini F., Arvanitidis K.,
Speletas M., Sideras P., Plebani A., Rossi P.;
"Identification of nine novel mutations in the Bruton's tyrosine
kinase gene in X-linked agammaglobulinaemia patients.";
Hum. Mutat. 15:117-117(2000).
[75]
VARIANTS [LARGE SCALE ANALYSIS] LYS-82 AND LYS-190.
PubMed=17344846; DOI=10.1038/nature05610;
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
[76]
VARIANT SER-481, AND CHARACTERIZATION OF VARIANT SER-481.
PubMed=24869598; DOI=10.1056/NEJMoa1400029;
Woyach J.A., Furman R.R., Liu T.M., Ozer H.G., Zapatka M.,
Ruppert A.S., Xue L., Li D.H., Steggerda S.M., Versele M., Dave S.S.,
Zhang J., Yilmaz A.S., Jaglowski S.M., Blum K.A., Lozanski A.,
Lozanski G., James D.F., Barrientos J.C., Lichter P., Stilgenbauer S.,
Buggy J.J., Chang B.Y., Johnson A.J., Byrd J.C.;
"Resistance mechanisms for the Bruton's tyrosine kinase inhibitor
ibrutinib.";
N. Engl. J. Med. 370:2286-2294(2014).
[77]
CHARACTERIZATION OF VARIANT SER-481.
PubMed=24869597; DOI=10.1056/NEJMc1402716;
Furman R.R., Cheng S., Lu P., Setty M., Perez A.R., Perez A.R.,
Guo A., Racchumi J., Xu G., Wu H., Ma J., Steggerda S.M., Coleman M.,
Leslie C., Wang Y.L.;
"Ibrutinib resistance in chronic lymphocytic leukemia.";
N. Engl. J. Med. 370:2352-2354(2014).
[78]
CHARACTERIZATION OF VARIANT SER-481.
PubMed=25189416; DOI=10.1038/leu.2014.263;
Cheng S., Guo A., Lu P., Ma J., Coleman M., Wang Y.L.;
"Functional characterization of BTK(C481S) mutation that confers
ibrutinib resistance: exploration of alternative kinase inhibitors.";
Leukemia 29:895-900(2015).
-!- FUNCTION: Non-receptor tyrosine kinase indispensable for B
lymphocyte development, differentiation and signaling. Binding of
antigen to the B-cell antigen receptor (BCR) triggers signaling
that ultimately leads to B-cell activation. After BCR engagement
and activation at the plasma membrane, phosphorylates PLCG2 at
several sites, igniting the downstream signaling pathway through
calcium mobilization, followed by activation of the protein kinase
C (PKC) family members. PLCG2 phosphorylation is performed in
close cooperation with the adapter protein B-cell linker protein
BLNK. BTK acts as a platform to bring together a diverse array of
signaling proteins and is implicated in cytokine receptor
signaling pathways. Plays an important role in the function of
immune cells of innate as well as adaptive immunity, as a
component of the Toll-like receptors (TLR) pathway. The TLR
pathway acts as a primary surveillance system for the detection of
pathogens and are crucial to the activation of host defense.
Especially, is a critical molecule in regulating TLR9 activation
in splenic B-cells. Within the TLR pathway, induces tyrosine
phosphorylation of TIRAP which leads to TIRAP degradation. BTK
plays also a critical role in transcription regulation. Induces
the activity of NF-kappa-B, which is involved in regulating the
expression of hundreds of genes. BTK is involved on the signaling
pathway linking TLR8 and TLR9 to NF-kappa-B. Transiently
phosphorylates transcription factor GTF2I on tyrosine residues in
response to BCR. GTF2I then translocates to the nucleus to bind
regulatory enhancer elements to modulate gene expression. ARID3A
and NFAT are other transcriptional target of BTK. BTK is required
for the formation of functional ARID3A DNA-binding complexes.
There is however no evidence that BTK itself binds directly to
DNA. BTK has a dual role in the regulation of apoptosis.
{ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:16415872,
ECO:0000269|PubMed:16517732, ECO:0000269|PubMed:16738337,
ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:9012831}.
-!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a
[protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE-
ProRule:PRU10028}.
-!- COFACTOR:
Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
Note=Binds 1 zinc ion per subunit.;
-!- ENZYME REGULATION: Activated by phosphorylation. In primary B
lymphocytes, is almost always non-phosphorylated and is thus
catalytically inactive. Stimulation of TLR8 and TLR9 causes BTK
activation. As a negative feedback mechanism to fine-tune BCR
signaling, activated PRKCB down-modulates BTK function via direct
phosphorylation of BTK at Ser-180, resulting in translocation of
BTK back to the cytoplasmic fraction. PIN1, SH3BP5, and IBTK were
also identified as BTK activity inhibitors. Interaction with CAV1
leads to dramatic down-regulation of the kinase activity of BTK.
LFM-13A is a specific inhibitor of BTK. Dasatinib, a cancer drug
acting as a tyrosine kinase inhibitor, also blocks BTK activity.
{ECO:0000269|PubMed:10339589, ECO:0000269|PubMed:11577348,
ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:11751885,
ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16644721,
ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:8630736}.
-!- SUBUNIT: Binds GTF2I through the PH domain. Interacts with SH3BP5
via the SH3 domain. Interacts with IBTK via its PH domain.
Interacts with ARID3A, CAV1, FASLG, PIN1, TLR8 and TLR9.
{ECO:0000269|PubMed:10196129, ECO:0000269|PubMed:10339589,
ECO:0000269|PubMed:11577348, ECO:0000269|PubMed:11751885,
ECO:0000269|PubMed:16644721, ECO:0000269|PubMed:16738337,
ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:19807924,
ECO:0000269|PubMed:20052711, ECO:0000269|PubMed:21280133,
ECO:0000269|PubMed:9218782, ECO:0000269|PubMed:9571151,
ECO:0000269|Ref.46, ECO:0000269|Ref.47}.
-!- INTERACTION:
Self; NbExp=3; IntAct=EBI-624835, EBI-624835;
Q99856:ARID3A; NbExp=3; IntAct=EBI-624835, EBI-5458244;
Q8WV28:BLNK; NbExp=4; IntAct=EBI-624835, EBI-2623522;
P78347:GTF2I; NbExp=6; IntAct=EBI-624835, EBI-359622;
P08238:HSP90AB1; NbExp=2; IntAct=EBI-624835, EBI-352572;
P21145:MAL; NbExp=5; IntAct=EBI-624835, EBI-3932027;
P50222:MEOX2; NbExp=3; IntAct=EBI-624835, EBI-748397;
Q04759:PRKCQ; NbExp=2; IntAct=EBI-624835, EBI-374762;
O60239:SH3BP5; NbExp=4; IntAct=EBI-624835, EBI-624860;
P42768:WAS; NbExp=4; IntAct=EBI-624835, EBI-346375;
-!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral
membrane protein. Nucleus. Note=In steady state, BTK is
predominantly cytosolic. Following B-cell receptor (BCR)
engagement by antigen, translocates to the plasma membrane through
its PH domain. Plasma membrane localization is a critical step in
the activation of BTK. A fraction of BTK also shuttles between the
nucleus and the cytoplasm, and nuclear export is mediated by the
nuclear export receptor CRM1.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative promoter usage; Named isoforms=2;
Name=BTK-A;
IsoId=Q06187-1; Sequence=Displayed;
Name=BTK-C;
IsoId=Q06187-2; Sequence=VSP_053838;
Note=Produced by alternative promoter usage. Predominant form in
many tumor cells where it may function as an anti-apoptotic cell
survival factor.;
-!- TISSUE SPECIFICITY: Predominantly expressed in B-lymphocytes.
-!- DOMAIN: The PH domain mediates the binding to inositol
polyphosphate and phosphoinositides, leading to its targeting to
the plasma membrane. It is extended in the BTK kinase family by a
region designated the TH (Tec homology) domain, which consists of
about 80 residues preceding the SH3 domain.
{ECO:0000269|PubMed:10196129, ECO:0000269|PubMed:10196179,
ECO:0000269|PubMed:11751885, ECO:0000269|PubMed:8070576}.
-!- PTM: Following B-cell receptor (BCR) engagement, translocates to
the plasma membrane where it gets phosphorylated at Tyr-551 by LYN
and SYK. Phosphorylation at Tyr-551 is followed by
autophosphorylation of Tyr-223 which may create a docking site for
a SH2 containing protein. Phosphorylation at Ser-180 by PRKCB,
leads in translocation of BTK back to the cytoplasmic fraction.
Phosphorylation at Ser-21 and Ser-115 creates a binding site for
PIN1 at these Ser-Pro motifs, and promotes it's recruitment.
{ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:12573241,
ECO:0000269|PubMed:15375214, ECO:0000269|PubMed:16644721,
ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:8630736,
ECO:0000269|PubMed:9012831}.
-!- DISEASE: X-linked agammaglobulinemia (XLA) [MIM:300755]: Humoral
immunodeficiency disease which results in developmental defects in
the maturation pathway of B-cells. Affected boys have normal
levels of pre-B-cells in their bone marrow but virtually no
circulating mature B-lymphocytes. This results in a lack of
immunoglobulins of all classes and leads to recurrent bacterial
infections like otitis, conjunctivitis, dermatitis, sinusitis in
the first few years of life, or even some patients present
overwhelming sepsis or meningitis, resulting in death in a few
hours. Treatment in most cases is by infusion of intravenous
immunoglobulin. {ECO:0000269|PubMed:10220140,
ECO:0000269|PubMed:10612838, ECO:0000269|PubMed:10678660,
ECO:0000269|PubMed:7627183, ECO:0000269|PubMed:7633420,
ECO:0000269|PubMed:7633429, ECO:0000269|PubMed:7711734,
ECO:0000269|PubMed:7809124, ECO:0000269|PubMed:7849006,
ECO:0000269|PubMed:7849697, ECO:0000269|PubMed:7849721,
ECO:0000269|PubMed:7880320, ECO:0000269|PubMed:7897635,
ECO:0000269|PubMed:8013627, ECO:0000269|PubMed:8162018,
ECO:0000269|PubMed:8162056, ECO:0000269|PubMed:8594569,
ECO:0000269|PubMed:8634718, ECO:0000269|PubMed:8695804,
ECO:0000269|PubMed:8723128, ECO:0000269|PubMed:8834236,
ECO:0000269|PubMed:9016530, ECO:0000269|PubMed:9260159,
ECO:0000269|PubMed:9280283, ECO:0000269|PubMed:9445504,
ECO:0000269|PubMed:9545398}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: X-linked hypogammaglobulinemia and isolated growth
hormone deficiency (XLA-IGHD) [MIM:307200]: In rare cases XLA is
inherited together with isolated growth hormone deficiency (IGHD).
{ECO:0000269|PubMed:8013627}. Note=The disease may be caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
kinase family. TEC subfamily. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/BTKID851chXq22.html";
-!- WEB RESOURCE: Name=BTKbase; Note=BTK mutation db;
URL="http://structure.bmc.lu.se/idbase/BTKbase/";
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; X58957; CAA41728.1; -; mRNA.
EMBL; U10087; AAB60639.1; -; Genomic_DNA.
EMBL; U10084; AAB60639.1; JOINED; Genomic_DNA.
EMBL; U10085; AAB60639.1; JOINED; Genomic_DNA.
EMBL; U10086; AAB60639.1; JOINED; Genomic_DNA.
EMBL; L31572; AAA61479.1; -; Genomic_DNA.
EMBL; L31557; AAA61479.1; JOINED; Genomic_DNA.
EMBL; L31558; AAA61479.1; JOINED; Genomic_DNA.
EMBL; L31559; AAA61479.1; JOINED; Genomic_DNA.
EMBL; L31561; AAA61479.1; JOINED; Genomic_DNA.
EMBL; L31563; AAA61479.1; JOINED; Genomic_DNA.
EMBL; L31564; AAA61479.1; JOINED; Genomic_DNA.
EMBL; L31565; AAA61479.1; JOINED; Genomic_DNA.
EMBL; L31566; AAA61479.1; JOINED; Genomic_DNA.
EMBL; L31567; AAA61479.1; JOINED; Genomic_DNA.
EMBL; L31568; AAA61479.1; JOINED; Genomic_DNA.
EMBL; L31569; AAA61479.1; JOINED; Genomic_DNA.
EMBL; L31570; AAA61479.1; JOINED; Genomic_DNA.
EMBL; L31571; AAA61479.1; JOINED; Genomic_DNA.
EMBL; U13433; AAC51347.1; -; Genomic_DNA.
EMBL; U13410; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13412; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13413; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13414; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13415; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13416; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13417; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13422; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13423; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13424; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13425; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13427; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13428; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13429; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13430; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13431; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U13432; AAC51347.1; JOINED; Genomic_DNA.
EMBL; U78027; AAB64205.1; -; Genomic_DNA.
EMBL; AK314382; BAG37008.1; -; mRNA.
EMBL; AL035422; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC109079; AAI09080.1; -; mRNA.
EMBL; BC109080; AAI09081.1; -; mRNA.
CCDS; CCDS14482.1; -. [Q06187-1]
CCDS; CCDS76003.1; -. [Q06187-2]
PIR; I37212; A45184.
RefSeq; NP_000052.1; NM_000061.2. [Q06187-1]
RefSeq; NP_001274273.1; NM_001287344.1. [Q06187-2]
RefSeq; NP_001274274.1; NM_001287345.1.
UniGene; Hs.159494; -.
UniGene; Hs.733206; -.
PDB; 1AWW; NMR; -; A=212-275.
PDB; 1AWX; NMR; -; A=212-275.
PDB; 1B55; X-ray; 2.40 A; A/B=2-170.
PDB; 1BTK; X-ray; 1.60 A; A/B=2-170.
PDB; 1BWN; X-ray; 2.10 A; A/B=2-170.
PDB; 1K2P; X-ray; 2.10 A; A/B=397-659.
PDB; 1QLY; NMR; -; A=216-273.
PDB; 2GE9; NMR; -; A=270-387.
PDB; 2Z0P; X-ray; 2.58 A; A/B/C/D=2-170.
PDB; 3GEN; X-ray; 1.60 A; A=382-659.
PDB; 3K54; X-ray; 1.94 A; A=382-659.
PDB; 3OCS; X-ray; 1.80 A; A=393-656.
PDB; 3OCT; X-ray; 1.95 A; A=393-656.
PDB; 3P08; X-ray; 2.30 A; A/B=393-659.
PDB; 3PIX; X-ray; 1.85 A; A=387-659.
PDB; 3PIY; X-ray; 2.55 A; A=387-659.
PDB; 3PIZ; X-ray; 2.21 A; A=387-659.
PDB; 3PJ1; X-ray; 2.00 A; A=387-659.
PDB; 3PJ2; X-ray; 1.75 A; A=387-659.
PDB; 3PJ3; X-ray; 1.85 A; A=387-659.
PDB; 4NWM; X-ray; 2.03 A; A/B=396-657.
PDB; 4OT5; X-ray; 1.55 A; A=378-659.
PDB; 4OT6; X-ray; 2.05 A; A=378-659.
PDB; 4OTF; X-ray; 1.95 A; A=393-657.
PDB; 4OTQ; X-ray; 1.55 A; A=378-659.
PDB; 4OTR; X-ray; 1.95 A; A=378-659.
PDB; 4RFY; X-ray; 1.70 A; A=378-659.
PDB; 4RFZ; X-ray; 1.17 A; A=378-659.
PDB; 4RG0; X-ray; 2.50 A; A=378-659.
PDB; 4RX5; X-ray; 1.36 A; A=393-657.
PDB; 4YHF; X-ray; 2.20 A; A/B=382-659.
PDB; 4Z3V; X-ray; 1.60 A; A=382-659.
PDB; 4ZLY; X-ray; 1.65 A; A=389-658.
PDB; 4ZLZ; X-ray; 2.00 A; A=389-658.
PDB; 5BPY; X-ray; 2.31 A; A/B=396-659.
PDB; 5BQ0; X-ray; 1.57 A; A=382-659.
PDB; 5FBN; X-ray; 1.80 A; C/D=389-659.
PDB; 5FBO; X-ray; 1.89 A; A=389-659.
PDB; 5J87; X-ray; 1.59 A; A/B/C/D=385-658.
PDB; 5JRS; X-ray; 1.97 A; A/B=396-659.
PDB; 5KUP; X-ray; 1.39 A; A=393-657.
PDB; 5P9F; X-ray; 1.71 A; A=382-659.
PDB; 5P9G; X-ray; 1.75 A; A=382-659.
PDB; 5P9H; X-ray; 1.95 A; A=382-659.
PDB; 5P9I; X-ray; 1.11 A; A=382-659.
PDB; 5P9J; X-ray; 1.08 A; A=382-659.
PDB; 5P9K; X-ray; 1.28 A; A=382-659.
PDB; 5P9L; X-ray; 1.25 A; A=382-659.
PDB; 5P9M; X-ray; 1.41 A; A=382-659.
PDB; 5T18; X-ray; 1.50 A; A=396-659.
PDB; 5U9D; X-ray; 1.33 A; A=389-659.
PDBsum; 1AWW; -.
PDBsum; 1AWX; -.
PDBsum; 1B55; -.
PDBsum; 1BTK; -.
PDBsum; 1BWN; -.
PDBsum; 1K2P; -.
PDBsum; 1QLY; -.
PDBsum; 2GE9; -.
PDBsum; 2Z0P; -.
PDBsum; 3GEN; -.
PDBsum; 3K54; -.
PDBsum; 3OCS; -.
PDBsum; 3OCT; -.
PDBsum; 3P08; -.
PDBsum; 3PIX; -.
PDBsum; 3PIY; -.
PDBsum; 3PIZ; -.
PDBsum; 3PJ1; -.
PDBsum; 3PJ2; -.
PDBsum; 3PJ3; -.
PDBsum; 4NWM; -.
PDBsum; 4OT5; -.
PDBsum; 4OT6; -.
PDBsum; 4OTF; -.
PDBsum; 4OTQ; -.
PDBsum; 4OTR; -.
PDBsum; 4RFY; -.
PDBsum; 4RFZ; -.
PDBsum; 4RG0; -.
PDBsum; 4RX5; -.
PDBsum; 4YHF; -.
PDBsum; 4Z3V; -.
PDBsum; 4ZLY; -.
PDBsum; 4ZLZ; -.
PDBsum; 5BPY; -.
PDBsum; 5BQ0; -.
PDBsum; 5FBN; -.
PDBsum; 5FBO; -.
PDBsum; 5J87; -.
PDBsum; 5JRS; -.
PDBsum; 5KUP; -.
PDBsum; 5P9F; -.
PDBsum; 5P9G; -.
PDBsum; 5P9H; -.
PDBsum; 5P9I; -.
PDBsum; 5P9J; -.
PDBsum; 5P9K; -.
PDBsum; 5P9L; -.
PDBsum; 5P9M; -.
PDBsum; 5T18; -.
PDBsum; 5U9D; -.
ProteinModelPortal; Q06187; -.
SMR; Q06187; -.
BioGrid; 107160; 80.
CORUM; Q06187; -.
DIP; DIP-34071N; -.
ELM; Q06187; -.
IntAct; Q06187; 50.
MINT; MINT-110243; -.
STRING; 9606.ENSP00000308176; -.
BindingDB; Q06187; -.
ChEMBL; CHEMBL5251; -.
DrugBank; DB09053; Ibrutinib.
DrugBank; DB05204; XL418.
GuidetoPHARMACOLOGY; 1948; -.
iPTMnet; Q06187; -.
PhosphoSitePlus; Q06187; -.
BioMuta; BTK; -.
DMDM; 547759; -.
EPD; Q06187; -.
MaxQB; Q06187; -.
PaxDb; Q06187; -.
PeptideAtlas; Q06187; -.
PRIDE; Q06187; -.
DNASU; 695; -.
Ensembl; ENST00000308731; ENSP00000308176; ENSG00000010671. [Q06187-1]
Ensembl; ENST00000621635; ENSP00000483570; ENSG00000010671. [Q06187-2]
GeneID; 695; -.
KEGG; hsa:695; -.
UCSC; uc004ehg.3; human. [Q06187-1]
CTD; 695; -.
DisGeNET; 695; -.
EuPathDB; HostDB:ENSG00000010671.15; -.
GeneCards; BTK; -.
GeneReviews; BTK; -.
HGNC; HGNC:1133; BTK.
HPA; CAB016689; -.
HPA; HPA001198; -.
HPA; HPA002028; -.
MalaCards; BTK; -.
MIM; 300300; gene.
MIM; 300755; phenotype.
MIM; 307200; phenotype.
neXtProt; NX_Q06187; -.
OpenTargets; ENSG00000010671; -.
Orphanet; 632; Short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia.
Orphanet; 47; X-linked agammaglobulinemia.
PharmGKB; PA25454; -.
eggNOG; KOG0197; Eukaryota.
eggNOG; COG0515; LUCA.
GeneTree; ENSGT00760000119011; -.
HOGENOM; HOG000233859; -.
HOVERGEN; HBG008761; -.
InParanoid; Q06187; -.
KO; K07370; -.
OMA; KYGKWQG; -.
OrthoDB; EOG091G0D46; -.
PhylomeDB; Q06187; -.
TreeFam; TF351634; -.
BRENDA; 2.7.10.2; 2681.
Reactome; R-HSA-1236974; ER-Phagosome pathway.
Reactome; R-HSA-166058; MyD88:Mal cascade initiated on plasma membrane.
Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
Reactome; R-HSA-2424491; DAP12 signaling.
Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization.
Reactome; R-HSA-5602498; MyD88 deficiency (TLR2/4).
Reactome; R-HSA-5603041; IRAK4 deficiency (TLR2/4).
Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs.
Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
SignaLink; Q06187; -.
SIGNOR; Q06187; -.
ChiTaRS; BTK; human.
EvolutionaryTrace; Q06187; -.
GeneWiki; Bruton%27s_tyrosine_kinase; -.
GenomeRNAi; 695; -.
PRO; PR:Q06187; -.
Proteomes; UP000005640; Chromosome X.
Bgee; ENSG00000010671; -.
CleanEx; HS_BTK; -.
ExpressionAtlas; Q06187; baseline and differential.
Genevisible; Q06187; HS.
GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl.
GO; GO:0005829; C:cytosol; IDA:UniProtKB.
GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
GO; GO:0042629; C:mast cell granule; IEA:GOC.
GO; GO:0045121; C:membrane raft; IDA:HGNC.
GO; GO:0005634; C:nucleus; TAS:UniProtKB.
GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
GO; GO:0005524; F:ATP binding; TAS:HGNC.
GO; GO:0042802; F:identical protein binding; IPI:IntAct.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; TAS:UniProtKB.
GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
GO; GO:0004713; F:protein tyrosine kinase activity; EXP:Reactome.
GO; GO:0005102; F:receptor binding; IBA:GO_Central.
GO; GO:0002250; P:adaptive immune response; TAS:UniProtKB.
GO; GO:0097190; P:apoptotic signaling pathway; TAS:ProtInc.
GO; GO:0042113; P:B cell activation; TAS:UniProtKB.
GO; GO:0002344; P:B cell affinity maturation; IEA:Ensembl.
GO; GO:0050853; P:B cell receptor signaling pathway; TAS:UniProtKB.
GO; GO:0019722; P:calcium-mediated signaling; TAS:HGNC.
GO; GO:0048469; P:cell maturation; IEA:Ensembl.
GO; GO:0098761; P:cellular response to interleukin-7; IEA:Ensembl.
GO; GO:0071226; P:cellular response to molecule of fungal origin; IEA:Ensembl.
GO; GO:0034614; P:cellular response to reactive oxygen species; IEA:Ensembl.
GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
GO; GO:0002553; P:histamine secretion by mast cell; IEA:Ensembl.
GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
GO; GO:0045087; P:innate immune response; TAS:UniProtKB.
GO; GO:0035556; P:intracellular signal transduction; TAS:HGNC.
GO; GO:0007498; P:mesoderm development; TAS:ProtInc.
GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
GO; GO:0030889; P:negative regulation of B cell proliferation; IEA:Ensembl.
GO; GO:0001818; P:negative regulation of cytokine production; IEA:Ensembl.
GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IBA:GO_Central.
GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:CACAO.
GO; GO:0045579; P:positive regulation of B cell differentiation; TAS:UniProtKB.
GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:UniProtKB.
GO; GO:0001812; P:positive regulation of type I hypersensitivity; IEA:Ensembl.
GO; GO:0001805; P:positive regulation of type III hypersensitivity; IEA:Ensembl.
GO; GO:0006468; P:protein phosphorylation; TAS:HGNC.
GO; GO:0002902; P:regulation of B cell apoptotic process; TAS:UniProtKB.
GO; GO:0002721; P:regulation of B cell cytokine production; TAS:UniProtKB.
GO; GO:0042127; P:regulation of cell proliferation; IBA:GO_Central.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
CDD; cd11906; SH3_BTK; 1.
Gene3D; 2.30.29.30; -; 1.
Gene3D; 3.30.505.10; -; 1.
InterPro; IPR035574; BTK_SH3.
InterPro; IPR011009; Kinase-like_dom.
InterPro; IPR011993; PH_dom-like.
InterPro; IPR001849; PH_domain.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
InterPro; IPR000980; SH2.
InterPro; IPR001452; SH3_domain.
InterPro; IPR008266; Tyr_kinase_AS.
InterPro; IPR020635; Tyr_kinase_cat_dom.
InterPro; IPR001562; Znf_Btk_motif.
Pfam; PF00779; BTK; 1.
Pfam; PF00169; PH; 1.
Pfam; PF07714; Pkinase_Tyr; 1.
Pfam; PF00017; SH2; 1.
Pfam; PF00018; SH3_1; 1.
PRINTS; PR00401; SH2DOMAIN.
PRINTS; PR00452; SH3DOMAIN.
PRINTS; PR00402; TECBTKDOMAIN.
PRINTS; PR00109; TYRKINASE.
SMART; SM00107; BTK; 1.
SMART; SM00233; PH; 1.
SMART; SM00252; SH2; 1.
SMART; SM00326; SH3; 1.
SMART; SM00219; TyrKc; 1.
SUPFAM; SSF50044; SSF50044; 1.
SUPFAM; SSF50729; SSF50729; 1.
SUPFAM; SSF55550; SSF55550; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS50003; PH_DOMAIN; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PROSITE; PS50001; SH2; 1.
PROSITE; PS50002; SH3; 1.
PROSITE; PS51113; ZF_BTK; 1.
1: Evidence at protein level;
3D-structure; Acetylation; Adaptive immunity;
Alternative promoter usage; Apoptosis; ATP-binding; Cell membrane;
Complete proteome; Cytoplasm; Direct protein sequencing;
Disease mutation; Immunity; Innate immunity; Kinase; Lipid-binding;
Membrane; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
Polymorphism; Reference proteome; SH2 domain; SH3 domain;
Transcription; Transcription regulation; Transferase;
Tyrosine-protein kinase; Zinc; Zinc-finger.
INIT_MET 1 1 Removed. {ECO:0000244|PubMed:25944712,
ECO:0000269|Ref.11}.
CHAIN 2 659 Tyrosine-protein kinase BTK.
/FTId=PRO_0000088065.
DOMAIN 3 133 PH. {ECO:0000255|PROSITE-
ProRule:PRU00145}.
DOMAIN 214 274 SH3. {ECO:0000255|PROSITE-
ProRule:PRU00192}.
DOMAIN 281 377 SH2. {ECO:0000255|PROSITE-
ProRule:PRU00191}.
DOMAIN 402 655 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
ZN_FING 135 171 Btk-type. {ECO:0000255|PROSITE-
ProRule:PRU00432}.
NP_BIND 408 416 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
REGION 12 24 Inositol-(1,3,4,5)-tetrakisphosphate 1-
binding.
REGION 474 479 Inhibitor-binding.
MOTIF 581 588 CAV1-binding.
ACT_SITE 521 521 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10028}.
METAL 143 143 Zinc. {ECO:0000269|PubMed:10196129,
ECO:0000269|PubMed:9218782,
ECO:0000269|Ref.47}.
METAL 154 154 Zinc. {ECO:0000269|PubMed:10196129,
ECO:0000269|PubMed:9218782,
ECO:0000269|Ref.47}.
METAL 155 155 Zinc. {ECO:0000269|PubMed:10196129,
ECO:0000269|PubMed:9218782,
ECO:0000269|Ref.47}.
METAL 165 165 Zinc. {ECO:0000269|PubMed:10196129,
ECO:0000269|PubMed:9218782,
ECO:0000269|Ref.47}.
BINDING 26 26 Inositol-(1,3,4,5)-tetrakisphosphate.
{ECO:0000269|PubMed:10196129}.
BINDING 28 28 Inositol-(1,3,4,5)-tetrakisphosphate.
{ECO:0000269|PubMed:10196129}.
BINDING 39 39 Inositol-(1,3,4,5)-tetrakisphosphate.
{ECO:0000269|PubMed:10196129}.
BINDING 53 53 Inositol-(1,3,4,5)-tetrakisphosphate; via
carbonyl oxygen.
{ECO:0000269|PubMed:10196129}.
BINDING 430 430 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
BINDING 445 445 Inhibitor. {ECO:0000269|PubMed:21280133,
ECO:0000269|Ref.46, ECO:0000269|Ref.47}.
BINDING 461 461 Inhibitor. {ECO:0000269|PubMed:21280133,
ECO:0000269|Ref.46, ECO:0000269|Ref.47}.
BINDING 477 477 Inhibitor. {ECO:0000269|PubMed:21280133,
ECO:0000269|Ref.46, ECO:0000269|Ref.47}.
BINDING 538 538 Inhibitor. {ECO:0000269|PubMed:21280133,
ECO:0000269|Ref.46, ECO:0000269|Ref.47}.
BINDING 539 539 Inhibitor; via amide nitrogen.
{ECO:0000269|PubMed:21280133,
ECO:0000269|Ref.46, ECO:0000269|Ref.47}.
BINDING 542 542 Inhibitor; via carbonyl oxygen.
{ECO:0000269|PubMed:21280133,
ECO:0000269|Ref.46, ECO:0000269|Ref.47}.
MOD_RES 2 2 N-acetylalanine.
{ECO:0000244|PubMed:25944712,
ECO:0000269|Ref.11}.
MOD_RES 21 21 Phosphoserine.
{ECO:0000269|PubMed:16644721}.
MOD_RES 40 40 Phosphotyrosine.
{ECO:0000250|UniProtKB:P35991}.
MOD_RES 55 55 Phosphoserine.
{ECO:0000244|PubMed:19369195}.
MOD_RES 115 115 Phosphoserine.
{ECO:0000269|PubMed:16644721}.
MOD_RES 180 180 Phosphoserine; by PKC/PRKCB.
{ECO:0000269|PubMed:11598012}.
MOD_RES 191 191 Phosphothreonine.
{ECO:0000244|PubMed:19369195,
ECO:0000244|PubMed:23186163}.
MOD_RES 223 223 Phosphotyrosine; by autocatalysis.
{ECO:0000244|PubMed:23186163,
ECO:0000269|PubMed:12573241,
ECO:0000269|PubMed:17932028,
ECO:0000269|PubMed:8630736,
ECO:0000269|PubMed:9012831}.
MOD_RES 344 344 Phosphotyrosine.
{ECO:0000250|UniProtKB:P35991}.
MOD_RES 361 361 Phosphotyrosine.
{ECO:0000244|PubMed:19369195}.
MOD_RES 551 551 Phosphotyrosine; by LYN and SYK.
{ECO:0000269|PubMed:8630736,
ECO:0000269|PubMed:9012831}.
MOD_RES 604 604 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 617 617 Phosphotyrosine.
{ECO:0000269|PubMed:15375214}.
MOD_RES 623 623 Phosphoserine.
{ECO:0000269|PubMed:15375214}.
MOD_RES 659 659 Phosphoserine.
{ECO:0000244|PubMed:19369195}.
VAR_SEQ 1 1 M -> MASWSIQQMVIGCPLCGRHCSGGEHTGELQKEEAM
(in isoform BTK-C). {ECO:0000305}.
/FTId=VSP_053838.
VARIANT 11 11 L -> P (in XLA).
/FTId=VAR_006216.
VARIANT 12 12 K -> R (in XLA).
{ECO:0000269|PubMed:8695804}.
/FTId=VAR_006217.
VARIANT 14 14 S -> F (in XLA).
/FTId=VAR_006218.
VARIANT 19 19 K -> E (in XLA).
{ECO:0000269|PubMed:9445504}.
/FTId=VAR_008291.
VARIANT 25 25 F -> S (in XLA).
{ECO:0000269|PubMed:7711734}.
/FTId=VAR_006219.
VARIANT 27 27 K -> R (in XLA).
/FTId=VAR_008292.
VARIANT 28 28 R -> C (in XLA; no effect on
phosphorylation of GTF2I).
/FTId=VAR_008293.
VARIANT 28 28 R -> H (in XLA; moderate;
dbSNP:rs128620185).
{ECO:0000269|PubMed:7849721,
ECO:0000269|PubMed:8162018,
ECO:0000269|PubMed:9445504}.
/FTId=VAR_006220.
VARIANT 28 28 R -> P (in XLA).
{ECO:0000269|PubMed:8695804}.
/FTId=VAR_006221.
VARIANT 33 33 T -> P (in XLA; severe;
dbSNP:rs128620189).
{ECO:0000269|PubMed:7633429,
ECO:0000269|PubMed:7849721}.
/FTId=VAR_006222.
VARIANT 39 39 Y -> S (in XLA).
{ECO:0000269|PubMed:10612838}.
/FTId=VAR_008960.
VARIANT 40 40 Y -> C (in XLA).
/FTId=VAR_008294.
VARIANT 40 40 Y -> N (in XLA).
/FTId=VAR_008295.
VARIANT 61 61 I -> N (in XLA).
{ECO:0000269|PubMed:9445504}.
/FTId=VAR_008296.
VARIANT 64 64 V -> D (in XLA).
/FTId=VAR_008297.
VARIANT 64 64 V -> F (in XLA).
{ECO:0000269|PubMed:7849006}.
/FTId=VAR_006223.
VARIANT 82 82 R -> K (in dbSNP:rs56035945).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_041676.
VARIANT 103 103 Q -> QSVFSSTR (in XLA).
/FTId=VAR_006224.
VARIANT 113 113 V -> D (in XLA; dbSNP:rs128621190).
{ECO:0000269|PubMed:7849697}.
/FTId=VAR_006225.
VARIANT 115 115 S -> F (in XLA).
/FTId=VAR_008298.
VARIANT 117 117 T -> P (in XLA).
{ECO:0000269|PubMed:9445504}.
/FTId=VAR_008299.
VARIANT 127 127 Q -> H (in XLA).
{ECO:0000269|PubMed:9445504}.
/FTId=VAR_008300.
VARIANT 154 154 C -> S (in XLA).
{ECO:0000269|PubMed:9280283}.
/FTId=VAR_008301.
VARIANT 155 155 C -> G (in XLA).
/FTId=VAR_008302.
VARIANT 155 155 C -> R (in XLA).
{ECO:0000269|PubMed:9280283,
ECO:0000269|PubMed:9445504}.
/FTId=VAR_008303.
VARIANT 184 184 T -> P (in XLA).
/FTId=VAR_008304.
VARIANT 190 190 P -> K (in a lung large cell carcinoma
sample; somatic mutation; requires 2
nucleotide substitutions).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_041677.
VARIANT 260 280 Missing (in XLA; severe).
{ECO:0000269|PubMed:7849721}.
/FTId=VAR_006226.
VARIANT 288 288 R -> Q (in XLA).
{ECO:0000269|PubMed:9545398}.
/FTId=VAR_008305.
VARIANT 288 288 R -> W (in XLA; dbSNP:rs128621194).
{ECO:0000269|PubMed:7711734,
ECO:0000269|PubMed:8162018,
ECO:0000269|PubMed:8162056,
ECO:0000269|PubMed:8834236}.
/FTId=VAR_006227.
VARIANT 295 295 L -> P (in XLA).
{ECO:0000269|PubMed:8723128,
ECO:0000269|PubMed:9445504}.
/FTId=VAR_006228.
VARIANT 302 302 G -> E (in XLA).
{ECO:0000269|PubMed:7627183,
ECO:0000269|PubMed:8695804}.
/FTId=VAR_006230.
VARIANT 302 302 G -> R (in XLA).
/FTId=VAR_008306.
VARIANT 302 302 Missing (in XLA).
{ECO:0000269|PubMed:7633429}.
/FTId=VAR_006229.
VARIANT 307 307 R -> G (in XLA; loss of activity;
dbSNP:rs128621195).
{ECO:0000269|PubMed:8162056}.
/FTId=VAR_006231.
VARIANT 307 307 R -> T (in XLA).
{ECO:0000269|PubMed:9545398}.
/FTId=VAR_008307.
VARIANT 308 308 D -> E (in XLA).
/FTId=VAR_008308.
VARIANT 319 319 V -> A (in XLA; moderate).
/FTId=VAR_008309.
VARIANT 334 334 Y -> S (in XLA; dbSNP:rs128621196).
{ECO:0000269|PubMed:7880320}.
/FTId=VAR_006232.
VARIANT 358 358 L -> F (in XLA).
{ECO:0000269|PubMed:7897635}.
/FTId=VAR_006233.
VARIANT 361 361 Y -> C (in XLA; mild; dbSNP:rs28935478).
{ECO:0000269|PubMed:7849697}.
/FTId=VAR_006234.
VARIANT 362 362 H -> Q (in XLA).
/FTId=VAR_006235.
VARIANT 364 364 H -> P (in XLA).
/FTId=VAR_006236.
VARIANT 365 365 N -> Y (in XLA).
/FTId=VAR_006237.
VARIANT 366 366 S -> F (in XLA).
/FTId=VAR_008310.
VARIANT 369 369 L -> F (in XLA).
{ECO:0000269|PubMed:9445504}.
/FTId=VAR_008311.
VARIANT 370 370 I -> M (in XLA).
{ECO:0000269|PubMed:7711734}.
/FTId=VAR_006238.
VARIANT 372 372 R -> G (in XLA).
{ECO:0000269|PubMed:9445504}.
/FTId=VAR_008312.
VARIANT 408 408 L -> P (in XLA; moderate;
dbSNP:rs128621198).
{ECO:0000269|PubMed:7849721}.
/FTId=VAR_006239.
VARIANT 414 414 G -> R (in XLA).
{ECO:0000269|PubMed:9445504}.
/FTId=VAR_008313.
VARIANT 418 418 Y -> H (in XLA; dbSNP:rs144079566).
/FTId=VAR_006240.
VARIANT 429 429 I -> N (in XLA).
{ECO:0000269|PubMed:8634718}.
/FTId=VAR_006241.
VARIANT 430 430 K -> E (in XLA; loss of phosphorylation
of GTF2I; dbSNP:rs128620184).
{ECO:0000269|PubMed:7809124}.
/FTId=VAR_006242.
VARIANT 430 430 K -> R (in XLA).
{ECO:0000269|PubMed:9545398}.
/FTId=VAR_008314.
VARIANT 445 445 E -> D (in XLA).
{ECO:0000269|PubMed:9545398}.
/FTId=VAR_008315.
VARIANT 462 462 G -> D (in XLA).
/FTId=VAR_008316.
VARIANT 462 462 G -> V (in XLA).
/FTId=VAR_008317.
VARIANT 476 476 Y -> D (in XLA).
{ECO:0000269|PubMed:7627183}.
/FTId=VAR_006243.
VARIANT 477 477 M -> R (in XLA).
{ECO:0000269|PubMed:8634718}.
/FTId=VAR_006244.
VARIANT 481 481 C -> S (found in patients with chronic
lymphocytic leukemia; unknown
pathological significance; results in
resistance to ibrutinib therapy; results
in a protein that is reversibly inhibited
by ibrutinib; disrupts the covalent
binding between the enzyme and
ibrutinib). {ECO:0000269|PubMed:24869597,
ECO:0000269|PubMed:24869598,
ECO:0000269|PubMed:25189416}.
/FTId=VAR_074309.
VARIANT 502 502 C -> F (in XLA).
/FTId=VAR_006245.
VARIANT 502 502 C -> W (in XLA; dbSNP:rs41310709).
{ECO:0000269|PubMed:8695804}.
/FTId=VAR_006246.
VARIANT 506 506 C -> R (in XLA; dbSNP:rs128621200).
{ECO:0000269|PubMed:7880320}.
/FTId=VAR_006247.
VARIANT 506 506 C -> Y (in XLA).
{ECO:0000269|PubMed:9445504}.
/FTId=VAR_006248.
VARIANT 508 508 A -> D (in XLA).
/FTId=VAR_008318.
VARIANT 509 509 M -> I (in XLA).
/FTId=VAR_008319.
VARIANT 509 509 M -> V (in XLA).
{ECO:0000269|PubMed:7711734}.
/FTId=VAR_006249.
VARIANT 512 512 L -> P (in XLA).
{ECO:0000269|PubMed:10612838}.
/FTId=VAR_008961.
VARIANT 512 512 L -> Q (in XLA).
{ECO:0000269|PubMed:10612838}.
/FTId=VAR_008962.
VARIANT 518 518 L -> R (in XLA).
/FTId=VAR_008320.
VARIANT 520 520 R -> Q (in XLA; severe; prevents
activation due to absence of contact
between the catalytic loop and the
regulatory phosphorylated residue;
dbSNP:rs128621202).
{ECO:0000269|PubMed:7633429,
ECO:0000269|PubMed:7809124,
ECO:0000269|PubMed:7849697,
ECO:0000269|PubMed:7880320}.
/FTId=VAR_006251.
VARIANT 521 521 D -> G (in XLA).
{ECO:0000269|PubMed:9445504}.
/FTId=VAR_008321.
VARIANT 521 521 D -> H (in XLA; severe).
{ECO:0000269|PubMed:8695804}.
/FTId=VAR_006252.
VARIANT 521 521 D -> N (in XLA; severe).
/FTId=VAR_006253.
VARIANT 523 523 A -> E (in XLA).
/FTId=VAR_008322.
VARIANT 525 525 R -> G (in XLA).
{ECO:0000269|PubMed:9545398}.
/FTId=VAR_008323.
VARIANT 525 525 R -> P (in XLA).
{ECO:0000269|PubMed:7711734}.
/FTId=VAR_006254.
VARIANT 525 525 R -> Q (in XLA; severe; disturbs ATP-
binding; dbSNP:rs128620183).
{ECO:0000269|PubMed:7809124,
ECO:0000269|PubMed:9445504}.
/FTId=VAR_006255.
VARIANT 526 526 N -> K (in XLA).
{ECO:0000269|PubMed:7711734}.
/FTId=VAR_006256.
VARIANT 535 535 V -> F (in XLA).
{ECO:0000269|PubMed:9545398}.
/FTId=VAR_008324.
VARIANT 542 542 L -> P (in XLA; growth hormone
deficiency; dbSNP:rs128621203).
{ECO:0000269|PubMed:7849697}.
/FTId=VAR_006257.
VARIANT 544 544 R -> G (in XLA).
{ECO:0000269|PubMed:10612838}.
/FTId=VAR_008963.
VARIANT 544 544 R -> K (in XLA).
{ECO:0000269|PubMed:8834236}.
/FTId=VAR_006258.
VARIANT 559 559 F -> S (in XLA).
{ECO:0000269|PubMed:9445504}.
/FTId=VAR_008325.
VARIANT 562 562 R -> P (in XLA; dbSNP:rs28935176).
{ECO:0000269|PubMed:10678660,
ECO:0000269|PubMed:7809124}.
/FTId=VAR_006259.
VARIANT 562 562 R -> W (in XLA; dbSNP:rs128621204).
{ECO:0000269|PubMed:7711734,
ECO:0000269|PubMed:7849697,
ECO:0000269|PubMed:7880320,
ECO:0000269|PubMed:9445504}.
/FTId=VAR_006260.
VARIANT 563 563 W -> L (in XLA).
{ECO:0000269|PubMed:9545398}.
/FTId=VAR_008326.
VARIANT 567 567 E -> K (in XLA; severe).
{ECO:0000269|PubMed:7633420}.
/FTId=VAR_006261.
VARIANT 578 578 S -> Y (in XLA).
{ECO:0000269|PubMed:10612838}.
/FTId=VAR_008964.
VARIANT 581 581 W -> R (in XLA; dbSNP:rs128621205).
/FTId=VAR_006262.
VARIANT 582 582 A -> V (in XLA).
{ECO:0000269|PubMed:7711734,
ECO:0000269|PubMed:7809124}.
/FTId=VAR_006263.
VARIANT 583 583 F -> S (in XLA).
/FTId=VAR_008327.
VARIANT 587 587 M -> L (in XLA; mild).
{ECO:0000269|PubMed:7633420}.
/FTId=VAR_006264.
VARIANT 589 589 E -> D (in XLA).
/FTId=VAR_008328.
VARIANT 589 589 E -> G (in XLA; moderate; interferes with
substrate binding; dbSNP:rs128621206).
{ECO:0000269|PubMed:7809124,
ECO:0000269|PubMed:7849721}.
/FTId=VAR_006265.
VARIANT 589 589 E -> K (in XLA).
{ECO:0000269|PubMed:10612838}.
/FTId=VAR_008965.
VARIANT 592 592 S -> P (in XLA).
{ECO:0000269|PubMed:8834236}.
/FTId=VAR_006267.
VARIANT 594 594 G -> E (in XLA; mild; interferes with
substrate binding).
{ECO:0000269|PubMed:7809124,
ECO:0000269|PubMed:9445504}.
/FTId=VAR_006268.
VARIANT 594 594 G -> R (in XLA).
{ECO:0000269|PubMed:7711734}.
/FTId=VAR_006269.
VARIANT 598 598 Y -> C (in XLA).
/FTId=VAR_006270.
VARIANT 607 607 A -> D (in XLA; mild; dbSNP:rs128621208).
{ECO:0000269|PubMed:8162056}.
/FTId=VAR_006271.
VARIANT 613 613 G -> D (in XLA; mild; interferes with
substrate binding and/or domain
interactions; dbSNP:rs128621209).
{ECO:0000269|PubMed:7809124,
ECO:0000269|PubMed:7849721}.
/FTId=VAR_006272.
VARIANT 619 619 P -> A (in XLA).
/FTId=VAR_008330.
VARIANT 619 619 P -> S (in XLA).
/FTId=VAR_006273.
VARIANT 619 619 P -> T (in XLA).
{ECO:0000269|PubMed:9445504}.
/FTId=VAR_008331.
VARIANT 622 622 A -> P (in XLA).
{ECO:0000269|PubMed:9545398}.
/FTId=VAR_008332.
VARIANT 626 626 V -> G (in XLA).
{ECO:0000269|PubMed:9445504}.
/FTId=VAR_008333.
VARIANT 630 630 M -> I (polymorphism, 35%).
/FTId=VAR_006274.
VARIANT 630 630 M -> K (in XLA; dbSNP:rs128621210).
{ECO:0000269|PubMed:7849697,
ECO:0000269|PubMed:7880320}.
/FTId=VAR_006275.
VARIANT 630 630 M -> T (in XLA).
/FTId=VAR_008334.
VARIANT 633 633 C -> Y (in XLA).
{ECO:0000269|PubMed:8695804}.
/FTId=VAR_006276.
VARIANT 641 641 R -> C (in XLA).
{ECO:0000269|PubMed:7633429}.
/FTId=VAR_006277.
VARIANT 641 641 R -> H (in XLA; severe).
{ECO:0000269|PubMed:7633420,
ECO:0000269|PubMed:9445504}.
/FTId=VAR_006278.
VARIANT 644 644 F -> L (in XLA).
/FTId=VAR_008335.
VARIANT 644 644 F -> S (in XLA).
{ECO:0000269|PubMed:8695804}.
/FTId=VAR_006279.
VARIANT 647 647 L -> P (in XLA).
/FTId=VAR_006280.
VARIANT 652 652 L -> P (in XLA; dbSNP:rs128622212).
{ECO:0000269|PubMed:7849697}.
/FTId=VAR_006281.
MUTAGEN 41 41 E->K: No effect on phosphorylation of
GTF2I. {ECO:0000269|PubMed:9012831}.
MUTAGEN 189 189 P->A: No effect on phosphorylation of
GTF2I. {ECO:0000269|PubMed:9012831}.
MUTAGEN 223 223 Y->F: Loss of phosphorylation of GTF2I.
{ECO:0000269|PubMed:8630736,
ECO:0000269|PubMed:9012831}.
MUTAGEN 251 252 WW->LL: Large decrease in binding by
SH3BP5. {ECO:0000269|PubMed:9571151}.
MUTAGEN 251 251 W->L: No effect on phosphorylation of
GTF2I. {ECO:0000269|PubMed:9012831}.
MUTAGEN 307 307 R->K: Loss of phosphorylation of GTF2I.
{ECO:0000269|PubMed:9012831}.
MUTAGEN 551 551 Y->F: Loss of phosphorylation of GTF2I.
{ECO:0000269|PubMed:9012831}.
MUTAGEN 617 617 Y->E: Defective in mediating calcium
response. {ECO:0000269|PubMed:15375214}.
CONFLICT 253 253 R -> K (in Ref. 7; BAG37008).
{ECO:0000305}.
STRAND 6 13 {ECO:0000244|PDB:1BTK}.
STRAND 18 20 {ECO:0000244|PDB:2Z0P}.
STRAND 25 32 {ECO:0000244|PDB:1BTK}.
STRAND 34 43 {ECO:0000244|PDB:1BTK}.
TURN 44 47 {ECO:0000244|PDB:1BTK}.
STRAND 48 57 {ECO:0000244|PDB:1BTK}.
HELIX 58 60 {ECO:0000244|PDB:1BTK}.
STRAND 61 66 {ECO:0000244|PDB:1BTK}.
HELIX 75 77 {ECO:0000244|PDB:1BTK}.
HELIX 93 96 {ECO:0000244|PDB:1BTK}.
STRAND 100 106 {ECO:0000244|PDB:1BTK}.
STRAND 111 116 {ECO:0000244|PDB:1BTK}.
HELIX 118 132 {ECO:0000244|PDB:1BTK}.
STRAND 140 142 {ECO:0000244|PDB:1BTK}.
STRAND 149 152 {ECO:0000244|PDB:2Z0P}.
TURN 153 155 {ECO:0000244|PDB:1BTK}.
STRAND 165 167 {ECO:0000244|PDB:1BTK}.
TURN 212 215 {ECO:0000244|PDB:1AWX}.
STRAND 218 223 {ECO:0000244|PDB:1AWW}.
STRAND 228 232 {ECO:0000244|PDB:1AWW}.
STRAND 240 242 {ECO:0000244|PDB:1AWW}.
STRAND 248 252 {ECO:0000244|PDB:1AWW}.
TURN 257 259 {ECO:0000244|PDB:1QLY}.
STRAND 261 265 {ECO:0000244|PDB:1AWX}.
TURN 266 268 {ECO:0000244|PDB:1AWW}.
STRAND 279 282 {ECO:0000244|PDB:2GE9}.
HELIX 288 298 {ECO:0000244|PDB:2GE9}.
STRAND 303 308 {ECO:0000244|PDB:2GE9}.
STRAND 310 312 {ECO:0000244|PDB:2GE9}.
STRAND 315 326 {ECO:0000244|PDB:2GE9}.
STRAND 330 335 {ECO:0000244|PDB:2GE9}.
STRAND 337 339 {ECO:0000244|PDB:2GE9}.
TURN 340 342 {ECO:0000244|PDB:2GE9}.
STRAND 343 347 {ECO:0000244|PDB:2GE9}.
STRAND 350 354 {ECO:0000244|PDB:2GE9}.
HELIX 355 363 {ECO:0000244|PDB:2GE9}.
STRAND 373 376 {ECO:0000244|PDB:2GE9}.
HELIX 393 395 {ECO:0000244|PDB:3PJ2}.
HELIX 399 401 {ECO:0000244|PDB:4RFZ}.
STRAND 402 411 {ECO:0000244|PDB:4RFZ}.
STRAND 414 421 {ECO:0000244|PDB:4RFZ}.
TURN 422 424 {ECO:0000244|PDB:4RFZ}.
STRAND 425 431 {ECO:0000244|PDB:4RFZ}.
TURN 434 436 {ECO:0000244|PDB:5FBO}.
HELIX 439 450 {ECO:0000244|PDB:4RFZ}.
STRAND 460 464 {ECO:0000244|PDB:4RFZ}.
STRAND 466 469 {ECO:0000244|PDB:4RFZ}.
STRAND 471 475 {ECO:0000244|PDB:4RFZ}.
HELIX 482 487 {ECO:0000244|PDB:4RFZ}.
HELIX 489 491 {ECO:0000244|PDB:4RFZ}.
HELIX 495 514 {ECO:0000244|PDB:4RFZ}.
HELIX 524 526 {ECO:0000244|PDB:4RFZ}.
STRAND 527 529 {ECO:0000244|PDB:4RFZ}.
STRAND 535 537 {ECO:0000244|PDB:4RFZ}.
HELIX 542 545 {ECO:0000244|PDB:4RFZ}.
HELIX 549 552 {ECO:0000244|PDB:4RFZ}.
TURN 554 556 {ECO:0000244|PDB:3PIX}.
HELIX 561 563 {ECO:0000244|PDB:4RFZ}.
HELIX 566 571 {ECO:0000244|PDB:4RFZ}.
HELIX 576 591 {ECO:0000244|PDB:4RFZ}.
TURN 592 594 {ECO:0000244|PDB:5U9D}.
TURN 597 600 {ECO:0000244|PDB:4RFZ}.
HELIX 603 611 {ECO:0000244|PDB:4RFZ}.
HELIX 624 632 {ECO:0000244|PDB:4RFZ}.
HELIX 638 640 {ECO:0000244|PDB:4RFZ}.
HELIX 644 657 {ECO:0000244|PDB:4RFZ}.
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


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