BTK_MOUSE
ID BTK_MOUSE Reviewed; 659 AA.
AC P35991; Q61365;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 210.
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;
DE AltName: Full=Kinase EMB;
GN Name=Btk; Synonyms=Bpk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8476425; DOI=10.1006/bbrc.1993.1404;
RA Yamada N., Kawakami Y., Kimura H., Fukamachi H., Baier G., Altman A.,
RA Kato T., Inagaki Y., Kawakami T.;
RT "Structure and expression of novel protein-tyrosine kinases, Emb and Emt,
RT in hematopoietic cells.";
RL Biochem. Biophys. Res. Commun. 192:231-240(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=7989760;
RA Sideras P., Mueller S., Shiels H., Jin H., Khan W.N., Nilsson L.,
RA Parkinson E., Thomas J.D., Branden L., Larsson I., Paul W.E., Rosen F.S.,
RA Alt F.W., Vetrie D., Smith C.I.E., Xanthopoulos K.G.;
RT "Genomic organization of mouse and human Bruton's agammaglobulinemia
RT tyrosine kinase (Btk) loci.";
RL J. Immunol. 153:5607-5617(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C129;
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 [5]
RP PROTEIN SEQUENCE OF 219-233, PHOSPHORYLATION AT TYR-223, AND MUTAGENESIS OF
RP TYR-223 AND LYS-430.
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 [6]
RP FUNCTION, AND MUTAGENESIS OF GLU-41 AND LYS-430.
RX PubMed=7538439; DOI=10.1016/1074-7613(95)90026-8;
RA Li T., Tsukada S., Satterthwaite A., Havlik M.H., Park H., Takatsu K.,
RA Witte O.N.;
RT "Activation of Bruton's tyrosine kinase (BTK) by a point mutation in its
RT pleckstrin homology (PH) domain.";
RL Immunity 2:451-460(1995).
RN [7]
RP FUNCTION, AND PHOSPHORYLATION AT TYR-551.
RX PubMed=8629002; DOI=10.1126/science.271.5250.822;
RA Rawlings D.J., Scharenberg A.M., Park H., Wahl M.I., Lin S., Kato R.M.,
RA Fluckiger A.C., Witte O.N., Kinet J.P.;
RT "Activation of BTK by a phosphorylation mechanism initiated by SRC family
RT kinases.";
RL Science 271:822-825(1996).
RN [8]
RP DOMAIN.
RX PubMed=9240435; DOI=10.1006/bbrc.1997.6947;
RA Kojima T., Fukuda M., Watanabe Y., Hamazato F., Mikoshiba K.;
RT "Characterization of the pleckstrin homology domain of Btk as an inositol
RT polyphosphate and phosphoinositide binding domain.";
RL Biochem. Biophys. Res. Commun. 236:333-339(1997).
RN [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=10811867; DOI=10.1084/jem.191.10.1745;
RA Petro J.B., Rahman S.M., Ballard D.W., Khan W.N.;
RT "Bruton's tyrosine kinase is required for activation of IkappaB kinase and
RT nuclear factor kappaB in response to B cell receptor engagement.";
RL J. Exp. Med. 191:1745-1754(2000).
RN [10]
RP FUNCTION, INTERACTION WITH ARID3A, SUBCELLULAR LOCATION, AND
RP CHARACTERIZATION OF VARIANT XID CYS-28.
RX PubMed=11120822; DOI=10.4049/jimmunol.165.12.6956;
RA Webb C.F., Yamashita Y., Ayers N., Evetts S., Paulin Y., Conley M.E.,
RA Smith E.A.;
RT "The transcription factor Bright associates with Bruton's tyrosine kinase,
RT the defective protein in immunodeficiency disease.";
RL J. Immunol. 165:6956-6965(2000).
RN [11]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=10852954; DOI=10.1073/pnas.120175097;
RA Kawakami Y., Kitaura J., Hartman S.E., Lowell C.A., Siraganian R.P.,
RA Kawakami T.;
RT "Regulation of protein kinase CbetaI by two protein-tyrosine kinases, Btk
RT and Syk.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7423-7428(2000).
RN [12]
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-40; TYR-344 AND TYR-551, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [14]
RP FUNCTION IN THE TLR PATHWAY.
RX PubMed=17725607; DOI=10.1111/j.1365-2567.2007.02693.x;
RA Hasan M., Lopez-Herrera G., Blomberg K.E., Lindvall J.M., Berglof A.,
RA Smith C.I., Vargas L.;
RT "Defective Toll-like receptor 9-mediated cytokine production in B cells
RT from Bruton's tyrosine kinase-deficient mice.";
RL Immunology 123:239-249(2008).
RN [15]
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 [16]
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 [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [18]
RP VARIANT XID CYS-28.
RX PubMed=8332901; DOI=10.1126/science.8332901;
RA Rawlings D.J., Saffran D.C., Tsukada S., Largaespada D.A., Grimaldi J.C.,
RA Cohen L., Mohr R.N., Bazan J.F., Howard M., Copeland N.G., Jenkins N.A.,
RA Witte O.N.;
RT "Mutation of unique region of Bruton's tyrosine kinase in immunodeficient
RT XID mice.";
RL Science 261:358-361(1993).
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:10852954,
CC ECO:0000269|PubMed:11120822, ECO:0000269|PubMed:16738337,
CC ECO:0000269|PubMed:17725607, ECO:0000269|PubMed:7538439,
CC ECO:0000269|PubMed:8629002}.
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; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
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:10852954}.
CC -!- SUBUNIT: Binds GTF2I through the PH domain. Interacts with SH3BP5 via
CC the SH3 domain. Interacts with IBTK via its PH domain (By similarity).
CC Interacts with ARID3A. Interacts with CAV1, FASLG, PIN1, TLR8 and TLR9
CC (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P35991; P27512: Cd40; NbExp=3; IntAct=EBI-625119, EBI-525742;
CC P35991; Q60631: Grb2; NbExp=4; IntAct=EBI-625119, EBI-1688;
CC P35991; P22366: Myd88; NbExp=2; IntAct=EBI-625119, EBI-525108;
CC P35991; Q80UF7: Ticam1; NbExp=2; IntAct=EBI-625119, EBI-3649271;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11120822}. Cell
CC membrane {ECO:0000269|PubMed:11120822}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11120822}. Nucleus {ECO:0000269|PubMed:11120822}.
CC Note=In steady state, BTK is predominantly cytosolic. Following B-cell
CC receptor (BCR) engagement by antigen, translocates to the plasma
CC membrane through its PH domain. Plasma membrane localization is a
CC critical step in the activation of BTK. A fraction of BTK also shuttles
CC between the nucleus and the cytoplasm, and nuclear export is mediated
CC by the nuclear export receptor CRM1. {ECO:0000250}.
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:9240435}.
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 (By similarity). {ECO:0000250}.
CC -!- DISEASE: Note=Defects in Btk are the cause of murine X-linked
CC immunodeficiency (XID).
CC -!- DISRUPTION PHENOTYPE: Prevents BCR-induced activation of NF-kappa-B.
CC {ECO:0000269|PubMed:10811867}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. TEC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; L08967; AAA37316.1; -; mRNA.
DR EMBL; L10627; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; L29788; AAA66943.1; -; mRNA.
DR EMBL; U58105; AAB47246.1; -; Genomic_DNA.
DR CCDS; CCDS30396.1; -.
DR PIR; I49553; I49553.
DR RefSeq; NP_038510.2; NM_013482.2.
DR RefSeq; XP_006528546.1; XM_006528483.3.
DR RefSeq; XP_006528547.1; XM_006528484.3.
DR RefSeq; XP_006528548.1; XM_006528485.3.
DR PDB; 4XI2; X-ray; 2.60 A; A=214-659.
DR PDBsum; 4XI2; -.
DR AlphaFoldDB; P35991; -.
DR BMRB; P35991; -.
DR SMR; P35991; -.
DR BioGRID; 198400; 25.
DR CORUM; P35991; -.
DR ELM; P35991; -.
DR IntAct; P35991; 29.
DR STRING; 10090.ENSMUSP00000033617; -.
DR BindingDB; P35991; -.
DR ChEMBL; CHEMBL3259478; -.
DR iPTMnet; P35991; -.
DR PhosphoSitePlus; P35991; -.
DR MaxQB; P35991; -.
DR PaxDb; P35991; -.
DR PeptideAtlas; P35991; -.
DR PRIDE; P35991; -.
DR ProteomicsDB; 265388; -.
DR Antibodypedia; 699; 1331 antibodies from 47 providers.
DR DNASU; 12229; -.
DR Ensembl; ENSMUST00000033617; ENSMUSP00000033617; ENSMUSG00000031264.
DR GeneID; 12229; -.
DR KEGG; mmu:12229; -.
DR UCSC; uc009uge.2; mouse.
DR CTD; 695; -.
DR MGI; MGI:88216; Btk.
DR VEuPathDB; HostDB:ENSMUSG00000031264; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000158469; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; P35991; -.
DR OMA; YYEYDFD; -.
DR OrthoDB; 1047190at2759; -.
DR PhylomeDB; P35991; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-MMU-2424491; DAP12 signaling.
DR Reactome; R-MMU-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-MMU-416476; G alpha (q) signalling events.
DR Reactome; R-MMU-416482; G alpha (12/13) signalling events.
DR Reactome; R-MMU-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-MMU-8964315; G beta:gamma signalling through BTK.
DR Reactome; R-MMU-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR BioGRID-ORCS; 12229; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Btk; mouse.
DR PRO; PR:P35991; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P35991; protein.
DR Bgee; ENSMUSG00000031264; Expressed in granulocyte and 72 other tissues.
DR ExpressionAtlas; P35991; baseline and differential.
DR Genevisible; P35991; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; ISO:MGI.
DR GO; GO:0016004; F:phospholipase activator activity; ISO:MGI.
DR GO; GO:0043274; F:phospholipase binding; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0002344; P:B cell affinity maturation; IMP:MGI.
DR GO; GO:0050853; P:B cell receptor signaling pathway; ISO:MGI.
DR GO; GO:0048469; P:cell maturation; IMP:MGI.
DR GO; GO:0098761; P:cellular response to interleukin-7; IMP:MGI.
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:0002553; P:histamine secretion by mast cell; IEA:Ensembl.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0061516; P:monocyte proliferation; IEA:Ensembl.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:MGI.
DR GO; GO:0001818; P:negative regulation of cytokine production; IMP:CACAO.
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:MGI.
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: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; IDA:MGI.
DR GO; GO:0030167; P:proteoglycan catabolic process; IEA:Ensembl.
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; Apoptosis; ATP-binding;
KW Cell membrane; Cytoplasm; Direct protein sequencing; Disease variant;
KW Immunity; 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:0000250|UniProtKB:Q06187"
FT CHAIN 2..659
FT /note="Tyrosine-protein kinase BTK"
FT /id="PRO_0000088066"
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 /evidence="ECO:0000250"
FT REGION 171..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 581..588
FT /note="CAV1-binding"
FT /evidence="ECO:0000250"
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:0000250"
FT BINDING 28
FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate"
FT /ligand_id="ChEBI:CHEBI:57895"
FT /evidence="ECO:0000250"
FT BINDING 39
FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate"
FT /ligand_id="ChEBI:CHEBI:57895"
FT /evidence="ECO:0000250"
FT BINDING 53
FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate"
FT /ligand_id="ChEBI:CHEBI:57895"
FT /evidence="ECO:0000250"
FT BINDING 143
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 155
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 165
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
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 MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q06187"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06187"
FT MOD_RES 40
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 55
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06187"
FT MOD_RES 115
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06187"
FT MOD_RES 180
FT /note="Phosphoserine; by PKC/PRKCB"
FT /evidence="ECO:0000250|UniProtKB:Q06187"
FT MOD_RES 191
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q06187"
FT MOD_RES 223
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8630736"
FT MOD_RES 344
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 361
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q06187"
FT MOD_RES 551
FT /note="Phosphotyrosine; by LYN and SYK"
FT /evidence="ECO:0000269|PubMed:8629002,
FT ECO:0007744|PubMed:17947660"
FT MOD_RES 604
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06187"
FT MOD_RES 617
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q06187"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06187"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06187"
FT VARIANT 28
FT /note="R -> C (in XID; prevents interaction with ARID3A)"
FT /evidence="ECO:0000269|PubMed:11120822,
FT ECO:0000269|PubMed:8332901"
FT MUTAGEN 41
FT /note="E->K: Constitutive activation."
FT /evidence="ECO:0000269|PubMed:7538439"
FT MUTAGEN 223
FT /note="Y->F: No autophosphorylation."
FT /evidence="ECO:0000269|PubMed:8630736"
FT MUTAGEN 430
FT /note="K->R: Loss of activity and no phosphorylation."
FT /evidence="ECO:0000269|PubMed:7538439,
FT ECO:0000269|PubMed:8630736"
FT CONFLICT 67
FT /note="V -> A (in Ref. 2; L10627)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="R -> P (in Ref. 1; AAA37316)"
FT /evidence="ECO:0000305"
FT CONFLICT 197
FT /note="I -> IWI (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 450
FT /note="Missing (in Ref. 2; L10627)"
FT /evidence="ECO:0000305"
FT STRAND 217..223
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 240..245
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 248..255
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 261..265
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 288..294
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 304..307
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 316..321
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 330..335
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 355..361
FT /evidence="ECO:0007829|PDB:4XI2"
FT TURN 362..364
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 388..391
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 401..407
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 412..414
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 416..421
FT /evidence="ECO:0007829|PDB:4XI2"
FT TURN 422..424
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 425..431
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 439..450
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 460..469
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 471..475
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 482..488
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 490..492
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 495..497
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 498..514
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 524..526
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 527..529
FT /evidence="ECO:0007829|PDB:4XI2"
FT STRAND 535..537
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 542..545
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 549..552
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 561..563
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 566..571
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 576..591
FT /evidence="ECO:0007829|PDB:4XI2"
FT TURN 592..594
FT /evidence="ECO:0007829|PDB:4XI2"
FT TURN 597..600
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 603..612
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 624..632
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 638..640
FT /evidence="ECO:0007829|PDB:4XI2"
FT HELIX 644..656
FT /evidence="ECO:0007829|PDB:4XI2"
SQ SEQUENCE 659 AA; 76437 MW; E502B798BC36E223 CRC64;
MAAVILESIF LKRSQQKKKT SPLNFKKRLF LLTVHKLSYY EYDFERGRRG SKKGSIDVEK
ITCVETVIPE KNPPPERQIP RRGEESSEME QISIIERFPY PFQVVYDEGP LYVFSPTEEL
RKRWIHQLKN VIRYNSDLVQ KYHPCFWIDG QYLCCSQTAK NAMGCQILEN RNGSLKPGSS
HRKTKKPLPP TPEEDQILKK PLPPEPTAAP ISTTELKKVV ALYDYMPMNA NDLQLRKGEE
YFILEESNLP WWRARDKNGQ EGYIPSNYIT EAEDSIEMYE WYSKHMTRSQ AEQLLKQEGK
EGGFIVRDSS KAGKYTVSVF AKSTGEPQGV IRHYVVCSTP QSQYYLAEKH LFSTIPELIN
YHQHNSAGLI SRLKYPVSKQ NKNAPSTAGL GYGSWEIDPK DLTFLKELGT GQFGVVKYGK
WRGQYDVAIK MIREGSMSED EFIEEAKVMM NLSHEKLVQL YGVCTKQRPI FIITEYMANG
CLLNYLREMR HRFQTQQLLE MCKDVCEAME YLESKQFLHR DLAARNCLVN DQGVVKVSDF
GLSRYVLDDE YTSSVGSKFP VRWSPPEVLM YSKFSSKSDI WAFGVLMWEI YSLGKMPYER
FTNSETAEHI AQGLRLYRPH LASERVYTIM YSCWHEKADE RPSFKILLSN ILDVMDEES
