ID   BTK_CHICK               Reviewed;         657 AA.
AC   Q8JH64;
DT   16-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   24-JAN-2024, entry version 143.
DE   RecName: Full=Tyrosine-protein kinase BTK;
DE            EC=2.7.10.2;
DE   AltName: Full=Bruton tyrosine kinase;
GN   Name=BTK;
OS   Gallus gallus (Chicken).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC   Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC   Phasianinae; Gallus.
OX   NCBI_TaxID=9031 {ECO:0000312|EMBL:AAN04043.2};
RN   [1] {ECO:0000312|EMBL:AAN04043.2}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Schmidt U., Haubenwallner S., Beug H., Nimpf J.;
RT   "Btk expressed in primary chicken erythroblasts.";
RL   Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION IN PHOSPHORYLATION OF PLCG2.
RX   PubMed=8691147; DOI=10.1084/jem.184.1.31;
RA   Takata M., Kurosaki T.;
RT   "A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated
RT   activation of phospholipase C-gamma 2.";
RL   J. Exp. Med. 184:31-40(1996).
RN   [3]
RP   ACTIVITY REGULATION.
RX   PubMed=10339589; DOI=10.1073/pnas.96.11.6341;
RA   Yamadori T., Baba Y., Mastushita M., Hashimoto S., Kurosaki M.,
RA   Kurosaki T., Kishimoto T., Tsukada S.;
RT   "Bruton's tyrosine kinase activity is negatively regulated by Sab, the Btk-
RT   SH3 domain-binding protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:6341-6346(1999).
RN   [4]
RP   FUNCTION IN REGULATION OF THE ACTIVITY OF NF-KAPPA-B.
RX   PubMed=10811866; DOI=10.1084/jem.191.10.1735;
RA   Bajpai U.D., Zhang K., Teutsch M., Sen R., Wortis H.H.;
RT   "Bruton's tyrosine kinase links the B cell receptor to nuclear factor
RT   kappaB activation.";
RL   J. Exp. Med. 191:1735-1744(2000).
RN   [5]
RP   FUNCTION.
RX   PubMed=12912915; DOI=10.1093/emboj/cdg401;
RA   Hao S., Kurosaki T., August A.;
RT   "Differential regulation of NFAT and SRF by the B cell receptor via a
RT   PLCgamma-Ca(2+)-dependent pathway.";
RL   EMBO J. 22:4166-4177(2003).
RN   [6]
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   [7]
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).
CC   -!- FUNCTION: Non-receptor tyrosine kinase indispensable for B lymphocyte
CC       development, differentiation and signaling (PubMed:8691147,
CC       PubMed:12912915). Binding of antigen to the B-cell antigen receptor
CC       (BCR) triggers signaling that ultimately leads to B-cell activation (By
CC       similarity). 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 (By
CC       similarity). PLCG2 phosphorylation is performed in close cooperation
CC       with the adapter protein B-cell linker protein BLNK (By similarity).
CC       BTK acts as a platform to bring together a diverse array of signaling
CC       proteins and is implicated in cytokine receptor signaling pathways (By
CC       similarity). Plays an important role in the function of immune cells of
CC       innate as well as adaptive immunity, as a component of the Toll-like
CC       receptors (TLR) pathway (By similarity). The TLR pathway acts as a
CC       primary surveillance system for the detection of pathogens and are
CC       crucial to the activation of host defense (By similarity). Especially,
CC       is a critical molecule in regulating TLR9 activation in splenic B-cells
CC       (By similarity). Within the TLR pathway, induces tyrosine
CC       phosphorylation of TIRAP which leads to TIRAP degradation (By
CC       similarity). BTK also plays a critical role in transcription regulation
CC       (By similarity). Induces the activity of NF-kappa-B, which is involved
CC       in regulating the expression of hundreds of genes (PubMed:10811866).
CC       BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-
CC       kappa-B (By similarity). Acts as an activator of NLRP3 inflammasome
CC       assembly by mediating phosphorylation of NLRP3 (By similarity).
CC       Transiently phosphorylates transcription factor GTF2I on tyrosine
CC       residues in response to BCR (By similarity). GTF2I then translocates to
CC       the nucleus to bind regulatory enhancer elements to modulate gene
CC       expression (By similarity). ARID3A and NFAT are other transcriptional
CC       target of BTK (By similarity). BTK is required for the formation of
CC       functional ARID3A DNA-binding complexes (By similarity). There is
CC       however no evidence that BTK itself binds directly to DNA (By
CC       similarity). BTK has a dual role in the regulation of apoptosis (By
CC       similarity). {ECO:0000250|UniProtKB:Q06187,
CC       ECO:0000269|PubMed:10811866, ECO:0000269|PubMed:12912915,
CC       ECO:0000269|PubMed:8691147}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC         [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC         COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:Q06187};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q06187};
CC   -!- ACTIVITY REGULATION: Activated by phosphorylation.
CC       {ECO:0000250|UniProtKB:Q06187}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q06187}. Cell
CC       membrane {ECO:0000250|UniProtKB:Q06187}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:Q06187}. Nucleus {ECO:0000250|UniProtKB:Q06187}.
CC       Membrane raft {ECO:0000250|UniProtKB:P35991}.
CC   -!- DOMAIN: The PH domain mediates the binding to inositol polyphosphate
CC       and phosphoinositides, leading to its targeting to the plasma membrane
CC       (By similarity). It is extended in the BTK kinase family by a region
CC       designated the TH (Tec homology) domain, which consists of about 80
CC       residues preceding the SH3 domain. {ECO:0000250|UniProtKB:Q06187}.
CC   -!- PTM: Following B-cell receptor (BCR) engagement, translocates to the
CC       plasma membrane where it gets phosphorylated at Tyr-549 by LYN and SYK.
CC       Phosphorylation at Tyr-549 is followed by autophosphorylation of Tyr-
CC       220 which may create a docking site for a SH2 containing protein (By
CC       similarity). Phosphorylation at Ser-179 by PRKCB, leads in
CC       translocation of BTK back to the cytoplasmic fraction (By similarity).
CC       {ECO:0000250|UniProtKB:Q06187}.
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; AF535118; AAN04043.2; -; mRNA.
DR   AlphaFoldDB; Q8JH64; -.
DR   SMR; Q8JH64; -.
DR   STRING; 9031.ENSGALP00000045102; -.
DR   PaxDb; 9031-ENSGALP00000007936; -.
DR   VEuPathDB; HostDB:geneid_374075; -.
DR   eggNOG; KOG0197; Eukaryota.
DR   InParanoid; Q8JH64; -.
DR   Proteomes; UP000000539; Unassembled WGS sequence.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR   GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR   GO; GO:0002250; P:adaptive immune response; IBA:GO_Central.
DR   GO; GO:0050853; P:B cell receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB.
DR   GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central.
DR   CDD; cd01238; PH_Btk; 1.
DR   CDD; cd05113; PTKc_Btk_Bmx; 1.
DR   CDD; cd10397; SH2_Tec_Btk; 1.
DR   CDD; cd11906; SH3_BTK; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   Gene3D; 3.30.505.10; SH2 domain; 1.
DR   Gene3D; 2.30.30.40; SH3 Domains; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR035574; BTK_SH3.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR001849; PH_domain.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; IPR000980; SH2.
DR   InterPro; IPR036860; SH2_dom_sf.
DR   InterPro; IPR036028; SH3-like_dom_sf.
DR   InterPro; IPR001452; SH3_domain.
DR   InterPro; IPR008266; Tyr_kinase_AS.
DR   InterPro; IPR020635; Tyr_kinase_cat_dom.
DR   InterPro; IPR001562; Znf_Btk_motif.
DR   PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1.
DR   PANTHER; PTHR24418:SF92; TYROSINE-PROTEIN KINASE BTK; 1.
DR   Pfam; PF00779; BTK; 1.
DR   Pfam; PF00169; PH; 1.
DR   Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR   Pfam; PF00017; SH2; 1.
DR   Pfam; PF00018; SH3_1; 1.
DR   PRINTS; PR00401; SH2DOMAIN.
DR   PRINTS; PR00452; SH3DOMAIN.
DR   PRINTS; PR00402; TECBTKDOMAIN.
DR   PRINTS; PR00109; TYRKINASE.
DR   SMART; SM00107; BTK; 1.
DR   SMART; SM00233; PH; 1.
DR   SMART; SM00252; SH2; 1.
DR   SMART; SM00326; SH3; 1.
DR   SMART; SM00219; TyrKc; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF55550; SH2 domain; 1.
DR   SUPFAM; SSF50044; SH3-domain; 1.
DR   PROSITE; PS50003; PH_DOMAIN; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR   PROSITE; PS50001; SH2; 1.
DR   PROSITE; PS50002; SH3; 1.
DR   PROSITE; PS51113; ZF_BTK; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Adaptive immunity; ATP-binding; Cell membrane; Cytoplasm;
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..657
FT                   /note="Tyrosine-protein kinase BTK"
FT                   /id="PRO_0000088067"
FT   DOMAIN          3..132
FT                   /note="PH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00145,
FT                   ECO:0000305"
FT   DOMAIN          211..271
FT                   /note="SH3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT   DOMAIN          276..366
FT                   /note="SH2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00191,
FT                   ECO:0000305"
FT   DOMAIN          400..653
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000305"
FT   ZN_FING         134..170
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|UniProtKB:Q06187"
FT   REGION          175..199
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           579..586
FT                   /note="CAV1-binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   ACT_SITE        519
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|UniProtKB:Q06187"
FT   BINDING         28
FT                   /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:57895"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   BINDING         39
FT                   /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:57895"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   BINDING         53
FT                   /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:57895"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   BINDING         142
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT   BINDING         153
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         164
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT   BINDING         406..414
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P08631,
FT                   ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         428
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P08631,
FT                   ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   MOD_RES         20
FT                   /note="Phosphothreonine"
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:0000250|UniProtKB:Q06187"
FT   MOD_RES         55
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   MOD_RES         179
FT                   /note="Phosphoserine; by PKC/PRKCB"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   MOD_RES         190
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   MOD_RES         220
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   MOD_RES         306
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   MOD_RES         321
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   MOD_RES         342
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   MOD_RES         359
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   MOD_RES         373
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   MOD_RES         549
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   MOD_RES         549
FT                   /note="Phosphotyrosine; by LYN and SYK"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
FT   MOD_RES         602
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q06187"
SQ   SEQUENCE   657 AA;  75879 MW;  FE5217E8E6195F6A CRC64;
     MASIILESIF LKRSQQKKKT SPLNFKKRLF LLTESKLSYY EYDFERGRRG SKKGSVDIEK
     ITCVETVVPE NNPPPERQVP KKGEDYNMEQ ISIIERFPYP FQVVYDEGPL YVFSPTEELR
     KRWIHQLKSV IRYNSDLVQK YHPCFWIDGQ YLCCSQTAKN AMGCKILESR NGSLKAGRSH
     RKTKKPLPPT PEEDTMVMKP LPPEPAPSAA GEMKKVVALY NYVPMNVQDL QLQKGEDYLI
     LEESHLPWWK ARDKNGREGY IPSNYVTATS NSLEIYEWYS KNITRSQAEQ LLKQEGKEGG
     FIVRDSTSKT GKYTVSVYAK SAVDPQGMIR HYVVCCTPQN QYYLAEKHLF NTIPELITYH
     QHNSAGLISR LKYPVSRHQK SAPSTAGLGY GSWEIDPKDL TFLKELGTGQ FGVVKYGKWR
     GQYNVAIKMI REGSMSEDEF IDEAKVMMNL SHEKLVQLYG VCTKQRPIFI ITEYMANGCL
     LNFLRETQRR FQPAELLEMC KDVCEAMEYL ESKQFLHRDL AARNCLVNDQ GIVKVSDFGL
     SRYVLDDEYT SSMGSKFPVR WSPPEVLLYS KFSSKSDVWS FGVLMWEVYS LGKMPYERFN
     NSETTEHVIQ GLRLYRPQQA SERVYAIMYS CWHEKAEERP TFSALLGSIV DITDEEP
//