BTK_CHICK
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 03-AUG-2022, entry version 135.
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. 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:10811866,
CC ECO:0000269|PubMed:12912915, 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. {ECO:0000250}.
CC -!- SUBUNIT: Binds GTF2I through the PH domain. Interacts with SH3BP5 via
CC the SH3 domain (By similarity). Interacts with IBTK via its PH domain
CC (By similarity). Interacts with ARID3A, CAV1, FASLG, PIN1, TLR8 and
CC TLR9 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Nucleus
CC {ECO:0000250}. Note=In steady state, BTK is predominantly cytosolic.
CC Following B-cell receptor (BCR) engagement by antigen, translocates to
CC the plasma membrane through its PH domain. Plasma membrane localization
CC is a critical step in the activation of BTK. A fraction of BTK also
CC shuttles between the nucleus and the cytoplasm. {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 (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}.
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}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. TEC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF535118; AAN04043.2; -; mRNA.
DR AlphaFoldDB; Q8JH64; -.
DR SMR; Q8JH64; -.
DR STRING; 9031.ENSGALP00000007936; -.
DR PaxDb; Q8JH64; -.
DR PRIDE; Q8JH64; -.
DR VEuPathDB; HostDB:geneid_374075; -.
DR eggNOG; KOG0197; Eukaryota.
DR InParanoid; Q8JH64; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
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 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"
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"
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"
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"
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 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"
FT MOD_RES 20
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 40
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 55
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 179
FT /note="Phosphoserine; by PKC/PRKCB"
FT /evidence="ECO:0000250"
FT MOD_RES 190
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
FT MOD_RES 220
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 342
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 359
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 373
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 549
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 549
FT /note="Phosphotyrosine; by LYN and SYK"
FT /evidence="ECO:0000250"
FT MOD_RES 602
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
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
