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Q8JH64

- BTK_CHICK

UniProt

Q8JH64 - BTK_CHICK

Protein

Tyrosine-protein kinase BTK

Gene

BTK

Organism
Gallus gallus (Chicken)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 95 (01 Oct 2014)
      Sequence version 1 (01 Oct 2002)
      Previous versions | rss
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    Functioni

    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.3 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

    Cofactori

    Binds 1 zinc ion per subunit.By similarity

    Enzyme regulationi

    Activated by phosphorylation.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei26 – 261Inositol-(1,3,4,5)-tetrakisphosphateBy similarity
    Binding sitei28 – 281Inositol-(1,3,4,5)-tetrakisphosphateBy similarity
    Binding sitei39 – 391Inositol-(1,3,4,5)-tetrakisphosphateBy similarity
    Binding sitei53 – 531Inositol-(1,3,4,5)-tetrakisphosphate; via carbonyl oxygenBy similarity
    Metal bindingi142 – 1421ZincBy similarity
    Metal bindingi153 – 1531ZincBy similarity
    Metal bindingi154 – 1541ZincBy similarity
    Metal bindingi164 – 1641ZincBy similarity
    Binding sitei428 – 4281ATPBy similarityPROSITE-ProRule annotation
    Binding sitei443 – 4431InhibitorBy similarity
    Binding sitei459 – 4591InhibitorBy similarity
    Binding sitei475 – 4751InhibitorBy similarity
    Active sitei519 – 5191Proton acceptorPROSITE-ProRule annotation
    Binding sitei536 – 5361InhibitorBy similarity
    Binding sitei537 – 5371Inhibitor; via amide nitrogenBy similarity
    Binding sitei540 – 5401Inhibitor; via carbonyl oxygenBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri134 – 17037Btk-typePROSITE-ProRule annotationAdd
    BLAST
    Nucleotide bindingi406 – 4149ATPBy similarityPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. lipid binding Source: UniProtKB-KW
    3. metal ion binding Source: UniProtKB-KW
    4. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC

    GO - Biological processi

    1. innate immune response Source: UniProtKB-KW
    2. intracellular signal transduction Source: InterPro
    3. regulation of transcription, DNA-templated Source: UniProtKB-KW
    4. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Adaptive immunity, Immunity, Innate immunity, Transcription, Transcription regulation

    Keywords - Ligandi

    ATP-binding, Lipid-binding, Metal-binding, Nucleotide-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase BTK (EC:2.7.10.2)
    Alternative name(s):
    Bruton tyrosine kinase
    Gene namesi
    Name:BTK
    OrganismiGallus gallus (Chicken)Imported
    Taxonomic identifieri9031 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiTestudines + Archosauria groupArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalliformesPhasianidaePhasianinaeGallus
    ProteomesiUP000000539: Unplaced

    Subcellular locationi

    Cytoplasm By similarity. Cell membrane By similarity; Peripheral membrane protein By similarity. Nucleus By similarity
    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.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell
    3. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 657656Tyrosine-protein kinase BTKPRO_0000088067Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei20 – 201PhosphothreonineBy similarity
    Modified residuei21 – 211PhosphoserineBy similarity
    Modified residuei40 – 401PhosphotyrosineBy similarity
    Modified residuei55 – 551PhosphoserineBy similarity
    Modified residuei179 – 1791Phosphoserine; by PKC/PRKCBBy similarity
    Modified residuei190 – 1901PhosphothreonineBy similarity
    Modified residuei220 – 2201Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei306 – 3061PhosphoserineBy similarity
    Modified residuei321 – 3211PhosphoserineBy similarity
    Modified residuei342 – 3421PhosphotyrosineBy similarity
    Modified residuei359 – 3591PhosphotyrosineBy similarity
    Modified residuei373 – 3731PhosphotyrosineBy similarity
    Modified residuei549 – 5491Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei549 – 5491Phosphotyrosine; by LYN and SYKBy similarity
    Modified residuei602 – 6021PhosphoserineBy similarity

    Post-translational modificationi

    Following B-cell receptor (BCR) engagement, translocates to the plasma membrane where it gets phosphorylated at Tyr-549 by LYN and SYK. Phosphorylation at Tyr-549 is followed by autophosphorylation of Tyr-220 which may create a docking site for a SH2 containing protein By similarity. Phosphorylation at Ser-179 by PRKCB, leads in translocation of BTK back to the cytoplasmic fraction By similarity.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Interactioni

    Subunit structurei

    Binds GTF2I through the PH domain. Interacts with SH3BP5 via the SH3 domain By similarity. Interacts with IBTK via its PH domain By similarity. Interacts with ARID3A, CAV1, FASLG, PIN1, TLR8 and TLR9 By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ8JH64.
    SMRiQ8JH64. Positions 2-169, 209-385, 395-652.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini3 – 132130PHCuratedPROSITE-ProRule annotationAdd
    BLAST
    Domaini214 – 27057SH3CuratedPROSITE-ProRule annotationAdd
    BLAST
    Domaini276 – 36691SH2CuratedPROSITE-ProRule annotationAdd
    BLAST
    Domaini400 – 653254Protein kinaseCuratedPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni12 – 2413Inositol-(1,3,4,5)-tetrakisphosphate 1-bindingBy similarityAdd
    BLAST
    Regioni472 – 4776Inhibitor-bindingBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi579 – 5868CAV1-bindingBy similarity

    Domaini

    The PH domain mediates the binding to inositol polyphosphate and phosphoinositides, leading to its targeting to the plasma membrane By similarity. 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.By similarity

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.PROSITE-ProRule annotation
    Contains 1 Btk-type zinc finger.PROSITE-ProRule annotation
    Contains 1 PH domain.CuratedPROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 SH2 domain.CuratedPROSITE-ProRule annotation
    Contains 1 SH3 domain.CuratedPROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri134 – 17037Btk-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    SH2 domain, SH3 domain, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233859.
    HOVERGENiHBG008761.
    InParanoidiQ8JH64.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    3.30.505.10. 1 hit.
    InterProiIPR011009. Kinase-like_dom.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR001562. Znf_Btk_motif.
    [Graphical view]
    PfamiPF00779. BTK. 1 hit.
    PF00169. PH. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    PR00402. TECBTKDOMAIN.
    PR00109. TYRKINASE.
    SMARTiSM00107. BTK. 1 hit.
    SM00233. PH. 1 hit.
    SM00252. SH2. 1 hit.
    SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 1 hit.
    SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS50003. PH_DOMAIN. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS50001. SH2. 1 hit.
    PS50002. SH3. 1 hit.
    PS51113. ZF_BTK. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q8JH64-1 [UniParc]FASTAAdd to Basket

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    MASIILESIF LKRSQQKKKT SPLNFKKRLF LLTESKLSYY EYDFERGRRG    50
    SKKGSVDIEK ITCVETVVPE NNPPPERQVP KKGEDYNMEQ ISIIERFPYP 100
    FQVVYDEGPL YVFSPTEELR KRWIHQLKSV IRYNSDLVQK YHPCFWIDGQ 150
    YLCCSQTAKN AMGCKILESR NGSLKAGRSH RKTKKPLPPT PEEDTMVMKP 200
    LPPEPAPSAA GEMKKVVALY NYVPMNVQDL QLQKGEDYLI LEESHLPWWK 250
    ARDKNGREGY IPSNYVTATS NSLEIYEWYS KNITRSQAEQ LLKQEGKEGG 300
    FIVRDSTSKT GKYTVSVYAK SAVDPQGMIR HYVVCCTPQN QYYLAEKHLF 350
    NTIPELITYH QHNSAGLISR LKYPVSRHQK SAPSTAGLGY GSWEIDPKDL 400
    TFLKELGTGQ FGVVKYGKWR GQYNVAIKMI REGSMSEDEF IDEAKVMMNL 450
    SHEKLVQLYG VCTKQRPIFI ITEYMANGCL LNFLRETQRR FQPAELLEMC 500
    KDVCEAMEYL ESKQFLHRDL AARNCLVNDQ GIVKVSDFGL SRYVLDDEYT 550
    SSMGSKFPVR WSPPEVLLYS KFSSKSDVWS FGVLMWEVYS LGKMPYERFN 600
    NSETTEHVIQ GLRLYRPQQA SERVYAIMYS CWHEKAEERP TFSALLGSIV 650
    DITDEEP 657
    Length:657
    Mass (Da):75,879
    Last modified:October 1, 2002 - v1
    Checksum:iFE5217E8E6195F6A
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF535118 mRNA. Translation: AAN04043.2.
    UniGeneiGga.1305.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF535118 mRNA. Translation: AAN04043.2 .
    UniGenei Gga.1305.

    3D structure databases

    ProteinModelPortali Q8JH64.
    SMRi Q8JH64. Positions 2-169, 209-385, 395-652.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233859.
    HOVERGENi HBG008761.
    InParanoidi Q8JH64.

    Miscellaneous databases

    PROi Q8JH64.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    3.30.505.10. 1 hit.
    InterProi IPR011009. Kinase-like_dom.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR001562. Znf_Btk_motif.
    [Graphical view ]
    Pfami PF00779. BTK. 1 hit.
    PF00169. PH. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    PR00402. TECBTKDOMAIN.
    PR00109. TYRKINASE.
    SMARTi SM00107. BTK. 1 hit.
    SM00233. PH. 1 hit.
    SM00252. SH2. 1 hit.
    SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 1 hit.
    SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS50003. PH_DOMAIN. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS50001. SH2. 1 hit.
    PS50002. SH3. 1 hit.
    PS51113. ZF_BTK. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Btk expressed in primary chicken erythroblasts."
      Schmidt U., Haubenwallner S., Beug H., Nimpf J.
      Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2."
      Takata M., Kurosaki T.
      J. Exp. Med. 184:31-40(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF PLCG2.
    3. "Bruton's tyrosine kinase activity is negatively regulated by Sab, the Btk-SH3 domain-binding protein."
      Yamadori T., Baba Y., Mastushita M., Hashimoto S., Kurosaki M., Kurosaki T., Kishimoto T., Tsukada S.
      Proc. Natl. Acad. Sci. U.S.A. 96:6341-6346(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    4. "Bruton's tyrosine kinase links the B cell receptor to nuclear factor kappaB activation."
      Bajpai U.D., Zhang K., Teutsch M., Sen R., Wortis H.H.
      J. Exp. Med. 191:1735-1744(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN REGULATION OF THE ACTIVITY OF NF-KAPPA-B.
    5. "Differential regulation of NFAT and SRF by the B cell receptor via a PLCgamma-Ca(2+)-dependent pathway."
      Hao S., Kurosaki T., August A.
      EMBO J. 22:4166-4177(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "Bruton's tyrosine kinase (BTK) as a dual-function regulator of apoptosis."
      Uckun F.M.
      Biochem. Pharmacol. 56:683-691(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION IN REGULATION OF APOPTOSIS.
    7. "Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain."
      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.
      Immunol. Rev. 228:58-73(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION, REVIEW ON ENZYME REGULATION.

    Entry informationi

    Entry nameiBTK_CHICK
    AccessioniPrimary (citable) accession number: Q8JH64
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 16, 2004
    Last sequence update: October 1, 2002
    Last modified: October 1, 2014
    This is version 95 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3