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P35991

- BTK_MOUSE

UniProt

P35991 - BTK_MOUSE

Protein

Tyrosine-protein kinase BTK

Gene

Btk

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 152 (01 Oct 2014)
      Sequence version 4 (23 Jan 2007)
      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.6 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. 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.1 Publication

    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 bindingi143 – 1431ZincBy similarity
    Metal bindingi154 – 1541ZincBy similarity
    Metal bindingi155 – 1551ZincBy similarity
    Metal bindingi165 – 1651ZincBy similarity
    Binding sitei430 – 4301ATPPROSITE-ProRule annotation
    Binding sitei445 – 4451InhibitorBy similarity
    Binding sitei461 – 4611InhibitorBy similarity
    Binding sitei477 – 4771InhibitorBy similarity
    Active sitei521 – 5211Proton acceptorPROSITE-ProRule annotation
    Binding sitei538 – 5381InhibitorBy similarity
    Binding sitei539 – 5391Inhibitor; via amide nitrogenBy similarity
    Binding sitei542 – 5421Inhibitor; via carbonyl oxygenBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri135 – 17137Btk-typePROSITE-ProRule annotationAdd
    BLAST
    Nucleotide bindingi408 – 4169ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. metal ion binding Source: UniProtKB-KW
    3. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
    4. phosphatidylinositol-3,4,5-trisphosphate binding Source: Ensembl
    5. protein binding Source: IntAct
    6. protein tyrosine kinase activity Source: MGI

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. cell maturation Source: MGI
    3. histamine secretion by mast cell Source: Ensembl
    4. I-kappaB kinase/NF-kappaB signaling Source: MGI
    5. innate immune response Source: UniProtKB-KW
    6. peptidyl-tyrosine phosphorylation Source: MGI
    7. protein autophosphorylation Source: Ensembl
    8. protein phosphorylation Source: MGI
    9. regulation of transcription, DNA-templated Source: UniProtKB-KW
    10. response to organic substance Source: Ensembl
    11. response to reactive oxygen species Source: Ensembl
    12. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

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

    Keywords - Ligandi

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

    Enzyme and pathway databases

    BRENDAi2.7.10.2. 3474.
    ReactomeiREACT_188185. DAP12 signaling.
    REACT_188194. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_188202. FCERI mediated Ca+2 mobilization.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase BTK (EC:2.7.10.2)
    Alternative name(s):
    Agammaglobulinemia tyrosine kinase
    Short name:
    ATK
    B-cell progenitor kinase
    Short name:
    BPK
    Bruton tyrosine kinase
    Kinase EMB
    Gene namesi
    Name:Btk
    Synonyms:Bpk
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome X

    Organism-specific databases

    MGIiMGI:88216. Btk.

    Subcellular locationi

    Cytoplasm 1 Publication. Cell membrane 1 Publication; Peripheral membrane protein 1 Publication. Nucleus 1 Publication
    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.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. cytoplasmic vesicle Source: MGI
    3. cytosol Source: Reactome
    4. mast cell granule Source: GOC
    5. membrane raft Source: Ensembl
    6. nucleus Source: MGI
    7. perinuclear region of cytoplasm Source: Ensembl
    8. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Defects in Btk are the cause of murine X-linked immunodeficiency (XID).

    Disruption phenotypei

    Prevents BCR-induced activation of NF-kappa-B.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi41 – 411E → K: Constitutive activation. 1 Publication
    Mutagenesisi223 – 2231Y → F: No autophosphorylation. 1 Publication
    Mutagenesisi430 – 4301K → R: Loss of activity and no phosphorylation. 2 Publications

    Keywords - Diseasei

    Disease mutation

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 659658Tyrosine-protein kinase BTKPRO_0000088066Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei21 – 211PhosphoserineBy similarity
    Modified residuei40 – 401Phosphotyrosine1 Publication
    Modified residuei55 – 551PhosphoserineBy similarity
    Modified residuei115 – 1151PhosphoserineBy similarity
    Modified residuei180 – 1801Phosphoserine; by PKC/PRKCBBy similarity
    Modified residuei191 – 1911PhosphothreonineBy similarity
    Modified residuei223 – 2231Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei344 – 3441Phosphotyrosine1 Publication
    Modified residuei361 – 3611PhosphotyrosineBy similarity
    Modified residuei551 – 5511Phosphotyrosine; by LYN and SYK2 Publications
    Modified residuei617 – 6171PhosphotyrosineBy similarity
    Modified residuei623 – 6231PhosphoserineBy similarity
    Modified residuei659 – 6591PhosphoserineBy similarity

    Post-translational modificationi

    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 By similarity.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP35991.
    PaxDbiP35991.
    PRIDEiP35991.

    PTM databases

    PhosphoSiteiP35991.

    Expressioni

    Gene expression databases

    ArrayExpressiP35991.
    BgeeiP35991.
    CleanExiMM_BTK.
    GenevestigatoriP35991.

    Interactioni

    Subunit structurei

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

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Cd40P275123EBI-625119,EBI-525742
    Grb2Q606314EBI-625119,EBI-1688
    Myd88P223662EBI-625119,EBI-525108
    Ticam1Q80UF72EBI-625119,EBI-3649271

    Protein-protein interaction databases

    BioGridi198400. 6 interactions.
    IntActiP35991. 29 interactions.
    MINTiMINT-1549372.

    Structurei

    3D structure databases

    ProteinModelPortaliP35991.
    SMRiP35991. Positions 2-170, 216-387, 395-657.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini3 – 133131PHPROSITE-ProRule annotationAdd
    BLAST
    Domaini214 – 27461SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini281 – 37797SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini402 – 655254Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni12 – 2413Inositol-(1,3,4,5)-tetrakisphosphate 1-bindingBy similarityAdd
    BLAST
    Regioni474 – 4796Inhibitor-bindingBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi581 – 5888CAV1-bindingBy similarity

    Domaini

    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.1 Publication

    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.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 SH2 domain.PROSITE-ProRule annotation
    Contains 1 SH3 domain.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri135 – 17137Btk-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    SH2 domain, SH3 domain, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00640000091251.
    HOGENOMiHOG000233859.
    HOVERGENiHBG008761.
    InParanoidiP35991.
    KOiK07370.
    OMAiSCRHYNI.
    OrthoDBiEOG7KM5SC.
    PhylomeDBiP35991.
    TreeFamiTF351634.

    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.

    P35991-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAAVILESIF LKRSQQKKKT SPLNFKKRLF LLTVHKLSYY EYDFERGRRG    50
    SKKGSIDVEK ITCVETVIPE KNPPPERQIP RRGEESSEME QISIIERFPY 100
    PFQVVYDEGP LYVFSPTEEL RKRWIHQLKN VIRYNSDLVQ KYHPCFWIDG 150
    QYLCCSQTAK NAMGCQILEN RNGSLKPGSS HRKTKKPLPP TPEEDQILKK 200
    PLPPEPTAAP ISTTELKKVV ALYDYMPMNA NDLQLRKGEE YFILEESNLP 250
    WWRARDKNGQ EGYIPSNYIT EAEDSIEMYE WYSKHMTRSQ AEQLLKQEGK 300
    EGGFIVRDSS KAGKYTVSVF AKSTGEPQGV IRHYVVCSTP QSQYYLAEKH 350
    LFSTIPELIN YHQHNSAGLI SRLKYPVSKQ NKNAPSTAGL GYGSWEIDPK 400
    DLTFLKELGT GQFGVVKYGK WRGQYDVAIK MIREGSMSED EFIEEAKVMM 450
    NLSHEKLVQL YGVCTKQRPI FIITEYMANG CLLNYLREMR HRFQTQQLLE 500
    MCKDVCEAME YLESKQFLHR DLAARNCLVN DQGVVKVSDF GLSRYVLDDE 550
    YTSSVGSKFP VRWSPPEVLM YSKFSSKSDI WAFGVLMWEI YSLGKMPYER 600
    FTNSETAEHI AQGLRLYRPH LASERVYTIM YSCWHEKADE RPSFKILLSN 650
    ILDVMDEES 659
    Length:659
    Mass (Da):76,437
    Last modified:January 23, 2007 - v4
    Checksum:iE502B798BC36E223
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti67 – 671V → A in L10627. (PubMed:8476425)Curated
    Sequence conflicti123 – 1231R → P in AAA37316. (PubMed:8425221)Curated
    Sequence conflicti197 – 1971I → IWI(PubMed:8476425)Curated
    Sequence conflicti450 – 4501Missing in L10627. (PubMed:8476425)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti28 – 281R → C in XID; prevents interaction with ARID3A. 1 Publication

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L08967 mRNA. Translation: AAA37316.1.
    L10627 mRNA. No translation available.
    L29788 mRNA. Translation: AAA66943.1.
    U58105 Genomic DNA. Translation: AAB47246.1.
    CCDSiCCDS30396.1.
    PIRiI49553.
    RefSeqiNP_038510.2. NM_013482.2.
    XP_006528546.1. XM_006528483.1.
    XP_006528547.1. XM_006528484.1.
    XP_006528548.1. XM_006528485.1.
    UniGeneiMm.4475.

    Genome annotation databases

    EnsembliENSMUST00000033617; ENSMUSP00000033617; ENSMUSG00000031264.
    GeneIDi12229.
    KEGGimmu:12229.
    UCSCiuc009uge.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L08967 mRNA. Translation: AAA37316.1 .
    L10627 mRNA. No translation available.
    L29788 mRNA. Translation: AAA66943.1 .
    U58105 Genomic DNA. Translation: AAB47246.1 .
    CCDSi CCDS30396.1.
    PIRi I49553.
    RefSeqi NP_038510.2. NM_013482.2.
    XP_006528546.1. XM_006528483.1.
    XP_006528547.1. XM_006528484.1.
    XP_006528548.1. XM_006528485.1.
    UniGenei Mm.4475.

    3D structure databases

    ProteinModelPortali P35991.
    SMRi P35991. Positions 2-170, 216-387, 395-657.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198400. 6 interactions.
    IntActi P35991. 29 interactions.
    MINTi MINT-1549372.

    PTM databases

    PhosphoSitei P35991.

    Proteomic databases

    MaxQBi P35991.
    PaxDbi P35991.
    PRIDEi P35991.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000033617 ; ENSMUSP00000033617 ; ENSMUSG00000031264 .
    GeneIDi 12229.
    KEGGi mmu:12229.
    UCSCi uc009uge.2. mouse.

    Organism-specific databases

    CTDi 695.
    MGIi MGI:88216. Btk.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00640000091251.
    HOGENOMi HOG000233859.
    HOVERGENi HBG008761.
    InParanoidi P35991.
    KOi K07370.
    OMAi SCRHYNI.
    OrthoDBi EOG7KM5SC.
    PhylomeDBi P35991.
    TreeFami TF351634.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 3474.
    Reactomei REACT_188185. DAP12 signaling.
    REACT_188194. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_188202. FCERI mediated Ca+2 mobilization.

    Miscellaneous databases

    NextBioi 280647.
    PROi P35991.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P35991.
    Bgeei P35991.
    CleanExi MM_BTK.
    Genevestigatori P35991.

    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. "Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia."
      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.
      Cell 72:279-290(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Structure and expression of novel protein-tyrosine kinases, Emb and Emt, in hematopoietic cells."
      Yamada N., Kawakami Y., Kimura H., Fukamachi H., Baier G., Altman A., Kato T., Inagaki Y., Kawakami T.
      Biochem. Biophys. Res. Commun. 192:231-240(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Genomic organization of mouse and human Bruton's agammaglobulinemia tyrosine kinase (Btk) loci."
      Sideras P., Mueller S., Shiels H., Jin H., Khan W.N., Nilsson L., Parkinson E., Thomas J.D., Branden L., Larsson I., Paul W.E., Rosen F.S., Alt F.W., Vetrie D., Smith C.I.E., Xanthopoulos K.G.
      J. Immunol. 153:5607-5617(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE.
    4. "Sixty-nine kilobases of contiguous human genomic sequence containing the alpha-galactosidase A and Bruton's tyrosine kinase loci."
      Oeltjen J.C., Liu X., Lu J., Allen R.C., Muzny D.M., Belmont J.W., Gibbs R.A.
      Mamm. Genome 6:334-338(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: C129.
    5. "Regulation of Btk function by a major autophosphorylation site within the SH3 domain."
      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.
      Immunity 4:515-525(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 219-233, PHOSPHORYLATION AT TYR-223, MUTAGENESIS OF TYR-223 AND LYS-430.
    6. "Activation of Bruton's tyrosine kinase (BTK) by a point mutation in its pleckstrin homology (PH) domain."
      Li T., Tsukada S., Satterthwaite A., Havlik M.H., Park H., Takatsu K., Witte O.N.
      Immunity 2:451-460(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF GLU-41 AND LYS-430.
    7. "Activation of BTK by a phosphorylation mechanism initiated by SRC family kinases."
      Rawlings D.J., Scharenberg A.M., Park H., Wahl M.I., Lin S., Kato R.M., Fluckiger A.C., Witte O.N., Kinet J.P.
      Science 271:822-825(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION AT TYR-551.
    8. "Characterization of the pleckstrin homology domain of Btk as an inositol polyphosphate and phosphoinositide binding domain."
      Kojima T., Fukuda M., Watanabe Y., Hamazato F., Mikoshiba K.
      Biochem. Biophys. Res. Commun. 236:333-339(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOMAIN.
    9. "Bruton's tyrosine kinase is required for activation of IkappaB kinase and nuclear factor kappaB in response to B cell receptor engagement."
      Petro J.B., Rahman S.M., Ballard D.W., Khan W.N.
      J. Exp. Med. 191:1745-1754(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    10. "The transcription factor Bright associates with Bruton's tyrosine kinase, the defective protein in immunodeficiency disease."
      Webb C.F., Yamashita Y., Ayers N., Evetts S., Paulin Y., Conley M.E., Smith E.A.
      J. Immunol. 165:6956-6965(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ARID3A, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT XID CYS-28.
    11. "Regulation of protein kinase CbetaI by two protein-tyrosine kinases, Btk and Syk."
      Kawakami Y., Kitaura J., Hartman S.E., Lowell C.A., Siraganian R.P., Kawakami T.
      Proc. Natl. Acad. Sci. U.S.A. 97:7423-7428(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ENZYME REGULATION.
    12. "Induction of immunoglobulin heavy-chain transcription through the transcription factor Bright requires TFII-I."
      Rajaiya J., Nixon J.C., Ayers N., Desgranges Z.P., Roy A.L., Webb C.F.
      Mol. Cell. Biol. 26:4758-4768(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GTF2I AND ARID3A, FUNCTION.
    13. "Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
      Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
      J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-40; TYR-344 AND TYR-551, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Mast cell.
    14. "Defective Toll-like receptor 9-mediated cytokine production in B cells from Bruton's tyrosine kinase-deficient mice."
      Hasan M., Lopez-Herrera G., Blomberg K.E., Lindvall J.M., Berglof A., Smith C.I., Vargas L.
      Immunology 123:239-249(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN THE TLR PATHWAY.
    15. "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.
    16. "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.
    17. Cited for: VARIANT XID CYS-28.

    Entry informationi

    Entry nameiBTK_MOUSE
    AccessioniPrimary (citable) accession number: P35991
    Secondary accession number(s): Q61365
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 152 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3