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Q06187

- BTK_HUMAN

UniProt

Q06187 - BTK_HUMAN

Protein

Tyrosine-protein kinase BTK

Gene

BTK

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 188 (01 Oct 2014)
      Sequence version 3 (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.

    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.8 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei26 – 261Inositol-(1,3,4,5)-tetrakisphosphate1 Publication
    Binding sitei28 – 281Inositol-(1,3,4,5)-tetrakisphosphate1 Publication
    Binding sitei39 – 391Inositol-(1,3,4,5)-tetrakisphosphate1 Publication
    Binding sitei53 – 531Inositol-(1,3,4,5)-tetrakisphosphate; via carbonyl oxygen1 Publication
    Metal bindingi143 – 1431Zinc3 Publications
    Metal bindingi154 – 1541Zinc3 Publications
    Metal bindingi155 – 1551Zinc3 Publications
    Metal bindingi165 – 1651Zinc3 Publications
    Binding sitei430 – 4301ATPPROSITE-ProRule annotation
    Binding sitei445 – 4451Inhibitor3 Publications
    Binding sitei461 – 4611Inhibitor3 Publications
    Binding sitei477 – 4771Inhibitor3 Publications
    Active sitei521 – 5211Proton acceptorPROSITE-ProRule annotation
    Binding sitei538 – 5381Inhibitor3 Publications
    Binding sitei539 – 5391Inhibitor; via amide nitrogen3 Publications
    Binding sitei542 – 5421Inhibitor; via carbonyl oxygen3 Publications

    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: HGNC
    2. identical protein binding Source: IntAct
    3. metal ion binding Source: UniProtKB-KW
    4. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
    5. phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB
    6. protein binding Source: UniProtKB
    7. protein tyrosine kinase activity Source: HGNC

    GO - Biological processi

    1. adaptive immune response Source: UniProtKB
    2. apoptotic signaling pathway Source: ProtInc
    3. B cell activation Source: UniProtKB
    4. B cell receptor signaling pathway Source: UniProtKB
    5. calcium-mediated signaling Source: HGNC
    6. cell maturation Source: Ensembl
    7. Fc-epsilon receptor signaling pathway Source: Reactome
    8. histamine secretion by mast cell Source: Ensembl
    9. I-kappaB kinase/NF-kappaB signaling Source: Ensembl
    10. innate immune response Source: UniProtKB
    11. intracellular signal transduction Source: HGNC
    12. mesoderm development Source: ProtInc
    13. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
    14. positive regulation of B cell differentiation Source: UniProtKB
    15. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
    16. protein autophosphorylation Source: Ensembl
    17. protein phosphorylation Source: HGNC
    18. regulation of B cell apoptotic process Source: UniProtKB
    19. regulation of B cell cytokine production Source: UniProtKB
    20. response to organic substance Source: Ensembl
    21. response to reactive oxygen species Source: Ensembl
    22. toll-like receptor 2 signaling pathway Source: Reactome
    23. toll-like receptor 4 signaling pathway Source: Reactome
    24. toll-like receptor signaling pathway Source: Reactome
    25. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
    26. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
    27. 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. 2681.
    ReactomeiREACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_147814. DAP12 signaling.
    REACT_160086. Regulation of actin dynamics for phagocytic cup formation.
    REACT_163834. FCERI mediated Ca+2 mobilization.
    REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
    SignaLinkiQ06187.

    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
    Gene namesi
    Name:BTK
    Synonyms:AGMX1, ATK, BPK
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome X

    Organism-specific databases

    HGNCiHGNC:1133. BTK.

    Subcellular locationi

    Cytoplasm. Cell membrane; Peripheral membrane protein. Nucleus
    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.

    GO - Cellular componenti

    1. cytoplasm Source: ProtInc
    2. cytoplasmic vesicle Source: Ensembl
    3. cytosol Source: UniProtKB
    4. intracellular membrane-bounded organelle Source: HPA
    5. mast cell granule Source: GOC
    6. membrane raft Source: HGNC
    7. nucleus Source: UniProtKB
    8. perinuclear region of cytoplasm Source: Ensembl
    9. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    X-linked agammaglobulinemia (XLA) [MIM:300755]: Humoral immunodeficiency disease which results in developmental defects in the maturation pathway of B-cells. Affected boys have normal levels of pre-B-cells in their bone marrow but virtually no circulating mature B-lymphocytes. This results in a lack of immunoglobulins of all classes and leads to recurrent bacterial infections like otitis, conjunctivitis, dermatitis, sinusitis in the first few years of life, or even some patients present overwhelming sepsis or meningitis, resulting in death in a few hours. Treatment in most cases is by infusion of intravenous immunoglobulin.24 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti11 – 111L → P in XLA.
    VAR_006216
    Natural varianti12 – 121K → R in XLA. 1 Publication
    VAR_006217
    Natural varianti14 – 141S → F in XLA.
    VAR_006218
    Natural varianti19 – 191K → E in XLA. 1 Publication
    VAR_008291
    Natural varianti25 – 251F → S in XLA. 1 Publication
    VAR_006219
    Natural varianti27 – 271K → R in XLA.
    VAR_008292
    Natural varianti28 – 281R → C in XLA; no effect on phosphorylation of GTF2I.
    VAR_008293
    Natural varianti28 – 281R → H in XLA; moderate. 3 Publications
    VAR_006220
    Natural varianti28 – 281R → P in XLA. 1 Publication
    VAR_006221
    Natural varianti33 – 331T → P in XLA; severe. 2 Publications
    VAR_006222
    Natural varianti39 – 391Y → S in XLA. 1 Publication
    VAR_008960
    Natural varianti40 – 401Y → C in XLA.
    VAR_008294
    Natural varianti40 – 401Y → N in XLA.
    VAR_008295
    Natural varianti61 – 611I → N in XLA. 1 Publication
    VAR_008296
    Natural varianti64 – 641V → D in XLA.
    VAR_008297
    Natural varianti64 – 641V → F in XLA. 1 Publication
    VAR_006223
    Natural varianti103 – 1031Q → QSVFSSTR in XLA.
    VAR_006224
    Natural varianti113 – 1131V → D in XLA. 1 Publication
    VAR_006225
    Natural varianti115 – 1151S → F in XLA.
    VAR_008298
    Natural varianti117 – 1171T → P in XLA. 1 Publication
    VAR_008299
    Natural varianti127 – 1271Q → H in XLA. 1 Publication
    VAR_008300
    Natural varianti154 – 1541C → S in XLA. 1 Publication
    VAR_008301
    Natural varianti155 – 1551C → G in XLA.
    VAR_008302
    Natural varianti155 – 1551C → R in XLA. 2 Publications
    VAR_008303
    Natural varianti184 – 1841T → P in XLA.
    VAR_008304
    Natural varianti260 – 28021Missing in XLA; severe.
    VAR_006226Add
    BLAST
    Natural varianti288 – 2881R → Q in XLA. 1 Publication
    VAR_008305
    Natural varianti288 – 2881R → W in XLA. 4 Publications
    VAR_006227
    Natural varianti295 – 2951L → P in XLA. 2 Publications
    VAR_006228
    Natural varianti302 – 3021G → E in XLA. 2 Publications
    VAR_006230
    Natural varianti302 – 3021G → R in XLA.
    VAR_008306
    Natural varianti302 – 3021Missing in XLA. 1 Publication
    VAR_006229
    Natural varianti307 – 3071R → G in XLA; loss of activity. 1 Publication
    VAR_006231
    Natural varianti307 – 3071R → T in XLA. 1 Publication
    VAR_008307
    Natural varianti308 – 3081D → E in XLA.
    VAR_008308
    Natural varianti319 – 3191V → A in XLA; moderate.
    VAR_008309
    Natural varianti334 – 3341Y → S in XLA. 1 Publication
    VAR_006232
    Natural varianti358 – 3581L → F in XLA. 1 Publication
    VAR_006233
    Natural varianti361 – 3611Y → C in XLA; mild. 1 Publication
    Corresponds to variant rs28935478 [ dbSNP | Ensembl ].
    VAR_006234
    Natural varianti362 – 3621H → Q in XLA.
    VAR_006235
    Natural varianti364 – 3641H → P in XLA.
    VAR_006236
    Natural varianti365 – 3651N → Y in XLA.
    VAR_006237
    Natural varianti366 – 3661S → F in XLA.
    VAR_008310
    Natural varianti369 – 3691L → F in XLA. 1 Publication
    VAR_008311
    Natural varianti370 – 3701I → M in XLA. 1 Publication
    VAR_006238
    Natural varianti372 – 3721R → G in XLA. 1 Publication
    VAR_008312
    Natural varianti408 – 4081L → P in XLA; moderate. 1 Publication
    VAR_006239
    Natural varianti414 – 4141G → R in XLA. 1 Publication
    VAR_008313
    Natural varianti418 – 4181Y → H in XLA.
    VAR_006240
    Natural varianti429 – 4291I → N in XLA. 1 Publication
    VAR_006241
    Natural varianti430 – 4301K → E in XLA; loss of phosphorylation of GTF2I. 1 Publication
    VAR_006242
    Natural varianti430 – 4301K → R in XLA. 1 Publication
    VAR_008314
    Natural varianti445 – 4451E → D in XLA. 1 Publication
    VAR_008315
    Natural varianti462 – 4621G → D in XLA.
    VAR_008316
    Natural varianti462 – 4621G → V in XLA.
    VAR_008317
    Natural varianti476 – 4761Y → D in XLA. 1 Publication
    VAR_006243
    Natural varianti477 – 4771M → R in XLA. 1 Publication
    VAR_006244
    Natural varianti502 – 5021C → F in XLA.
    VAR_006245
    Natural varianti502 – 5021C → W in XLA. 1 Publication
    VAR_006246
    Natural varianti506 – 5061C → R in XLA. 1 Publication
    VAR_006247
    Natural varianti506 – 5061C → Y in XLA. 1 Publication
    VAR_006248
    Natural varianti508 – 5081A → D in XLA.
    VAR_008318
    Natural varianti509 – 5091M → I in XLA.
    VAR_008319
    Natural varianti509 – 5091M → V in XLA. 1 Publication
    VAR_006249
    Natural varianti512 – 5121L → P in XLA. 1 Publication
    VAR_008961
    Natural varianti512 – 5121L → Q in XLA. 1 Publication
    VAR_008962
    Natural varianti518 – 5181L → R in XLA.
    VAR_008320
    Natural varianti520 – 5201R → Q in XLA; severe; prevents activation due to absence of contact between the catalytic loop and the regulatory phosphorylated residue. 4 Publications
    VAR_006251
    Natural varianti521 – 5211D → G in XLA. 1 Publication
    VAR_008321
    Natural varianti521 – 5211D → H in XLA; severe. 1 Publication
    VAR_006252
    Natural varianti521 – 5211D → N in XLA; severe.
    VAR_006253
    Natural varianti523 – 5231A → E in XLA.
    VAR_008322
    Natural varianti525 – 5251R → G in XLA. 1 Publication
    VAR_008323
    Natural varianti525 – 5251R → P in XLA. 1 Publication
    VAR_006254
    Natural varianti525 – 5251R → Q in XLA; severe; disturbs ATP-binding. 2 Publications
    VAR_006255
    Natural varianti526 – 5261N → K in XLA. 1 Publication
    VAR_006256
    Natural varianti535 – 5351V → F in XLA. 1 Publication
    VAR_008324
    Natural varianti542 – 5421L → P in XLA; growth hormone deficiency. 1 Publication
    VAR_006257
    Natural varianti544 – 5441R → G in XLA. 1 Publication
    VAR_008963
    Natural varianti544 – 5441R → K in XLA. 1 Publication
    VAR_006258
    Natural varianti559 – 5591F → S in XLA. 1 Publication
    VAR_008325
    Natural varianti562 – 5621R → P in XLA. 2 Publications
    Corresponds to variant rs28935176 [ dbSNP | Ensembl ].
    VAR_006259
    Natural varianti562 – 5621R → W in XLA. 4 Publications
    VAR_006260
    Natural varianti563 – 5631W → L in XLA. 1 Publication
    VAR_008326
    Natural varianti567 – 5671E → K in XLA; severe. 1 Publication
    VAR_006261
    Natural varianti578 – 5781S → Y in XLA. 1 Publication
    VAR_008964
    Natural varianti581 – 5811W → R in XLA.
    VAR_006262
    Natural varianti582 – 5821A → V in XLA. 2 Publications
    VAR_006263
    Natural varianti583 – 5831F → S in XLA.
    VAR_008327
    Natural varianti587 – 5871M → L in XLA; mild. 1 Publication
    VAR_006264
    Natural varianti589 – 5891E → D in XLA.
    VAR_008328
    Natural varianti589 – 5891E → G in XLA; moderate; interferes with substrate binding. 2 Publications
    VAR_006265
    Natural varianti589 – 5891E → K in XLA. 1 Publication
    VAR_008965
    Natural varianti592 – 5921S → P in XLA. 1 Publication
    VAR_006267
    Natural varianti594 – 5941G → E in XLA; mild; interferes with substrate binding. 2 Publications
    VAR_006268
    Natural varianti594 – 5941G → R in XLA. 1 Publication
    VAR_006269
    Natural varianti598 – 5981Y → C in XLA.
    VAR_006270
    Natural varianti607 – 6071A → D in XLA; mild. 1 Publication
    VAR_006271
    Natural varianti613 – 6131G → D in XLA; mild; interferes with substrate binding and/or domain interactions. 2 Publications
    VAR_006272
    Natural varianti619 – 6191P → A in XLA.
    VAR_008330
    Natural varianti619 – 6191P → S in XLA.
    VAR_006273
    Natural varianti619 – 6191P → T in XLA. 1 Publication
    VAR_008331
    Natural varianti622 – 6221A → P in XLA. 1 Publication
    VAR_008332
    Natural varianti626 – 6261V → G in XLA. 1 Publication
    VAR_008333
    Natural varianti630 – 6301M → K in XLA. 2 Publications
    VAR_006275
    Natural varianti630 – 6301M → T in XLA.
    VAR_008334
    Natural varianti633 – 6331C → Y in XLA. 1 Publication
    VAR_006276
    Natural varianti641 – 6411R → C in XLA. 1 Publication
    VAR_006277
    Natural varianti641 – 6411R → H in XLA; severe. 2 Publications
    VAR_006278
    Natural varianti644 – 6441F → L in XLA.
    VAR_008335
    Natural varianti644 – 6441F → S in XLA. 1 Publication
    VAR_006279
    Natural varianti647 – 6471L → P in XLA.
    VAR_006280
    Natural varianti652 – 6521L → P in XLA. 1 Publication
    VAR_006281
    X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA-IGHD) [MIM:307200]: In rare cases XLA is inherited together with isolated growth hormone deficiency (IGHD).
    Note: The disease may be caused by mutations affecting the gene represented in this entry.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi41 – 411E → K: No effect on phosphorylation of GTF2I. 2 Publications
    Mutagenesisi189 – 1891P → A: No effect on phosphorylation of GTF2I. 2 Publications
    Mutagenesisi223 – 2231Y → F: Loss of phosphorylation of GTF2I. 3 Publications
    Mutagenesisi251 – 2522WW → LL: Large decrease in binding by SH3BP5. 2 Publications
    Mutagenesisi251 – 2511W → L: No effect on phosphorylation of GTF2I. 2 Publications
    Mutagenesisi307 – 3071R → K: Loss of phosphorylation of GTF2I. 2 Publications
    Mutagenesisi551 – 5511Y → F: Loss of phosphorylation of GTF2I. 2 Publications
    Mutagenesisi617 – 6171Y → E: Defective in mediating calcium response. 2 Publications

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi300755. phenotype.
    307200. phenotype.
    Orphaneti632. Short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia.
    47. X-linked agammaglobulinemia.
    PharmGKBiPA25454.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 659658Tyrosine-protein kinase BTKPRO_0000088065Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine1 Publication
    Modified residuei21 – 211Phosphoserine1 Publication
    Modified residuei40 – 401PhosphotyrosineBy similarity
    Modified residuei55 – 551Phosphoserine1 Publication
    Modified residuei115 – 1151Phosphoserine1 Publication
    Modified residuei180 – 1801Phosphoserine; by PKC/PRKCB1 Publication
    Modified residuei191 – 1911Phosphothreonine1 Publication
    Modified residuei223 – 2231Phosphotyrosine; by autocatalysis4 Publications
    Modified residuei344 – 3441PhosphotyrosineBy similarity
    Modified residuei361 – 3611Phosphotyrosine1 Publication
    Modified residuei551 – 5511Phosphotyrosine; by LYN and SYK2 Publications
    Modified residuei617 – 6171Phosphotyrosine1 Publication
    Modified residuei623 – 6231Phosphoserine1 Publication
    Modified residuei659 – 6591Phosphoserine1 Publication

    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.8 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiQ06187.
    PaxDbiQ06187.
    PRIDEiQ06187.

    PTM databases

    PhosphoSiteiQ06187.

    Expressioni

    Tissue specificityi

    Predominantly expressed in B-lymphocytes.

    Gene expression databases

    ArrayExpressiQ06187.
    BgeeiQ06187.
    CleanExiHS_BTK.
    GenevestigatoriQ06187.

    Organism-specific databases

    HPAiCAB016689.
    HPA001198.
    HPA002028.

    Interactioni

    Subunit structurei

    Binds GTF2I through the PH domain. Interacts with SH3BP5 via the SH3 domain. Interacts with IBTK via its PH domain. Interacts with ARID3A, CAV1, FASLG, PIN1, TLR8 and TLR9.14 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself2EBI-624835,EBI-624835
    ARID3AQ998563EBI-624835,EBI-5458244
    BLNKQ8WV282EBI-624835,EBI-2623522
    GTF2IP783476EBI-624835,EBI-359622
    HSP90AB1P082382EBI-624835,EBI-352572
    MALP211455EBI-624835,EBI-3932027
    PRKCQQ047592EBI-624835,EBI-374762
    SH3BP5O602394EBI-624835,EBI-624860

    Protein-protein interaction databases

    BioGridi107160. 69 interactions.
    DIPiDIP-34071N.
    IntActiQ06187. 44 interactions.
    MINTiMINT-110243.
    STRINGi9606.ENSP00000308176.

    Structurei

    Secondary structure

    1
    659
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi6 – 138
    Beta strandi18 – 203
    Beta strandi25 – 328
    Beta strandi34 – 4310
    Turni44 – 474
    Beta strandi48 – 5710
    Helixi58 – 603
    Beta strandi61 – 666
    Helixi75 – 773
    Helixi93 – 964
    Beta strandi100 – 1067
    Beta strandi111 – 1166
    Helixi118 – 13215
    Beta strandi140 – 1423
    Beta strandi149 – 1524
    Turni153 – 1553
    Beta strandi165 – 1673
    Turni212 – 2154
    Beta strandi218 – 2236
    Beta strandi228 – 2325
    Beta strandi240 – 2423
    Beta strandi248 – 2525
    Turni257 – 2593
    Beta strandi261 – 2655
    Turni266 – 2683
    Beta strandi279 – 2824
    Helixi288 – 29811
    Beta strandi303 – 3086
    Beta strandi310 – 3123
    Beta strandi315 – 32612
    Beta strandi330 – 3356
    Beta strandi337 – 3393
    Turni340 – 3423
    Beta strandi343 – 3475
    Beta strandi350 – 3545
    Helixi355 – 3639
    Beta strandi373 – 3764
    Helixi393 – 3953
    Helixi399 – 4013
    Beta strandi402 – 41110
    Beta strandi414 – 4218
    Turni422 – 4243
    Beta strandi425 – 4317
    Helixi439 – 44911
    Beta strandi460 – 4645
    Beta strandi466 – 4694
    Beta strandi471 – 4755
    Helixi482 – 4876
    Helixi489 – 4913
    Helixi495 – 51420
    Helixi524 – 5263
    Beta strandi527 – 5293
    Beta strandi535 – 5373
    Helixi542 – 5454
    Helixi549 – 5524
    Turni554 – 5563
    Helixi561 – 5633
    Helixi566 – 5716
    Helixi576 – 59116
    Turni592 – 5943
    Turni597 – 6004
    Helixi603 – 6119
    Helixi624 – 6329
    Helixi638 – 6403
    Helixi644 – 65714

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1AWWNMR-A212-275[»]
    1AWXNMR-A212-275[»]
    1B55X-ray2.40A/B2-170[»]
    1BTKX-ray1.60A/B2-170[»]
    1BWNX-ray2.10A/B2-170[»]
    1K2PX-ray2.10A/B397-659[»]
    1QLYNMR-A216-273[»]
    2GE9NMR-A270-387[»]
    2Z0PX-ray2.58A/B/C/D2-170[»]
    3GENX-ray1.60A382-659[»]
    3K54X-ray1.94A382-659[»]
    3OCSX-ray1.80A393-656[»]
    3OCTX-ray1.95A393-656[»]
    3P08X-ray2.30A/B393-659[»]
    3PIXX-ray1.85A387-659[»]
    3PIYX-ray2.55A387-659[»]
    3PIZX-ray2.21A387-659[»]
    3PJ1X-ray2.00A387-659[»]
    3PJ2X-ray1.75A387-659[»]
    3PJ3X-ray1.85A387-659[»]
    4NWMX-ray2.03A/B396-657[»]
    4OT5X-ray1.55A378-659[»]
    4OT6X-ray2.05A378-659[»]
    4OTQX-ray1.55A378-659[»]
    4OTRX-ray1.95A378-659[»]
    ProteinModelPortaliQ06187.
    SMRiQ06187. Positions 2-170, 216-387, 395-657.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ06187.

    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-bindingAdd
    BLAST
    Regioni474 – 4796Inhibitor-binding

    Motif

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

    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.4 Publications

    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.
    HOGENOMiHOG000233859.
    HOVERGENiHBG008761.
    InParanoidiQ06187.
    KOiK07370.
    OMAiSCRHYNI.
    PhylomeDBiQ06187.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative promoter usage. Align

    Isoform BTK-A (identifier: Q06187-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAAVILESIF LKRSQQKKKT SPLNFKKRLF LLTVHKLSYY EYDFERGRRG    50
    SKKGSIDVEK ITCVETVVPE KNPPPERQIP RRGEESSEME QISIIERFPY 100
    PFQVVYDEGP LYVFSPTEEL RKRWIHQLKN VIRYNSDLVQ KYHPCFWIDG 150
    QYLCCSQTAK NAMGCQILEN RNGSLKPGSS HRKTKKPLPP TPEEDQILKK 200
    PLPPEPAAAP VSTSELKKVV ALYDYMPMNA NDLQLRKGDE YFILEESNLP 250
    WWRARDKNGQ EGYIPSNYVT EAEDSIEMYE WYSKHMTRSQ AEQLLKQEGK 300
    EGGFIVRDSS KAGKYTVSVF AKSTGDPQGV IRHYVVCSTP QSQYYLAEKH 350
    LFSTIPELIN YHQHNSAGLI SRLKYPVSQQ NKNAPSTAGL GYGSWEIDPK 400
    DLTFLKELGT GQFGVVKYGK WRGQYDVAIK MIKEGSMSED EFIEEAKVMM 450
    NLSHEKLVQL YGVCTKQRPI FIITEYMANG CLLNYLREMR HRFQTQQLLE 500
    MCKDVCEAME YLESKQFLHR DLAARNCLVN DQGVVKVSDF GLSRYVLDDE 550
    YTSSVGSKFP VRWSPPEVLM YSKFSSKSDI WAFGVLMWEI YSLGKMPYER 600
    FTNSETAEHI AQGLRLYRPH LASEKVYTIM YSCWHEKADE RPTFKILLSN 650
    ILDVMDEES 659
    Length:659
    Mass (Da):76,281
    Last modified:January 23, 2007 - v3
    Checksum:iDF06B5D1FEC257CC
    GO
    Isoform BTK-C (identifier: Q06187-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MASWSIQQMVIGCPLCGRHCSGGEHTGELQKEEAM

    Note: Produced by alternative promoter usage. Predominant form in many tumor cells where it may function as an anti-apoptotic cell survival factor.

    Show »
    Length:693
    Mass (Da):79,937
    Checksum:i8C582E0CD4D6280F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti253 – 2531R → K in BAG37008. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti11 – 111L → P in XLA.
    VAR_006216
    Natural varianti12 – 121K → R in XLA. 1 Publication
    VAR_006217
    Natural varianti14 – 141S → F in XLA.
    VAR_006218
    Natural varianti19 – 191K → E in XLA. 1 Publication
    VAR_008291
    Natural varianti25 – 251F → S in XLA. 1 Publication
    VAR_006219
    Natural varianti27 – 271K → R in XLA.
    VAR_008292
    Natural varianti28 – 281R → C in XLA; no effect on phosphorylation of GTF2I.
    VAR_008293
    Natural varianti28 – 281R → H in XLA; moderate. 3 Publications
    VAR_006220
    Natural varianti28 – 281R → P in XLA. 1 Publication
    VAR_006221
    Natural varianti33 – 331T → P in XLA; severe. 2 Publications
    VAR_006222
    Natural varianti39 – 391Y → S in XLA. 1 Publication
    VAR_008960
    Natural varianti40 – 401Y → C in XLA.
    VAR_008294
    Natural varianti40 – 401Y → N in XLA.
    VAR_008295
    Natural varianti61 – 611I → N in XLA. 1 Publication
    VAR_008296
    Natural varianti64 – 641V → D in XLA.
    VAR_008297
    Natural varianti64 – 641V → F in XLA. 1 Publication
    VAR_006223
    Natural varianti82 – 821R → K.1 Publication
    Corresponds to variant rs56035945 [ dbSNP | Ensembl ].
    VAR_041676
    Natural varianti103 – 1031Q → QSVFSSTR in XLA.
    VAR_006224
    Natural varianti113 – 1131V → D in XLA. 1 Publication
    VAR_006225
    Natural varianti115 – 1151S → F in XLA.
    VAR_008298
    Natural varianti117 – 1171T → P in XLA. 1 Publication
    VAR_008299
    Natural varianti127 – 1271Q → H in XLA. 1 Publication
    VAR_008300
    Natural varianti154 – 1541C → S in XLA. 1 Publication
    VAR_008301
    Natural varianti155 – 1551C → G in XLA.
    VAR_008302
    Natural varianti155 – 1551C → R in XLA. 2 Publications
    VAR_008303
    Natural varianti184 – 1841T → P in XLA.
    VAR_008304
    Natural varianti190 – 1901P → K in a lung large cell carcinoma sample; somatic mutation; requires 2 nucleotide substitutions. 1 Publication
    VAR_041677
    Natural varianti260 – 28021Missing in XLA; severe.
    VAR_006226Add
    BLAST
    Natural varianti288 – 2881R → Q in XLA. 1 Publication
    VAR_008305
    Natural varianti288 – 2881R → W in XLA. 4 Publications
    VAR_006227
    Natural varianti295 – 2951L → P in XLA. 2 Publications
    VAR_006228
    Natural varianti302 – 3021G → E in XLA. 2 Publications
    VAR_006230
    Natural varianti302 – 3021G → R in XLA.
    VAR_008306
    Natural varianti302 – 3021Missing in XLA. 1 Publication
    VAR_006229
    Natural varianti307 – 3071R → G in XLA; loss of activity. 1 Publication
    VAR_006231
    Natural varianti307 – 3071R → T in XLA. 1 Publication
    VAR_008307
    Natural varianti308 – 3081D → E in XLA.
    VAR_008308
    Natural varianti319 – 3191V → A in XLA; moderate.
    VAR_008309
    Natural varianti334 – 3341Y → S in XLA. 1 Publication
    VAR_006232
    Natural varianti358 – 3581L → F in XLA. 1 Publication
    VAR_006233
    Natural varianti361 – 3611Y → C in XLA; mild. 1 Publication
    Corresponds to variant rs28935478 [ dbSNP | Ensembl ].
    VAR_006234
    Natural varianti362 – 3621H → Q in XLA.
    VAR_006235
    Natural varianti364 – 3641H → P in XLA.
    VAR_006236
    Natural varianti365 – 3651N → Y in XLA.
    VAR_006237
    Natural varianti366 – 3661S → F in XLA.
    VAR_008310
    Natural varianti369 – 3691L → F in XLA. 1 Publication
    VAR_008311
    Natural varianti370 – 3701I → M in XLA. 1 Publication
    VAR_006238
    Natural varianti372 – 3721R → G in XLA. 1 Publication
    VAR_008312
    Natural varianti408 – 4081L → P in XLA; moderate. 1 Publication
    VAR_006239
    Natural varianti414 – 4141G → R in XLA. 1 Publication
    VAR_008313
    Natural varianti418 – 4181Y → H in XLA.
    VAR_006240
    Natural varianti429 – 4291I → N in XLA. 1 Publication
    VAR_006241
    Natural varianti430 – 4301K → E in XLA; loss of phosphorylation of GTF2I. 1 Publication
    VAR_006242
    Natural varianti430 – 4301K → R in XLA. 1 Publication
    VAR_008314
    Natural varianti445 – 4451E → D in XLA. 1 Publication
    VAR_008315
    Natural varianti462 – 4621G → D in XLA.
    VAR_008316
    Natural varianti462 – 4621G → V in XLA.
    VAR_008317
    Natural varianti476 – 4761Y → D in XLA. 1 Publication
    VAR_006243
    Natural varianti477 – 4771M → R in XLA. 1 Publication
    VAR_006244
    Natural varianti502 – 5021C → F in XLA.
    VAR_006245
    Natural varianti502 – 5021C → W in XLA. 1 Publication
    VAR_006246
    Natural varianti506 – 5061C → R in XLA. 1 Publication
    VAR_006247
    Natural varianti506 – 5061C → Y in XLA. 1 Publication
    VAR_006248
    Natural varianti508 – 5081A → D in XLA.
    VAR_008318
    Natural varianti509 – 5091M → I in XLA.
    VAR_008319
    Natural varianti509 – 5091M → V in XLA. 1 Publication
    VAR_006249
    Natural varianti512 – 5121L → P in XLA. 1 Publication
    VAR_008961
    Natural varianti512 – 5121L → Q in XLA. 1 Publication
    VAR_008962
    Natural varianti518 – 5181L → R in XLA.
    VAR_008320
    Natural varianti520 – 5201R → Q in XLA; severe; prevents activation due to absence of contact between the catalytic loop and the regulatory phosphorylated residue. 4 Publications
    VAR_006251
    Natural varianti521 – 5211D → G in XLA. 1 Publication
    VAR_008321
    Natural varianti521 – 5211D → H in XLA; severe. 1 Publication