Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q06187

- BTK_HUMAN

UniProt

Q06187 - BTK_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Tyrosine-protein kinase BTK

Gene

BTK

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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

Zn2+Note: 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 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
Complete GO annotation...

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
Complete GO annotation...

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. 1 Publication
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. 1 Publication
Mutagenesisi189 – 1891P → A: No effect on phosphorylation of GTF2I. 1 Publication
Mutagenesisi223 – 2231Y → F: Loss of phosphorylation of GTF2I. 2 Publications
Mutagenesisi251 – 2522WW → LL: Large decrease in binding by SH3BP5. 1 Publication
Mutagenesisi251 – 2511W → L: No effect on phosphorylation of GTF2I. 1 Publication
Mutagenesisi307 – 3071R → K: Loss of phosphorylation of GTF2I. 1 Publication
Mutagenesisi551 – 5511Y → F: Loss of phosphorylation of GTF2I. 1 Publication
Mutagenesisi617 – 6171Y → E: Defective in mediating calcium response. 1 Publication

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

BgeeiQ06187.
CleanExiHS_BTK.
ExpressionAtlasiQ06187. baseline and differential.
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 – 138Combined sources
Beta strandi18 – 203Combined sources
Beta strandi25 – 328Combined sources
Beta strandi34 – 4310Combined sources
Turni44 – 474Combined sources
Beta strandi48 – 5710Combined sources
Helixi58 – 603Combined sources
Beta strandi61 – 666Combined sources
Helixi75 – 773Combined sources
Helixi93 – 964Combined sources
Beta strandi100 – 1067Combined sources
Beta strandi111 – 1166Combined sources
Helixi118 – 13215Combined sources
Beta strandi140 – 1423Combined sources
Beta strandi149 – 1524Combined sources
Turni153 – 1553Combined sources
Beta strandi165 – 1673Combined sources
Turni212 – 2154Combined sources
Beta strandi218 – 2236Combined sources
Beta strandi228 – 2325Combined sources
Beta strandi240 – 2423Combined sources
Beta strandi248 – 2525Combined sources
Turni257 – 2593Combined sources
Beta strandi261 – 2655Combined sources
Turni266 – 2683Combined sources
Beta strandi279 – 2824Combined sources
Helixi288 – 29811Combined sources
Beta strandi303 – 3086Combined sources
Beta strandi310 – 3123Combined sources
Beta strandi315 – 32612Combined sources
Beta strandi330 – 3356Combined sources
Beta strandi337 – 3393Combined sources
Turni340 – 3423Combined sources
Beta strandi343 – 3475Combined sources
Beta strandi350 – 3545Combined sources
Helixi355 – 3639Combined sources
Beta strandi373 – 3764Combined sources
Helixi393 – 3953Combined sources
Helixi399 – 4013Combined sources
Beta strandi402 – 41110Combined sources
Beta strandi414 – 4218Combined sources
Turni422 – 4243Combined sources
Beta strandi425 – 4317Combined sources
Helixi439 – 44911Combined sources
Beta strandi460 – 4645Combined sources
Beta strandi466 – 4694Combined sources
Beta strandi471 – 4755Combined sources
Helixi482 – 4876Combined sources
Helixi489 – 4913Combined sources
Helixi495 – 51420Combined sources
Helixi524 – 5263Combined sources
Beta strandi527 – 5293Combined sources
Beta strandi535 – 5373Combined sources
Helixi542 – 5454Combined sources
Helixi549 – 5524Combined sources
Turni554 – 5563Combined sources
Helixi561 – 5633Combined sources
Helixi566 – 5716Combined sources
Helixi576 – 59116Combined sources
Turni592 – 5943Combined sources
Turni597 – 6004Combined sources
Helixi603 – 6119Combined sources
Helixi624 – 6329Combined sources
Helixi638 – 6403Combined sources
Helixi644 – 65714Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00760000119011.
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

        10         20         30         40         50
MAAVILESIF LKRSQQKKKT SPLNFKKRLF LLTVHKLSYY EYDFERGRRG
60 70 80 90 100
SKKGSIDVEK ITCVETVVPE KNPPPERQIP RRGEESSEME QISIIERFPY
110 120 130 140 150
PFQVVYDEGP LYVFSPTEEL RKRWIHQLKN VIRYNSDLVQ KYHPCFWIDG
160 170 180 190 200
QYLCCSQTAK NAMGCQILEN RNGSLKPGSS HRKTKKPLPP TPEEDQILKK
210 220 230 240 250
PLPPEPAAAP VSTSELKKVV ALYDYMPMNA NDLQLRKGDE YFILEESNLP
260 270 280 290 300
WWRARDKNGQ EGYIPSNYVT EAEDSIEMYE WYSKHMTRSQ AEQLLKQEGK
310 320 330 340 350
EGGFIVRDSS KAGKYTVSVF AKSTGDPQGV IRHYVVCSTP QSQYYLAEKH
360 370 380 390 400
LFSTIPELIN YHQHNSAGLI SRLKYPVSQQ NKNAPSTAGL GYGSWEIDPK
410 420 430 440 450
DLTFLKELGT GQFGVVKYGK WRGQYDVAIK MIKEGSMSED EFIEEAKVMM
460 470 480 490 500
NLSHEKLVQL YGVCTKQRPI FIITEYMANG CLLNYLREMR HRFQTQQLLE
510 520 530 540 550
MCKDVCEAME YLESKQFLHR DLAARNCLVN DQGVVKVSDF GLSRYVLDDE
560 570 580 590 600
YTSSVGSKFP VRWSPPEVLM YSKFSSKSDI WAFGVLMWEI YSLGKMPYER
610 620 630 640 650
FTNSETAEHI AQGLRLYRPH LASEKVYTIM YSCWHEKADE RPTFKILLSN

ILDVMDEES
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. 1 Publication
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