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Protein

Tyrosine-protein kinase BTK

Gene

BTK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
Binding sitei26Inositol-(1,3,4,5)-tetrakisphosphate1 Publication1
Binding sitei28Inositol-(1,3,4,5)-tetrakisphosphate1 Publication1
Binding sitei39Inositol-(1,3,4,5)-tetrakisphosphate1 Publication1
Binding sitei53Inositol-(1,3,4,5)-tetrakisphosphate; via carbonyl oxygen1 Publication1
Metal bindingi143Zinc3 Publications1
Metal bindingi154Zinc3 Publications1
Metal bindingi155Zinc3 Publications1
Metal bindingi165Zinc3 Publications1
Binding sitei430ATPPROSITE-ProRule annotation1
Binding sitei445Inhibitor3 Publications1
Binding sitei461Inhibitor3 Publications1
Binding sitei477Inhibitor3 Publications1
Active sitei521Proton acceptorPROSITE-ProRule annotation1
Binding sitei538Inhibitor3 Publications1
Binding sitei539Inhibitor; via amide nitrogen3 Publications1
Binding sitei542Inhibitor; via carbonyl oxygen3 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri135 – 171Btk-typePROSITE-ProRule annotationAdd BLAST37
Nucleotide bindingi408 – 416ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: HGNC
  • metal ion binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
  • phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB
  • protein tyrosine kinase activity Source: HGNC

GO - Biological processi

  • adaptive immune response Source: UniProtKB
  • apoptotic signaling pathway Source: ProtInc
  • B cell activation Source: UniProtKB
  • B cell receptor signaling pathway Source: UniProtKB
  • calcium-mediated signaling Source: HGNC
  • cell maturation Source: Ensembl
  • cellular response to molecule of fungal origin Source: Ensembl
  • cellular response to reactive oxygen species Source: Ensembl
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • histamine secretion by mast cell Source: Ensembl
  • I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  • innate immune response Source: UniProtKB
  • intracellular signal transduction Source: HGNC
  • mesoderm development Source: ProtInc
  • MyD88-dependent toll-like receptor signaling pathway Source: Reactome
  • negative regulation of cytokine production Source: Ensembl
  • peptidyl-tyrosine autophosphorylation Source: GO_Central
  • peptidyl-tyrosine phosphorylation Source: CACAO
  • positive regulation of B cell differentiation Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of type I hypersensitivity Source: Ensembl
  • positive regulation of type III hypersensitivity Source: Ensembl
  • protein phosphorylation Source: HGNC
  • regulation of B cell apoptotic process Source: UniProtKB
  • regulation of B cell cytokine production Source: UniProtKB
  • regulation of cell proliferation Source: GO_Central
  • transcription, DNA-templated Source: UniProtKB-KW
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
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

BioCyciZFISH:HS00290-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-1236974. ER-Phagosome pathway.
R-HSA-166058. MyD88:Mal cascade initiated on plasma membrane.
R-HSA-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-HSA-2424491. DAP12 signaling.
R-HSA-2871809. FCERI mediated Ca+2 mobilization.
R-HSA-5602498. MyD88 deficiency (TLR2/4).
R-HSA-5603041. IRAK4 deficiency (TLR2/4).
R-HSA-5663213. RHO GTPases Activate WASPs and WAVEs.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
SignaLinkiQ06187.
SIGNORiQ06187.

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
Proteomesi
  • UP000005640 Componenti: 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

  • cytoplasm Source: ProtInc
  • cytoplasmic vesicle Source: Ensembl
  • cytosol Source: UniProtKB
  • extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  • intracellular membrane-bounded organelle Source: HPA
  • mast cell granule Source: GOC
  • membrane raft Source: HGNC
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: Ensembl
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

X-linked agammaglobulinemia (XLA)24 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionHumoral 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.
See also OMIM:300755
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00621611L → P in XLA. 1
Natural variantiVAR_00621712K → R in XLA. 1 Publication1
Natural variantiVAR_00621814S → F in XLA. 1
Natural variantiVAR_00829119K → E in XLA. 1 Publication1
Natural variantiVAR_00621925F → S in XLA. 1 Publication1
Natural variantiVAR_00829227K → R in XLA. 1
Natural variantiVAR_00829328R → C in XLA; no effect on phosphorylation of GTF2I. 1
Natural variantiVAR_00622028R → H in XLA; moderate. 3 PublicationsCorresponds to variant rs128620185dbSNPEnsembl.1
Natural variantiVAR_00622128R → P in XLA. 1 Publication1
Natural variantiVAR_00622233T → P in XLA; severe. 2 PublicationsCorresponds to variant rs128620189dbSNPEnsembl.1
Natural variantiVAR_00896039Y → S in XLA. 1 Publication1
Natural variantiVAR_00829440Y → C in XLA. 1
Natural variantiVAR_00829540Y → N in XLA. 1
Natural variantiVAR_00829661I → N in XLA. 1 Publication1
Natural variantiVAR_00829764V → D in XLA. 1
Natural variantiVAR_00622364V → F in XLA. 1 Publication1
Natural variantiVAR_006224103Q → QSVFSSTR in XLA. 1
Natural variantiVAR_006225113V → D in XLA. 1 PublicationCorresponds to variant rs128621190dbSNPEnsembl.1
Natural variantiVAR_008298115S → F in XLA. 1
Natural variantiVAR_008299117T → P in XLA. 1 Publication1
Natural variantiVAR_008300127Q → H in XLA. 1 Publication1
Natural variantiVAR_008301154C → S in XLA. 1 Publication1
Natural variantiVAR_008302155C → G in XLA. 1
Natural variantiVAR_008303155C → R in XLA. 2 Publications1
Natural variantiVAR_008304184T → P in XLA. 1
Natural variantiVAR_006226260 – 280Missing in XLA; severe. 1 PublicationAdd BLAST21
Natural variantiVAR_008305288R → Q in XLA. 1 Publication1
Natural variantiVAR_006227288R → W in XLA. 4 PublicationsCorresponds to variant rs128621194dbSNPEnsembl.1
Natural variantiVAR_006228295L → P in XLA. 2 Publications1
Natural variantiVAR_006230302G → E in XLA. 2 Publications1
Natural variantiVAR_008306302G → R in XLA. 1
Natural variantiVAR_006229302Missing in XLA. 1 Publication1
Natural variantiVAR_006231307R → G in XLA; loss of activity. 1 PublicationCorresponds to variant rs128621195dbSNPEnsembl.1
Natural variantiVAR_008307307R → T in XLA. 1 Publication1
Natural variantiVAR_008308308D → E in XLA. 1
Natural variantiVAR_008309319V → A in XLA; moderate. 1
Natural variantiVAR_006232334Y → S in XLA. 1 PublicationCorresponds to variant rs128621196dbSNPEnsembl.1
Natural variantiVAR_006233358L → F in XLA. 1 Publication1
Natural variantiVAR_006234361Y → C in XLA; mild. 1 PublicationCorresponds to variant rs28935478dbSNPEnsembl.1
Natural variantiVAR_006235362H → Q in XLA. 1
Natural variantiVAR_006236364H → P in XLA. 1
Natural variantiVAR_006237365N → Y in XLA. 1
Natural variantiVAR_008310366S → F in XLA. 1
Natural variantiVAR_008311369L → F in XLA. 1 Publication1
Natural variantiVAR_006238370I → M in XLA. 1 Publication1
Natural variantiVAR_008312372R → G in XLA. 1 Publication1
Natural variantiVAR_006239408L → P in XLA; moderate. 1 PublicationCorresponds to variant rs128621198dbSNPEnsembl.1
Natural variantiVAR_008313414G → R in XLA. 1 Publication1
Natural variantiVAR_006240418Y → H in XLA. Corresponds to variant rs144079566dbSNPEnsembl.1
Natural variantiVAR_006241429I → N in XLA. 1 Publication1
Natural variantiVAR_006242430K → E in XLA; loss of phosphorylation of GTF2I. 1 PublicationCorresponds to variant rs128620184dbSNPEnsembl.1
Natural variantiVAR_008314430K → R in XLA. 1 Publication1
Natural variantiVAR_008315445E → D in XLA. 1 Publication1
Natural variantiVAR_008316462G → D in XLA. 1
Natural variantiVAR_008317462G → V in XLA. 1
Natural variantiVAR_006243476Y → D in XLA. 1 Publication1
Natural variantiVAR_006244477M → R in XLA. 1 Publication1
Natural variantiVAR_006245502C → F in XLA. 1
Natural variantiVAR_006246502C → W in XLA. 1 PublicationCorresponds to variant rs41310709dbSNPEnsembl.1
Natural variantiVAR_006247506C → R in XLA. 1 PublicationCorresponds to variant rs128621200dbSNPEnsembl.1
Natural variantiVAR_006248506C → Y in XLA. 1 Publication1
Natural variantiVAR_008318508A → D in XLA. 1
Natural variantiVAR_008319509M → I in XLA. 1
Natural variantiVAR_006249509M → V in XLA. 1 Publication1
Natural variantiVAR_008961512L → P in XLA. 1 Publication1
Natural variantiVAR_008962512L → Q in XLA. 1 Publication1
Natural variantiVAR_008320518L → R in XLA. 1
Natural variantiVAR_006251520R → Q in XLA; severe; prevents activation due to absence of contact between the catalytic loop and the regulatory phosphorylated residue. 4 PublicationsCorresponds to variant rs128621202dbSNPEnsembl.1
Natural variantiVAR_008321521D → G in XLA. 1 Publication1
Natural variantiVAR_006252521D → H in XLA; severe. 1 Publication1
Natural variantiVAR_006253521D → N in XLA; severe. 1
Natural variantiVAR_008322523A → E in XLA. 1
Natural variantiVAR_008323525R → G in XLA. 1 Publication1
Natural variantiVAR_006254525R → P in XLA. 1 Publication1
Natural variantiVAR_006255525R → Q in XLA; severe; disturbs ATP-binding. 2 PublicationsCorresponds to variant rs128620183dbSNPEnsembl.1
Natural variantiVAR_006256526N → K in XLA. 1 Publication1
Natural variantiVAR_008324535V → F in XLA. 1 Publication1
Natural variantiVAR_006257542L → P in XLA; growth hormone deficiency. 1 PublicationCorresponds to variant rs128621203dbSNPEnsembl.1
Natural variantiVAR_008963544R → G in XLA. 1 Publication1
Natural variantiVAR_006258544R → K in XLA. 1 Publication1
Natural variantiVAR_008325559F → S in XLA. 1 Publication1
Natural variantiVAR_006259562R → P in XLA. 2 PublicationsCorresponds to variant rs28935176dbSNPEnsembl.1
Natural variantiVAR_006260562R → W in XLA. 4 PublicationsCorresponds to variant rs128621204dbSNPEnsembl.1
Natural variantiVAR_008326563W → L in XLA. 1 Publication1
Natural variantiVAR_006261567E → K in XLA; severe. 1 Publication1
Natural variantiVAR_008964578S → Y in XLA. 1 Publication1
Natural variantiVAR_006262581W → R in XLA. Corresponds to variant rs128621205dbSNPEnsembl.1
Natural variantiVAR_006263582A → V in XLA. 2 Publications1
Natural variantiVAR_008327583F → S in XLA. 1
Natural variantiVAR_006264587M → L in XLA; mild. 1 Publication1
Natural variantiVAR_008328589E → D in XLA. 1
Natural variantiVAR_006265589E → G in XLA; moderate; interferes with substrate binding. 2 PublicationsCorresponds to variant rs128621206dbSNPEnsembl.1
Natural variantiVAR_008965589E → K in XLA. 1 Publication1
Natural variantiVAR_006267592S → P in XLA. 1 Publication1
Natural variantiVAR_006268594G → E in XLA; mild; interferes with substrate binding. 2 Publications1
Natural variantiVAR_006269594G → R in XLA. 1 Publication1
Natural variantiVAR_006270598Y → C in XLA. 1
Natural variantiVAR_006271607A → D in XLA; mild. 1 PublicationCorresponds to variant rs128621208dbSNPEnsembl.1
Natural variantiVAR_006272613G → D in XLA; mild; interferes with substrate binding and/or domain interactions. 2 PublicationsCorresponds to variant rs128621209dbSNPEnsembl.1
Natural variantiVAR_008330619P → A in XLA. 1
Natural variantiVAR_006273619P → S in XLA. 1
Natural variantiVAR_008331619P → T in XLA. 1 Publication1
Natural variantiVAR_008332622A → P in XLA. 1 Publication1
Natural variantiVAR_008333626V → G in XLA. 1 Publication1
Natural variantiVAR_006275630M → K in XLA. 2 PublicationsCorresponds to variant rs128621210dbSNPEnsembl.1
Natural variantiVAR_008334630M → T in XLA. 1
Natural variantiVAR_006276633C → Y in XLA. 1 Publication1
Natural variantiVAR_006277641R → C in XLA. 1 Publication1
Natural variantiVAR_006278641R → H in XLA; severe. 2 Publications1
Natural variantiVAR_008335644F → L in XLA. 1
Natural variantiVAR_006279644F → S in XLA. 1 Publication1
Natural variantiVAR_006280647L → P in XLA. 1
Natural variantiVAR_006281652L → P in XLA. 1 PublicationCorresponds to variant rs128622212dbSNPEnsembl.1
X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA-IGHD)
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionIn rare cases XLA is inherited together with isolated growth hormone deficiency (IGHD).
See also OMIM:307200

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi41E → K: No effect on phosphorylation of GTF2I. 1 Publication1
Mutagenesisi189P → A: No effect on phosphorylation of GTF2I. 1 Publication1
Mutagenesisi223Y → F: Loss of phosphorylation of GTF2I. 2 Publications1
Mutagenesisi251 – 252WW → LL: Large decrease in binding by SH3BP5. 1 Publication2
Mutagenesisi251W → L: No effect on phosphorylation of GTF2I. 1 Publication1
Mutagenesisi307R → K: Loss of phosphorylation of GTF2I. 1 Publication1
Mutagenesisi551Y → F: Loss of phosphorylation of GTF2I. 1 Publication1
Mutagenesisi617Y → E: Defective in mediating calcium response. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi695.
MalaCardsiBTK.
MIMi300755. phenotype.
307200. phenotype.
OpenTargetsiENSG00000010671.
Orphaneti632. Short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia.
47. X-linked agammaglobulinemia.
PharmGKBiPA25454.

Chemistry databases

ChEMBLiCHEMBL5251.
DrugBankiDB09053. Ibrutinib.
GuidetoPHARMACOLOGYi1948.

Polymorphism and mutation databases

BioMutaiBTK.
DMDMi547759.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00000880652 – 659Tyrosine-protein kinase BTKAdd BLAST658

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei21Phosphoserine1 Publication1
Modified residuei40PhosphotyrosineBy similarity1
Modified residuei55PhosphoserineCombined sources1
Modified residuei115Phosphoserine1 Publication1
Modified residuei180Phosphoserine; by PKC/PRKCB1 Publication1
Modified residuei191PhosphothreonineCombined sources1
Modified residuei223Phosphotyrosine; by autocatalysisCombined sources4 Publications1
Modified residuei344PhosphotyrosineBy similarity1
Modified residuei361PhosphotyrosineCombined sources1
Modified residuei551Phosphotyrosine; by LYN and SYK2 Publications1
Modified residuei604PhosphoserineCombined sources1
Modified residuei617Phosphotyrosine1 Publication1
Modified residuei623Phosphoserine1 Publication1
Modified residuei659PhosphoserineCombined sources1

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.7 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ06187.
MaxQBiQ06187.
PaxDbiQ06187.
PeptideAtlasiQ06187.
PRIDEiQ06187.

PTM databases

iPTMnetiQ06187.
PhosphoSitePlusiQ06187.

Expressioni

Tissue specificityi

Predominantly expressed in B-lymphocytes.

Gene expression databases

BgeeiENSG00000010671.
CleanExiHS_BTK.
ExpressionAtlasiQ06187. baseline and differential.
GenevisibleiQ06187. HS.

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
WASP427684EBI-624835,EBI-346375

Protein-protein interaction databases

BioGridi107160. 78 interactors.
DIPiDIP-34071N.
IntActiQ06187. 48 interactors.
MINTiMINT-110243.
STRINGi9606.ENSP00000308176.

Chemistry databases

BindingDBiQ06187.

Structurei

Secondary structure

1659
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 13Combined sources8
Beta strandi18 – 20Combined sources3
Beta strandi25 – 32Combined sources8
Beta strandi34 – 43Combined sources10
Turni44 – 47Combined sources4
Beta strandi48 – 57Combined sources10
Helixi58 – 60Combined sources3
Beta strandi61 – 66Combined sources6
Helixi75 – 77Combined sources3
Helixi93 – 96Combined sources4
Beta strandi100 – 106Combined sources7
Beta strandi111 – 116Combined sources6
Helixi118 – 132Combined sources15
Beta strandi140 – 142Combined sources3
Beta strandi149 – 152Combined sources4
Turni153 – 155Combined sources3
Beta strandi165 – 167Combined sources3
Turni212 – 215Combined sources4
Beta strandi218 – 223Combined sources6
Beta strandi228 – 232Combined sources5
Beta strandi240 – 242Combined sources3
Beta strandi248 – 252Combined sources5
Turni257 – 259Combined sources3
Beta strandi261 – 265Combined sources5
Turni266 – 268Combined sources3
Beta strandi279 – 282Combined sources4
Helixi288 – 298Combined sources11
Beta strandi303 – 308Combined sources6
Beta strandi310 – 312Combined sources3
Beta strandi315 – 326Combined sources12
Beta strandi330 – 335Combined sources6
Beta strandi337 – 339Combined sources3
Turni340 – 342Combined sources3
Beta strandi343 – 347Combined sources5
Beta strandi350 – 354Combined sources5
Helixi355 – 363Combined sources9
Beta strandi373 – 376Combined sources4
Helixi393 – 395Combined sources3
Helixi399 – 401Combined sources3
Beta strandi402 – 411Combined sources10
Beta strandi414 – 421Combined sources8
Turni422 – 424Combined sources3
Beta strandi425 – 431Combined sources7
Turni434 – 436Combined sources3
Helixi439 – 450Combined sources12
Beta strandi460 – 464Combined sources5
Beta strandi466 – 469Combined sources4
Beta strandi471 – 475Combined sources5
Helixi482 – 487Combined sources6
Helixi489 – 491Combined sources3
Helixi495 – 514Combined sources20
Helixi524 – 526Combined sources3
Beta strandi527 – 529Combined sources3
Beta strandi535 – 537Combined sources3
Helixi542 – 545Combined sources4
Helixi549 – 552Combined sources4
Turni554 – 556Combined sources3
Helixi561 – 563Combined sources3
Helixi566 – 571Combined sources6
Helixi576 – 591Combined sources16
Turni592 – 594Combined sources3
Turni597 – 600Combined sources4
Helixi603 – 611Combined sources9
Helixi624 – 632Combined sources9
Helixi638 – 640Combined sources3
Helixi644 – 657Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4OTFX-ray1.95A393-657[»]
4OTQX-ray1.55A378-659[»]
4OTRX-ray1.95A378-659[»]
4RFYX-ray1.70A378-659[»]
4RFZX-ray1.17A378-659[»]
4RG0X-ray2.50A378-659[»]
4RX5X-ray1.36A393-657[»]
4YHFX-ray2.20A/B382-659[»]
4Z3VX-ray1.60A382-659[»]
4ZLYX-ray1.65A389-658[»]
4ZLZX-ray2.00A389-658[»]
5BPYX-ray2.31A/B396-659[»]
5BQ0X-ray1.57A382-659[»]
5FBNX-ray1.80C/D389-659[»]
5FBOX-ray1.89A389-659[»]
5JRSX-ray1.97A/B396-659[»]
5KUPX-ray1.39A393-657[»]
ProteinModelPortaliQ06187.
SMRiQ06187.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ06187.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini3 – 133PHPROSITE-ProRule annotationAdd BLAST131
Domaini214 – 274SH3PROSITE-ProRule annotationAdd BLAST61
Domaini281 – 377SH2PROSITE-ProRule annotationAdd BLAST97
Domaini402 – 655Protein kinasePROSITE-ProRule annotationAdd BLAST254

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni12 – 24Inositol-(1,3,4,5)-tetrakisphosphate 1-bindingAdd BLAST13
Regioni474 – 479Inhibitor-binding6

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi581 – 588CAV1-binding8

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)DescriptionActionsGraphical viewLength
Zinc fingeri135 – 171Btk-typePROSITE-ProRule annotationAdd BLAST37

Keywords - Domaini

SH2 domain, SH3 domain, Zinc-finger

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000119011.
HOGENOMiHOG000233859.
HOVERGENiHBG008761.
InParanoidiQ06187.
KOiK07370.
OMAiELGTGQF.
OrthoDBiEOG091G0D46.
PhylomeDBiQ06187.
TreeFamiTF351634.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
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.
SSF50729. SSF50729. 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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti253R → K in BAG37008 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00621611L → P in XLA. 1
Natural variantiVAR_00621712K → R in XLA. 1 Publication1
Natural variantiVAR_00621814S → F in XLA. 1
Natural variantiVAR_00829119K → E in XLA. 1 Publication1
Natural variantiVAR_00621925F → S in XLA. 1 Publication1
Natural variantiVAR_00829227K → R in XLA. 1
Natural variantiVAR_00829328R → C in XLA; no effect on phosphorylation of GTF2I. 1
Natural variantiVAR_00622028R → H in XLA; moderate. 3 PublicationsCorresponds to variant rs128620185dbSNPEnsembl.1
Natural variantiVAR_00622128R → P in XLA. 1 Publication1
Natural variantiVAR_00622233T → P in XLA; severe. 2 PublicationsCorresponds to variant rs128620189dbSNPEnsembl.1
Natural variantiVAR_00896039Y → S in XLA. 1 Publication1
Natural variantiVAR_00829440Y → C in XLA. 1
Natural variantiVAR_00829540Y → N in XLA. 1
Natural variantiVAR_00829661I → N in XLA. 1 Publication1
Natural variantiVAR_00829764V → D in XLA. 1
Natural variantiVAR_00622364V → F in XLA. 1 Publication1
Natural variantiVAR_04167682R → K.1 PublicationCorresponds to variant rs56035945dbSNPEnsembl.1
Natural variantiVAR_006224103Q → QSVFSSTR in XLA. 1
Natural variantiVAR_006225113V → D in XLA. 1 PublicationCorresponds to variant rs128621190dbSNPEnsembl.1
Natural variantiVAR_008298115S → F in XLA. 1
Natural variantiVAR_008299117T → P in XLA. 1 Publication1
Natural variantiVAR_008300127Q → H in XLA. 1 Publication1
Natural variantiVAR_008301154C → S in XLA. 1 Publication1
Natural variantiVAR_008302155C → G in XLA. 1
Natural variantiVAR_008303155C → R in XLA. 2 Publications1
Natural variantiVAR_008304184T → P in XLA. 1
Natural variantiVAR_041677190P → K in a lung large cell carcinoma sample; somatic mutation; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_006226260 – 280Missing in XLA; severe. 1 PublicationAdd BLAST21
Natural variantiVAR_008305288R → Q in XLA. 1 Publication1
Natural variantiVAR_006227288R → W in XLA. 4 PublicationsCorresponds to variant rs128621194dbSNPEnsembl.1
Natural variantiVAR_006228295L → P in XLA. 2 Publications1
Natural variantiVAR_006230302G → E in XLA. 2 Publications1
Natural variantiVAR_008306302G → R in XLA. 1
Natural variantiVAR_006229302Missing in XLA. 1 Publication1
Natural variantiVAR_006231307R → G in XLA; loss of activity. 1 PublicationCorresponds to variant rs128621195dbSNPEnsembl.1
Natural variantiVAR_008307307R → T in XLA. 1 Publication1
Natural variantiVAR_008308308D → E in XLA. 1
Natural variantiVAR_008309319V → A in XLA; moderate. 1
Natural variantiVAR_006232334Y → S in XLA. 1 PublicationCorresponds to variant rs128621196dbSNPEnsembl.1
Natural variantiVAR_006233358L → F in XLA. 1 Publication1
Natural variantiVAR_006234361Y → C in XLA; mild. 1 PublicationCorresponds to variant rs28935478dbSNPEnsembl.1
Natural variantiVAR_006235362H → Q in XLA. 1
Natural variantiVAR_006236364H → P in XLA. 1
Natural variantiVAR_006237365N → Y in XLA. 1
Natural variantiVAR_008310366S → F in XLA. 1
Natural variantiVAR_008311369L → F in XLA. 1 Publication1
Natural variantiVAR_006238370I → M in XLA. 1 Publication1
Natural variantiVAR_008312372R → G in XLA. 1 Publication1
Natural variantiVAR_006239408L → P in XLA; moderate. 1 PublicationCorresponds to variant rs128621198dbSNPEnsembl.1
Natural variantiVAR_008313414G → R in XLA. 1 Publication1
Natural variantiVAR_006240