SASDC52: Bruton tyrosine kinase (Tyrosine-protein kinase BTK (R28C mutant)...

Basic information

• Entry: Database: SASBDB / ID: SASDC52

Sample

Bruton tyrosine kinase

• Tyrosine-protein kinase BTK (R28C mutant) (protein), BTK, Homo sapiens

Function / homology

Function:

regulation of B cell cytokine production / proteoglycan catabolic process / monocyte proliferation / positive regulation of interleukin-17A production / eosinophil homeostasis / regulation of B cell apoptotic process / positive regulation of type III hypersensitivity / B cell affinity maturation / positive regulation of synoviocyte proliferation / histamine secretion by mast cell / neutrophil homeostasis / cellular response to molecule of fungal origin / positive regulation of type I hypersensitivity / cellular response to interleukin-7 / MyD88 deficiency (TLR2/4) / MyD88-dependent toll-like receptor signaling pathway / IRAK4 deficiency (TLR2/4) / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / positive regulation of immunoglobulin production / positive regulation of B cell differentiation / phospholipase activator activity / positive regulation of NLRP3 inflammasome complex assembly / negative regulation of interleukin-10 production / negative regulation of B cell proliferation / Fc-epsilon receptor signaling pathway / mesoderm development / phosphatidylinositol-3,4,5-trisphosphate binding / B cell activation / phospholipase binding / RHO GTPases Activate WASPs and WAVEs / positive regulation of phagocytosis / cell maturation / positive regulation of B cell proliferation / FCERI mediated Ca+2 mobilization / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / apoptotic signaling pathway / cellular response to reactive oxygen species / B cell receptor signaling pathway / FCGR3A-mediated phagocytosis / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / calcium-mediated signaling / Regulation of actin dynamics for phagocytic cup formation / peptidyl-tyrosine phosphorylation / positive regulation of interleukin-6 production / G beta:gamma signalling through BTK / positive regulation of tumor necrosis factor production / G alpha (12/13) signalling events / DAP12 signaling / T cell receptor signaling pathway / positive regulation of NF-kappaB transcription factor activity / ER-Phagosome pathway / protein tyrosine kinase activity / cytoplasmic vesicle / G alpha (q) signalling events / adaptive immune response / Potential therapeutics for SARS / response to lipopolysaccharide / intracellular signal transduction / membrane raft / innate immune response / protein phosphorylation / perinuclear region of cytoplasm / ATP binding / identical protein binding / nucleus / metal ion binding / plasma membrane / cytosol / cytoplasm

Domain/homology:

Tyrosine-protein kinase BTK, SH3 domain / Zinc finger, Btk motif / BTK motif / Zinc finger Btk-type profile. / Bruton's tyrosine kinase Cys-rich motif / PH domain / : / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / Src homology 3 domains / SH2 domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / PH-like domain superfamily / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily

Component:

Tyrosine-protein kinase BTK

• Biological species: Homo sapiens (human)
• Citation: Journal: EMBO J / Year: 2003; Title: Conformation of full-length Bruton tyrosine kinase (Btk) from synchrotron X-ray solution scattering.; Authors: José A Márquez / C I Edvard Smith / Maxim V Petoukhov / Paola Lo Surdo / Pekka T Mattsson / Marika Knekt / Anna Westlund / Klaus Scheffzek / Matti Saraste / Dmitri I Svergun / ; Abstract: Brutons's tyrosine kinase (Btk) is a non-receptor protein tyrosine kinase (nrPTK) essential for the development of B lymphocytes in humans and mice. Like Src and Abl PTKs, Btk contains a conserved cassette formed by SH3, SH2 and protein kinase domains, but differs from them by the presence of an N-terminal PH domain and the Tec homology region. The domain structure of Btk was analysed using X-ray synchrotron radiation scattering in solution. Low resolution shapes of the full-length protein and several deletion mutants determined ab initio from the scattering data indicated a linear arrangement of domains. This arrangement was further confirmed by rigid body modelling using known high resolution structures of individual domains. The final model of Btk displays an extended conformation with no, or little, inter-domain interactions. In agreement with these results, deletion of non-catalytic domains failed to enhance the activity of Btk. Taken together, our results indicate that, contrary to Src and Abl, Btk might not require an assembled conformation for the regulation of its activity.

Contact author

• Dmitri Svergun (EMBL-Hamburg, European Molecular Biology Laboratory (EMBL) - Hamburg outstation, Notkestraße 85, Geb. 25A, 22607 Hamburg, Deutschland, Germany)

Models

• Model #1149: ; Type: dummy / Radius of dummy atoms: 1.90 A / Chi-square value: 0.3481 / P-value: 0.790000; Search similar-shape structures of this assembly by Omokage search (details)
• Model #1150: ; Type: mix / Radius of dummy atoms: 1.90 A / Chi-square value: 0.4096 / P-value: 0.003000; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Bruton tyrosine kinase / Specimen concentration: 1.00-10.00
• Buffer: Name: 20 mM HEPES 200 mM NaCl, 2 mM DTT and 1 mM MgCl2 / pH: 7.5

Entity #599

Name: BTK / Type: protein / Description: Tyrosine-protein kinase BTK (R28C mutant) / Formula weight: 76.227 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: Q06187
Sequence:

MAAVILESIF LKRSQQKKKT SPLNFKKCLF LLTVHKLSYY EYDFERGRRG SKKGSIDVEK ITCVETVVPE KNPPPERQIP RRGEESSEME QISIIERFPY PFQVVYDEGP LYVFSPTEEL RKRWIHQLKN VIRYNSDLVQ KYHPCFWIDG QYLCCSQTAK NAMGCQILEN RNGSLKPGSS HRKTKKPLPP TPEEDQILKK PLPPEPAAAP VSTSELKKVV ALYDYMPMNA NDLQLRKGDE YFILEESNLP WWRARDKNGQ EGYIPSNYVT EAEDSIEMYE WYSKHMTRSQ AEQLLKQEGK EGGFIVRDSS KAGKYTVSVF AKSTGDPQGV IRHYVVCSTP QSQYYLAEKH LFSTIPELIN YHQHNSAGLI SRLKYPVSQQ NKNAPSTAGL GYGSWEIDPK DLTFLKELGT GQFGVVKYGK WRGQYDVAIK MIKEGSMSED EFIEEAKVMM NLSHEKLVQL YGVCTKQRPI FIITEYMANG CLLNYLREMR HRFQTQQLLE MCKDVCEAME YLESKQFLHR DLAARNCLVN DQGVVKVSDF GLSRYVLDDE YTSSVGSKFP VRWSPPEVLM YSKFSSKSDI WAFGVLMWEI YSLGKMPYER FTNSETAEHI AQGLRLYRPH LASEKVYTIM YSCWHEKADE RPTFKILLSN ILDVMDEES

Experimental information

• Beam: Instrument name: DORIS III X33 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotron / Wavelength: 0.15 Å / Dist. spec. to detc.: 3 mm
• Detector: Name: 1D Gas detector

Scan

Title: Bruton tyrosine kinase / Measurement date: Apr 2, 2002 / Storage temperature: 6 °C / Cell temperature: 10 °C / Exposure time: 60 sec. / Number of frames: 15 / Unit: 1/A /

	Min	Max
Q	0.0216	0.4575

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 400 /

	Min	Max
Q	0.02164	0.4575
P(R) point	1	400
R	0	200

Result

Type of curve: merged
Comments: The Guinier range is very short subject to experimental conditions

	Experimental	Standard	Standard error	Porod
MW	76 kDa	76 kDa	10	75 kDa
Volume	-	-	-	130 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	190	13	183	16
Radius of gyration, Rg	5.6 nm	0.35	5 nm	4

	Min	Max	Error
D	-	20	2
Guinier point	1	8	-