Product Details

Purity

Greater than 90% as determined by SDS-PAGE.

Target Names

BTK

Uniprot No.

Q06187

Research Area

Immunology

Alternative Names

Agammaglobulinaemia tyrosine kinase; AGMX 1; AGMX1; AT; ATK; B cell progenitor kinase; B-cell progenitor kinase; BPK; Bruton agammaglobulinemia tyrosine kinase; Bruton tyrosine kinase; Bruton鈥檚 Tyrosine Kinase; Btk; BTK_HUMAN; dominant-negative kinase-deficient Brutons tyrosine kinase; IMD 1; IMD1; MGC126261; MGC126262; OTTHUMP00000063593; PSCTK 1; PSCTK1; truncated Bruton agammaglobulinemia tyrosine kinase; Tyrosine protein kinase BTK; Tyrosine-protein kinase BTK; tyrosine-protein kinase BTK isoform (lacking exon 14; XLA

Species

Homo sapiens (Human)

Source

Baculovirus

Expression Region

1- 659aa

Target Protein Sequence

MAAVILESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERGRRGSKKGSIDVEKITCVETVVPEKNPPPERQIPRRGEESSEMEQISIIERFPYPFQVVYDEGPLYVFSPTEELRKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILENRNGSLKPGSSHRKTKKPLPPTPEEDQILKKPLPPEPAAAPVSTSELKKVVALYDYMPMNANDLQLRKGDEYFILEESNLPWWRARDKNGQEGYIPSNYVTEAEDSIEMYEWYSKHMTRSQAEQLLKQEGKEGGFIVRDSSKAGKYTVSVFAKSTGDPQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELINYHQHNSAGLISRLKYPVSQQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEES
Note: The complete sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
If the exact amino acid sequence of this recombinant protein is critical to your application, please explicitly request the full and complete sequence of this protein before ordering.

Mol. Weight

78.3 kDa

Protein Length

Full Length

Tag Info

N-terminal 10xHis-tagged

Form

Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.

Buffer

If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose.

Reconstitution

We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.

Troubleshooting and FAQs

Protein FAQs

Storage Condition

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.

Shelf Life

The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.

Lead Time

3-7 business days

Notes

Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Datasheet & COA

Please contact us to get it.

Description

The recombinant human tyrosine-protein kinase BTK was produced using a baculovirus system. The gene encoding the 1- 659aa of the human BTK was co-integrated into a plasmid with the N-terminal 10xHis-tag gene and then transfected into the baculovirus system for protein expression. The recombinant human BTK was purified from the cell lysate of the transfected baculovirus through affinity chromatography. Its purity is greater than 90% as determined by SDS-PAGE.

BTK is a cytoplasmic protein tyrosine kinase crucial for various cellular processes, especially in B cell development, activation, and survival [1]. It is expressed in B lymphocytes, myeloid cells, lung, and pancreas, but not in the T cell lineage [2]. BTK is expressed throughout B cell differentiation, from early precursor B cell to mature B cell stages [2]. The Btk-SH3 domain-binding protein Sab negatively regulates BTK [3]. It is also involved in apoptosis regulation and JNK/SAPK kinase activity [4].

References:
[1] B. Duriez, P. Duquesnoy, F. Dastot, P. Bougnères, S. Amselem, & M. Goossens, An exon‐skipping mutation in thebtk gene of a patient with x‐linked agammaglobulinemia and isolated growth hormone deficiency, Febs Letters, vol. 346, no. 2-3, p. 165-170, 1994. https://doi.org/10.1016/0014-5793(94)00457-9
[2] Y. Kawakami, T. Miura, R. Bissonnette, D. Hata, W. Khan, T. Kitamuraet al., Bruton’s tyrosine kinase regulates apoptosis and jnk/sapk kinase activity, Proceedings of the National Academy of Sciences, vol. 94, no. 8, p. 3938-3942, 1997. https://doi.org/10.1073/pnas.94.8.3938
[3] J. Debnath, M. Chamorro, M. Czar, E. Schaeffer, M. Lenardo, H. Varmuset al., rlk/txk encodes two forms of a novel cysteine string tyrosine kinase activated by src family kinases, Molecular and Cellular Biology, vol. 19, no. 2, p. 1498-1507, 1999. https://doi.org/10.1128/mcb.19.2.1498
[4] S. Guo, M. Wahl, & O. Witte, Mutational analysis of the sh2-kinase linker region of bruton's tyrosine kinase defines alternative modes of regulation for cytoplasmic tyrosine kinase families, International Immunology, vol. 18, no. 1, p. 79-87, 2005. https://doi.org/10.1093/intimm/dxh351z

Target Background

Function

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.

Gene References into Functions

Btk acts in the TLR7/8 pathway and mediates Ser-536 phosphorylation of p65 RelA and subsequent nuclear entry in primary human macrophages. PMID: 29567473
Study shows that high BTK expression predicts poor outcome in patients with glioma. Its overexpression is required for EGFR-induced NF-kappaB activation. PMID: 28946903
The Btk-dependent PIP5K1gamma lipid kinase activation by Fas counteracts FasL-induced cell death. PMID: 28879546
Study utilized bone biopsies from patients with metastatic multiple myeloma and demonstrated that tyrosine phosphorylation by Bruton kinase may be a key disease event: Bruton kinase remained translocated to the membrane; upregulation of transcripts of several factors like activins A; increased expression of numerous cytokines that support osteolytic activity. PMID: 29480835
BTK-inhibitor ibrutinib and FK866 resulted in a significant and synergistic anti-Waldenstrom macroglobulinemia cell death, regardless of MYD88 and CXCR4 mutational status. PMID: 27287071
Strong synergism was observed with pimasertib combined with the PI3K inhibitor idelalisib and the BTK inhibitor ibrutinib in cell lines derived from diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma. The data were confirmed in an in vivo experiment treating DLBCL xenografts with pimasertib and ibrutinib. PMID: 26961147
these data show that BTK is a critical NLRP3 inflammasome regulator PMID: 28216434
Resistant BTK mutants reconstituted B cell receptor-triggered chemokine secretion in the presence of corresponding inhibitors, demonstrating that BTK activity is connected with cell-intrinsic functions of malignant B cells with importance for their dialogue with the micro-environment. PMID: 28573668
Bone marrow mesenchymal stem cells could increase myeloma stemness via activation of the BTK signal pathway. PMID: 28273548
the results show that the interaction between BTK and ANKRD54 is highly selective, since it was also identified in a screen using human SH3-domainome. A novel finding is that BTK not only binds to ANKRD54, but stands out as the preferred interactor, being highly dominant over all other human SH3-domains. PMID: 28369144
BTK, via p65BTK expression, is a novel and powerful oncogene acting downstream of the RAS/MAPK pathway and suggest that its targeting may be a promising therapeutic approach. PMID: 26804170
We conclude that despite being involved in oncogenic signals in blood malignancies, BTK has antineoplastic properties in other contexts, such as the enhancement of p53's tumor suppressor responses PMID: 27630139
Inhibition of Btk by inhalation of aerosolized RN983 may be effective as a stand-alone asthma therapy. PMID: 27111445
LMP2A signaling results in STAT3 phosphorylation in B cells through a PI3K/BTK-dependent pathway. PMID: 27792904
Case Report: Btk mutation responsible for X-Linked agammaglobulinemia manifesting as Pseudomonas aeruginosa liver abscess. PMID: 28398200
this review describes contributions of BTK to immune tolerance, including studies testing BTK-inhibitors for treatment of autoimmune diseases PMID: 26864273
The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin. PMID: 28422989
report that BTK is expressed by murine and human MDSCs, and that ibrutinib is able to inhibit BTK phosphorylation in these cells PMID: 26880800
Novel BTK mutations have been described in a large cohort of North African patients with X-Linked agammagobulinemia. PMID: 26931785
mutational analysis in cohort of Iranian patients with congenital agammaglobulinemia PMID: 26910880
We report that BTK regulates B-cell and macrophage-mediated T-cell suppression in pancreas adenocarcinomas. PMID: 26715645
Data show that Bruton tyrosine kinase (BTK)inhibitor Ibrutinib augments MALT lymphoma associated translocation protein (MALT1) inhibition by S-Mepazine in CD79 antigen mutant activated B cell-subtype (ABC) of diffuse large B cell lymphoma (DLBCL). PMID: 26540570
BTK-C is a survival factor in prostate cancer cells. PMID: 26383180
BTK RNA interference inhibits proliferation of FLT3-ITD acute myeloid leukemia cells. PMID: 26292723
Activates PKC independent of BTK. PMID: 26089373
study investigated all single-nucleotide substitution-caused amino acid variations in the kinase domain of Bruton tyrosine kinase; most disease-causing variations affect conserved and buried residues disturbing protein stability; sixty-seven percent of variations are predicted to be harmful PMID: 25777788
Data show that Bruton tyrosine kinase (Btk) inhibitor PLS-123 suggested a new direction to pharmacologically modulate Btk function and develop novel therapeutic drug for B-cell lymphoma treatment. PMID: 25944695
FcgammaRIIB requires Btk and p38 MAPK to mediate antigen-independent inhibition in human B cells. PMID: 26475492
We found that chemoresistance was dependent on Btk and JAK2/STAT3, which maintained CSC by inducing Sox-2 and prosurvival genes. We suggest that addition of ibrutinib to cisplatin may improve treatment outcome in ovarian cancer. PMID: 26036311
Letter: report BTK inhibitor ibrutinib induced panniculitis in lymphoid leukemia patients. PMID: 26182170
study indicates that BTK is essential for NLRP3 inflammasome activation and could be a potent therapeutic target in ischaemic stroke PMID: 26059659
Data indicate that the X linked agammaglobulinemia (XLA) diagnosis was confirmed for six patients with six different mutations. PMID: 26387629
The immunoglobulin tail tyrosine motif in the cytoplasmic segments of membrane-bound IgGs acts as the principle signal amplifier by incorporating a Grb2-Btk signaling. PMID: 25413232
Btk not only plays a fundamental role in the regulation of BCR signalling, but may also mediate crosstalk with cytokine signalling pathways through regulation of IL-21-induced phosphorylation of STAT1 in the nuclei of human B cells. PMID: 25724205
The BTK missense mutation resulted in B cells with reduced BTK and high IgM expression. PMID: 25589397
BTK is involved in determining proliferative, quiescent or metastatic phenotypes of myeloma cells. PMID: 25083818
report of a case in a male with variant form of X-linked agammaglobulinemia (XLA) with partial B cell function that results from a missense mutation (c.1117C > G) in exon 13 of the BTK gene; four female carriers were found in the family PMID: 25316352
miR-155 affects chemoimmunotherapy outcome and is modulated by Bruton's tyrosine kinase inhibition with Ibrutinib PMID: 25486872
BTK is a positive regulator of myeloma stemness PMID: 25589346
Cysteine 481 to serine BTK mutation confers ibrutinib resistance of chronic lymphocytic leukemia cells. PMID: 25189416
FLT3-ITD and TLR9 use Bruton tyrosine kinase to activate distinct transcriptional programs mediating AML cell survival and proliferation PMID: 25605370
Data indicate that dual inhibition of Brutons tyrosine kinase (BTK) and mTOR serine-threonine kinases as a potential treatment for ABC-subtype diffuse large B cell lymphoma. PMID: 24970801
Docking and physicochemical studies indicated that BTK was involved in close contact with Tyr86 and Tyr106 of MAL, whereas PKCdelta may phosphorylate Tyr106 only. PMID: 24840642
X-linked agammaglobulinemia is reported in two siblings with a novel mutation in the BTK gene. They presented with polyarticular juvenile idiopathic arthritis. PMID: 25757060
Data indicate RN486 as potent and selective Bruton's tyrosine kinase (BTK) inhibitor and potential treatments for Rheumatoid arthritis. PMID: 24712864
we report the pattern of expression of Btk in a large collection of different types of lymphoma. PMID: 25433814
Data indicate that ibrutinib-resistant Bruton tyrosine kinase (BTK) mutation is one of the genetic causes of ibrutinib resistance in chronic lymphocytic leukemia (CLL). PMID: 25498455
Unfolded protein response activation following surface immunoglobulin M stimulation in vitro is dependent on the activity of BTK and SYK. PMID: 25170122
We observed that Nef interacts with the Tec family members Bmx, Btk, and Itk but not Tec or Txk. PMID: 24722985
These results suggest that the function of BTK warrants further investigation, and BTK expression might be used as a prognostic indicator for patients with MM. PMID: 23581641

Hide All

Involvement in disease

X-linked agammaglobulinemia (XLA); X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA-IGHD)

Subcellular Location

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.

Protein Families

Protein kinase superfamily, Tyr protein kinase family, TEC subfamily

Tissue Specificity

Predominantly expressed in B-lymphocytes.

Database Links

HGNC: 1133

OMIM: 300300

KEGG: hsa:695

STRING: 9606.ENSP00000308176

UniGene: Hs.159494

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Code	CSB-BP002867HU(A4)
MSDS	MSDS Datasheet
Size	$352
	Order now
Image	(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Recombinant Human Tyrosine-protein kinase BTK (BTK)

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