General Information of the Ferroptosis Regulator (ID: REG10383)
Regulator Name Tyrosine-protein kinase BTK (BTK)
Synonyms
AGMX1; ATK; BPK; Agammaglobulinemia tyrosine kinase; B-cell progenitor kinase; Bruton tyrosine kinase
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Gene Name BTK
Gene ID 695
Regulator Type Protein coding
Uniprot ID Q06187
Sequence
MAAVILESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERGRRGSKKGSIDVEK
ITCVETVVPEKNPPPERQIPRRGEESSEMEQISIIERFPYPFQVVYDEGPLYVFSPTEEL
RKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILENRNGSLKPGSS
HRKTKKPLPPTPEEDQILKKPLPPEPAAAPVSTSELKKVVALYDYMPMNANDLQLRKGDE
YFILEESNLPWWRARDKNGQEGYIPSNYVTEAEDSIEMYEWYSKHMTRSQAEQLLKQEGK
EGGFIVRDSSKAGKYTVSVFAKSTGDPQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELIN
YHQHNSAGLISRLKYPVSQQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGK
WRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANG
CLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDF
GLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYER
FTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEES

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Family Tyr protein kinase family
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 also plays 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. Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3. 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. { | , | , | , | , | , | , | , | , | }.

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HGNC ID
HGNC:1133
KEGG ID hsa:695
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
BTK can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Browse Drug
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Colorectal cancer ICD-11: 2B91
Responsed Drug Ibrutinib Investigative
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
NCI-H508 cells Cecum adenocarcinoma Homo sapiens CVCL_1564
LoVo cells Colon adenocarcinoma Homo sapiens CVCL_0399
LS513 cells Cecum adenocarcinoma Homo sapiens CVCL_1386
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
SW480 cells Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 cells Colon adenocarcinoma Homo sapiens CVCL_0547
SW1116 cells Colon adenocarcinoma Homo sapiens CVCL_0544
DLD-1 cells Colon adenocarcinoma Homo sapiens CVCL_0248
HT-29 cells Colon adenocarcinoma Homo sapiens CVCL_0320
Caco-2 cells Colon adenocarcinoma Homo sapiens CVCL_0025
In Vivo Model
Sixty mice were randomly divided into six groups, (1) the CRC model group (model), (2) mice with RSL3 treatment, (3) mice with Erastin treatment, (4) mice with Ibrutinib treatment, (5) mice with RSL3 and Ibrutinib treatment, and (6) Erastin and Ibrutinib group. Murine subcutaneous tumor model and xenograft tumor mouse model were established and please refer to supplemental method for details. For CRC model group, the mice were treated with PBS for two weeks. For RSL3 group, the mice were intraperitoneal injected with RSL3 (5 mg/kg daily) for two weeks. For Erastin group, the mice were intraperitoneal injected with Erastin (30 mg/kg, twice every other day) for two weeks. For Ibrutinib treatment group, mice were administered in drinking water at a concentration of 0.16 mg/ml for two weeks. Mice were also treated in combination with RSL and Ibrutinib or Erastin and Ibrutinib.

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Response regulation Ibrutinib inhibited BTK, which prevented Nrf2 translocating to cell nucleus and the activation of the Nrf2 dependent antioxidant genes during oxidative stress conditions and eventually enhanced the sensitivity of Colorectal cancer (CRC) cells to ferroptosis.
Colorectal cancer [ICD-11: 2B91]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Tyrosine-protein kinase BTK (BTK) Protein coding
Responsed Drug Ibrutinib Investigative
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
NCI-H508 cells Cecum adenocarcinoma Homo sapiens CVCL_1564
LoVo cells Colon adenocarcinoma Homo sapiens CVCL_0399
LS513 cells Cecum adenocarcinoma Homo sapiens CVCL_1386
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
SW480 cells Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 cells Colon adenocarcinoma Homo sapiens CVCL_0547
SW1116 cells Colon adenocarcinoma Homo sapiens CVCL_0544
DLD-1 cells Colon adenocarcinoma Homo sapiens CVCL_0248
HT-29 cells Colon adenocarcinoma Homo sapiens CVCL_0320
Caco-2 cells Colon adenocarcinoma Homo sapiens CVCL_0025
In Vivo Model
Sixty mice were randomly divided into six groups, (1) the CRC model group (model), (2) mice with RSL3 treatment, (3) mice with Erastin treatment, (4) mice with Ibrutinib treatment, (5) mice with RSL3 and Ibrutinib treatment, and (6) Erastin and Ibrutinib group. Murine subcutaneous tumor model and xenograft tumor mouse model were established and please refer to supplemental method for details. For CRC model group, the mice were treated with PBS for two weeks. For RSL3 group, the mice were intraperitoneal injected with RSL3 (5 mg/kg daily) for two weeks. For Erastin group, the mice were intraperitoneal injected with Erastin (30 mg/kg, twice every other day) for two weeks. For Ibrutinib treatment group, mice were administered in drinking water at a concentration of 0.16 mg/ml for two weeks. Mice were also treated in combination with RSL and Ibrutinib or Erastin and Ibrutinib.

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Response regulation Ibrutinib inhibited BTK, which prevented Nrf2 translocating to cell nucleus and the activation of the Nrf2 dependent antioxidant genes during oxidative stress conditions and eventually enhanced the sensitivity of Colorectal cancer (CRC) cells to ferroptosis.
Ibrutinib [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Nuclear factor erythroid 2-related factor 2 (NFE2L2) Suppressor; Marker
Responsed Disease Colorectal cancer ICD-11: 2B91
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
NCI-H508 cells Cecum adenocarcinoma Homo sapiens CVCL_1564
LoVo cells Colon adenocarcinoma Homo sapiens CVCL_0399
LS513 cells Cecum adenocarcinoma Homo sapiens CVCL_1386
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
SW480 cells Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 cells Colon adenocarcinoma Homo sapiens CVCL_0547
SW1116 cells Colon adenocarcinoma Homo sapiens CVCL_0544
DLD-1 cells Colon adenocarcinoma Homo sapiens CVCL_0248
HT-29 cells Colon adenocarcinoma Homo sapiens CVCL_0320
Caco-2 cells Colon adenocarcinoma Homo sapiens CVCL_0025
In Vivo Model
Sixty mice were randomly divided into six groups, (1) the CRC model group (model), (2) mice with RSL3 treatment, (3) mice with Erastin treatment, (4) mice with Ibrutinib treatment, (5) mice with RSL3 and Ibrutinib treatment, and (6) Erastin and Ibrutinib group. Murine subcutaneous tumor model and xenograft tumor mouse model were established and please refer to supplemental method for details. For CRC model group, the mice were treated with PBS for two weeks. For RSL3 group, the mice were intraperitoneal injected with RSL3 (5 mg/kg daily) for two weeks. For Erastin group, the mice were intraperitoneal injected with Erastin (30 mg/kg, twice every other day) for two weeks. For Ibrutinib treatment group, mice were administered in drinking water at a concentration of 0.16 mg/ml for two weeks. Mice were also treated in combination with RSL and Ibrutinib or Erastin and Ibrutinib.

    Click to Show/Hide
Response regulation Ibrutinib inhibited BTK, which prevented Nrf2 translocating to cell nucleus and the activation of the Nrf2 dependent antioxidant genes during oxidative stress conditions and eventually enhanced the sensitivity of Colorectal cancer (CRC) cells to ferroptosis.
References
Ref 1 Ibrutinib facilitates the sensitivity of colorectal cancer cells to ferroptosis through BTK/NRF2 pathway. Cell Death Dis. 2023 Feb 23;14(2):151. doi: 10.1038/s41419-023-05664-9.