DegronMD - Q06187(BTK)

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. {ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16517732, ECO:0000269|PubMed:16738337, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:9012831}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.K218N	TCGA-BS-A0UF	UCEC	TCGA	PVSTS	DEG_SPOP_SBC_1	210:214	Mutation substituting flanking lysine	0.3333
p.K218N	DO41488	UCEC	ICGC	PVSTS	DEG_SPOP_SBC_1	210:214	Mutation substituting flanking lysine	0.3333
p.P203Q	DO228952	LICA	ICGC	PVSTS	DEG_SPOP_SBC_1	210:214	Mutation rewiring degron network	0.1389
p.P203Q	ACH-001526	Bone Cancer	CCLE	PVSTS	DEG_SPOP_SBC_1	210:214	Mutation rewiring degron network	0.1389
p.P203Q	HuO9	bone	COSMIC	PVSTS	DEG_SPOP_SBC_1	210:214	Mutation rewiring degron network	0.1389
p.L202I	DO229036	LICA	ICGC	PVSTS	DEG_SPOP_SBC_1	210:214	Mutation rewiring degron network	0.1111
p.A221D	DO229009	LICA	ICGC	PVSTS	DEG_SPOP_SBC_1	210:214	Mutation rewiring degron network	0.1389
p.P221S	SIDM00057	Neuroblastoma	GDSC	PVSTS	DEG_SPOP_SBC_1	210:214	Mutation rewiring degron network	0.1389
p.P221S	ACN	autonomic ganglia	COSMIC	PVSTS	DEG_SPOP_SBC_1	210:214	Mutation rewiring degron network	0.1389
p.P210K	ACH-000390	Lung Cancer	CCLE	PVSTS	DEG_SPOP_SBC_1	210:214	Mutation altering degron motif	0.7312
p.P210T	ACH-000390	Lung Cancer	CCLE	PVSTS	DEG_SPOP_SBC_1	210:214	Mutation altering degron motif	0.7031
p.T213I	ACH-000985	Colon/Colorectal Cancer	CCLE	PVSTS	DEG_SPOP_SBC_1	210:214	Mutation altering degron motif	0.7078
p.P206Q	ACH-001091	Colon/Colorectal Cancer	CCLE	PVSTS	DEG_SPOP_SBC_1	210:214	Mutation rewiring degron network	0.2222

DegronMD: protein-targeted degradation, mutation and drug response to degrons

BTK

UniProt ID: Q06187

Entrez ID: 695

Protein name: Tyrosine-protein kinase BTK (EC 2.7.10.2) (Agammaglobulinemia tyrosine kinase) (ATK) (B-cell progenitor kinase) (BPK) (Bruton tyrosine kinase)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for BTK in