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Details on Person UniProt:Q06187-1 BTK
| Class:Id | ReferenceIsoform:8976901 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 17 2017;chain:2-659 added on Fri February 17 2017;initiator methionine:1 for 8976901 removed on Fri Nov 03 2023;initiator methionine: for 8976901 added on Fri Nov 03 2023;initiator methionine: for 8976901 removed on Fri Aug 15 2025;initiator methionine:1 for 8976901 added on Fri Aug 15 2025 |
| _displayName | UniProt:Q06187-1 BTK |
| _timestamp | 2026-02-20 22:19:29 |
| chain | initiator methionine:1 chain:2-659 |
| checksum | DF06B5D1FEC257CC |
| comment | FUNCTION Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:19290921). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubMed:19290921). 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 (PubMed:11606584). PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK (PubMed:11606584). BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways (PubMed:16517732, PubMed:17932028). 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 (PubMed:16517732). The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense (PubMed:16517732). Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells (PubMed:16517732, PubMed:17932028). Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation (PubMed:16415872). BTK also plays a critical role in transcription regulation (PubMed:19290921). Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes (PubMed:19290921). BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B (PubMed:19290921). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (PubMed:34554188). Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR (PubMed:9012831). GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression (PubMed:9012831). ARID3A and NFAT are other transcriptional target of BTK (PubMed:16738337). BTK is required for the formation of functional ARID3A DNA-binding complexes (PubMed:16738337). There is however no evidence that BTK itself binds directly to DNA (PubMed:16738337). BTK has a dual role in the regulation of apoptosis (PubMed:9751072). Plays a role in STING1-mediated induction of type I interferon (IFN) response by phosphorylating DDX41 (PubMed:25704810).CATALYTIC ACTIVITY L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)COFACTOR Binds 1 zinc ion per subunit.ACTIVITY REGULATION 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.SUBUNIT Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, GAB2, TEC and BTK; complex formation increases in the presence of TNFSF11/RANKL (By similarity). 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. Interacts with MPL/TPOR (PubMed:24607955).INTERACTION 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.ALTERNATIVE PRODUCTS Predominantly expressed in B-lymphocytes.DOMAIN 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.PTM 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 its recruitment.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease may be caused by variants affecting the gene represented in this entry.MISCELLANEOUS Produced by alternative promoter usage. Predominant form in many tumor cells where it may function as an anti-apoptotic cell survival factor.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.ONLINE INFORMATION BTK mutation db |
| created | [InstanceEdit:8964659] Weiser, JD |
| description | recommendedName: Tyrosine-protein kinase BTK ecNumber evidence="20 43"2.7.10.2 alternativeName: Agammaglobulinemia tyrosine kinase shortName: ATK alternativeName: B-cell progenitor kinase shortName: BPK alternativeName: Bruton tyrosine kinase |
| geneName | BTK AGMX1 ATK BPK |
| identifier | Q06187 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Adaptive immunity Alternative promoter usage Apoptosis ATP-binding Cell membrane Cytoplasm Direct protein sequencing Disease variant Dwarfism Immunity Innate immunity Kinase Lipid-binding Membrane Metal-binding Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Reference proteome SH2 domain SH3 domain Transcription Transcription regulation Transferase Tyrosine-protein kinase Zinc Zinc-finger |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | BTK |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8989402] ENSEMBL:ENSG00000010671 BTK [Homo sapiens] |
| secondaryIdentifier | BTK_HUMAN B2RAW1 Q32ML5 |
| sequenceLength | 659 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | Q06187-1 |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:Q06187-1 BTK (8976901)
