Homo sapiens Protein: BTK | |||||||||||||||||||||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||||||||||||||||||||
InnateDB Protein | IDBP-79655.6 | ||||||||||||||||||||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||||||||||||||||
Gene Symbol | BTK | ||||||||||||||||||||||||||||||||||||||||||
Protein Name | Bruton agammaglobulinemia tyrosine kinase | ||||||||||||||||||||||||||||||||||||||||||
Synonyms | AGMX1; AT; ATK; BPK; IMD1; PSCTK1; XLA; | ||||||||||||||||||||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||||||||||||||||||||
Ensembl Protein | ENSP00000308176 | ||||||||||||||||||||||||||||||||||||||||||
InnateDB Gene | IDBG-79651 (BTK) | ||||||||||||||||||||||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||||||||||||||||||||||
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:0000269PubMed:11606584, ECO:0000269PubMed:16415872, ECO:0000269PubMed:16517732, ECO:0000269PubMed:16738337, ECO:0000269PubMed:17932028, ECO:0000269PubMed:9012831}. | ||||||||||||||||||||||||||||||||||||||||||
Subcellular Localization | 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. | ||||||||||||||||||||||||||||||||||||||||||
Disease Associations | X-linked agammaglobulinemia (XLA) [MIM:300755]: Humoral immunodeficiency disease which results in developmental defects in the maturation pathway of B-cells. Affected boys have normal levels of pre-B-cells in their bone marrow but virtually no circulating mature B-lymphocytes. This results in a lack of immunoglobulins of all classes and leads to recurrent bacterial infections like otitis, conjunctivitis, dermatitis, sinusitis in the first few years of life, or even some patients present overwhelming sepsis or meningitis, resulting in death in a few hours. Treatment in most cases is by infusion of intravenous immunoglobulin. {ECO:0000269PubMed:10220140, ECO:0000269PubMed:10612838, ECO:0000269PubMed:10678660, ECO:0000269PubMed:7627183, ECO:0000269PubMed:7633420, ECO:0000269PubMed:7633429, ECO:0000269PubMed:7711734, ECO:0000269PubMed:7809124, ECO:0000269PubMed:7849006, ECO:0000269PubMed:7849697, ECO:0000269PubMed:7849721, ECO:0000269PubMed:7880320, ECO:0000269PubMed:7897635, ECO:0000269PubMed:8013627, ECO:0000269PubMed:8162018, ECO:0000269PubMed:8162056, ECO:0000269PubMed:8634718, ECO:0000269PubMed:8695804, ECO:0000269PubMed:8723128, ECO:0000269PubMed:8834236, ECO:0000269PubMed:9260159, ECO:0000269PubMed:9280283, ECO:0000269PubMed:9445504, ECO:0000269PubMed:9545398}. Note=The disease is caused by mutations affecting the gene represented in this entry.X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA-IGHD) [MIM:307200]: In rare cases XLA is inherited together with isolated growth hormone deficiency (IGHD). Note=The disease may be caused by mutations affecting the gene represented in this entry. | ||||||||||||||||||||||||||||||||||||||||||
Tissue Specificity | Predominantly expressed in B-lymphocytes. | ||||||||||||||||||||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 106 experimentally validated interaction(s) in this database.
They are also associated with 37 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||||||||||||||||||||
InterPro |
IPR000719
Protein kinase domain IPR000980 SH2 domain IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain IPR001452 SH3 domain IPR001562 Zinc finger, Btk motif IPR001849 Pleckstrin homology domain IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain IPR011009 Protein kinase-like domain IPR011511 Variant SH3 domain IPR020635 Tyrosine-protein kinase, catalytic domain |
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PFAM |
PF00069
PF00017 PF14633 PF07714 PF00018 PF14604 PF00779 PF00169 PF07653 |
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PRINTS |
PR00401
PR00109 PR00452 PR00402 |
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PIRSF | |||||||||||||||||||||||||||||||||||||||||||
SMART |
SM00252
SM00326 SM00107 SM00233 SM00220 SM00219 |
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TIGRFAMs | |||||||||||||||||||||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||||||||||||||||||||
SwissProt | Q06187 | ||||||||||||||||||||||||||||||||||||||||||
PhosphoSite | PhosphoSite-Q06187 | ||||||||||||||||||||||||||||||||||||||||||
TrEMBL | Q9P0L4 | ||||||||||||||||||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||||||||||||||||||
Entrez Gene | 695 | ||||||||||||||||||||||||||||||||||||||||||
UniGene | Hs.159494 | ||||||||||||||||||||||||||||||||||||||||||
RefSeq | NP_000052 | ||||||||||||||||||||||||||||||||||||||||||
HUGO | HGNC:1133 | ||||||||||||||||||||||||||||||||||||||||||
OMIM | 300300 | ||||||||||||||||||||||||||||||||||||||||||
CCDS | CCDS14482 | ||||||||||||||||||||||||||||||||||||||||||
HPRD | 02248 | ||||||||||||||||||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||||||||||||||||||
EMBL | AF153763 AK314382 AL035422 AM051276 BC109079 BC109080 L31557 L31558 L31559 L31561 L31563 L31564 L31565 L31566 L31567 L31568 L31569 L31570 L31571 L31572 U10084 U10085 U10086 U10087 U13410 U13412 U13413 U13414 U13415 U13416 U13417 U13422 U13423 U13424 U13425 U13427 U13428 U13429 U13430 U13431 U13432 U13433 U78027 X58957 | ||||||||||||||||||||||||||||||||||||||||||
GenPept | AAA61479 AAB60639 AAB64205 AAC51347 AAF37340 AAI09080 AAI09081 BAG37008 CAA41728 CAB55876 CAJ19682 | ||||||||||||||||||||||||||||||||||||||||||