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From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/BCAP_HUMAN BCAP_HUMAN]] Signaling adapter that contributes to B-cell development by linking B-cell receptor (BCR) signaling to the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Has a complementary role to the BCR coreceptor CD19, coupling BCR and PI3K activation by providing a docking site for the PI3K subunit PIK3R1. Alternatively, links Toll-like receptor (TLR) signaling to PI3K activation, a process preventing excessive inflammatory cytokine production. Also involved in the activation of PI3K in natural killer cells. May be involved in the survival of mature B-cells via activation of REL.<ref>PMID:15893754</ref> | [[http://www.uniprot.org/uniprot/BCAP_HUMAN BCAP_HUMAN]] Signaling adapter that contributes to B-cell development by linking B-cell receptor (BCR) signaling to the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Has a complementary role to the BCR coreceptor CD19, coupling BCR and PI3K activation by providing a docking site for the PI3K subunit PIK3R1. Alternatively, links Toll-like receptor (TLR) signaling to PI3K activation, a process preventing excessive inflammatory cytokine production. Also involved in the activation of PI3K in natural killer cells. May be involved in the survival of mature B-cells via activation of REL.<ref>PMID:15893754</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Ligand binding to Toll-like receptors (TLRs) results in dimerization of their cytosolic TIR domains and recruitment of post-receptor signal transducers into a complex signalosome. TLR activation leads to the production of transcription factors, pro-inflammatory molecules and the activation of Phosphoinositide 3-kinases (PI3K) in a process that requires the multi-modular B-cell Adaptor for Phosphoinositide 3-kinase (BCAP). BCAP has a sequence previously proposed as a "cryptic" TIR domain. Here, we present the structure of the N-terminal region of human BCAP and show that it possesses a canonical TIR-fold. Dimeric BCAP associates with the TIR domains of TLR2/4 and Mal/TIRAP suggesting that it is recruited to the TLR signalosome by multitypic TIR-TIR interactions. BCAP also interacts with the p85 subunit of PI3K and phospholipase Cgamma, enzymes that deplete plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) and these interactions provide a molecular explanation for BCAP mediated down-regulation of inflammatory signalling. | ||
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| + | Structure of the TIR domain of BCAP which links phosphoinositide metabolism with the negative regulation of the TLR signalosome.,Halabi S, Sekine E, Verstack B, Gay NJ, Moncrieffe MC J Biol Chem. 2016 Dec 1. pii: jbc.M116.761528. PMID:27909057<ref>PMID:27909057</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5for" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 11:21, 15 December 2016
Cryptic TIR
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