LMPD Database

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LMP006577

UniProt Annotations

Entry Information
Gene Namephosphoinositide-3-kinase adaptor protein 1
Protein EntryBCAP_MOUSE
UniProt IDQ9EQ32
SpeciesMouse
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; Synonyms=BCAP-L; IsoId=Q9EQ32-1; Sequence=Displayed; Name=2; Synonyms=BCAP-S; IsoId=Q9EQ32-2; Sequence=VSP_034241; Name=3; IsoId=Q9EQ32-3; Sequence=VSP_034242, VSP_034243;
Disruption PhenotypeMice lacking Pik3ap1 display altered B-cell maturation and impaired immune function. Pik3ap1 depletion has an opposite effect in NK cells by promoting their maturation. Mice lacking Pik3ap1 and Cd19 have severe defects in generation of immature and mature B-cells. Moreover, mice lacking Pik3ap1 display increased IL-10, Il-12 and TNF proinflammatory cytokine secretion upon activation of the Toll-like receptors TLR4, TLR7 and TLR9. {ECO:0000269|PubMed:11877477, ECO:0000269|PubMed:18025150, ECO:0000269|PubMed:18337558, ECO:0000269|PubMed:22187458}.
DomainThe DBB domain is required for dimerization.
FunctionSignaling 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. {ECO:0000269|PubMed:11781242, ECO:0000269|PubMed:11877477, ECO:0000269|PubMed:12833156, ECO:0000269|PubMed:18025150, ECO:0000269|PubMed:18337558, ECO:0000269|PubMed:22187458, ECO:0000269|PubMed:22187460}.
InteractionSelf; NbExp=3; IntAct=EBI-643949, EBI-643949; P22366:Myd88; NbExp=2; IntAct=EBI-643949, EBI-525108; Q99JY1:Tirap; NbExp=2; IntAct=EBI-643949, EBI-6559589;
PtmConstitutively phosphorylated. Phosphorylated on tyrosine residues in C-terminal region by ABL1 (By similarity). Phosphorylated on tyrosine residues within the YXXM motifs by BTK and SYK. Isoform 1 and isoform 2 are phosphorylated on tyrosine residues, most likely within the YXXM motifs, via CD19 activation. Toll-like receptor activation induces appearance of a phosphorylated form associated with membranes. {ECO:0000250, ECO:0000269|PubMed:11163197, ECO:0000269|PubMed:18025150, ECO:0000269|PubMed:20728433, ECO:0000269|PubMed:22187458, ECO:0000269|PubMed:22187460}.
SimilarityContains 1 DBB domain. {ECO:0000255|PROSITE- ProRule:PRU00707}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:22187458}. Cell membrane {ECO:0000305|PubMed:22187458}; Peripheral membrane protein {ECO:0000305|PubMed:22187458}.
SubunitHomooligomer (Probable). Interacts (phosphorylated on tyrosine residues within YXXM motifs) with PIK3R1 (via SH2 domain); required for BCR- and TLR-mediated activation of phosphoinositide 3-kinase. Interacts (via polyproline C-terminal region) with ABI1 (via SH3 domain); the interaction promotes phosphorylation of PIK3AP1 by ABL1 (By similarity). May interact with MYD88 and TIRAP. {ECO:0000250, ECO:0000269|PubMed:11163197, ECO:0000269|PubMed:18025150, ECO:0000269|PubMed:22187460, ECO:0000305}.
Tissue SpecificityPredominantly expressed in spleen (at protein level). Expressed at lower levels in thymus, liver and lung. Expressed in B-cells, macrophages and natural killer (NK) cells. {ECO:0000269|PubMed:11163197, ECO:0000269|PubMed:18337558}.