Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
Also known as: PIK3CD
Function
Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Plays a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Plays important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity.
Classification
- Family (Pfam)
- PF00454 PI3_PI4_kinase, PF00792 PI3K_C2, PF02192 PI3K_p85B, PF00794 PI3K_rbd, PF00613 PI3Ka
- InterPro
- ARM-type_fold, C2_domain_sf, Kinase-like_dom_sf, PI3-kinase_delta_cat, PI3/4_kinase, PI3/4_kinase_cat_dom, PI3/4_kinase_cat_sf, PI3/4_kinase_CS, PI3K-type_C2_dom, PI3K_ABD, PI3K_accessory_dom, PI3K_accessory_sf, PI3K_Ras-bd_dom, Ubiquitin-like_domsf
- Functional cluster
- Eukaryotic Transcription Factors & related
Experimental structures · PDB · 18
- 5DXU X-ray 2.64A
- 5M6U X-ray 2.85A
- 5T8F X-ray 2.91A
- 5UBT X-ray 2.83A
- 5VLR X-ray 2.80A
- 6G6W X-ray 2.72A
- 6OCO X-ray 2.58A
- 6OCU X-ray 2.77A
- 6PYR X-ray 2.21A
- 6PYU X-ray 2.54A
- 7JIS X-ray 2.42A
- 7LM2 X-ray 2.79A
- … and 6 more
A predicted model is available from AlphaFold.
Gene Ontology · 46
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005942 phosphatidylinositol 3-kinase complex
- GO:0005943 phosphatidylinositol 3-kinase complex, class IA
- GO:0005886 plasma membrane
- GO:0016303 1-phosphatidylinositol-3-kinase activity
- GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity
- GO:0035005 1-phosphatidylinositol-4-phosphate 3-kinase activity
- GO:0005524 ATP binding
- GO:0002250 adaptive immune response
- GO:0042113 B cell activation
- GO:0035754 B cell chemotaxis
- GO:0030183 B cell differentiation
- GO:0050853 B cell receptor signaling pathway
- GO:0016477 cell migration
- GO:0006955 immune response
- GO:0006954 inflammatory response
- GO:0045087 innate immune response
- GO:0002551 mast cell chemotaxis
- GO:0043303 mast cell degranulation
- GO:0060374 mast cell differentiation
- GO:0030101 natural killer cell activation
- GO:0035747 natural killer cell chemotaxis
- GO:0001779 natural killer cell differentiation
- GO:0030593 neutrophil chemotaxis
- GO:0072672 neutrophil extravasation
- GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process
- GO:0048015 phosphatidylinositol-mediated signaling
- GO:0045766 positive regulation of angiogenesis
- GO:0030335 positive regulation of cell migration
- GO:0001819 positive regulation of cytokine production
- GO:0010595 positive regulation of endothelial cell migration
- GO:0001938 positive regulation of endothelial cell proliferation
- GO:1905278 positive regulation of epithelial tube formation
- GO:0010628 positive regulation of gene expression
- GO:0033031 positive regulation of neutrophil apoptotic process
- GO:0006468 protein phosphorylation
- GO:0002679 respiratory burst involved in defense response
- GO:0007165 signal transduction
- GO:0042110 T cell activation
- GO:0010818 T cell chemotaxis
- GO:0031295 T cell costimulation
- GO:0030217 T cell differentiation
- GO:0050852 T cell receptor signaling pathway
- GO:0038084 vascular endothelial growth factor signaling pathway
Disease associations
- combined immunodeficiency with faciooculoskeletal anomalies MONDO:0013226
- immunodeficiency 14 MONDO:0014222
- immunodeficiency 14b, autosomal recessive MONDO:0023655
Drugs targeting this protein · 41
- PF-04691502 inhibitor
- OMIPALISIB inhibitor
- IZORLISIB inhibitor
- DACTOLISIB inhibitor
- APITOLISIB inhibitor
- BUPARLISIB inhibitor
- AZD-6482 inhibitor
- NEMIRALISIB inhibitor
- IDELALISIB inhibitor
- RECILISIB inhibitor
- TG100-115 inhibitor
- SF-1126 inhibitor
- TASELISIB inhibitor
- COPANLISIB inhibitor
- PILARALISIB inhibitor
- VS-5584 inhibitor
- AZD-8186 inhibitor
- GSK-1059615 inhibitor
- COPANLISIB HYDROCHLORIDE inhibitor
- BGT-226 inhibitor
- VOXTALISIB inhibitor
- FIMEPINOSTAT inhibitor
- LENIOLISIB inhibitor
- PAXALISIB inhibitor
- UMBRALISIB TOSYLATE inhibitor
- LENIOLISIB PHOSPHATE inhibitor
- SONOLISIB inhibitor
- SAMOTOLISIB inhibitor
- TENALISIB inhibitor
- PARSACLISIB inhibitor
- SELETALISIB inhibitor
- ACALISIB inhibitor
- AMG-319 inhibitor
- PUQUITINIB MESYLATE DIHYDRATE inhibitor
- ZANDELISIB inhibitor
- PANULISIB inhibitor
- PICTILISIB inhibitor
- GSK-2269557 inhibitor
- DUVELISIB MONOHYDRATE inhibitor
- ZSTK-474 inhibitor
- GEDATOLISIB inhibitor
Related proteins · sequence + function similarity
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform 0.99
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform 0.82
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 0.81
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform 0.81
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 0.80
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform 0.80
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 0.79
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 0.79
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 0.79
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 0.78
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 0.78
- Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma 0.74
Co-cited proteins · studied together in the literature
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform 2 shared papers
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 2 shared papers
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform 2 shared papers
- Microtubule-associated protein 4 1 shared papers
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 2 shared papers
- Small kinetochore-associated protein 1 shared papers
- Forkhead box protein M1 1 shared papers
- Phosphatidylinositol 3-kinase regulatory subunit alpha 1 shared papers
Literature · 17 cited papers
- PI3K activation is enhanced by FOXM1D binding to p110 and p85 subunits. Signal Transduct. Target. Ther. · 2020
- Human primary immunodeficiency caused by expression of a kinase-dead p110delta mutant. J. Allergy Clin. Immunol. · 2019
- Primary immunodeficiency disorder caused by phosphoinositide 3-kinase delta deficiency. J. Allergy Clin. Immunol. · 2018
- Dual loss of p110delta PI3-kinase and SKAP (KNSTRN) expression leads to combined immunodeficiency and multisystem syndromic features. J. Allergy Clin. Immunol. · 2018
- Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory infection and airway damage. Science · 2013
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- p37delta is a new isoform of PI3K p110delta that increases cell proliferation and is overexpressed in tumors. Oncogene · 2012
- Phosphoinositide 3-kinase delta (PI3Kdelta) in leukocyte signaling and function. Cell. Signal. · 2011
- PI3K p110delta regulates T-cell cytokine production during primary and secondary immune responses in mice and humans. Blood · 2010
- Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
- PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid arthritis and beyond? Nat. Rev. Immunol. · 2007
- The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
- … and 5 more in the literature graph