Protein: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (PI3-kinase subunit delta) (PI3K-delta) (PI3Kdelta) (PtdIns-3-kinase subunit delta) (EC 2.7.1.137) (EC 2.7.1.153) (Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta) (PtdIns-3-kinase subunit p110-delta) (p110delta) (O00329)
Organism: Homo sapiens (Human)
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.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:22020336}.
Sequence: MPPGVDCPMEFWTKEENQSVVVDFLLPTGVYLNFPVSRNANLSTIKQLLWHRAQYEPLFHMLSGPEAYVFTCINQTAEQQELEDEQRRLCDVQPFLPVLRLVAREGDRVKKLINSQISLLIGKGLHEFDSLCDPEVNDFRAKMCQFCEEAAARRQQLGWEAWLQYSFPLQLEPSAQTWGPGTLRLPNRALLVNVKFEGSEESFTFQVSTKDVPLALMACALRKKATVFRQPLVEQPEDYTLQVNGRHEYLYGSYPLCQFQYICSCLHSGLTPHLTMVHSSSILAMRDEQSNPAPQVQKPRAKPPPIPAKKPSSVSLWSLEQPFRIELIQGSKVNADERMKLVVQAGLFHGNEMLCKTVSSSEVSVCSEPVWKQRLEFDINICDLPRMARLCFALYAVIEKAKKARSTKKKSKKADCPIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPTGTVRSNPNTDSAAALLICLPEVAPHPVYYPALEKILELGRHSECVHVTEEEQLQLREILERRGSGELYEHEKDLVWKLRHEVQEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDFSFPDCHVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLDRALANRKIGHFLFWHLRSEMHVPSVALRFGLILEAYCRGSTHHMKVLMKQGEALSKLKALNDFVKLSSQKTPKPQTKELMHLCMRQEAYLEALSHLQSPLDPSTLLAEVCVEQCTFMDSKMKPLWIMYSNEEAGSGGSVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLRSDTIANIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDNRQ
InterPro domains: - IPR016024: Armadillo-type fold (homologous_superfamily) [482-674]
- IPR035892: C2 domain superfamily (homologous_superfamily) [319-481]
- IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [678-1033]
- IPR015433: Phosphatidylinositol 3-/4-kinase (family) [37-1039]
- IPR000341: Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain (domain) [175-281]
- IPR029071: Ubiquitin-like domain superfamily (homologous_superfamily) [106-285]
- IPR002420: C2 phosphatidylinositol 3-kinase-type domain (domain) [309-476]
- IPR003113: Phosphatidylinositol 3-kinase, adaptor-binding domain (domain) [16-108]
- IPR037703: Phosphatidylinositol 3-kinase delta, catalytic domain (domain) [676-1042]
- IPR042236: Phosphoinositide 3-kinase, accessory (PIK) domain superfamily (homologous_superfamily) [482-675]
- IPR018936: Phosphatidylinositol 3-/4-kinase, conserved site (conserved_site) [778-898]
- IPR036940: Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily (homologous_superfamily) [830-1034]
- IPR000403: Phosphatidylinositol 3-/4-kinase, catalytic domain (domain) [745-1041]
- IPR001263: Phosphoinositide 3-kinase, accessory (PIK) domain (domain) [497-685]
Interaction partners: - Phosphoinositide 3-kinase regulatory subunit 5
- Phosphatidylinositol 3-kinase regulatory subunit beta
- Phosphatidylinositol 3-kinase regulatory subunit gamma
- Phosphatidylinositol 3-kinase regulatory subunit alpha
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
- Ras-related protein R-Ras
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
- Ras-related protein R-Ras2
- Tyrosine-protein kinase BTK
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0004672 (protein kinase activity), GO:0016301 (kinase activity), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0052742 (phosphatidylinositol kinase activity), GO:0035004 (phosphatidylinositol 3-kinase activity), GO:0016303 (1-phosphatidylinositol-3-kinase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0008152 (metabolic process), GO:0040011 (locomotion), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0023057 (negative regulation of signaling), GO:0048870 (cell motility), GO:0042221 (response to chemical), GO:0042330 (taxis), GO:0051240 (positive regulation of multicellular organismal process), GO:0051241 (negative regulation of multicellular organismal process), GO:0051239 (regulation of multicellular organismal process), GO:0065008 (regulation of biological quality), GO:0050793 (regulation of developmental process), GO:0009607 (response to biotic stimulus), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0051093 (negative regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0051707 (response to other organism), GO:0007165 (signal transduction), GO:0009628 (response to abiotic stimulus), GO:0023056 (positive regulation of signaling), GO:0001775 (cell activation), GO:0009058 (biosynthetic process), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0007155 (cell adhesion), GO:0032879 (regulation of localization), GO:0071704 (organic substance metabolic process), GO:0044237 (cellular metabolic process), GO:0050817 (coagulation), GO:0009893 (positive regulation of metabolic process), GO:0065009 (regulation of molecular function), GO:0006950 (response to stress), GO:0048585 (negative regulation of response to stimulus), GO:0007154 (cell communication), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0090287 (regulation of cellular response to growth factor stimulus), GO:0001666 (response to hypoxia), GO:0009968 (negative regulation of signal transduction), GO:0010942 (positive regulation of cell death), GO:0043207 (response to external biotic stimulus), GO:0060548 (negative regulation of cell death), GO:0080134 (regulation of response to stress), GO:0070482 (response to oxygen levels), GO:0009966 (regulation of signal transduction), GO:0030155 (regulation of cell adhesion), GO:0044255 (cellular lipid metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0032101 (regulation of response to external stimulus), GO:0060627 (regulation of vesicle-mediated transport), GO:0090288 (negative regulation of cellular response to growth factor stimulus), GO:1901343 (negative regulation of vasculature development), GO:0006793 (phosphorus metabolic process), GO:0009894 (regulation of catabolic process), GO:0010632 (regulation of epithelial cell migration), GO:0050878 (regulation of body fluid levels), GO:0007186 (G protein-coupled receptor signaling pathway), GO:0022603 (regulation of anatomical structure morphogenesis), GO:0007166 (cell surface receptor signaling pathway), GO:0051128 (regulation of cellular component organization), GO:0006935 (chemotaxis), GO:0016477 (cell migration), GO:0009967 (positive regulation of signal transduction), GO:0030168 (platelet activation), GO:0050790 (regulation of catalytic activity), GO:0010648 (negative regulation of cell communication), GO:0044093 (positive regulation of molecular function), GO:0051049 (regulation of transport), GO:1901576 (organic substance biosynthetic process), GO:0035556 (intracellular signal transduction), GO:0009611 (response to wounding), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0098609 (cell-cell adhesion), GO:0019637 (organophosphate metabolic process), GO:0044249 (cellular biosynthetic process), GO:2000147 (positive regulation of cell motility), GO:2000026 (regulation of multicellular organismal development), GO:0007596 (blood coagulation), GO:0006629 (lipid metabolic process), GO:0010941 (regulation of cell death), GO:0010646 (regulation of cell communication), GO:0031325 (positive regulation of cellular metabolic process), GO:0010647 (positive regulation of cell communication), GO:0031323 (regulation of cellular metabolic process), GO:0009896 (positive regulation of catabolic process), GO:0051341 (regulation of oxidoreductase activity), GO:0034109 (homotypic cell-cell adhesion), GO:0010810 (regulation of cell-substrate adhesion), GO:0043067 (regulation of programmed cell death), GO:0006644 (phospholipid metabolic process), GO:0030334 (regulation of cell migration), GO:0045017 (glycerolipid biosynthetic process), GO:0010468 (regulation of gene expression), GO:0046486 (glycerolipid metabolic process), GO:0010594 (regulation of endothelial cell migration), GO:0010508 (positive regulation of autophagy), GO:0036293 (response to decreased oxygen levels), GO:0090407 (organophosphate biosynthetic process), GO:0030335 (positive regulation of cell migration), GO:1902533 (positive regulation of intracellular signal transduction), GO:0043085 (positive regulation of catalytic activity), GO:0008610 (lipid biosynthetic process), GO:2000181 (negative regulation of blood vessel morphogenesis), GO:1900746 (regulation of vascular endothelial growth factor signaling pathway), GO:0016525 (negative regulation of angiogenesis), GO:0030100 (regulation of endocytosis), GO:0007167 (enzyme-linked receptor protein signaling pathway), GO:0043068 (positive regulation of programmed cell death), GO:0070527 (platelet aggregation), GO:1901342 (regulation of vasculature development), GO:0010506 (regulation of autophagy), GO:0010628 (positive regulation of gene expression), GO:0006796 (phosphate-containing compound metabolic process), GO:1902532 (negative regulation of intracellular signal transduction), GO:0048017 (inositol lipid-mediated signaling), GO:1902547 (regulation of cellular response to vascular endothelial growth factor stimulus), GO:0042060 (wound healing), GO:0010634 (positive regulation of epithelial cell migration), GO:0031331 (positive regulation of cellular catabolic process), GO:0045765 (regulation of angiogenesis), GO:0007599 (hemostasis), GO:0031329 (regulation of cellular catabolic process), GO:1902531 (regulation of intracellular signal transduction), GO:0048015 (phosphatidylinositol-mediated signaling), GO:0051353 (positive regulation of oxidoreductase activity), GO:0042981 (regulation of apoptotic process), GO:1903670 (regulation of sprouting angiogenesis), GO:0001952 (regulation of cell-matrix adhesion), GO:0051897 (positive regulation of protein kinase B signaling), GO:0051057 (positive regulation of small GTPase mediated signal transduction), GO:0016310 (phosphorylation), GO:0008654 (phospholipid biosynthetic process), GO:0051896 (regulation of protein kinase B signaling), GO:0007169 (transmembrane receptor protein tyrosine kinase signaling pathway), GO:0043065 (positive regulation of apoptotic process), GO:0048259 (regulation of receptor-mediated endocytosis), GO:0046474 (glycerophospholipid biosynthetic process), GO:0010595 (positive regulation of endothelial cell migration), GO:0006650 (glycerophospholipid metabolic process), GO:0051898 (negative regulation of protein kinase B signaling), GO:0051056 (regulation of small GTPase mediated signal transduction), GO:0032768 (regulation of monooxygenase activity), GO:2000106 (regulation of leukocyte apoptotic process), GO:0046578 (regulation of Ras protein signal transduction), GO:2000369 (regulation of clathrin-dependent endocytosis), GO:2000108 (positive regulation of leukocyte apoptotic process), GO:0032770 (positive regulation of monooxygenase activity), GO:0046579 (positive regulation of Ras protein signal transduction), GO:0033032 (regulation of myeloid cell apoptotic process), GO:0046488 (phosphatidylinositol metabolic process), GO:0050999 (regulation of nitric-oxide synthase activity), GO:0014065 (phosphatidylinositol 3-kinase signaling), GO:0006661 (phosphatidylinositol biosynthetic process), GO:0035020 (regulation of Rac protein signal transduction), GO:0035022 (positive regulation of Rac protein signal transduction), GO:0051000 (positive regulation of nitric-oxide synthase activity), GO:0046854 (phosphatidylinositol phosphate biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0016020 (membrane), GO:0005829 (cytosol), GO:0098796 (membrane protein complex), GO:0030496 (midbody), GO:1902494 (catalytic complex), GO:0019898 (extrinsic component of membrane), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:1990234 (transferase complex), GO:0043229 (intracellular organelle), GO:0043228 (non-membrane-bounded organelle), GO:0043233 (organelle lumen), GO:0005942 (phosphatidylinositol 3-kinase complex), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0061695 (transferase complex, transferring phosphorus-containing groups), GO:0070013 (intracellular organelle lumen), GO:0005730 (nucleolus), GO:0005634 (nucleus), GO:0031981 (nuclear lumen)