PIK3CD - Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform - human protein (Function)
 
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PIK3CD »  Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform   [ EC 2.7.1.153 ]  (PI3Kdelta)
 
Protein also known as:  Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta (p110delta).
Gene name:  PIK3CD
Family name: PI3/PI4-kinase
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(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. Have 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. Have 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.  
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  • UniProtKB
Isoform  Iso 2   May be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity.  
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  • UniProtKB
GO molecular function 
1-phosphatidylinositol-3-kinase activitydefinition[GO:0016303]  
1
  • UniProtKB
1-phosphatidylinositol-4-phosphate 3-kinase activitydefinition[GO:0035005]  
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  • RefGenome
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Phosphatidylinositol 3-kinase activitydefinition[GO:0035004]  
1
  • UniProtKB
Phosphatidylinositol-4,5-bisphosphate 3-kinase activitydefinition[GO:0046934]  
1
  • RefGenome
Isoform  Iso 2   Protein bindingdefinition[GO:0005515]  
1
  • IntAct
GO biological process 
Adaptive immune responsedefinition[GO:0002250]  
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  • UniProtKB
B cell activationdefinition[GO:0042113]  
1
  • UniProtKB
B cell chemotaxisdefinition[GO:0035754]  
1
  • UniProtKB
B cell homeostasisdefinition[GO:0001782] silver  
1
  • Ortholog Compara
B cell receptor signaling pathwaydefinition[GO:0050853]  
1
  • UniProtKB
Cytokine productiondefinition[GO:0001816]  
1
  • UniProtKB
Inflammatory responsedefinition[GO:0006954]  
2
  • UniProtKB
Innate immune responsedefinition[GO:0045087]  
2
  • UniProtKB
Mast cell chemotaxisdefinition[GO:0002551]  
1
  • UniProtKB
Mast cell degranulationdefinition[GO:0043303]  
1
  • UniProtKB
Mast cell differentiationdefinition[GO:0060374]  
1
  • UniProtKB
Natural killer cell activationdefinition[GO:0030101]  
1
  • UniProtKB
Natural killer cell chemotaxisdefinition[GO:0035747]  
1
  • UniProtKB
Natural killer cell differentiationdefinition[GO:0001779]  
1
  • UniProtKB
Neutrophil chemotaxisdefinition[GO:0030593]  
1
  • UniProtKB
Neutrophil extravasationdefinition[GO:0072672]  
1
  • UniProtKB
Phosphatidylinositol 3-kinase signalingdefinition[GO:0014065]  
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  • UniProtKB
Phosphatidylinositol phosphorylationdefinition[GO:0046854] silver  
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  • InterPro 2 GO
Phosphatidylinositol-3-phosphate biosynthetic processdefinition[GO:0036092]  
1
  • GOC
Positive regulation of cell migrationdefinition[GO:0030335] silver  
1
  • CACAO
Positive regulation of gene expressiondefinition[GO:0010628] silver  
1
  • CACAO
Protein phosphorylationdefinition[GO:0006468]  
1
  • UniProtKB
Respiratory burst involved in defense responsedefinition[GO:0002679]  
1
  • UniProtKB
Signal transductiondefinition[GO:0007165]  
1
  • UniProtKB
T cell activationdefinition[GO:0042110]  
1
  • UniProtKB
T cell chemotaxisdefinition[GO:0010818]  
1
  • UniProtKB
T cell differentiationdefinition[GO:0030217]  
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  • UniProtKB
T cell receptor signaling pathwaydefinition[GO:0050852]  
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  • UniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.1.153: ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate.  
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  • UniProtKB
It is regulated in the following manner
Activated by growth factors and cytokine receptors through a tyrosine-kinase-dependent mechanism. Activated by RAS. IC87114 inhibits lipid kinase activity and is selective in cells at doses up to 5-10 uM. IC87114 blocks T-cell receptor signaling in naive and memory T-cells and reduces cytokine production by memory T-cells.  
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More information is available from:
Pathways 
This protein is involved in the following pathway
Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis  
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According to KEGG, this protein belongs to the following pathways:
Acute myeloid leukemia  hsa05221+5293  
Aldosterone-regulated sodium reabsorption  hsa04960+5293  
Amoebiasis  hsa05146+5293  
Apoptosis  hsa04210+5293  
B cell receptor signaling pathway  hsa04662+5293  
Bacterial invasion of epithelial cells  hsa05100+5293  
Carbohydrate digestion and absorption  hsa04973+5293  
Chagas disease (American trypanosomiasis)  hsa05142+5293  
Chemokine signaling pathway  hsa04062+5293  
Cholinergic synapse  hsa04725+5293  
Colorectal cancer  hsa05210+5293  
Endometrial cancer  hsa05213+5293  
ErbB signaling pathway  hsa04012+5293  
Fc epsilon RI signaling pathway  hsa04664+5293  
Fc gamma R-mediated phagocytosis  hsa04666+5293  
Focal adhesion  hsa04510+5293  
Glioma  hsa05214+5293  
Hepatitis C  hsa05160+5293  
HTLV-I infection  hsa05166+5293  
Influenza A  hsa05164+5293  
Inositol phosphate metabolism  hsa00562+5293  
Insulin signaling pathway  hsa04910+5293  
Jak-STAT signaling pathway  hsa04630+5293  
Leukocyte transendothelial migration  hsa04670+5293  
Measles  hsa05162+5293  
Melanoma  hsa05218+5293  
mTOR signaling pathway  hsa04150+5293  
Natural killer cell mediated cytotoxicity  hsa04650+5293  
Neurotrophin signaling pathway  hsa04722+5293  
Non-small cell lung cancer  hsa05223+5293  
Osteoclast differentiation  hsa04380+5293  
Pancreatic cancer  hsa05212+5293  
Pathways in cancer  hsa05200+5293  
Phosphatidylinositol signaling system  hsa04070+5293  
Progesterone-mediated oocyte maturation  hsa04914+5293  
Prostate cancer  hsa05215+5293  
Regulation of actin cytoskeleton  hsa04810+5293  
Renal cell carcinoma  hsa05211+5293  
Small cell lung cancer  hsa05222+5293  
T cell receptor signaling pathway  hsa04660+5293  
Toll-like receptor signaling pathway  hsa04620+5293  
Toxoplasmosis  hsa05145+5293  
Type II diabetes mellitus  hsa04930+5293  
VEGF signaling pathway  hsa04370+5293  
According to Reactome, this protein belongs to the following pathways:
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers  REACT_118700  
Constitutive PI3K/AKT Signaling in Cancer  REACT_147727  
G beta:gamma signalling through PI3Kgamma  REACT_19290  
GPVI-mediated activation cascade  REACT_1695  
Interleukin receptor SHC signaling  REACT_23891  
Interleukin-3, 5 and GM-CSF signaling  REACT_23837  
PIP3 activates AKT signaling  REACT_75829  
Regulation of signaling by CBL  REACT_23787  
Synthesis of PIPs at the plasma membrane  REACT_121025  
 
More information is available from:
Note 
IC87114 inhibitor reduces passive cutaneous anaphylaxis, attenuates allergic airway inflammation and hyperresponsiveness and allergen induced rhinitis response. Inhibitors may have therapeutic potential for the treatment of immune system-mediated diseases such as auto-immune diseases, inflammation and allergy (PubMed:20940048; PubMed:17290298).  
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  • UniProtKB
 

Keywords

Biological process 
Adaptive immunity  definition   [KW-1064]
Chemotaxis  definition   [KW-0145]
Differentiation  definition   [KW-0221]
Immunity  definition   [KW-0391]
Inflammatory response  definition   [KW-0395]
Innate immunity  definition   [KW-0399]
Molecular function 
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: P110%CE%B4
GenomeRNAi: 5293
PRO: PR:O00329
Chemistry
GuidetoPHARMACOLOGY: 2155