General Information of Drug Therapeutic Target (DTT) (ID: TTK5FVJ)

DTT Name HUMAN PI3-kinase delta (PIK3CD)
Synonyms
PtdIns-3-kinase subunit p110-delta; PtdIns-3-kinase subunit delta; Phosphoinositide 3-kinase delta; Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, delta isoform; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform; Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta; PI3Kdelta; PI3K-delta; PI3-kinase subunit delta; PI3-kinase p110 subunit delta; P110delta
Gene Name PIK3CD
BioChemical Class
Kinase
UniProt ID
PK3CD_HUMAN
TTD ID
T94119
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
EC 2.7.1.153
Sequence
MPPGVDCPMEFWTKEENQSVVVDFLLPTGVYLNFPVSRNANLSTIKQLLWHRAQYEPLFH
MLSGPEAYVFTCINQTAEQQELEDEQRRLCDVQPFLPVLRLVAREGDRVKKLINSQISLL
IGKGLHEFDSLCDPEVNDFRAKMCQFCEEAAARRQQLGWEAWLQYSFPLQLEPSAQTWGP
GTLRLPNRALLVNVKFEGSEESFTFQVSTKDVPLALMACALRKKATVFRQPLVEQPEDYT
LQVNGRHEYLYGSYPLCQFQYICSCLHSGLTPHLTMVHSSSILAMRDEQSNPAPQVQKPR
AKPPPIPAKKPSSVSLWSLEQPFRIELIQGSKVNADERMKLVVQAGLFHGNEMLCKTVSS
SEVSVCSEPVWKQRLEFDINICDLPRMARLCFALYAVIEKAKKARSTKKKSKKADCPIAW
ANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPTGTVRSNPNTDSAAALLICLPEVAP
HPVYYPALEKILELGRHSECVHVTEEEQLQLREILERRGSGELYEHEKDLVWKLRHEVQE
HFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDFSFPDCHVGSFAIKSL
RKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLDRALANRKIGHFLFWHLRSEMHVPSV
ALRFGLILEAYCRGSTHHMKVLMKQGEALSKLKALNDFVKLSSQKTPKPQTKELMHLCMR
QEAYLEALSHLQSPLDPSTLLAEVCVEQCTFMDSKMKPLWIMYSNEEAGSGGSVGIIFKN
GDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLRSDTIANIQLN
KSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIM
IRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYC
ERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFRVKFN
EALRESWKTKVNWLAHNVSKDNRQ
Function
Phosphoinositide-3-kinase (PI3K) that phosphorylates 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. 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. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity.
KEGG Pathway
Inositol phosphate metabolism (hsa00562 )
Metabolic pathways (hsa01100 )
EGFR tyrosine kinase inhibitor resistance (hsa01521 )
Endocrine resistance (hsa01522 )
Platinum drug resistance (hsa01524 )
ErbB signaling pathway (hsa04012 )
Ras signaling pathway (hsa04014 )
Rap1 signaling pathway (hsa04015 )
cAMP signaling pathway (hsa04024 )
Chemokine signaling pathway (hsa04062 )
HIF-1 signaling pathway (hsa04066 )
FoxO signaling pathway (hsa04068 )
Phosphatidylinositol signaling system (hsa04070 )
Sphingolipid signaling pathway (hsa04071 )
Phospholipase D signaling pathway (hsa04072 )
Autophagy - animal (hsa04140 )
mTOR signaling pathway (hsa04150 )
PI3K-Akt signaling pathway (hsa04151 )
AMPK signaling pathway (hsa04152 )
Apoptosis (hsa04210 )
Longevity regulating pathway (hsa04211 )
Longevity regulating pathway - multiple species (hsa04213 )
Cellular senescence (hsa04218 )
Axon guidance (hsa04360 )
VEGF signaling pathway (hsa04370 )
Osteoclast differentiation (hsa04380 )
Focal adhesion (hsa04510 )
Signaling pathways regulating pluripotency of stem cells (hsa04550 )
Platelet activation (hsa04611 )
Neutrophil extracellular trap formation (hsa04613 )
Toll-like receptor signaling pathway (hsa04620 )
C-type lectin receptor signaling pathway (hsa04625 )
JAK-STAT signaling pathway (hsa04630 )
Natural killer cell mediated cytotoxicity (hsa04650 )
T cell receptor signaling pathway (hsa04660 )
B cell receptor signaling pathway (hsa04662 )
Fc epsilon RI signaling pathway (hsa04664 )
Fc gamma R-mediated phagocytosis (hsa04666 )
TNF signaling pathway (hsa04668 )
Leukocyte transendothelial migration (hsa04670 )
Neurotrophin signaling pathway (hsa04722 )
Cholinergic synapse (hsa04725 )
Inflammatory mediator regulation of TRP channels (hsa04750 )
Regulation of actin cytoskeleton (hsa04810 )
Insulin signaling pathway (hsa04910 )
Progesterone-mediated oocyte maturation (hsa04914 )
Estrogen signaling pathway (hsa04915 )
Prolactin signaling pathway (hsa04917 )
Thyroid hormone signaling pathway (hsa04919 )
Regulation of lipolysis in adipocytes (hsa04923 )
Relaxin signaling pathway (hsa04926 )
GnRH secretion (hsa04929 )
Type II diabetes mellitus (hsa04930 )
Insulin resistance (hsa04931 )
Non-alcoholic fatty liver disease (hsa04932 )
AGE-RAGE signaling pathway in diabetic complications (hsa04933 )
Growth hormone synthesis, secretion and action (hsa04935 )
Aldosterone-regulated sodium reabsorption (hsa04960 )
Carbohydrate digestion and absorption (hsa04973 )
Alzheimer disease (hsa05010 )
Spinocerebellar ataxia (hsa05017 )
Prion disease (hsa05020 )
Bacterial invasion of epithelial cells (hsa05100 )
Shigellosis (hsa05131 )
Salmonella infection (hsa05132 )
Yersinia infection (hsa05135 )
Chagas disease (hsa05142 )
Amoebiasis (hsa05146 )
Hepatitis C (hsa05160 )
Hepatitis B (hsa05161 )
Measles (hsa05162 )
Human cytomegalovirus infection (hsa05163 )
Influenza A (hsa05164 )
Human papillomavirus infection (hsa05165 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Herpes simplex virus 1 infection (hsa05168 )
Epstein-Barr virus infection (hsa05169 )
Human immunodeficiency virus 1 infection (hsa05170 )
Coronavirus disease - COVID-19 (hsa05171 )
Pathways in cancer (hsa05200 )
Viral carcinogenesis (hsa05203 )
Proteoglycans in cancer (hsa05205 )
MicroRNAs in cancer (hsa05206 )
Chemical carcinogenesis - receptor activation (hsa05207 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Colorectal cancer (hsa05210 )
Renal cell carcinoma (hsa05211 )
Pancreatic cancer (hsa05212 )
Endometrial cancer (hsa05213 )
Glioma (hsa05214 )
Prostate cancer (hsa05215 )
Melanoma (hsa05218 )
Chronic myeloid leukemia (hsa05220 )
Acute myeloid leukemia (hsa05221 )
Small cell lung cancer (hsa05222 )
Non-small cell lung cancer (hsa05223 )
Breast cancer (hsa05224 )
Hepatocellular carcinoma (hsa05225 )
Gastric cancer (hsa05226 )
Central carbon metabolism in cancer (hsa05230 )
Choline metabolism in cancer (hsa05231 )
PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235 )
Diabetic cardiomyopathy (hsa05415 )
Lipid and atherosclerosis (hsa05417 )
Fluid shear stress and atherosclerosis (hsa05418 )
Reactome Pathway
Synthesis of PIPs at the plasma membrane (R-HSA-1660499 )
Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 )
Interleukin-3, Interleukin-5 and GM-CSF signaling (R-HSA-512988 )
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558 )
RET signaling (R-HSA-8853659 )
Erythropoietin activates Phosphoinositide-3-kinase (PI3K) (R-HSA-9027276 )
Interleukin receptor SHC signaling (R-HSA-912526 )
Regulation of signaling by CBL (R-HSA-912631 )
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695 )
PIP3 activates AKT signaling (R-HSA-1257604 )
BioCyc Pathway
MetaCyc:ENSG00000171608-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Drugs in Phase 2 Trial Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Duvelisib DM7USVA Follicular lymphoma 2A80 Phase 2 Trial [1]
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References

1 ClinicalTrials.gov (NCT04372602) Duvelisib to Combat COVID-19. U.S. National Institutes of Health.