InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PIK3CD

Summary

InnateDB Protein

IDBP-88556.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PIK3CD

Protein Name

phosphoinositide-3-kinase, catalytic, delta polypeptide

Synonyms

APDS; IMD14; p110D; P110DELTA; PI3K;

Species

Homo sapiens

Ensembl Protein

ENSP00000366563

InnateDB Gene

IDBG-88554 (PIK3CD)

Protein Structure

UniProt Annotation

Function

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. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity. {ECO:0000269PubMed:20081091, ECO:0000269PubMed:22020336}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:22020336}.

Disease Associations

Activated PI3K-delta syndrome (APDS) [MIM:615513]: A disorder characterized by recurrent respiratory infections, progressive airway damage, lymphopenia, increased circulating transitional B cells, increased immunoglobulin M, reduced immunoglobulin G2 levels in serum, and impaired vaccine responses. {ECO:0000269PubMed:24136356}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Isoform 2 is expressed in normal thymus, lung and spleen tissues, and is detected at low levels in normal lysates from colon and ovarian biopsies, at elevated levels in lysates from colorectal tumors and is abundantly expressed in some ovarian tumors (at protein level). Both isoform 1 and isoform 2 are widely expressed. Isoform 1 is expressed predominantly in leukocytes. {ECO:0000269PubMed:22020336}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 16 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	16 [view]
Protein-Protein	16 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005488	binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016303	1-phosphatidylinositol-3-kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0035004	phosphatidylinositol 3-kinase activity
GO:0035005	1-phosphatidylinositol-4-phosphate 3-kinase activity
GO:0046934	phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Biological Process

GO:0001779	natural killer cell differentiation
GO:0001782	B cell homeostasis
GO:0001816	cytokine production
GO:0002250	adaptive immune response
GO:0002551	mast cell chemotaxis
GO:0002679	respiratory burst involved in defense response
GO:0006468	protein phosphorylation
GO:0006644	phospholipid metabolic process
GO:0006661	phosphatidylinositol biosynthetic process
GO:0006954	inflammatory response
GO:0007165	signal transduction
GO:0007166	cell surface receptor signaling pathway
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0010818	T cell chemotaxis
GO:0014065	phosphatidylinositol 3-kinase signaling
GO:0030101	natural killer cell activation
GO:0030217	T cell differentiation
GO:0030593	neutrophil chemotaxis
GO:0035747	natural killer cell chemotaxis
GO:0035754	B cell chemotaxis
GO:0036092	phosphatidylinositol-3-phosphate biosynthetic process
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0042110	T cell activation
GO:0042113	B cell activation
GO:0043303	mast cell degranulation
GO:0044281	small molecule metabolic process
GO:0045087	innate immune response
GO:0046854	phosphatidylinositol phosphorylation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0050852	T cell receptor signaling pathway
GO:0050853	B cell receptor signaling pathway
GO:0060374	mast cell differentiation
GO:0072672	neutrophil extravasation

Cellular Component

GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005942	phosphatidylinositol 3-kinase complex
GO:0042629	mast cell granule

Protein Structure and Domains

PDB ID

InterPro

IPR000008 C2 domain
IPR000341 Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain
IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR001263 Phosphoinositide 3-kinase, accessory (PIK) domain
IPR002420 Phosphatidylinositol 3-kinase, C2 domain
IPR003113 Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain
IPR011009 Protein kinase-like domain
IPR016024 Armadillo-type fold
IPR029071 Ubiquitin-related domain

PFAM

PF00168
PF00794
PF00454
PF00613
PF00792
PF02192

PRINTS

PR00360

PIRSF

SMART

SM00239
SM00144
SM00146
SM00145
SM00142
SM00143

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt