InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PIK3C2A

Summary

InnateDB Protein

IDBP-33680.5

Last Modified

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

Gene Symbol

PIK3C2A

Protein Name

phosphoinositide-3-kinase, class 2, alpha polypeptide

Synonyms

CPK; PI3-K-C2(ALPHA); PI3-K-C2A;

Species

Homo sapiens

Ensembl Protein

ENSP00000265970

InnateDB Gene

IDBG-33678 (PIK3C2A)

Protein Structure

UniProt Annotation

Function

Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin- mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin- independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. {ECO:0000269PubMed:10766823, ECO:0000269PubMed:10805725, ECO:0000269PubMed:11239472, ECO:0000269PubMed:12719431, ECO:0000269PubMed:16215232, ECO:0000269PubMed:21081650, ECO:0000269PubMed:9337861}.

Subcellular Localization

Cell membrane. Golgi apparatus. Cytoplasmic vesicle, clathrin-coated vesicle. Nucleus. Cytoplasm. Note=According to PubMed:10766823 and PubMed:11239472, it is found in the cell membrane, the Golgi apparatus and in clathrin-coated vesicles. According to PubMed:17038310 it inserts preferentially into membranes containing PtdIns(4,5)P2. According to PubMed:11606566, it is nuclear and cytoplasmic. Associated with RNA-containing structures. According to PubMed:14563213, it is mainly cytoplasmic.

Disease Associations

Tissue Specificity

Expressed in columnar and transitional epithelia, mononuclear cells, smooth muscle cells, and endothelial cells lining capillaries and small venules (at protein level). Ubiquitously expressed, with highest levels in heart, placenta and ovary, and lowest levels in the kidney. Detected at low levels in islets of Langerhans from type 2 diabetes mellitus individuals. {ECO:0000269PubMed:14563213, ECO:0000269PubMed:21127054, ECO:0000269PubMed:9337861}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 22 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	22 [view]
Protein-Protein	22 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [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:0035091	phosphatidylinositol binding

Biological Process

GO:0006644	phospholipid metabolic process
GO:0006661	phosphatidylinositol biosynthetic process
GO:0006887	exocytosis
GO:0006897	endocytosis
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0008286	insulin receptor signaling pathway
GO:0014829	vascular smooth muscle contraction
GO:0036092	phosphatidylinositol-3-phosphate biosynthetic process
GO:0044281	small molecule metabolic process
GO:0046854	phosphatidylinositol phosphorylation
GO:0048008	platelet-derived growth factor receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0048268	clathrin coat assembly

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005942	phosphatidylinositol 3-kinase complex
GO:0016020	membrane
GO:0030136	clathrin-coated vesicle
GO:0031982	vesicle
GO:0070062	extracellular vesicular exosome

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
IPR001683 Phox homologous domain
IPR002420 Phosphatidylinositol 3-kinase, C2 domain
IPR011009 Protein kinase-like domain
IPR016024 Armadillo-type fold
IPR029071 Ubiquitin-related domain

PFAM

PF00168
PF00794
PF00454
PF00613
PF00787
PF00792

PRINTS

PR00360

PIRSF

SMART

SM00239
SM00144
SM00146
SM00145
SM00312
SM00142

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt