InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PIP5K1A

Summary

InnateDB Protein

IDBP-102327.6

Last Modified

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

Gene Symbol

PIP5K1A

Protein Name

phosphatidylinositol-4-phosphate 5-kinase, type I, alpha

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000357883

InnateDB Gene

IDBG-102321 (PIP5K1A)

Protein Structure

UniProt Annotation

Function

Catalyzes the phosphorylation of phosphatidylinositol 4- phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of cellular processes and is the substrate to form phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), another second messenger. The majority of PtdIns(4,5)P2 is thought to occur via type I phosphatidylinositol 4-phosphate 5-kinases given the abundance of PtdIns4P. Participates in a variety of cellular processes such as actin cytoskeleton organization, cell adhesion, migration and phagocytosis. Required for membrane ruffling formation, actin organization and focal adhesion formation during directional cell migration by controlling integrin-induced translocation of RAC1 to the plasma membrane. Together with PIP5K1C is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle ingestion by activating WAS that induces Arp2/3 dependent actin polymerization at the nascent phagocytic cup. Together with PIP5K1B is required after stimulation of G-protein coupled receptors for stable platelet adhesion. Plays a role during calcium-induced keratinocyte differentiation. Recruited to the plasma membrane by the E-cadherin/beta-catenin complex where it provides the substrate PtdIns(4,5)P2 for the production of PtdIns(3,4,5)P3, diacylglycerol and inositol 1,4,5-trisphosphate that mobilize internal calcium and drive keratinocyte differentiation. Together with PIP5K1C have a role during embryogenesis. Functions also in the nucleus where acts as an activator of TUT1 adenylyltransferase activity in nuclear speckles, thereby regulating mRNA polyadenylation of a select set of mRNAs. {ECO:0000269PubMed:18288197, ECO:0000269PubMed:19158393, ECO:0000269PubMed:20660631}.

Subcellular Localization

Cell membrane. Cytoplasm {ECO:0000250}. Nucleus speckle. Cell projection, ruffle. Note=Colocalizes with RAC1 at actin-rich membrane ruffles. Localizes to nuclear speckles and associates with TUT1 to regulate polyadenylation of selected mRNAs.

Disease Associations

Tissue Specificity

Highly expressed in heart, placenta, skeletal muscle, kidney and pancreas. Detected at lower levels in brain, lung and liver.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 14 experimentally validated interaction(s) in this database.

Experimentally validated
Total	14 [view]
Protein-Protein	12 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016307	phosphatidylinositol phosphate kinase activity
GO:0016308	1-phosphatidylinositol-4-phosphate 5-kinase activity
GO:0019900	kinase binding

Biological Process

GO:0006644	phospholipid metabolic process
GO:0006650	glycerophospholipid metabolic process
GO:0006661	phosphatidylinositol biosynthetic process
GO:0006909	phagocytosis
GO:0007165	signal transduction
GO:0008654	phospholipid biosynthetic process
GO:0010761	fibroblast migration
GO:0016477	cell migration
GO:0030216	keratinocyte differentiation
GO:0031532	actin cytoskeleton reorganization
GO:0032863	activation of Rac GTPase activity
GO:0044281	small molecule metabolic process
GO:0046488	phosphatidylinositol metabolic process
GO:0046854	phosphatidylinositol phosphorylation
GO:0048041	focal adhesion assembly
GO:0060326	cell chemotaxis
GO:0072661	protein targeting to plasma membrane
GO:0097178	ruffle assembly

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005847	mRNA cleavage and polyadenylation specificity factor complex
GO:0005886	plasma membrane
GO:0016607	nuclear speck
GO:0030027	lamellipodium
GO:0032587	ruffle membrane