InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PIP5K1C

Summary

InnateDB Protein

IDBP-17650.6

Last Modified

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

Gene Symbol

PIP5K1C

Protein Name

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

Synonyms

LCCS3; PIP5K-GAMMA; PIP5K1-gamma; PIP5Kgamma;

Species

Homo sapiens

Ensembl Protein

ENSP00000335333

InnateDB Gene

IDBG-17648 (PIP5K1C)

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 vesicle mediated transport, cell adhesion, cell polarization and cell migration. Together with PIP5K1A is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle attachment by generating the pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to facilitate Fc-gamma-R clustering. Mediates RAC1-dependent reorganization of actin filaments. Required for synaptic vesicle transport. Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis. Plays a role in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2). Required for clathrin-coated pits assembly at the synapse. Participates in cell junction assembly. Modulates adherens junctions formation by facilitating CDH1 trafficking. Required for focal adhesion dynamics. Modulates the targeting of talins (TLN1 and TLN2) to the plasma membrane and their efficient assembly into focal adhesions. Regulates the interaction between talins (TLN1 and TLN2) and beta-integrins. Required for uropodium formation and retraction of the cell rear during directed migration. Has a role in growth factor- stimulated directional cell migration and adhesion. Required for talin assembly into nascent adhesions forming at the leading edge toward the direction of the growth factor. Negative regulator of T-cell activation and adhesion. Negatively regulates integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T-cell receptor. Together with PIP5K1A have a role during embryogenesis and together with PIP5K1B may have a role immediately after birth. {ECO:0000269PubMed:12422219, ECO:0000269PubMed:12847086, ECO:0000269PubMed:17261850, ECO:0000269PubMed:17635937}.

Subcellular Localization

Cell membrane; Peripheral membrane protein; Cytoplasmic side. Endomembrane system. Cytoplasm. Cell junction, focal adhesion. Cell junction, adherens junction. Cell projection, ruffle membrane. Cell projection, phagocytic cup. Cell projection, uropodium. Note=Detected in plasma membrane invaginations. Isoform 3 is detected in intracellular vesicle-like structures.Isoform 2: Cytoplasm. Nucleus.

Disease Associations

Lethal congenital contracture syndrome 3 (LCCS3) [MIM:611369]: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non-progressive joint contractures (arthrogryposis). The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS3 patients present at birth with severe multiple joint contractures and severe muscle wasting and atrophy, mainly in the legs. Death occurs minutes to hours after birth due to respiratory insufficiency. The phenotype can be distinguished from that of LCCS1 by the absence of hydrops, fractures and multiple pterygia, and from LCCS2 by the absence of neurogenic bladder defect. {ECO:0000269PubMed:17701898}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Isoform 1 is strongly expressed in brain and also detected in heart and lung. Isoform 2 is strongly expressed in pancreas and liver and in lesser quantities in brain, heart, lung and kidney. Isoform 3 is detected in large amounts in heart and large intestine, is also present in lung, pancreas and thyroid, and to a lesser extent in brain, stomach and kidney. {ECO:0000269PubMed:19548880}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 17 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	17 [view]
Protein-Protein	17 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

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

Biological Process

GO:0006644	phospholipid metabolic process
GO:0006661	phosphatidylinositol biosynthetic process
GO:0006909	phagocytosis
GO:0007411	axon guidance
GO:0016079	synaptic vesicle exocytosis
GO:0016337	single organismal cell-cell adhesion
GO:0030036	actin cytoskeleton organization
GO:0030593	neutrophil chemotaxis
GO:0034333	adherens junction assembly
GO:0044281	small molecule metabolic process
GO:0046488	phosphatidylinositol metabolic process
GO:0046854	phosphatidylinositol phosphorylation
GO:0048488	synaptic vesicle endocytosis
GO:0072583	clathrin-mediated endocytosis

Cellular Component

GO:0001891	phagocytic cup
GO:0001931	uropod
GO:0005634	nucleus
GO:0005829	cytosol
GO:0005925	focal adhesion
GO:0012505	endomembrane system
GO:0032587	ruffle membrane