InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Inppl1

Summary

InnateDB Protein

IDBP-202186.6

Last Modified

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

Gene Symbol

Inppl1

Protein Name

inositol polyphosphate phosphatase-like 1

Synonyms

51C; SHIP2;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000048057

InnateDB Gene

IDBG-202184 (Inppl1)

Protein Structure

UniProt Annotation

Function

Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol- 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear. While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking. Confers resistance to dietary obesity. May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane. Part of a signaling pathway that regulates actin cytoskeleton remodeling. Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling. Regulates cell adhesion and cell spreading. Required for HGF-mediated lamellipodium formation, cell scattering and spreading. Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation. Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth. Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Involved in EGF signaling pathway. Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3. Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity. Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1. In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification (By similarity). {ECO:0000250}.

Subcellular Localization

Cytoplasm, cytosol. Cytoplasm, cytoskeleton {ECO:0000250}. Membrane; Peripheral membrane protein. Cell projection, filopodium {ECO:0000250}. Cell projection, lamellipodium {ECO:0000250}. Note=Translocates to membrane ruffles when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type. Partly translocated via its SH2 domain which mediates interaction with tyrosine phosphorylated receptors such as the FC-gamma-RIIB receptor (FCGR2B). Tyrosine phosphorylation may also participate in membrane localization. Insulin specifically stimulates its redistribution from the cytosol to the plasma membrane. Recruited to the membrane following M-CSF stimulation. In activated spreading platelets, localizes with actin at filopodia, lamellipodia and the central actin ring.

Disease Associations

Tissue Specificity

Widely expressed. {ECO:0000269PubMed:10610720}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 7 experimentally validated interaction(s) in this database.
They are also associated with 61 interaction(s) predicted by orthology.

Experimentally validated
Total	7 [view]
Protein-Protein	7 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	61 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003779	actin binding
GO:0005515	protein binding
GO:0016787	hydrolase activity
GO:0017124	SH3 domain binding
GO:0042169	SH2 domain binding

Biological Process

GO:0001958	endochondral ossification
GO:0002376	immune system process
GO:0006006	glucose metabolic process
GO:0006661	phosphatidylinositol biosynthetic process
GO:0006897	endocytosis
GO:0007015	actin filament organization
GO:0007155	cell adhesion
GO:0008285	negative regulation of cell proliferation
GO:0009791	post-embryonic development
GO:0010629	negative regulation of gene expression
GO:0032868	response to insulin
GO:0044255	cellular lipid metabolic process
GO:0046856	phosphatidylinositol dephosphorylation
GO:0097178	ruffle assembly

Cellular Component

GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0005886	plasma membrane
GO:0030027	lamellipodium
GO:0030175	filopodium

Protein Structure and Domains

PDB ID

MGI:1333787

InterPro

IPR000300 Inositol polyphosphate-related phosphatase
IPR000980 SH2 domain
IPR001660 Sterile alpha motif domain
IPR005135 Endonuclease/exonuclease/phosphatase
IPR011510 Sterile alpha motif, type 2
IPR013761 Sterile alpha motif/pointed domain
IPR021129 Sterile alpha motif, type 1

PFAM

PF00017
PF14633
PF03372
PF14529
PF07647
PF00536

PRINTS

PR00401

PIRSF

SMART

SM00128
SM00252
SM00454

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt