InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Inpp5d

Summary

InnateDB Protein

IDBP-627894.2

Last Modified

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

Gene Symbol

Inpp5d

Protein Name

inositol polyphosphate-5-phosphatase D

Synonyms

p150Ship; s-SHIP; SHIP; SHIP-1; SHIP1; SIP-145;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000131244

InnateDB Gene

IDBG-178553 (Inpp5d)

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. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. {ECO:0000269PubMed:11136821, ECO:0000269PubMed:11222379, ECO:0000269PubMed:11359765, ECO:0000269PubMed:11896575, ECO:0000269PubMed:12161749, ECO:0000269PubMed:12370370, ECO:0000269PubMed:12447389, ECO:0000269PubMed:12882960, ECO:0000269PubMed:14993273, ECO:0000269PubMed:15166241, ECO:0000269PubMed:17142780, ECO:0000269PubMed:17173042, ECO:0000269PubMed:8654924, ECO:0000269PubMed:8805703, ECO:0000269PubMed:9244303, ECO:0000269PubMed:9620849, ECO:0000269PubMed:9736736, ECO:0000269PubMed:9763612, ECO:0000269PubMed:9857188}.

Subcellular Localization

Cytoplasm. Cell membrane; Peripheral membrane protein. Note=Translocates to the plasma membrane 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) or CD16/FCGR3. Tyrosine phosphorylation may also participate in membrane localization.Isoform 5: Cell membrane; Peripheral membrane protein. Note=Constitutively present at the cell membrane.

Disease Associations

Tissue Specificity

Specifically expressed in immune and hematopoietic cells. Levels vary considerably within this compartment. Lost during erythropoiesis when erythroid cells become Ter119+. Increases substantially with T-cell maturation and when resting B-cells are activated. Also present in mature granulocytes, monocyte/macrophages, mast cells and platelets. Isoform 5 is the only form expressed in embryonic stem (ES) cells and is coexpressed with other isoforms in hematopoietic stem cells, and disappears with differentiation. {ECO:0000269PubMed:10068665, ECO:0000269PubMed:8643691, ECO:0000269PubMed:8654924, ECO:0000269PubMed:9531585}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 46 experimentally validated interaction(s) in this database.
They are also associated with 39 interaction(s) predicted by orthology.

Experimentally validated
Total	46 [view]
Protein-Protein	46 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	39 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004445	inositol-polyphosphate 5-phosphatase activity
GO:0005515	protein binding
GO:0017124	SH3 domain binding
GO:0034594	phosphatidylinositol trisphosphate phosphatase activity
GO:0051425	PTB domain binding

Biological Process

GO:0006915	apoptotic process
GO:0008285	negative regulation of cell proliferation
GO:0008340	determination of adult lifespan
GO:0009968	negative regulation of signal transduction
GO:0016064	immunoglobulin mediated immune response
GO:0016311	dephosphorylation
GO:0030853	negative regulation of granulocyte differentiation
GO:0030889	negative regulation of B cell proliferation
GO:0035556	intracellular signal transduction
GO:0043065	positive regulation of apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0045409	negative regulation of interleukin-6 biosynthetic process
GO:0045579	positive regulation of B cell differentiation
GO:0045621	positive regulation of lymphocyte differentiation
GO:0045648	positive regulation of erythrocyte differentiation
GO:0045656	negative regulation of monocyte differentiation
GO:0045659	negative regulation of neutrophil differentiation
GO:0045671	negative regulation of osteoclast differentiation
GO:0045779	negative regulation of bone resorption
GO:0046856	phosphatidylinositol dephosphorylation
GO:0050777	negative regulation of immune response
GO:0050869	negative regulation of B cell activation