InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: INPP5D

Summary

InnateDB Protein

IDBP-83443.6

Last Modified

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

Gene Symbol

INPP5D

Protein Name

inositol polyphosphate-5-phosphatase, 145kDa

Synonyms

hp51CN; p150Ship; SHIP; SHIP-1; SHIP1; SIP-145;

Species

Homo sapiens

Ensembl Protein

ENSP00000352575

InnateDB Gene

IDBG-83441 (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:12421919, ECO:0000269PubMed:16682172}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:10822173}. Membrane {ECO:0000269PubMed:10822173}; Peripheral membrane protein {ECO:0000269PubMed:10822173}. 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 (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Specifically expressed in immune and hematopoietic cells. Expressed in bone marrow and blood cells. Levels vary considerably within this compartment. Present in at least 74% of immature CD34+ cells, whereas within the more mature population of CD33+ cells, it is present in only 10% of cells. Present in the majority of T-cells, while it is present in a minority of B-cells (at protein level). {ECO:0000269PubMed:8769125, ECO:0000269PubMed:8874179, ECO:0000269PubMed:9058707, ECO:0000269PubMed:9108392}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 58 experimentally validated interaction(s) in this database.
They are also associated with 29 interaction(s) predicted by orthology.

Experimentally validated
Total	58 [view]
Protein-Protein	58 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	29 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding

Biological Process

GO:0006644	phospholipid metabolic process
GO:0006661	phosphatidylinositol biosynthetic process
GO:0006796	phosphate-containing compound metabolic process
GO:0006915	apoptotic process
GO:0007165	signal transduction
GO:0007596	blood coagulation
GO:0043647	inositol phosphate metabolic process
GO:0044281	small molecule metabolic process
GO:0045087	innate immune response (InnateDB)
GO:0046856	phosphatidylinositol dephosphorylation
GO:0050852	T cell receptor signaling pathway
GO:0050900	leukocyte migration