INPP5D

This gene is a member of the inositol polyphosphate-5-phosphatase (INPP5) family and encodes a protein with an N-terminal SH2 domain, an inositol phosphatase domain, and two C-terminal protein interaction domains. Expression of this protein is restricted to hematopoietic cells where its movement from the cytosol to the plasma membrane is mediated by tyrosine phosphorylation. At the plasma membrane, the protein hydrolyzes the 5' phosphate from phosphatidylinositol (3,4,5)-trisphosphate and inositol-1,3,4,5-tetrakisphosphate, thereby affecting multiple signaling pathways. The protein is also partly localized to the nucleus, where it may be involved in nuclear inositol phosphate signaling processes. Overall, the protein functions as a negative regulator of myeloid cell proliferation and survival. Mutations in this gene are associated with defects and cancers of the immune system. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

Inositol Polyphosphate-5-Phosphatase D

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 (PubMed:8723348, PubMed:10764818, PubMed:8769125).
Able also to hydrolyzes the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (PubMed:9108392, PubMed:10764818, PubMed:8769125).
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 (PubMed:16682172).
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.

Apoptotic processIEA:UniProtKB-KW
Determination of adult lifespanIEA:Ensembl
Immunoglobulin mediated immune responseIEA:Ensembl
Intracellular signal transductionIEA:Ensembl
Negative regulation of B cell proliferationIEA:Ensembl
Negative regulation of bone resorptionIEA:Ensembl
Negative regulation of immune responseIEA:Ensembl
Negative regulation of interleukin-6 productionIEA:Ensembl
Negative regulation of monocyte differentiationIEA:Ensembl
Negative regulation of neutrophil differentiationIEA:Ensembl
Negative regulation of osteoclast differentiationIEA:Ensembl
Negative regulation of signal transductionIEA:Ensembl
Phosphate-containing compound metabolic processManual Assertion Based On ExperimentTAS:ProtInc
Phosphatidylinositol biosynthetic processTAS:Reactome
Phosphatidylinositol dephosphorylationIEA:InterPro
Positive regulation of apoptotic processIEA:Ensembl
Positive regulation of B cell differentiationIEA:Ensembl
Positive regulation of erythrocyte differentiationIEA:Ensembl
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
T cell receptor signaling pathwayTAS:Reactome

Cytoplasm; Cell membrane; Membrane raft; Cytoplasm, cytoskeleton; Membrane. Translocates to the plasma membrane when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type. Translocates from the cytoplasm to membrane ruffles in a FCGR3/CD16-dependent manner. Colocalizes with FC-gamma-RIIB receptor (FCGR2B) or FCGR3/CD16 at membrane ruffles. Tyrosine phosphorylation may also participate in membrane localization.

Tyrosine phosphorylated by the members of the SRC family after exposure to a diverse array of extracellular stimuli such as cytokines, growth factors, antibodies, chemokines, integrin ligands and hypertonic and oxidative stress. Phosphorylated upon IgG receptor FCGR2B-binding.