INPP5D
INPP5D (inositol polyphosphate-5-phosphatase D, also known as SHIP1 or SHIP) is a lipid phosphatase that removes the 5-phosphate from PtdIns(3,4,5)P3, restraining PI3K signalling. It is expressed in haematopoietic cells, where it acts as a brake on immune receptor signalling. Browse Assay Genie's current range of INPP5D research reagents below, or read on for the biology behind the target.
INPP5D is a phosphatidylinositol phosphatase that specifically hydrolyses the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating PI3K (phosphoinositide 3-kinase) pathways. It can also hydrolyse the 5-phosphate of PtdIns(4,5)P3, 1D-myo-inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate. Through this activity it terminates signal transduction from activating immune and haematopoietic cell receptor systems, including signalling downstream of the FC-gamma-RIIB receptor (FCGR2B).
The INPP5D gene belongs to the inositol polyphosphate-5-phosphatase (INPP5) family. The encoded protein has an N-terminal SH2 domain, an inositol phosphatase domain and two C-terminal protein interaction domains. Expression is restricted to haematopoietic cells, where tyrosine phosphorylation moves the protein from the cytosol to the plasma membrane. There it hydrolyses PtdIns(3,4,5)P3 and inositol-1,3,4,5-tetrakisphosphate. The protein is also partly nuclear, where it may contribute to nuclear inositol phosphate signalling. Alternative splicing produces multiple transcript variants.
Functionally, INPP5D negatively regulates B-cell antigen receptor signalling, myeloid cell proliferation and survival, chemotaxis, mast cell degranulation, integrin alpha-IIb/beta-3 signalling in platelets and JNK signalling in B-cells. It also regulates osteoclast precursor proliferation, macrophage programming, phagocytosis and activation, and is required for endotoxin tolerance. In neutrophils it governs leading-edge formation and polarisation during migration, and in NK cells it modulates FCGR3/CD16-mediated cytotoxicity. Mutations in the gene are associated with defects and cancers of the immune system, and SHIP1 deficiency has been linked to inflammatory bowel disease, including Crohn's disease and ulcerative colitis.
INPP5D terminates signalling from activating immune and haematopoietic receptors, including B-cell antigen receptor and FCGR2B, making it central to receptor-proximal signalling studies.
By converting PtdIns(3,4,5)P3 to PtdIns(3,4)P2, INPP5D negatively regulates PI3K pathways and is a focus for phosphoinositide signalling research.
INPP5D controls neutrophil leading-edge formation and polarisation, and restrains myeloid cell proliferation, survival and chemotaxis.
SHIP1 deficiency has been associated with Crohn's disease and ulcerative colitis, and gene mutations with immune system defects and cancers.
INPP5D hydrolyses the 5-phosphate of PtdIns(3,4,5)P3 to give PtdIns(3,4)P2, negatively regulating PI3K pathways. It also acts on PtdIns(4,5)P3, inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate, and dampens signalling from B-cell, FCGR2B and other immune receptors.
INPP5D is also called SHIP, SHIP1 and hp51CN, and its UniProt name is phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1. Earlier names were inositol polyphosphate-5-phosphatase, 145kD. Alternative splicing of the gene gives multiple transcript variants.
Mouse and rat both have an Inpp5d ortholog. In humans, mutations in the gene are associated with defects and cancers of the immune system, and SHIP1 deficiency has been linked to Crohn's disease and ulcerative colitis. Check the datasheet of any product for its validated reactivity.
Other inositol polyphosphate phosphatases and phosphoinositide-metabolising enzymes with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q92835; product specifications from Assay Genie datasheets.