INPP5D - Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 - human protein (Function)
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INPP5D »  Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1   [ EC ]
Protein also known as:  SH2 domain-containing inositol 5'-phosphatase 1 (SHIP-1).
Gene name:  INPP5D
Entry whose protein(s) existence is based on evidence at protein level
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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.  
  • CuratedUniProtKB
GO molecular function 
Inositol-polyphosphate 5-phosphatase activitydefinition[GO:0004445] silver  
  • IEAOrtholog Compara
Phosphatidylinositol trisphosphate phosphatase activitydefinition[GO:0034594] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
  • IPIUniProtKB
  • IPIIntAct
PTB domain bindingdefinition[GO:0051425] silver  
  • IEAOrtholog Compara
SH3 domain bindingdefinition[GO:0017124] silver  
  • IEAOrtholog Compara
GO biological process 
Apoptotic processdefinition[GO:0006915]  
  • IEAUniProtKB KW
Determination of adult lifespandefinition[GO:0008340] silver  
  • IEAOrtholog Compara
Immunoglobulin mediated immune responsedefinition[GO:0016064] silver  
  • IEAOrtholog Compara
Intracellular signal transductiondefinition[GO:0035556] silver  
  • IEAOrtholog Compara
Negative regulation of B cell proliferationdefinition[GO:0030889] silver  
  • IEAOrtholog Compara
Negative regulation of bone resorptiondefinition[GO:0045779] silver  
  • IEAOrtholog Compara
Negative regulation of immune responsedefinition[GO:0050777] silver  
  • IEAOrtholog Compara
Negative regulation of interleukin-6 biosynthetic processdefinition[GO:0045409] silver  
  • IEAOrtholog Compara
Negative regulation of monocyte differentiationdefinition[GO:0045656] silver  
  • IEAOrtholog Compara
Negative regulation of neutrophil differentiationdefinition[GO:0045659] silver  
  • IEAOrtholog Compara
Negative regulation of osteoclast differentiationdefinition[GO:0045671] silver  
  • IEAOrtholog Compara
Negative regulation of signal transductiondefinition[GO:0009968] silver  
  • IEAOrtholog Compara
Phosphate-containing compound metabolic processdefinition[GO:0006796]  
Phosphatidylinositol dephosphorylationdefinition[GO:0046856] silver  
  • IEAInterPro 2 GO
Positive regulation of apoptotic processdefinition[GO:0043065] silver  
  • IEAOrtholog Compara
Positive regulation of B cell differentiationdefinition[GO:0045579] silver  
  • IEAOrtholog Compara
Positive regulation of erythrocyte differentiationdefinition[GO:0045648] silver  
  • IEAOrtholog Compara
Signal transductiondefinition[GO:0007165]  
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate + H(2)O 1-phosphatidyl-1D-myo-inositol 3,4-diphosphate + phosphate.  
  • CuratedUniProtKB
It is regulated in the following manner
Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane (By similarity).  
  • CuratedUniProtKB
According to KEGG, this protein belongs to the following pathways:
B cell receptor signaling pathway  hsa04662+3635  
Fc epsilon RI signaling pathway  hsa04664+3635  
Fc gamma R-mediated phagocytosis  hsa04666+3635  
Insulin signaling pathway  hsa04910+3635  
Phosphatidylinositol signaling system  hsa04070+3635  
According to Reactome, this protein belongs to the following pathways:
Downstream TCR signaling  REACT_12555  
Interleukin receptor SHC signaling  REACT_23891  
PECAM1 interactions  REACT_12519  
Synthesis of IP3 and IP4 in the cytosol  REACT_150312  
Synthesis of PIPs at the plasma membrane  REACT_121025  
More information is available from:


Biological process 
Apoptosis  definition   [KW-0053]
Immunity  definition   [KW-0391]
Molecular function 
Hydrolase  definition   [KW-0378]
Technical term 
Reference proteome  definition   [KW-1185]

Further external links

GeneWiki: INPP5D
GenomeRNAi: 3635
PRO: PR:Q92835