INPPL1 - Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 - human protein (Function)
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INPPL1 »  Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2   [ EC ]
Protein also known as:  Inositol polyphosphate phosphatase-like protein 1 (INPPL-1).
Gene name:  INPPL1
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. Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear. While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking. Confers resistance to dietary obesity. May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane. Part of a signaling pathway that regulates actin cytoskeleton remodeling. Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling. Regulates cell adhesion and cell spreading. Required for HGF-mediated lamellipodium formation, cell scattering and spreading. Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation. Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth. Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Involved in EGF signaling pathway. Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3. Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity. Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1. In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification.  
  • CuratedUniProtKB
GO molecular function 
Actin bindingdefinition[GO:0003779]  
  • IEAUniProtKB KW
Hydrolase activitydefinition[GO:0016787]  
  • IEAUniProtKB KW
Protein bindingdefinition[GO:0005515]  
  • IPIIntAct
  • IPIUniProtKB
SH2 domain bindingdefinition[GO:0042169]  
  • IPIUniProtKB
SH3 domain bindingdefinition[GO:0017124]  
  • IEAUniProtKB KW
GO biological process 
Actin filament organizationdefinition[GO:0007015]  
  • IMPUniProtKB
Cell adhesiondefinition[GO:0007155]  
  • TASUniProtKB
Endochondral ossificationdefinition[GO:0001958]  
  • IMPUniProtKB
  • IMPUniProtKB
Glucose metabolic processdefinition[GO:0006006] silver  
  • IEAOrtholog Compara
Immune system processdefinition[GO:0002376]  
  • IEAUniProtKB KW
Negative regulation of cell proliferationdefinition[GO:0008285] silver  
  • IEAOrtholog Compara
Negative regulation of gene expressiondefinition[GO:0010629] silver  
  • IEAOrtholog Compara
Phosphatidylinositol dephosphorylationdefinition[GO:0046856] silver  
  • IEAInterPro 2 GO
Post-embryonic developmentdefinition[GO:0009791] silver  
  • IEAOrtholog Compara
Response to insulindefinition[GO:0032868] silver  
  • IEAOrtholog Compara
Ruffle assemblydefinition[GO:0097178] silver  
  • IEAOrtholog Compara
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. Enzymatic activity is enhanced in the presence of phosphatidylserine.  
  • CuratedUniProtKB
According to KEGG, this protein belongs to the following pathways:
Inositol phosphate metabolism  hsa00562+3636  
Metabolic pathways  hsa01100+3636  
Phosphatidylinositol signaling system  hsa04070+3636  
According to Reactome, this protein belongs to the following pathways:
Interleukin receptor SHC signaling  REACT_23891  
Synthesis of IP3 and IP4 in the cytosol  REACT_150312  
Synthesis of PIPs at the plasma membrane  REACT_121025  
More information is available from:
Its ability to confer resistance to dietary obesity suggests that it may serve as a possible therapeutic target in cases of type 2 diabetes and obesity.  
  • CuratedUniProtKB


Biological process 
Cell adhesion  definition   [KW-0130]
Immunity  definition   [KW-0391]
Molecular function 
Hydrolase  definition   [KW-0378]
Technical term 
Reference proteome  definition   [KW-1185]

Further external links

Enzyme and pathway databases
SABIO-RK: O15357
GeneWiki: INPPL1
GenomeRNAi: 3636
PRO: PR:O15357