BioPAX pathway converted from "PI(3,4)P2 is dephosphorylated to PI3P by INPP4A/B at the early endosome membrane" in the Reactome database.LEFT-TO-RIGHT3.1.3.66PI(3,4)P2 is dephosphorylated to PI3P by INPP4A/B at the early endosome membraneAt the early endosome membrane, type I (INPP4A) (Norris et al. 1995, Ivetac et al. 2005) and type II inositol-3,4-bisphosphate 4-phosphatase (INPP4B) (Norris et al. 1997) colocalise with early and recycling endosomes through their C2 domains which bind to the phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) present in these membranes. It is here that phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) is dephosphorylated by INPP4A/B to phosphatidylinositol 3-phosphate (PI3P).Authored: Williams, MG, 2011-10-18Reviewed: Wakelam, Michael, 2012-05-14Edited: Williams, MG, 2011-08-12PI(3,4)P21-phosphatidyl-1D-myo-inositol 3,4-bisphosphates1-phosphatidyl-1D-myo-inositol 3,4-bisphosphateReactome DB_ID: 1806238early endosome membraneGENE ONTOLOGYGO:00319011-phosphatidyl-1D-myo-inositol 3,4-bisphosphate [ChEBI:16152]1-phosphatidyl-1D-myo-inositol 3,4-bisphosphateChEBICHEBI:16152Reactome Database ID Release 751806238Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1806238ReactomeR-ALL-18062383Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1806238.3Reactomehttp://www.reactome.orgH2OwaterReactome DB_ID: 29356cytosolGENE ONTOLOGYGO:0005829water [ChEBI:15377]waterChEBICHEBI:15377Reactome Database ID Release 7529356Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29356ReactomeR-ALL-293565Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29356.5COMPOUNDC00001additional informationMIMI:0361PI3PPtdIns3P1-phosphatidyl-1D-myo-inositol 3-phosphateReactome DB_ID: 18062001-phosphatidyl-1D-myo-inositol 3-phosphate [ChEBI:17283]1-phosphatidyl-1D-myo-inositol 3-phosphatePtdIns3PPtdIns-3-P1,2-Diacyl-sn-glycero-3-phospho-(1'-myo-inositol-3'-phosphate)Phosphatidylinositol 3-phosphateChEBICHEBI:17283Reactome Database ID Release 751806200Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1806200ReactomeR-ALL-18062003Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1806200.3PiOrthophosphatehydrogenphosphatePhosphateInorganic PhosphateReactome DB_ID: 29372hydrogenphosphate [ChEBI:43474]hydrogenphosphatehydrogen phosphatephosphate[PO3(OH)](2-)INORGANIC PHOSPHATE GROUPHYDROGENPHOSPHATE IONHPO4(2-)[P(OH)O3](2-)ChEBICHEBI:43474Reactome Database ID Release 7529372Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29372ReactomeR-ALL-293724Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29372.4COMPOUNDC00009ACTIVATIONConverted from EntitySet in ReactomeINPP4A/BReactome DB_ID: 1806281INPP4AReactome DB_ID: 1604579UniProt:Q96PE3 INPP4AINPP4AFUNCTION Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) (PubMed:20463662, PubMed:15716355). Catalyzes also inositol 1,3,4-trisphosphate and inositol 1,4-bisphosphate (By similarity). Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (PubMed:30071275) (By similarity). May protect neurons from excitotoxic cell death by regulating the synaptic localization of cell surface N-methyl-D-aspartate-type glutamate receptors (NMDARs) and NMDAR-mediated excitatory postsynaptic current (By similarity).PATHWAY Signal transduction; phosphatidylinositol signaling pathway.SUBUNIT Interacts with INPP5F.TISSUE SPECIFICITY Isoform 1 is expressed in the platelets, MEG-01 megakaryocytes and Jurkat T-cells. Isoform 2 is expressed in the brain.SIMILARITY Belongs to the inositol 3,4-bisphosphate 4-phosphatase family.Homo sapiensNCBI Taxonomy9606UniProtQ96PE31EQUAL977EQUALReactome Database ID Release 751604579Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1604579ReactomeR-HSA-16045791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1604579.1INPP4BReactome DB_ID: 1604582UniProt:O15327 INPP4BINPP4BFUNCTION Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate and inositol 3,4-trisphosphate (PubMed:24070612, PubMed:24591580). Plays a role in the late stages of macropinocytosis by dephosphorylating phosphatidylinositol 3,4-bisphosphate in membrane ruffles (PubMed:24591580). The lipid phosphatase activity is critical for tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (PubMed:19647222, PubMed:24070612).ACTIVITY REGULATION Strongly inhibited by inositol hexakisphosphate.PATHWAY Signal transduction; phosphatidylinositol signaling pathway.TISSUE SPECIFICITY Widely expressed with highest levels occurring in the skeletal muscle and heart.SIMILARITY Belongs to the inositol 3,4-bisphosphate 4-phosphatase family.UniProtO153271EQUAL924EQUALReactome Database ID Release 751604582Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1604582ReactomeR-HSA-16045821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1604582.1Reactome Database ID Release 751806281Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1806281ReactomeR-HSA-18062811Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1806281.1GENE ONTOLOGYGO:0016316gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 751806174Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1806174Reactome Database ID Release 751676162Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1676162ReactomeR-HSA-16761621Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1676162.115716355Pubmed2005The type Ialpha inositol polyphosphate 4-phosphatase generates and terminates phosphoinositide 3-kinase signals on endosomes and the plasma membraneIvetac, IMunday, ADKisseleva, MVZhang, XMLuff, STiganis, TWhisstock, JCRowe, TMajerus, PWMitchell, CAMol Biol Cell 16:2218-337608176Pubmed1995The isolation and characterization of cDNA encoding human and rat brain inositol polyphosphate 4-phosphataseNorris, FAAuethavekiat, VMajerus, PWJ Biol Chem 270:16128-339295334Pubmed1997The cDNA cloning and characterization of inositol polyphosphate 4-phosphatase type II. Evidence for conserved alternative splicing in the 4-phosphatase familyNorris, FAAtkins, RCMajerus, PWJ Biol Chem 272:23859-64