Inositol phosphate metabolism (Homo sapiens)

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44, 45, 50, 65, 6640, 489, 472621, 27, 5637, 4221, 27, 5621, 2743, 514942, 43, 511, 3, 4, 8, 46...11, 13, 31, 49, 59...27, 566, 14, 21, 27675, 28, 33, 41262726, 4211, 13, 31, 49, 59...21, 274726, 32, 426711, 13, 31, 49, 59...556, 10, 14, 24, 6310, 29, 3214, 277, 19, 20, 5434, 385, 3396, 10, 14, 6321, 27, 562627, 565, 3314, 27405, 3326, 32, 4214, 21, 2710, 29, 3218, 2311, 13, 31, 49, 59...5, 33, 4210, 29, 3242, 5137, 422, 15, 30, 36, 39...3721, 27, 565, 3312, 17, 20, 22, 25...7, 19, 203342, 513363264016, 3512, 20, 22, 2518, 2314, 275, 33PLCD3:Ca2+ [plasmamembrane]NUDT3:Mg2+ [cytosol]ITPK1:Mg2+ [cytosol]PLCZ1:Ca2+ [cytosol]PLCdegh [plasmamembrane]PLCB4:Ca2+ [cytosol]Mg2+/Mn2+ [cytosol]ITPKB:Ca2+:CALM1[cytosol]IMPA1:Mg2+ [cytosol]PLCH1:Ca2+ [plasmamembrane]Mg2+/Mn2+ [cytosol]PLCH2:Ca2+ [plasmamembrane]NUDT3:Mg2+ [cytosol]Mg2+/Mn2+ [cytosol]NUDT3:Mg2+ [cytosol]Mg2+/Mn2+ [cytosol]IMPA1 dimer[cytosol]ITPKA:Ca2+:CALM1[cytosol]endoplasmic reticulum lumenIMPA2 dimer[cytosol]NUDT4:Mg2+/Mn2+[cytosol]PLCG1:Ca2+ [plasmamembrane]NUDT(1) [cytosol]NUDT4:Mg2+/Mn2+[cytosol]NUDT10:Mg2+/Mn2+[cytosol]PLCB3:Ca2+ [cytosol]IMPA1:Mg2+ [cytosol]PTEN:Mg2+ [cytosol]PLCD4:Ca2+[endoplasmicreticulum membrane]IMPA2:Mg2+ [cytosol]INPP1:Mg2+ [cytosol]ITPKA/B/C [cytosol]PLCB2:Ca2+ [cytosol]PLCbz [cytosol]ITPKC:Ca2+:CALM1[cytosol]IMPA2:Mg2+ [cytosol]NUDT4:Mg2+/Mn2+[cytosol]PLCB1:Ca2+ [cytosol]NUDT11:Mg2+/Mn2+[cytosol]INPP1:Mg2+ [cytosol]IMPA1 dimer[cytosol]endoplasmic reticulum lumenMg2+/Mn2+ [cytosol]nucleoplasmNUDT11:Mg2+/Mn2+[cytosol]PLCD1:Ca2+ [plasmamembrane]NUDT3:Mg2+ [cytosol]NUDT11:Mg2+/Mn2+[cytosol]NUDT4:Mg2+/Mn2+[cytosol]NUDT(1) [cytosol]NUDT11:Mg2+/Mn2+[cytosol]NUDT10:Mg2+/Mn2+[cytosol]NUDT10:Mg2+/Mn2+[cytosol]ITPK1:Mg2+ [cytosol]PLCG2:Ca2+ [plasmamembrane]NUDT4:Mg2+/Mn2+[cytosol]PLCE1:Ca2+ [plasmamembrane]cytosolITPK1:Mg2+ [cytosol]IMPA1/2 [cytosol]NUDT(1) [cytosol]ISYNA1:NAD+[cytosol]NUDT(1) [cytosol]NUDT10:Mg2+/Mn2+[cytosol]ITPK1:Mg2+ [cytosol]IMPA1/2 [cytosol]IMPA2 dimer[cytosol]H2OITPK1 [cytosol]ATPH2OITPK1:Mg2+H2OATPIMPA1 [cytosol]Mg2+ [cytosol]IP6I(3,4,5,6)P4I(1,3,4,5,6)P5INPP1 [cytosol]H2OMg2+ [cytosol]H2OINPP1:Mg2+ADPINPP1:Mg2+PiADPPLCD1 [plasmamembrane]NAD+ [cytosol]Mg2+ [cytosol]NUDT11 [cytosol]PiATPPTEN:Mg2+H2OPiPLCbzMn2+ [cytosol]ADPNUDT10 [cytosol]NUDT3 [cytosol]ITPKC [cytosol]Mg2+ [cytosol]INPP4A/B5-PPP-IP5IPPKMg2+ [cytosol]I(1,3,4)P3I4PPLCB1 [cytosol]IPMK(1-416)1,5-(PP)2-IP3ADPI(1,2,4,5,6)P5PiADPMg2+ [cytosol]Mn2+ [cytosol]ATPNUDT10 [cytosol]PTEN [cytosol]ATP1-PP-IP5PLD4(1-762)[endoplasmicreticulum membrane]1-PP-IP5ISYNA1:NAD+ADPPiPLCB4 [cytosol]NUDT11 [cytosol]NUDT4 [cytosol]1,5-(PP)2-IP4I(1,4)P2PLCdegh1-PP-IP4H2OIMPA1/25-PP-IP5PiPiI(1,3,4,5)P4Mn2+ [cytosol]ISYNA1 [cytosol]Ca2+ [cytosol]5-PP-IP5H2OITPKB [cytosol]Mg2+ [cytosol]H2ONUDT10 [cytosol]I3PMg2+ [cytosol]ATPPLCE1 [plasmamembrane]PiATPADPH2ONUDT4 [cytosol]H2OITPK1:Mg2+5-PPP-IP5I(3,4,6)P3PI(4,5)P2ITPK1 [cytosol]H2OH2ONUDT11 [cytosol]NUDT3 [cytosol]NUDT(1)IPPKI(1,4,5,6)P4ATPITPK1 [cytosol]IPMK(1-416)PLCD3 [plasmamembrane]ATPIP6K1/2PLCB3(2-1234)[cytosol]H2OPLCG2 [plasmamembrane]PI(4,5)P2InsPLCH1 [plasmamembrane]ADPH2ONUDT(1)PP-IP4ATPINPP5B(321-993)IP6K1/3I(1,3,4,6)P4PLCD4:Ca2+IP6K1/2IMPA2 [cytosol]H2OI(1,3,4,5)P4PLCZ1 [cytosol]ATPPiNUDT4 [cytosol]I1P1,5-(PP)2-IP4IMPA1/2NUDT4 [cytosol]I(1,4,5)P3MINPP1IP6K1/21/3-PP-IP5Mg2+ [cytosol]1/3-PP-IP5ITPKA [cytosol]ADPI(1,4,5)P3Mg2+ [cytosol]PPIP5K1/2ADPADPINPP5(3)/ITPK1PiPiPiINPP4A/BI(1,3,4,5,6)P5Mg2+ [cytosol]H2OIP6Ca2+ [plasmamembrane]INPP1 [cytosol]PiADPATPDAGADPNUDT4 [cytosol]ADPH2ODAG and IP3signaling(PP)2-IP4NUDT4:Mg2+/Mn2+Pi5-PP-IP4MINPP1ATPCALM1 [cytosol]ADPCa2+ [cytosol]NUDT3 [cytosol]IP6K1/3PLCH2 [plasmamembrane]ATPIP6ATPIP6K1/3ITPK1:Mg2+INPP5A/BITPK1 [cytosol]1,5-(PP)2-IP3ITPKA/B/CI(1,3,4,5,6)P5IMPA1 [cytosol]PLCG1(2-1290)[plasma membrane]NUDT11 [cytosol]H2OI(1,3,4,6)P4ATPNUDT(1)IPMK(1-416)5-PP-IP4(PP)2-IP4H2OATPADPMn2+ [cytosol]I(1,4,5)P3H2OADPH2OGlc6PCa2+ [endoplasmicreticulum membrane]I(1,4,5,6)P4PiPLCB2 [cytosol]IMPA2 [cytosol]IP6K1/3Mn2+ [cytosol]I(1,3)P2Mg2+ [cytosol]PiITPK1:Mg2+ATPMg2+ [cytosol]Mg2+ [cytosol]ATPPiADPADPADPNUDT(1)I(3,4)P2NUDT10 [cytosol]INPP5(4)DAGNUDT3 [cytosol]PiADPI(1,3,4,5)P4Pi64


Description

Inositol phosphates (IPs) are molecules involves in signalling processes in eukaryotes. myo-Inositol consists of a six-carbon cyclic alcohol with an axial 2-hydroxy and five equatorial hydroxyls. Mono-, di-, and triphosphorylation of the inositol ring generates a wide variety of stereochemically distinct signalling entities. Inositol 1,4,5-trisphosphate (I(1,4,5)P3), is formed when the phosphoinositide phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is hydrolysed by a phospholipase C isozyme. An array of inositol trisphosphate (IP3) and tetrakisphosphate (IP4) molecules are synthesised by the action of various kinases and phosphatases in the cytosol. These species then transport between the cytosol and the nucleus where they are acted on by inositol polyphosphate multikinase (IPMK), inositol-pentakisphosphate 2-kinase (IPPK), inositol hexakisphosphate kinase 1 (IP6K1) and 2 (IP6K2), to produce IP5, IP6, IP7, and IP8 molecules. Some of these nuclear produced IPs transport back to the cytosol where they are converted to an even wider variety of IPs, by kinases and phosphatases, including the di- and triphospho inositol phosphates aka pyrophosphates (Irvine & Schell 2001, Bunney & Katan 2010, Alcazar-Romain & Wente 2008, York 2006, Monserrate and York 2010).Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=1483249

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Bibliography

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History

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114963view16:49, 25 January 2021ReactomeTeamReactome version 75
113407view11:48, 2 November 2020ReactomeTeamReactome version 74
112610view15:58, 9 October 2020ReactomeTeamReactome version 73
101526view11:39, 1 November 2018ReactomeTeamreactome version 66
101061view21:21, 31 October 2018ReactomeTeamreactome version 65
100592view19:55, 31 October 2018ReactomeTeamreactome version 64
100141view16:40, 31 October 2018ReactomeTeamreactome version 63
99691view15:09, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99279view12:45, 31 October 2018ReactomeTeamreactome version 62
93768view13:34, 16 August 2017ReactomeTeamreactome version 61
93292view11:19, 9 August 2017ReactomeTeamreactome version 61
87135view18:50, 18 July 2016MkutmonOntology Term : 'inositol phosphate metabolic pathway' added !
86378view09:16, 11 July 2016ReactomeTeamreactome version 56
83150view10:10, 18 November 2015ReactomeTeamVersion54
81502view13:02, 21 August 2015ReactomeTeamVersion53
76978view08:26, 17 July 2014ReactomeTeamFixed remaining interactions
76683view12:05, 16 July 2014ReactomeTeamFixed remaining interactions
76010view10:07, 11 June 2014ReactomeTeamRe-fixing comment source
75718view11:08, 10 June 2014ReactomeTeamReactome 48 Update
75070view13:58, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74715view08:47, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
(PP)2-IP4MetaboliteREACT_151108 (Reactome)
(PP)2-IP4MetaboliteREACT_151687 (Reactome)
1,5-(PP)2-IP3MetaboliteCHEBI:62931 (ChEBI)
1,5-(PP)2-IP4MetaboliteCHEBI:62923 (ChEBI)
1-PP-IP4MetaboliteCHEBI:62926 (ChEBI)
1-PP-IP5MetaboliteCHEBI:62919 (ChEBI)
1/3-PP-IP5MetaboliteREACT_151826 (Reactome)
1/3-PP-IP5MetaboliteREACT_152042 (Reactome)
5-PP-IP4MetaboliteCHEBI:62928 (ChEBI)
5-PP-IP5MetaboliteCHEBI:30164 (ChEBI)
5-PPP-IP5MetaboliteCHEBI:62985 (ChEBI)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
CALM1 [cytosol]ProteinP62158 (Uniprot-TrEMBL)
Ca2+ [cytosol]MetaboliteCHEBI:29108 (ChEBI)
Ca2+ [endoplasmic reticulum membrane]MetaboliteCHEBI:29108 (ChEBI)
Ca2+ [plasma membrane]MetaboliteCHEBI:29108 (ChEBI)
DAG and IP3 signalingPathwayWP2688 (WikiPathways) This pathway describes the generation of DAG and IP3 by the PLCgamma-mediated hydrolysis of PIP2 and the subsequent downstream signaling events.
DAGMetaboliteCHEBI:17815 (ChEBI)
Glc6PMetaboliteCHEBI:4170 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
I(1,2,4,5,6)P5MetaboliteCHEBI:16507 (ChEBI)
I(1,3)P2MetaboliteCHEBI:18225 (ChEBI)
I(1,3,4)P3MetaboliteCHEBI:18228 (ChEBI)
I(1,3,4,5)P4MetaboliteCHEBI:16783 (ChEBI)
I(1,3,4,5,6)P5MetaboliteCHEBI:16322 (ChEBI)
I(1,3,4,6)P4MetaboliteCHEBI:16155 (ChEBI)
I(1,4)P2MetaboliteCHEBI:17816 (ChEBI)
I(1,4,5)P3MetaboliteCHEBI:16595 (ChEBI)
I(1,4,5,6)P4MetaboliteCHEBI:16067 (ChEBI)
I(3,4)P2MetaboliteCHEBI:28858 (ChEBI)
I(3,4,5,6)P4MetaboliteCHEBI:15844 (ChEBI)
I(3,4,6)P3MetaboliteCHEBI:62918 (ChEBI)
I1PMetaboliteCHEBI:18297 (ChEBI)
I3PMetaboliteCHEBI:18169 (ChEBI)
I4PMetaboliteCHEBI:18384 (ChEBI)
IMPA1 [cytosol]ProteinP29218 (Uniprot-TrEMBL)
IMPA1/2ComplexREACT_151896 (Reactome)
IMPA2 [cytosol]ProteinO14732 (Uniprot-TrEMBL)
INPP1 [cytosol]ProteinP49441 (Uniprot-TrEMBL)
INPP1:Mg2+ComplexREACT_150912 (Reactome)
INPP4A/BProteinREACT_121439 (Reactome)
INPP5(3)/ITPK1ProteinREACT_152089 (Reactome)
INPP5(4)ProteinREACT_151616 (Reactome)
INPP5A/BProteinREACT_152071 (Reactome)
INPP5B(321-993)ProteinP32019 (Uniprot-TrEMBL)
IP6MetaboliteCHEBI:17401 (ChEBI)
IP6K1/2ProteinREACT_151275 (Reactome)
IP6K1/3ProteinREACT_151004 (Reactome)
IPMK(1-416)ProteinQ8NFU5 (Uniprot-TrEMBL)
IPPKProteinQ9H8X2 (Uniprot-TrEMBL)
ISYNA1 [cytosol]ProteinQ9NPH2 (Uniprot-TrEMBL)
ISYNA1:NAD+ComplexREACT_150931 (Reactome)
ITPK1 [cytosol]ProteinQ13572 (Uniprot-TrEMBL)
ITPK1:Mg2+ComplexREACT_150860 (Reactome)
ITPKA [cytosol]ProteinP23677 (Uniprot-TrEMBL)
ITPKA/B/CComplexREACT_150733 (Reactome)
ITPKB [cytosol]ProteinP27987 (Uniprot-TrEMBL)
ITPKC [cytosol]ProteinQ96DU7 (Uniprot-TrEMBL)
InsMetaboliteCHEBI:17268 (ChEBI)
MINPP1ProteinQ9UNW1 (Uniprot-TrEMBL)
Mg2+ [cytosol]MetaboliteCHEBI:18420 (ChEBI)
Mn2+ [cytosol]MetaboliteCHEBI:18291 (ChEBI)
NAD+ [cytosol]MetaboliteCHEBI:15846 (ChEBI)
NUDT(1)ComplexREACT_151416 (Reactome)
NUDT10 [cytosol]ProteinQ8NFP7 (Uniprot-TrEMBL)
NUDT11 [cytosol]ProteinQ96G61 (Uniprot-TrEMBL)
NUDT3 [cytosol]ProteinO95989 (Uniprot-TrEMBL)
NUDT4 [cytosol]ProteinQ9NZJ9 (Uniprot-TrEMBL)
NUDT4:Mg2+/Mn2+ComplexREACT_151588 (Reactome)
PI(4,5)P2MetaboliteCHEBI:18348 (ChEBI)
PLCB1 [cytosol]ProteinQ9NQ66 (Uniprot-TrEMBL)
PLCB2 [cytosol]ProteinQ00722 (Uniprot-TrEMBL)
PLCB3(2-1234) [cytosol]ProteinQ01970 (Uniprot-TrEMBL)
PLCB4 [cytosol]ProteinQ15147 (Uniprot-TrEMBL)
PLCD1 [plasma membrane]ProteinP51178 (Uniprot-TrEMBL)
PLCD3 [plasma membrane]ProteinQ8N3E9 (Uniprot-TrEMBL)
PLCD4:Ca2+ComplexREACT_151453 (Reactome)
PLCE1 [plasma membrane]ProteinQ9P212 (Uniprot-TrEMBL)
PLCG1(2-1290) [plasma membrane]ProteinP19174 (Uniprot-TrEMBL)
PLCG2 [plasma membrane]ProteinP16885 (Uniprot-TrEMBL)
PLCH1 [plasma membrane]ProteinQ4KWH8 (Uniprot-TrEMBL)
PLCH2 [plasma membrane]ProteinO75038 (Uniprot-TrEMBL)
PLCZ1 [cytosol]ProteinQ86YW0 (Uniprot-TrEMBL)
PLCbzComplexREACT_151954 (Reactome)
PLCdeghComplexREACT_151148 (Reactome)
PLD4(1-762)

[endoplasmic

reticulum membrane]		ProteinQ96BZ4 (Uniprot-TrEMBL)
PP-IP4MetaboliteREACT_150700 (Reactome)
PPIP5K1/2ProteinREACT_152423 (Reactome)
PTEN [cytosol]ProteinP60484 (Uniprot-TrEMBL)
PTEN:Mg2+ComplexREACT_12877 (Reactome)
PiMetaboliteCHEBI:18367 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
(PP)2-IP4ArrowREACT_150419 (Reactome)
(PP)2-IP4REACT_150184 (Reactome)
(PP)2-IP4REACT_150371 (Reactome)
(PP)2-IP4REACT_150419 (Reactome)
1,5-(PP)2-IP3ArrowREACT_150313 (Reactome)
1,5-(PP)2-IP3ArrowREACT_150415 (Reactome)
1,5-(PP)2-IP4ArrowREACT_150168 (Reactome)
1,5-(PP)2-IP4ArrowREACT_150291 (Reactome)
1,5-(PP)2-IP4ArrowREACT_150348 (Reactome)
1-PP-IP4REACT_150415 (Reactome)
1-PP-IP5ArrowREACT_150370 (Reactome)
1-PP-IP5REACT_150168 (Reactome)
1-PP-IP5REACT_150348 (Reactome)
1/3-PP-IP5ArrowREACT_150212 (Reactome)
1/3-PP-IP5ArrowREACT_150371 (Reactome)
1/3-PP-IP5REACT_150167 (Reactome)
1/3-PP-IP5REACT_150212 (Reactome)
5-PP-IP4ArrowREACT_150336 (Reactome)
5-PP-IP4ArrowREACT_150356 (Reactome)
5-PP-IP4ArrowREACT_150450 (Reactome)
5-PP-IP4REACT_150313 (Reactome)
5-PP-IP4REACT_150356 (Reactome)
5-PP-IP5ArrowREACT_150150 (Reactome)
5-PP-IP5ArrowREACT_150153 (Reactome)
5-PP-IP5ArrowREACT_150184 (Reactome)
5-PP-IP5ArrowREACT_150465 (Reactome)
5-PP-IP5REACT_150137 (Reactome)
5-PP-IP5REACT_150145 (Reactome)
5-PP-IP5REACT_150150 (Reactome)
5-PP-IP5REACT_150291 (Reactome)
5-PP-IP5REACT_150467 (Reactome)
5-PPP-IP5ArrowREACT_150137 (Reactome)
5-PPP-IP5ArrowREACT_150145 (Reactome)
ADPArrowREACT_150137 (Reactome)
ADPArrowREACT_150145 (Reactome)
ADPArrowREACT_150153 (Reactome)
ADPArrowREACT_150157 (Reactome)
ADPArrowREACT_150168 (Reactome)
ADPArrowREACT_150202 (Reactome)
ADPArrowREACT_150236 (Reactome)
ADPArrowREACT_150254 (Reactome)
ADPArrowREACT_150282 (Reactome)
ADPArrowREACT_150291 (Reactome)
ADPArrowREACT_150313 (Reactome)
ADPArrowREACT_150321 (Reactome)
ADPArrowREACT_150336 (Reactome)
ADPArrowREACT_150348 (Reactome)
ADPArrowREACT_150360 (Reactome)
ADPArrowREACT_150368 (Reactome)
ADPArrowREACT_150370 (Reactome)
ADPArrowREACT_150383 (Reactome)
ADPArrowREACT_150392 (Reactome)
ADPArrowREACT_150415 (Reactome)
ADPArrowREACT_150431 (Reactome)
ADPArrowREACT_150450 (Reactome)
ADPArrowREACT_150465 (Reactome)
ATPREACT_150137 (Reactome)
ATPREACT_150145 (Reactome)
ATPREACT_150153 (Reactome)
ATPREACT_150157 (Reactome)
ATPREACT_150168 (Reactome)
ATPREACT_150202 (Reactome)
ATPREACT_150236 (Reactome)
ATPREACT_150254 (Reactome)
ATPREACT_150282 (Reactome)
ATPREACT_150291 (Reactome)
ATPREACT_150313 (Reactome)
ATPREACT_150321 (Reactome)
ATPREACT_150336 (Reactome)
ATPREACT_150348 (Reactome)
ATPREACT_150360 (Reactome)
ATPREACT_150368 (Reactome)
ATPREACT_150370 (Reactome)
ATPREACT_150383 (Reactome)
ATPREACT_150392 (Reactome)
ATPREACT_150415 (Reactome)
ATPREACT_150431 (Reactome)
ATPREACT_150450 (Reactome)
ATPREACT_150465 (Reactome)
DAGArrowREACT_150317 (Reactome)
DAGArrowREACT_150328 (Reactome)
DAGArrowREACT_150377 (Reactome)
Glc6PREACT_150300 (Reactome)
H2OREACT_150158 (Reactome)
H2OREACT_150167 (Reactome)
H2OREACT_150176 (Reactome)
H2OREACT_150184 (Reactome)
H2OREACT_150193 (Reactome)
H2OREACT_150198 (Reactome)
H2OREACT_150200 (Reactome)
H2OREACT_150218 (Reactome)
H2OREACT_150220 (Reactome)
H2OREACT_150231 (Reactome)
H2OREACT_150242 (Reactome)
H2OREACT_150296 (Reactome)
H2OREACT_150309 (Reactome)
H2OREACT_150317 (Reactome)
H2OREACT_150323 (Reactome)
H2OREACT_150328 (Reactome)
H2OREACT_150329 (Reactome)
H2OREACT_150330 (Reactome)
H2OREACT_150347 (Reactome)
H2OREACT_150351 (Reactome)
H2OREACT_150358 (Reactome)
H2OREACT_150371 (Reactome)
H2OREACT_150377 (Reactome)
H2OREACT_150382 (Reactome)
H2OREACT_150429 (Reactome)
H2OREACT_150467 (Reactome)
I(1,2,4,5,6)P5ArrowREACT_150382 (Reactome)
I(1,3)P2ArrowREACT_150198 (Reactome)
I(1,3,4)P3ArrowREACT_150158 (Reactome)
I(1,3,4)P3ArrowREACT_150220 (Reactome)
I(1,3,4)P3ArrowREACT_150351 (Reactome)
I(1,3,4)P3REACT_150157 (Reactome)
I(1,3,4)P3REACT_150176 (Reactome)
I(1,3,4)P3REACT_150198 (Reactome)
I(1,3,4)P3REACT_150236 (Reactome)
I(1,3,4,5)P4ArrowREACT_150236 (Reactome)
I(1,3,4,5)P4ArrowREACT_150282 (Reactome)
I(1,3,4,5)P4ArrowREACT_150307 (Reactome)
I(1,3,4,5)P4ArrowREACT_150392 (Reactome)
I(1,3,4,5)P4ArrowREACT_150413 (Reactome)
I(1,3,4,5)P4REACT_150158 (Reactome)
I(1,3,4,5)P4REACT_150220 (Reactome)
I(1,3,4,5)P4REACT_150242 (Reactome)
I(1,3,4,5)P4REACT_150254 (Reactome)
I(1,3,4,5)P4REACT_150307 (Reactome)
I(1,3,4,5)P4REACT_150358 (Reactome)
I(1,3,4,5)P4REACT_150413 (Reactome)
I(1,3,4,5,6)P5ArrowREACT_150140 (Reactome)
I(1,3,4,5,6)P5ArrowREACT_150202 (Reactome)
I(1,3,4,5,6)P5ArrowREACT_150233 (Reactome)
I(1,3,4,5,6)P5ArrowREACT_150254 (Reactome)
I(1,3,4,5,6)P5ArrowREACT_150309 (Reactome)
I(1,3,4,5,6)P5ArrowREACT_150321 (Reactome)
I(1,3,4,5,6)P5ArrowREACT_150342 (Reactome)
I(1,3,4,5,6)P5ArrowREACT_150368 (Reactome)
I(1,3,4,5,6)P5ArrowREACT_150404 (Reactome)
I(1,3,4,5,6)P5REACT_150140 (Reactome)
I(1,3,4,5,6)P5REACT_150233 (Reactome)
I(1,3,4,5,6)P5REACT_150329 (Reactome)
I(1,3,4,5,6)P5REACT_150330 (Reactome)
I(1,3,4,5,6)P5REACT_150336 (Reactome)
I(1,3,4,5,6)P5REACT_150342 (Reactome)
I(1,3,4,5,6)P5REACT_150360 (Reactome)
I(1,3,4,5,6)P5REACT_150383 (Reactome)
I(1,3,4,5,6)P5REACT_150404 (Reactome)
I(1,3,4,5,6)P5REACT_150450 (Reactome)
I(1,3,4,6)P4ArrowREACT_150157 (Reactome)
I(1,3,4,6)P4ArrowREACT_150431 (Reactome)
I(1,3,4,6)P4ArrowREACT_150457 (Reactome)
I(1,3,4,6)P4REACT_150200 (Reactome)
I(1,3,4,6)P4REACT_150351 (Reactome)
I(1,3,4,6)P4REACT_150368 (Reactome)
I(1,3,4,6)P4REACT_150457 (Reactome)
I(1,4)P2ArrowREACT_150347 (Reactome)
I(1,4)P2ArrowREACT_150429 (Reactome)
I(1,4)P2REACT_150296 (Reactome)
I(1,4,5)P3ArrowREACT_150242 (Reactome)
I(1,4,5)P3ArrowREACT_150270 (Reactome)
I(1,4,5)P3ArrowREACT_150317 (Reactome)
I(1,4,5)P3ArrowREACT_150328 (Reactome)
I(1,4,5)P3ArrowREACT_150358 (Reactome)
I(1,4,5)P3ArrowREACT_150377 (Reactome)
I(1,4,5)P3ArrowREACT_150402 (Reactome)
I(1,4,5)P3REACT_150270 (Reactome)
I(1,4,5)P3REACT_150282 (Reactome)
I(1,4,5)P3REACT_150347 (Reactome)
I(1,4,5)P3REACT_150392 (Reactome)
I(1,4,5)P3REACT_150402 (Reactome)
I(1,4,5)P3REACT_150429 (Reactome)
I(1,4,5,6)P4ArrowREACT_150284 (Reactome)
I(1,4,5,6)P4ArrowREACT_150329 (Reactome)
I(1,4,5,6)P4REACT_150202 (Reactome)
I(1,4,5,6)P4REACT_150284 (Reactome)
I(3,4)P2ArrowREACT_150176 (Reactome)
I(3,4)P2REACT_150323 (Reactome)
I(3,4,5,6)P4ArrowREACT_150330 (Reactome)
I(3,4,5,6)P4REACT_150321 (Reactome)
I(3,4,6)P3ArrowREACT_150200 (Reactome)
I(3,4,6)P3REACT_150431 (Reactome)
I1PREACT_150218 (Reactome)
I3PArrowREACT_150300 (Reactome)
I3PArrowREACT_150323 (Reactome)
I3PREACT_150231 (Reactome)
I4PArrowREACT_150296 (Reactome)
I4PREACT_150193 (Reactome)
IMPA1/2mim-catalysisREACT_150193 (Reactome)
IMPA1/2mim-catalysisREACT_150218 (Reactome)
IMPA1/2mim-catalysisREACT_150231 (Reactome)
INPP1:Mg2+mim-catalysisREACT_150176 (Reactome)
INPP1:Mg2+mim-catalysisREACT_150296 (Reactome)
INPP4A/Bmim-catalysisREACT_150198 (Reactome)
INPP4A/Bmim-catalysisREACT_150323 (Reactome)
INPP5(3)/ITPK1mim-catalysisREACT_150220 (Reactome)
INPP5(4)mim-catalysisREACT_150347 (Reactome)
INPP5A/Bmim-catalysisREACT_150429 (Reactome)
INPP5B(321-993)mim-catalysisREACT_150158 (Reactome)
IP6ArrowREACT_150151 (Reactome)
IP6ArrowREACT_150167 (Reactome)
IP6ArrowREACT_150257 (Reactome)
IP6ArrowREACT_150360 (Reactome)
IP6ArrowREACT_150383 (Reactome)
IP6ArrowREACT_150393 (Reactome)
IP6ArrowREACT_150467 (Reactome)
IP6K1/2mim-catalysisREACT_150137 (Reactome)
IP6K1/2mim-catalysisREACT_150168 (Reactome)
IP6K1/2mim-catalysisREACT_150313 (Reactome)
IP6K1/2mim-catalysisREACT_150336 (Reactome)
IP6K1/2mim-catalysisREACT_150465 (Reactome)
IP6K1/3mim-catalysisREACT_150145 (Reactome)
IP6K1/3mim-catalysisREACT_150153 (Reactome)
IP6K1/3mim-catalysisREACT_150348 (Reactome)
IP6K1/3mim-catalysisREACT_150415 (Reactome)
IP6K1/3mim-catalysisREACT_150450 (Reactome)
IP6REACT_150151 (Reactome)
IP6REACT_150153 (Reactome)
IP6REACT_150257 (Reactome)
IP6REACT_150370 (Reactome)
IP6REACT_150382 (Reactome)
IP6REACT_150393 (Reactome)
IP6REACT_150465 (Reactome)
IPMK(1-416)mim-catalysisREACT_150202 (Reactome)
IPMK(1-416)mim-catalysisREACT_150254 (Reactome)
IPMK(1-416)mim-catalysisREACT_150368 (Reactome)
IPMK(1-416)mim-catalysisREACT_150392 (Reactome)
IPPKmim-catalysisREACT_150360 (Reactome)
IPPKmim-catalysisREACT_150383 (Reactome)
ISYNA1:NAD+mim-catalysisREACT_150300 (Reactome)
ITPK1:Mg2+mim-catalysisREACT_150157 (Reactome)
ITPK1:Mg2+mim-catalysisREACT_150200 (Reactome)
ITPK1:Mg2+mim-catalysisREACT_150236 (Reactome)
ITPK1:Mg2+mim-catalysisREACT_150321 (Reactome)
ITPK1:Mg2+mim-catalysisREACT_150330 (Reactome)
ITPK1:Mg2+mim-catalysisREACT_150351 (Reactome)
ITPK1:Mg2+mim-catalysisREACT_150431 (Reactome)
ITPKA/B/Cmim-catalysisREACT_150282 (Reactome)
InsArrowREACT_150193 (Reactome)
InsArrowREACT_150218 (Reactome)
InsArrowREACT_150231 (Reactome)
MINPP1mim-catalysisREACT_150329 (Reactome)
MINPP1mim-catalysisREACT_150358 (Reactome)
MINPP1mim-catalysisREACT_150382 (Reactome)
NUDT(1)mim-catalysisREACT_150167 (Reactome)
NUDT(1)mim-catalysisREACT_150184 (Reactome)
NUDT(1)mim-catalysisREACT_150371 (Reactome)
NUDT(1)mim-catalysisREACT_150467 (Reactome)
NUDT4:Mg2+/Mn2+mim-catalysisREACT_150309 (Reactome)
PI(4,5)P2REACT_150317 (Reactome)
PI(4,5)P2REACT_150328 (Reactome)
PI(4,5)P2REACT_150377 (Reactome)
PLCD4:Ca2+mim-catalysisREACT_150317 (Reactome)
PLCbzmim-catalysisREACT_150328 (Reactome)
PLCdeghmim-catalysisREACT_150377 (Reactome)
PP-IP4REACT_150309 (Reactome)
PPIP5K1/2mim-catalysisREACT_150291 (Reactome)
PPIP5K1/2mim-catalysisREACT_150370 (Reactome)
PTEN:Mg2+mim-catalysisREACT_150242 (Reactome)
PiArrowREACT_150158 (Reactome)
PiArrowREACT_150167 (Reactome)
PiArrowREACT_150176 (Reactome)
PiArrowREACT_150184 (Reactome)
PiArrowREACT_150193 (Reactome)
PiArrowREACT_150198 (Reactome)
PiArrowREACT_150200 (Reactome)
PiArrowREACT_150218 (Reactome)
PiArrowREACT_150220 (Reactome)
PiArrowREACT_150231 (Reactome)
PiArrowREACT_150242 (Reactome)
PiArrowREACT_150296 (Reactome)
PiArrowREACT_150309 (Reactome)
PiArrowREACT_150323 (Reactome)
PiArrowREACT_150329 (Reactome)
PiArrowREACT_150330 (Reactome)
PiArrowREACT_150347 (Reactome)
PiArrowREACT_150351 (Reactome)
PiArrowREACT_150358 (Reactome)
PiArrowREACT_150371 (Reactome)
PiArrowREACT_150382 (Reactome)
PiArrowREACT_150429 (Reactome)
PiArrowREACT_150467 (Reactome)
REACT_150137 (Reactome) In the nucleus, inositol hexakisphosphate kinase 1 (IP6K1) and 2 (IP6K2) phosphorylate inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5) to inositol 5-triphospho- 1,2,3,4,6-pentakisphosphate (5-PPP-IP5) (Saiardi et al. 2001, Draskovic et al. 2008) and IP6K2 (Saiardi et al. 2001, Draskovic et al. 2008). While this reaction has been demonstrated to occur in vitro, the extent to which it occurs in vivo is less clear.
REACT_150140 (Reactome) Inositol 1,3,4,5,6-pentakisphosphate I(1,3,4,5,6)P5 translocates from the cytosol to the endoplasmic reticulum (ER) lumen (Caffrey et al. 1999, Chi et al. 1999).
REACT_150145 (Reactome) Inositol hexakisphosphate kinase 1 (IP6K1) and 3 (IP6K3) phosphorylate inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5) to inositol 5-triphospho- 1,2,3,4,6-pentakisphosphate (5-PPP-IP5).

The following lists the above proteins with their corresponding literature references: IP6K1 (Saiardi et al. 2001, Draskovic et al. 2008) and IP6K3 (Saiardi et al. 2001, Draskovic et al. 2008).
REACT_150150 (Reactome) Inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5) translocates from the nucleus to the cytosol (Fridy et al. 2007).
REACT_150151 (Reactome) Inositol 1,2,3,4,5,6-hexakisphosphate (IP6) translocates from the cytosol to the nucleus (Saiardi et al. 2001).
REACT_150153 (Reactome) Inositol hexakisphosphate kinase 1 (IP6K1) and 3 (IP6K3) phosphorylate inositol 1,2,3,4,5,6-hexakisphosphate (IP6) to inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5).

The following lists the above proteins with their corresponding literature references: IP6K1 (Saiardi et al. 2001, Mulugu et al. 2007, Draskovic et al. 2008; Lin et al. 2009) and IP6K3 (Saiardi et al. 2001, Draskovic et al. 2008).
REACT_150157 (Reactome) Inositol-tetrakisphosphate 1-kinase (ITPK1) phosphorylates inositol 1,3,4-trisphosphate (I(1,3,4)P3) to inositol 1,3,4,6-tetrakisphosphate (I(1,3,4,6)P4) (Wilson & Majerus 1996, Yang & Shears 2000).
REACT_150158 (Reactome) Type II inositol-1,4,5-trisphosphate 5-phosphatase (INPP5B) is attached to the plasma membrane where it dephosphorylates inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) to inositol 1,3,4-trisphosphate (I(1,3,4)P3 (Jefferson & Majerus 1995, Ross et al. 1991, Schmid et al. 2004). INPP5B is isoprenylated at its C-terminus for membrane attachment.
REACT_150167 (Reactome) Diphosphoinositol polyphosphate phosphohydrolases, also known as nucleoside diphosphate-linked moiety X motif (NUDT) proteins, dephosphorylate inositol diphospho-pentakisphosphate (PP-IP5) to inositol 1,2,3,4,5,6-hexakisphosphate (IP6). The NUDT proteins involved are: nucleoside diphosphate-linked moiety X motif 3 (NUDT3), 4 (NUDT4), 10 (NUDT10), and 11 (NUDT11). The reactants consumed are: inositol 1-diphospho-2,3,4,5,6-pentakisphosphate (1-PP-IP5) and 3-diphospho-1,2,4,5,6-pentakisphosphate (3-PP-IP5).

The following lists the above proteins with their corresponding literature references: NUDT3 (Safrany et al. 1999, Safrany et al. 1998, Yang et al. 1999, Caffrey et al. 2000), NUDT4 (Caffrey et al. 2000), NUDT10 (Leslie et al. 2002, Hidaka et al. 2002) and NUDT11 (Leslie et al. 2002, Hidaka et al. 2002).
REACT_150168 (Reactome) In the nucleus, inositol hexakisphosphate kinase 1 (IP6K1) and 2 (IP6K2) phosphorylate 1-diphospho-2,3,4,5,6-pentakisphosphate (1-PP-IP5) to make inositol 1,5-bisdiphospho-2,3,4,6-tetrakisphosphate (1,5-(PP)2-IP4) (Saiardi et al. 2001, Mulugu et al. 2007).
REACT_150176 (Reactome) Inositol polyphosphate 1-phosphatase (INPP1) dephosphorylates inositol 1,3,4-trisphosphate (I(1,3,4)P3) to inositol 3,4-bisphosphate (I(3,4)P2) (York et al. 1993).
REACT_150184 (Reactome) Diphosphoinositol polyphosphate phosphohydrolases (DIPP), also known as nucleoside diphosphate-linked moiety X motif (NUDT) proteins, dephosphorylate inositol bisdiphospho-tetrakisphosphate ((PP)2-IP4) to inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5). The NUDT proteins involved are: nucleoside diphosphate-linked moiety X motif 3 (NUDT3), 4 (NUDT4), 10 (NUDT10), and 11 (NUDT11). The reactants consumed are: inositol 1,5-bisdiphospho-2,3,4,6-tetrakisphosphate (1,5-(PP)2-IP4) and inositol 3,5-bisdiphospho-1,2,4,6-tetrakisphosphate (3,5-(PP)2-IP4).

The following lists the above proteins with their corresponding literature references: NUDT3 (Safrany et al. 1999, Safrany et al. 1998, Yang et al. 1999, Caffrey et al. 2000), NUDT4 (Caffrey et al. 2000), NUDT10 (Leslie et al. 2002, Hidaka et al. 2002) and NUDT11 (Leslie et al. 2002, Hidaka et al. 2002).
REACT_150193 (Reactome) Inositol monophosphatase 1 (IMPA1) and 2 (IMPA2) homodimers dephosphorylate inositol 4-phosphate (I4P) to inositol (Ins). In vitro, IMPA1 and 2 differ in their pH optima and IMPA1 has a significantly greater activity on IP4 than does IMPA2 (Ohnishi et al. 2007).
REACT_150198 (Reactome) Type I (INPP4A) and type II inositol-3,4-bisphosphate 4-phosphatase (INPP4B) dephosphorylate inositol 1,3,4-trisphosphate (I(1,3,4)P3) to inositol 1,3-bisphosphate (I(1,3)P2) (Norris et al. 1995, Norris et al. 1997).
REACT_150200 (Reactome) Inositol-tetrakisphosphate 1-kinase (ITPK1) dephosphorylates inositol 1,3,4,6-tetrakisphosphate (I(1,3,4,6)P4) to inositol 3,4,6-trisphosphate (I(3,4,6)P3) (Ho et al. 2002).
REACT_150202 (Reactome) In the nucleus, inositol polyphosphate multikinase (IPMK) phosphorylates inositol 1,4,5,6-tetrakisphosphate (I(1,4,5,6)P4) to inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) (Nalaskowski et al. 2002, Chang & Majerus 2006).
REACT_150212 (Reactome) 1-diphospho-2,3,4,5,6-pentakisphosphate (1-PP-IP5) and 3-diphospho-1,2,4,5,6-pentakisphosphate (3-PP-IP5) translocate from the cytosol to the nucleus (Saiardi et al. 2001, Mulugu et al. 2007).
REACT_150218 (Reactome) Inositol monophosphatase 1 (IMPA1) and 2 (IMPA2) homodimers dephosphorylate inositol 1-phosphate (I1P) to inositol (Ins). In vitro, IMPA1 and 2 differ in their pH optima and IMPA1 has a significantly greater activity on IP4 than does IMPA2 (McAllister et al. 1992, Ohnishi et al. 2007).
REACT_150220 (Reactome) A group of inositol phosphatases and the broad specificity enzyme inositol-tetrakisphosphate 1-kinase (ITPK1) dephosphorylate inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) to inositol 1,3,4-trisphosphate (I(1,3,4)P3). The group of inositol phosphatases involved are: inositol polyphosphate 5-phosphatase OCRL-1 (OCRL), phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) aka SHIP1, phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2 (INPPL1) aka SHIP2, phosphatidylinositol 4,5-bisphosphate 5-phosphatase A (INPP5J) aka PIPP, and synaptic inositol-1,4,5-trisphosphate 5-phosphatase 1 (SYNJ1).

The following lists the above proteins with their corresponding literature references: OCRL (Chang et al. 2002, Zhang et al. 1995, Zhang et al. 1998, Schmid et al. 2004); INPP5D (Drayer et al. 1996, Kavanaugh et al. 1996); INPPL1 (Chi et al. 2004); INPP5J (Mochizuki & Thompson 1999); SYNJ1 (Schmid et al. 2004); ITPK1 (Ho et al. 2002).
REACT_150231 (Reactome) Inositol monophosphatase 1 (IMPA1) and 2 (IMPA2) homodimers dephosphorylate inositol 3-phosphate (I3P) to inositol (Ins). In vitro, IMPA1 and 2 differ in their pH optima and IMPA1 has a significantly greater activity on IP4 than does IMPA2 (Ohnishi et al. 2007).
REACT_150233 (Reactome) Inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) translocates from the endoplasmic reticulum (ER) lumen to the nucleus (Verbsky et al. 2002, Brehm et al. 2007, Choi et al. 2007).
REACT_150236 (Reactome) The broad-specificity enzyme inositol-tetrakisphosphate 1-kinase (ITPK1) phosphorylates inositol 1,3,4-trisphosphate (I(1,3,4)P3) to inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) (Wilson & Majerus 1996).
REACT_150242 (Reactome) Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase aka phosphatase and tensin homolog (PTEN) dephosphorylates inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) to inositol 1,4,5-trisphosphate (I(1,4,5)P3) (Maehama & Dixon 1998, Han et al. 2000).
REACT_150254 (Reactome) In the nucleus, inositol polyphosphate multikinase (IPMK) phosphorylates inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) to inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) (Nalaskowski et al. 2002, Chang & Majerus 2006).
REACT_150257 (Reactome) Inositol 1,2,3,4,5,6-hexakisphosphate (IP6) translocates from the nucleus to the endoplasmic reticulum (ER) lumen (Caffrey et al. 1999).
REACT_150270 (Reactome) Inositol 1,4,5-trisphosphate (I(1,4,5)P3) translocates from the endoplasmic reticulum (ER) lumen to the cytosol (Caffrey et al. 1999, Chi et al. 1999).
REACT_150282 (Reactome) Inositol-trisphosphate 3-kinase A (ITPKA), B (ITPKB), and C (ITPKC) phosphorylate inositol 1,4,5-trisphosphate (I(1,4,5)P3) to inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) (Dewaste et al. 2003).
REACT_150284 (Reactome) Inositol 1,4,5,6-tetrakisphosphate (I(1,4,5,6)P4) translocates from the endoplasmic reticulum (ER) lumen to the nucleus (Caffrey et al. 1999, Chi et al. 1999, Nalaskowski et al. 2002).
REACT_150291 (Reactome) Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1/2 (PPIP5K1) and 2 (PPIP5K2) phosphorylate inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5) to inositol 1,5-bisdiphospho-2,3,4,6-tetrakisphosphate (1,5-(PP)2-IP4) (Fridy et al. 2007, Mulugu et al. 2007, Choi et al. 2007, Lin et al. 2009).
REACT_150296 (Reactome) Inositol polyphosphate 1-phosphatase (INPP1) dephosphorylates inositol 1,4-bisphosphate (I(1,4)P2) to inositol 4-phosphate (I4P) (York et al. 1993).
REACT_150300 (Reactome) Inositol-3-phosphate synthase 1 (ISYNA1) aka hIPS isomerises glucose 6-phosphate (Glc6P) to inositol 3-phosphate (I3P) (Ju et al. 2004).
REACT_150307 (Reactome) Inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) translocates from the cytosol to the nucleus (Dewaste et al. 2003, Nalaskowski et al. 2002).
REACT_150309 (Reactome) Diphosphoinositol polyphosphate phosphohydrolase 2, also known as nucleoside diphosphate-linked moiety X motif 4 (NUDT4), dephosphorylates diphospho- tetrakisphosphate (PP-IP4) to inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5). The products made are: inositol 5-diphospho-1,3,4,6-tetrakisphosphate (5-PP-IP4); inositol 1-diphospho-3,4,5,6-tetrakisphosphate (1-PP-IP4); and inositol 3-diphospho-1,4,5,6-tetrakisphosphate (3-PP-IP4).

The following lists the above protein with its corresponding literature references: NUDT4 (Saiardi et al. 2001, Saiardi et al. 2000).
REACT_150313 (Reactome) In the nucleus, inositol hexakisphosphate kinase 1 (IP6K1) and 2 (IP6K2) phosphorylate5-diphospho-1,3,4,6-tetrakisphosphate (5-PP-IP4) to inositol 1,5-bisdiphospho-3,4,6-trisphosphate (1,5-(PP)2-IP3) (Saiardi et al. 2001, Saiardi et al. 2000, Draskovic et al. 2008).
REACT_150317 (Reactome) At the endoplasmic reticulum (ER) membrane, phosphoinositide phospholipase C delta-4 (PLCD4) hydrolyses phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) to inositol 1,4,5-trisphosphate (I(1,4,5)P3) and diacylglycerol (DAG). PLCD4 (Leung et al. 2004, Lee et al. 2004) is attached to the ER membrane via its PH domain while its C2 domain binds to the PI(4,5)P2 in the membrane.
REACT_150321 (Reactome) Inositoltetrakisphosphate 1-kinase (ITPK1) phosphorylates inositol 3,4,5,6-tetrakisphosphate (I(3,4,5,6)P4) to inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) (Yang & Shears 2000).
REACT_150323 (Reactome) Type I (INPP4A) and type II inositol-3,4-bisphosphate 4-phosphatase (INPP4B) dephosphorylate inositol 3,4-bisphosphate (I(3,4)P2) to inositol 3-phosphate (I3P) (Norris et al. 1995, Norris et al. 1997).
REACT_150328 (Reactome) At the plasma membrane, a group of phospholipase C (“PLC(bz))” proteins hydrolyse phosphatidylinositol 4,5 bisphosphate (PI(4,5)P2) to inositol 1,4,5 trisphosphate (I(1,4,5)P3) and diacylglycerol (DAG). This group of phospholipase C proteins lack a PH domain and so are is cytosolic. Their C2 domains bind to PI(4,5)P2 at the membrane. The PLC-beta proteins are thought to be responsible for the majority of PI(4,5)P2 hydrolysis.

The phospholipase C isoforms involved and their corresponding literature references are: phosphoinositide phospholipase C beta-1 (PLCB1) (Caricasole et al. 2000, Jhon et al. 1993, Park et al. 1992); beta-2 (PLCB2) (Jhon et al. 1993, Park et al. 1992); beta-3 (PLCB3) (Carozzi et al. 1992, Jhon et al. 1993); beta-4 (PLCB4) (Alvarez et al. 1995, Lee et al. 1993); and zeta-1 (PLCZ1) (Kouchi et al. 2005, Rogers et al. 2004).
REACT_150329 (Reactome) In the endoplasmic reticulum (ER) lumen, multiple inositol polyphosphate phosphatase 1 (MINPP1) dephosphorylates inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) to inositol 1,4,5,6-tetrakisphosphate (I(1,4,5,6)P4) (Caffrey et al. 1999, Chi et al. 1999).
REACT_150330 (Reactome) Inositol-tetrakisphosphate 1-kinase (ITPK1) dephosphorylates inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) to inositol 3,4,5,6-tetrakisphosphate (I(3,4,5,6)P4) (Ho et al. 2002).
REACT_150336 (Reactome) In the nucleus, inositol hexakisphosphate kinase 1 (IP6K1) and 2 (IP6K2) phosphorylate inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) to inositol 5-diphospho-(1,3,4,6)-tetrakisphosphate (5-PP-IP4) (Saiardi et al. 2001, Saiardi et al. 2000, Draskovic et al. 2008).
REACT_150342 (Reactome) Inositol 1,3,4,5,6-pentakisphosphate I(1,3,4,5,6)P5 translocates from the nucleus to the cytosol (Nalaskowski et al. 2002; Ho et al. 2002, Brehm et al. 2007).
REACT_150347 (Reactome) A group of inositol phosphatases dephosphorylate inositol 1,4,5-trisphosphate (I(1,4,5)P3) to inositol 1,4-bisphosphate (I(1,4)P2). The group of inositol phosphatases involved are: inositol polyphosphate 5-phosphatase OCRL-1 (OCRL), phosphatidylinositol 4,5-bisphosphate 5-phosphatase A (INPP5J), and synaptic inositol-1,4,5-trisphosphate 5-phosphatase 1 (SYNJ1).

The following lists the above proteins with their corresponding literature references: OCRL (Zhang et al. 1995, Zhang et al. 1998, Schmid et al. 2004); INPP5J (Mochizuki & Thompson 1999); SYNJ1 (Schmid et al. 2004).
REACT_150348 (Reactome) Inositol hexakisphosphate kinase 1 (IP6K1) and 3 (IP6K3) phosphorylate 1-diphospho-2,3,4,5,6-pentakisphosphate (1-PP-IP5) to form inositol 1,5-bisdiphospho-2,3,4,6-tetrakisphosphate (1,5-(PP)2-IP4) (Saiardi et al. 2001, Mulugu et al. 2007).
REACT_150351 (Reactome) Inositol-tetrakisphosphate 1-kinase (ITPK1) dephosphorylates inositol 1,3,4,6-tetrakisphosphate (I(1,3,4,6)P4) to inositol 1,3,4-trisphosphate (I(1,3,4)P3) (Ho et al. 2002).
REACT_150356 (Reactome) Inositol 5-diphospho-1,3,4,6-tetrakisphosphate (5-PP-IP4) translocates from the nucleus to the cytosol (Saiardi et al. 2001, Saiardi et al. 2000).
REACT_150358 (Reactome) In the endoplasmic reticulum (ER) lumen, multiple inositol polyphosphate phosphatase 1 (MINPP1) dephosphorylates inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) to inositol 1,4,5-trisphosphate (I(1,4,5)P3) (Caffrey et al. 1999, Chi et al. 1999).
REACT_150360 (Reactome) Inositolpentakisphosphate 2-kinase (IPPK), also known as IP52K, phosphorylates inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) to inositol 1,2,3,4,5,6-hexakisphosphate (IP6) (Verbski et al. 2002, Brehm et al. 2007, Choi et al. 2007).
REACT_150368 (Reactome) In the nucleus, inositol polyphosphate multikinase (IPMK) phosphorylates inositol 1,3,4,6-tetrakisphosphate (I(1,3,4,6)P4) to inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) (Chang et al. 2002, Chang & Majerus 2006).
REACT_150370 (Reactome) Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1/2 (PPIP5K1) and 2 (PPIP5K2) phosphorylate inositol 1,2,3,4,5,6-hexakisphosphate (IP6) to inositol 1-diphospho-2,3,4,5,6-pentakisphosphate (1-PP-IP5)) (Fridy et al. 2007, Mulugu et al. 2007, Choi et al. 2007, Lin et al. 2009; Wang et al. 2011).
REACT_150371 (Reactome) Diphosphoinositol polyphosphate phosphohydrolases (DIPP), also known as nucleoside diphosphate-linked moiety X motif (NUDT) proteins, dephosphorylate inositol bisdiphospho-tetrakisphosphate ((PP)2-IP4) to inositol diphospho-pentakisphosphate (PP-IP5). The NUDT proteins involved are: nucleoside diphosphate-linked moiety X motif 3 (NUDT3), 4 (NUDT4), 10 (NUDT10), and 11 (NUDT11). The reactants consumed are: inositol 1,5-bisdiphospho-2,3,4,6-tetrakisphosphate (1,5-(PP)2-IP4) and inositol 3,5-bisdiphospho-1,2,4,6-tetrakisphosphate (3,5-(PP)2-IP4). The products made are: inositol 1-diphospho-2,3,4,5,6-pentakisphosphate (1-PP-IP5) and 3-diphospho-1,2,4,5,6-pentakisphosphate (3-PP-IP5).

The following lists the above proteins with their corresponding literature references: NUDT3 (Safrany et al. 1999, Safrany et al. 1998, Yang et al. 1999, Caffrey et al. 2000), NUDT4 (Caffrey et al. 2000), NUDT10 (Leslie et al. 2002, Hidaka et al. 2002) and NUDT11 (Leslie et al. 2002, Hidaka et al. 2002).
REACT_150377 (Reactome) A group of phospholipase C proteins (“PLC(degh)”) bind to the plasma membrane via their PH domains. These phospholipases hydrolyse phosphatidylinositol 4,5 bisphosphate (PI(4,5)P2) to inositol 1,4,5 trisphosphate (I(1,4,5)P3) and diacylglycerol (DAG). The C2 domains of the enzymes bind to PI(4,5)P2 at the membrane.

The phospholipase C isoforms involved and their corresponding literature references are: phosphoinositide phospholipase C delta-1(PLCD1) (Cheng et al. 1995); epsilon-1 (PLCE1) (Song et al. 2001, Lopez et al. 2001); delta-3 (PLCD3) (Pawelczyk & Matecki 1997); gamma-1 (PLCG1) (Harita et al. 2009, Baldassare et al. 1989); gamma-2 (PLCG2) (Banno et al. 1988); eta-1 (PLCH1) (Hwang et al. 2005); and eta-2 (PLCH2) (Zhou et al 2005).
REACT_150382 (Reactome) In the endoplasmic reticulum (ER) lumen, multiple inositol polyphosphate phosphatase 1 (MINPP1) dephosphorylates 1,2,3,4,5,6-hexakisphosphate (IP6) to inositol 1,2,4,5,6-pentakisphosphate (I(1,2,4,5,6)P5) (Caffrey et al. 1999, Chi et al. 1999, Deleu et al. 2006, Nogimori et al. 1991).
REACT_150383 (Reactome) In the nucleus, inositol-pentakisphosphate 2-kinase (IPPK - also known as IP5-2K) phosphorylates inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) to inositol 1,2,3,4,5,6-hexakisphosphate (IP6) (Verbsky et al. 2002, Brehm et al. 2007, Choi et al. 2007).
REACT_150392 (Reactome) In the nucleus, inositol polyphosphate multikinase (IPMK) phosphorylates inositol 1,4,5-trisphosphate (I(1,4,5)P3) to inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) (Nalaskowski et al. 2002, Chang et al. 2002, Chang & Majerus 2006).
REACT_150393 (Reactome) 1,2,3,4,5,6-hexakisphosphate (IP6) translocates from the cytosol to the endoplasmic reticulum (ER) lumen (Caffrey et al. 1999).
REACT_150402 (Reactome) Inositol 1,4,5-trisphosphate (I(1,4,5)P3) translocates from the cytosol to the nucleus (Dewaste et al. 2003, Nalaskowski et al. 2002).
REACT_150404 (Reactome) Inositol 1,3,4,5,6-pentakisphosphate I(1,3,4,5,6)P5 translocates from the endoplasmic reticulum (ER) lumen to the cytosol (Nalaskowski et al. 2002, Ho et al. 2002, Brehm et al. 2007).
REACT_150413 (Reactome) Inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) translocates from the cytosol to the endoplasmic reticulum (ER) lumen (Caffrey et al. 1999, Chi et al. 1999).
REACT_150415 (Reactome) Inositol hexakisphosphate kinase 1 (IP6K1) and 3 (IP6K3) phosphorylate inositol 1-diphospho-3,4,5,6-tetrakisphosphate (1-PP-IP4) to form inositol 1,5-bisdiphospho-3,4,6-trisphosphate (1,5-(PP)2-IP3) (Saiardi et al. 2001, Saiardi et al. 2000, Draskovic et al. 2008).
REACT_150419 (Reactome) Inositol 1,5-bisdiphospho-2,3,4,6-tetrakisphosphate (1,5-(PP)2-IP4) and inositol 3,5-bisdiphospho-1,2,4,6-tetrakisphosphate (3,5-(PP)2-IP4) translocate from the nucleus to the cytosol (Leslie et al. 2002).
REACT_150429 (Reactome) Type I inositol-1,4,5-trisphosphate 5-phosphatase (INPP5A) and the Type II phosphatase (INPP5B) are isoprenylated to the plasma membrane and act as a lipid anchor. Here they dephosphorylate inositol 1,4,5-trisphosphate (I(1,4,5)P3) to inositol 1,4-bisphosphate I(1,4)P2. ).

The following lists the above proteins with their corresponding literature references: INPP5A (Laxminarayan et al. 1994); INPP5B (Jefferson & Majerus 1995, Ross et al. 1991, Schmid et al. 2004).
REACT_150431 (Reactome) Inositol-tetrakisphosphate 1-kinase (ITPK1) phosphorylates inositol 3,4,6-trisphosphate (I(3,4,6)P3) to inositol 1,3,4,6-tetrakisphosphate (I(1,3,4,6)P4) (Ho et al. 2002).
REACT_150450 (Reactome) Inositol hexakisphosphate kinase 1 (IP6K1) and 3 (IP6K3) phosphorylate inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) to inositol 5-diphospho-(1,3,4,6)-tetrakisphosphate (5-PP-IP4) (Saiardi et al. 2001, Saiardi et al. 2000, Draskovic et al. 2008).
REACT_150457 (Reactome) Inositol 1,3,4,6-tetrakisphosphate (I(1,3,4,6)P4) translocates from the cytosol to the nucleus (Ho et al. 2002, Nalaskowski et al. 2002).
REACT_150465 (Reactome) In the nucleus, inositol hexakisphosphate kinase 1 (IP6K1) and 2 (IP6K2) phosphorylate inositol 1,2,3,4,5,6-hexakisphosphate (IP6) to inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5).

The following lists the above proteins with their corresponding literature references: IP6K1 (Saiardi et al. 2001, Mulugu et al. 2007, Draskovic et al. 2008) and IP6K2 (Saiardi et al. 2001, Mulugu et al. 2007, Draskovic et al. 2008).
REACT_150467 (Reactome) Diphosphoinositol polyphosphate phosphohydrolases (DIPP), also known as nucleoside diphosphate-linked moiety X motif (NUDT) proteins, dephosphorylate inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5) to inositol 1,2,3,4,5,6-hexakisphosphate (IP6). The NUDT proteins involved are: nucleoside diphosphate-linked moiety X motif 3 (NUDT3), 4 (NUDT4), 10 (NUDT10), and 11 (NUDT11).

The following lists the above proteins with their corresponding literature references: NUDT3 (Safrany et al. 1999, Safrany et al. 1998, Yang et al. 1999, Caffrey et al. 2000), NUDT4 (Caffrey et al. 2000), NUDT10 (Leslie et al. 2002, Hidaka et al. 2002) and NUDT11 (Leslie et al. 2002, Hidaka et al. 2002).
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