Phosphoinositides metabolism (Homo sapiens)

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61533155Oculocerebrorenal syndrome of LoweDAGBeta isotypes:MyotubularinPLCG1PLCB2PLCB1PIK3CGSHIPPIP-4 kinasePTENPLCH1OCRLPI-3 kinase IPIP4P14-phosphatasePtdIns(5)PPtdIns(4,5)P2DAGPI-4 kinasePTENPIP-5 kinase alphaPIKfyveP5P4P54P1P14Myotubularin2PIP-5 kinase gammaPIP-5 kinase alphaPIP-5 kinase gamma4-phosphatase4-phosphatasePIP4K2APIP4K2CPIP4K2BDAGPtdIns(3,5)P2P1P3P5DAGPtdInsP1DAGPtdIns(3)PP1P3DAGPtdIns(3,4)P2P3P1P4DAGPtdIns(4)PP4P1DAGPtdIns(3,4,5)P3P3P4P5P1DAGIns(1,4,5)P3P5P4P1PIP4P2PIP-5 kinase betaPIK3CBPIK3CAPIK3CDPhospholipase CPLCB3PLCB4Gamma isotypes:PLCG2Epsilon isotype:PLCE1Delta isotypes:PLCD1PLCD3PLCD4Eta isotypes:Zeta isotype:PLCH2PLCZ1


Phosphatidylinositols and their interactions. The proteins that catalyse some of these reactions are shown. Not all conversions of metabolites

have a protein or a protein group catalysing the reaction in this pathway. This is because the lack of information on what protein(s) are involved

in these reactions.

Quality Tags

Ontology Terms



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  1. Munday AD, Norris FA, Caldwell KK, Brown S, Majerus PW, Mitchell CA; ''The inositol polyphosphate 4-phosphatase forms a complex with phosphatidylinositol 3-kinase in human platelet cytosol.''; Proc Natl Acad Sci U S A, 1999 PubMed Europe PMC Scholia
  2. Poli A, Zaurito AE, Abdul-Hamid S, Fiume R, Faenza I, Divecha N; ''Phosphatidylinositol 5 Phosphate (PI5P): From Behind the Scenes to the Front (Nuclear) Stage.''; Int J Mol Sci, 2019 PubMed Europe PMC Scholia
  3. Rameh LE, Tolias KF, Duckworth BC, Cantley LC; ''A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate.''; Nature, 1997 PubMed Europe PMC Scholia
  4. Ungewickell A, Hugge C, Kisseleva M, Chang SC, Zou J, Feng Y, Galyov EE, Wilson M, Majerus PW; ''''; , PubMed Europe PMC Scholia
  5. Malek M, Kielkowska A, Chessa T, Anderson KE, Barneda D, Pir P, Nakanishi H, Eguchi S, Koizumi A, Sasaki J, Juvin V, Kiselev VY, Niewczas I, Gray A, Valayer A, Spensberger D, Imbert M, Felisbino S, Habuchi T, Beinke S, Cosulich S, Le Novère N, Sasaki T, Clark J, Hawkins PT, Stephens LR; ''PTEN Regulates PI(3,4)P2Signaling Downstream of Class I PI3K.''; Mol Cell, 2017 PubMed Europe PMC Scholia
  6. Rusten TE, Stenmark H; ''Analyzing phosphoinositides and their interacting proteins.''; Nat Methods, 2006 PubMed Europe PMC Scholia


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107307view14:41, 19 September 2019EgonwRemoved empty ChEBI identifiers
107178view14:26, 17 September 2019MaintBotChEBI identifier normalization
105091view16:01, 5 July 2019DeSlAdded phospolipase C subtypes
105090view15:52, 5 July 2019DeSlAdded IDs for (1,4,5) reaction.
105067view19:16, 3 July 2019DeSlAdded correct IDs for (4,5) to (3,4,5), checked all genes and Rhea IDs.
105066view18:58, 3 July 2019DeSlAdded pip-kinase beta, conenected to correct Rhea
105064view14:41, 3 July 2019DeSlAdded correct conversion back from (4,5) to (5).
105052view09:20, 3 July 2019DeSlAdded all phosphorylation sites on metabolites, changed names (no IDs yet).
105042view14:16, 2 July 2019DeSlStarted adding the DAg and phosphorylation sites.
105041view14:09, 2 July 2019DeSlChanged layout of upper part.
105040view14:08, 2 July 2019DeSlAdded first phosporylated sites and DAG as textlabel for visualisation purposes.
105039view14:05, 2 July 2019DeSlChecked first step and adapted according to phosphorylation sites.
105038view11:35, 2 July 2019DeSlAdapted title
104970view13:52, 27 June 2019ChrisChanged title of the pathway
104954view10:16, 27 June 2019ChrisModified description
104953view10:14, 27 June 2019ChrisOntology Term : 'phosphatidylinositol metabolic pathway' added !
104901view21:14, 23 June 2019EgonwFixed the data sources.
104900view20:49, 23 June 2019EgonwFixed the data source.
104899view20:48, 23 June 2019EgonwRemoved the RHEA: prefix.
104817view12:36, 19 June 2019ChrisAdded a legend and added a PUBMED article as literature
104816view12:25, 19 June 2019ChrisModified title
104809view09:34, 19 June 2019ChrisAdded CHEBI identifier to phosphatidylinositol 3,4-biphosphate
104808view09:08, 19 June 2019ChrisNew pathway

External references


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NameTypeDatabase referenceComment
4-phosphataseProtein3.1.3.78 (Enzyme Nomenclature) From [ and] :"Two pathways exist in mammalian cells to degrade 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate [PtdIns(4,5)P2] [2]. One is catalysed by this enzyme... The enzyme from human is specific for PtdIns(4,5)P2 as substrate, as it cannot use PtdIns(3,4,5)P3, PtdIns(3,4)P2, PtdIns(3,5)P2, PtdIns5P, PtdIns4P or PtdIns3P [2].In humans, the enzyme is localized to late endosomal/lysosomal membranes [2]." [2]: [PMID: 16365287]
4-phosphataseProteinQ9Y2H2 (Uniprot-TrEMBL)
DAGMetaboliteCHEBI:17815 (ChEBI) Diacylglycerol
Ins(1,4,5)P3MetaboliteCHEBI:203600 (ChEBI) phosphorylated on position 1,4 and 5.
MyotubularinProteinQ13496 (Uniprot-TrEMBL)
OCRLProteinQ01968 (Uniprot-TrEMBL)
PI-3 kinase IProtein2.7.1.137 (Enzyme Nomenclature)
PI-4 kinase ProteinP42356 (Uniprot-TrEMBL)
PIK3CAProteinP42336 (Uniprot-TrEMBL)
PIK3CBProteinP42338 (Uniprot-TrEMBL)
PIK3CDProteinO00329 (Uniprot-TrEMBL)
PIK3CGProteinP48736 (Uniprot-TrEMBL)
PIKfyveProteinQ9Y2I7 (Uniprot-TrEMBL)
PIP-4 kinaseProtein2.7.1.149 (Enzyme Nomenclature) According to Rhea, this is the EC class.
PIP-5 kinase alphaProteinQ99755 (Uniprot-TrEMBL)
PIP-5 kinase betaProteinO14986 (Uniprot-TrEMBL)
PIP-5 kinase gammaProteinO60331 (Uniprot-TrEMBL)
PIP4K2AProteinP48426 (Uniprot-TrEMBL)
PIP4K2BProteinP78356 (Uniprot-TrEMBL)
PIP4K2CProteinQ8TBX8 (Uniprot-TrEMBL)
PIP4P1ProteinQ86T03 (Uniprot-TrEMBL)
PIP4P2ProteinQ8N4L2 (Uniprot-TrEMBL)
PLCB1ProteinQ9NQ66 (Uniprot-TrEMBL)
PTENGeneProductENSG00000171862 (Ensembl)
PTENProteinP60484 (Uniprot-TrEMBL)
Phospholipase CProtein
PtdIns(3)PMetaboliteCHEBI: (ChEBI) phosphorylated on position 1 and 3; position 1 connected to DAG.
PtdIns(3,4)P2MetaboliteCHEBI: (ChEBI) phosphorylated on position 1, 3 and 4; position 1 connected to DAG.
PtdIns(3,4,5)P3MetaboliteCHEBI:57836 (ChEBI) phosphorylated on position 1, 3, 4 and 5; position 1 connected to DAG.
PtdIns(3,5)P2MetaboliteCHEBI: (ChEBI) phosphorylated on position 1, 3 and 5; position 1 connected to DAG.
PtdIns(4)PMetaboliteCHEBI:58178 (ChEBI) phosphorylated on position 1 and 4; position 1 connected to DAG.
PtdIns(4,5)P2MetaboliteCHEBI:58456 (ChEBI) phosphatidylinositol 4,5-bisphosphate
PtdIns(5)PMetaboliteCHEBI:57795 (ChEBI)
  • aka phosphatidylinositol 5-phosphate
  • phosphorylated on position 1 and 5; position 1 connected to DAG.
PtdInsMetaboliteCHEBI: (ChEBI) phosphorylated on position 1; position 1 connected to DAG.
SHIPProteinO15357 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
DAGmim-conversion33180 (Rhea)
PtdIns(3,4,5)P3PtdIns(4,5)P2mim-conversion21294 (Rhea)
PtdIns(4)PPtdIns(4,5)P2mim-conversion14427 (Rhea)
PtdIns(4,5)P2Ins(1,4,5)P3mim-conversion33180 (Rhea)
PtdIns(4,5)P2PtdIns(3,4,5)P3mim-conversion21293 (Rhea)
PtdIns(4,5)P2PtdIns(4)Pmim-conversion14426 (Rhea)
PtdIns(4,5)P2PtdIns(5)Pmim-conversion12282 (Rhea)
PtdIns(5)PPtdIns(4,5)P2mim-conversion12281 (Rhea) The addition of a third phosphate to obtain PtdIns(4,5)P2 can be performed by two enzymes, which either add the phosphate at the D4 or D5 position in the inositol ring. This last phosphorylation step is depending on where the second phosphphate is located (D5 or D4 repectively). Rephrased from [PMID: 9367159]: "The type I enzyme PIP-4-kinase phosphorylates PtdIns-4-P at the D-5 position (of the inositol ring).The type II enzyme however ( abundant in some tissues), phosphorylates PtdIns-5-P at the D-4 position, and thus should be considered as a 4-OH kinase, or PIP(4)K."
mim-conversion12316 (Rhea)
mim-conversion13609 (Rhea)
mim-conversion14425 (Rhea)
mim-conversion19877 (Rhea)
mim-conversion24056 (Rhea)
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