Phosphoinositides metabolism (Homo sapiens)
From WikiPathways
Description
Phosphatidylinositols are a family of lipids under the phosphatidylglyceride class. This pathway specifies several metabolic conversions between PIP, PIP2, PIP3 and other metabolites. Phosphorylation sites on the individual metabolites are drawn as states, with the location added as a number.
The main interactions within this pathway are based on Figure 1 of Rusten et al, annotated with biochemical interaction database Rhea, and diseases (depicted in pink) with corresponding OMIM-identifiers.. Dashed lines depict proposed interactions which have not been characterized (yet).
Quality Tags
Ontology Terms
Bibliography
View all... |
- Laporte J, Hu LJ, Kretz C, Mandel JL, Kioschis P, Coy JF, Klauck SM, Poustka A, Dahl N; ''A gene mutated in X-linked myotubular myopathy definesa new putative tyrosine phosphatase family conserved in yeast.''; Nat Genet, 1996 PubMed Europe PMC Scholia
- Ungewickell A, Hugge C, Kisseleva M, Chang SC, Zou J, Feng Y, Galyov EE, Wilson M, Majerus PW; ''''; , PubMed Europe PMC Scholia
- Rameh LE, Tolias KF, Duckworth BC, Cantley LC; ''A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate.''; Nature, 1997 PubMed Europe PMC Scholia
- Rohrschneider LR, Fuller JF, Wolf I, Liu Y, Lucas DM; ''Structure, function, and biology of SHIP proteins.''; Genes Dev, 2000 PubMed Europe PMC Scholia
- Li S, Tiab L, Jiao X, Munier FL, Zografos L, Frueh BE, Sergeev Y, Smith J, Rubin B, Meallet MA, Forster RK, Hejtmancik JF, Schorderet DF; ''Mutations in PIP5K3 are associated with François-Neetens mouchetée fleck corneal dystrophy.''; Am J Hum Genet, 2005 PubMed Europe PMC Scholia
- Bolino A, Muglia M, Conforti FL, LeGuern E, Salih MA, Georgiou DM, Christodoulou K, Hausmanowa-Petrusewicz I, Mandich P, Schenone A, Gambardella A, Bono F, Quattrone A, Devoto M, Monaco AP; ''Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2.''; Nat Genet, 2000 PubMed Europe PMC Scholia
- Rusten TE, Stenmark H; ''Analyzing phosphoinositides and their interacting proteins.''; Nat Methods, 2006 PubMed Europe PMC Scholia
- 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
- 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
- Backer JM; ''The regulation and function of Class III PI3Ks:novel roles for Vps34.''; Biochem J, 2008 PubMed Europe PMC Scholia
History
View all... |
External references
DataNodes
View all... |
Name | Type | Database reference | Comment |
---|---|---|---|
4-phosphatase | Protein | 3.1.3.78 (Enzyme Nomenclature) | From [https://www.qmul.ac.uk/sbcs/iubmb/enzyme/EC3/1/3/78.html and https://enzyme.expasy.org/EC/3.1.3.78] :"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] |
ADP | Metabolite | CHEBI:456216 (ChEBI) | |
ATP | Metabolite | CHEBI:30616 (ChEBI) | |
DAG | Metabolite | CHEBI:17815 (ChEBI) | Diacylglycerol |
H+ | Metabolite | CHEBI:15378 (ChEBI) | |
H2O | Metabolite | CHEBI:15377 (ChEBI) | |
Ins(1,4,5)P3 | Metabolite | CHEBI:203600 (ChEBI) | phosphorylated on position 1,4 and 5. |
MTM1 | Protein | Q13496 (Uniprot-TrEMBL) | aka Myotubularin; gene name given in Fig. 1 of [PMID:16554828]. |
MTMR10 | Protein | Q9NXD2 (Uniprot-TrEMBL) | |
MTMR11 | Protein | A4FU01 (Uniprot-TrEMBL) | |
MTMR12 | Protein | Q9C0I1 (Uniprot-TrEMBL) | |
MTMR1 | Protein | Q13613 (Uniprot-TrEMBL) | |
MTMR2 | Protein | Q13614 (Uniprot-TrEMBL) | |
MTMR3 | Protein | Q13615 (Uniprot-TrEMBL) | |
MTMR4 | Protein | Q9NYA4 (Uniprot-TrEMBL) | |
MTMR6 | Protein | Q9Y217 (Uniprot-TrEMBL) | |
MTMR7 | Protein | Q9Y216 (Uniprot-TrEMBL) | |
MTMR8 | Protein | Q96EF0 (Uniprot-TrEMBL) | |
MTMR9 | Protein | Q96QG7 (Uniprot-TrEMBL) | |
OCRL | Protein | Q01968 (Uniprot-TrEMBL) | |
PI-3 kinase I | Protein | 2.7.1.137 (Enzyme Nomenclature) | |
PI-3 kinase II | Protein | 2.7.1.154 (Enzyme Nomenclature) | See also https://en.wikipedia.org/wiki/Class_II_PI_3-kinases |
PI-3 kinase III | Protein | 2.7.1.137 (Enzyme Nomenclature) | |
PI3K-C2α | Protein | O00443 (Uniprot-TrEMBL) | |
PI3K-C2β | Protein | O00750 (Uniprot-TrEMBL) | |
PI3K-C2γ | Protein | O75747 (Uniprot-TrEMBL) | |
PIK3C3 | Protein | Q8NEB9 (Uniprot-TrEMBL) | |
PIK3CA | Protein | P42336 (Uniprot-TrEMBL) | |
PIK3CB | Protein | P42338 (Uniprot-TrEMBL) | |
PIK3CD | Protein | O00329 (Uniprot-TrEMBL) | |
PIK3CG | Protein | P48736 (Uniprot-TrEMBL) | |
PIK3R4 | Protein | Q99570 (Uniprot-TrEMBL) | |
PIKfyve | Protein | Q9Y2I7 (Uniprot-TrEMBL) | |
PIP-4 kinase | Protein | 2.7.1.149 (Enzyme Nomenclature) | According to Rhea, this is the EC class. |
PIP-5 kinase alpha | Protein | Q99755 (Uniprot-TrEMBL) | |
PIP-5 kinase beta | Protein | O14986 (Uniprot-TrEMBL) | |
PIP-5 kinase gamma | Protein | O60331 (Uniprot-TrEMBL) | "PIP5Kγ, has three splicing variance; PIP5Kγ635, PIP5γ661, and PIP5Kγ687, making it one of the key regulators for producing PI(4,5)P2" [https://en.wikipedia.org/wiki/Phosphatidylinositol-4-phosphate_5-_kinases_(PIP5K)_in_neuronal_development] |
PIP4K2A | Protein | P48426 (Uniprot-TrEMBL) | |
PIP4K2B | Protein | P78356 (Uniprot-TrEMBL) | |
PIP4K2C | Protein | Q8TBX8 (Uniprot-TrEMBL) | |
PIP4P1 | Protein | Q86T03 (Uniprot-TrEMBL) | |
PIP4P2 | Protein | Q8N4L2 (Uniprot-TrEMBL) | |
PLCB1 | Protein | Q9NQ66 (Uniprot-TrEMBL) | |
PLCB2 | Protein | Q00722 (Uniprot-TrEMBL) | |
PLCB3 | Protein | Q01970 (Uniprot-TrEMBL) | |
PLCB4 | Protein | Q15147 (Uniprot-TrEMBL) | |
PLCD1 | Protein | P51178 (Uniprot-TrEMBL) | |
PLCD3 | Protein | Q8N3E9 (Uniprot-TrEMBL) | |
PLCD4 | Protein | Q9BRC7 (Uniprot-TrEMBL) | |
PLCE1 | Protein | Q9P212 (Uniprot-TrEMBL) | |
PLCG1 | Protein | P19174 (Uniprot-TrEMBL) | |
PLCG2 | Protein | P16885 (Uniprot-TrEMBL) | |
PLCH1 | Protein | Q4KWH8 (Uniprot-TrEMBL) | |
PLCH2 | Protein | O75038 (Uniprot-TrEMBL) | |
PLCZ1 | Protein | Q86YW0 (Uniprot-TrEMBL) | |
PTEN | Protein | P60484 (Uniprot-TrEMBL) | |
Phosphate | Metabolite | CHEBI:43474 (ChEBI) | |
Phospholipase C | Protein | 3.1.4.11 (Enzyme Nomenclature) | |
PtdIns(3)P | Metabolite | CHEBI:58088 (ChEBI) |
|
PtdIns(3,4)P2 | Metabolite | CHEBI:57658 (ChEBI) |
|
PtdIns(3,4,5)P3 | Metabolite | CHEBI:57836 (ChEBI) |
|
PtdIns(3,5)P2 | Metabolite | CHEBI:57923 (ChEBI) |
|
PtdIns(4)P | Metabolite | CHEBI:58178 (ChEBI) |
|
PtdIns(4,5)P2 | Metabolite | CHEBI:58456 (ChEBI) |
|
PtdIns(5)P | Metabolite | CHEBI:57795 (ChEBI) |
|
PtdIns | Metabolite | CHEBI:57880 (ChEBI) | phosphorylated on position 1; position 1 connected to DAG. |
SACM1L | Protein | Q9NTJ5 (Uniprot-TrEMBL) | Annotation based on Uniprot " Can also catalyze the hydrolysis of phosphatidylinositol 3-phosphate (PtdIns3P)" and EC.3.1.3.64 |
SBF1 | Protein | O95248 (Uniprot-TrEMBL) | aka Myotubularin-related protein 5 |
SBF2 | Protein | Q86WG5 (Uniprot-TrEMBL) | aka Myotubularin-related protein 13 |
SHIP (1) | Protein | Q92835 (Uniprot-TrEMBL) | EC:3.1.3.86. Annotated based on caption of Fig. 1 [PMID:16554828] and "Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1 (SHIP1)" [https://en.wikipedia.org/wiki/INPP5D] |
Annotated Interactions
View all... |
Source | Target | Type | Database reference | Comment |
---|---|---|---|---|
DAG | mim-conversion | 33180 (Rhea) | ||
PtdIns(3)P | PtdIns(3,4)P2 | mim-conversion | 17195 (Rhea) | |
PtdIns(3)P | PtdIns(3,5)P2 | mim-conversion | 13610 (Rhea) | |
PtdIns(3)P | PtdIns | mim-conversion | 12317 (Rhea) | |
PtdIns(3,4)P2 | PtdIns(3)P | mim-conversion | 17194 (Rhea) | |
PtdIns(3,4)P2 | PtdIns(3,4,5)P3 | mim-conversion | 25530 (Rhea) | |
PtdIns(3,4)P2 | PtdIns(4)P | mim-conversion | 18374 (Rhea) | "PTEN protein acts as a phosphatase to dephosphorylate phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5)P3 or PIP3)." [https://en.wikipedia.org/wiki/PTEN_(gene)] |
PtdIns(3,4,5)P3 | PtdIns(3,4)P2 | mim-conversion | 25529 (Rhea) | |
PtdIns(3,4,5)P3 | PtdIns(4,5)P2 | mim-conversion | 21294 (Rhea) | |
PtdIns(4)P | PtdIns(3,4)P2 | mim-conversion | 18375 (Rhea) | |
PtdIns(4)P | PtdIns(4,5)P2 | mim-conversion | 14427 (Rhea) | |
PtdIns(4)P | PtdIns | mim-conversion | 55653 (Rhea) | |
PtdIns(4,5)P2 | Ins(1,4,5)P3 | mim-conversion | 33180 (Rhea) | |
PtdIns(4,5)P2 | PtdIns(3,4,5)P3 | mim-conversion | 21293 (Rhea) | |
PtdIns(4,5)P2 | PtdIns(4)P | mim-conversion | 14426 (Rhea) | |
PtdIns(4,5)P2 | PtdIns(5)P | mim-conversion | 12282 (Rhea) | |
PtdIns(5)P | PtdIns(4,5)P2 | mim-conversion | 12281 (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." |
PtdIns | PtdIns(3)P | mim-conversion | 12318 (Rhea) | |
PtdIns | PtdIns(3)P | mim-conversion | 12710 (Rhea) | |
PtdIns | PtdIns(4)P | mim-conversion | 55654 (Rhea) |