Phosphoinositides metabolism (WP4971)

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 [https://doi.org/10.1038/nmeth867 Rusten et al], annotated with biochemical interaction database [https://www.rhea-db.org/ Rhea], and diseases (depicted in pink) with corresponding [https://www.omim.org/ OMIM-identifiers.]. Dashed lines depict proposed interactions which have not been characterised (yet)
last edited

Authors

DeSl and Egonw

Cited In

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Organism

Homo sapiens

Communities

Inborn Errors of Metabolism (IEM) Pathways Lipids and LIPID MAPS Rare Diseases

Annotations

Disease Ontology: oculocerebrorenal syndrome Charcot-Marie-Tooth disease type 4B1 Fleck corneal dystrophy centronuclear myopathy

Pathway Ontology: phosphatidylinositol metabolic pathway

Participants

Label Type Compact Identifier
PI-3 kinase III Protein eccode:2.7.1.137
PIP-5 kinase alpha Protein uniprot:Q99755
PtdIns(5)P Metabolite chebi:57795
DAG Metabolite chebi:17815
4-phosphatase Protein eccode:3.1.3.78
PTEN Protein uniprot:P60484
SACM1L Protein uniprot:Q9NTJ5
PIP-4 kinase Protein eccode:2.7.1.149
ATP Metabolite chebi:30616
PLCB2 Protein uniprot:Q00722
MTMR1 Protein uniprot:Q13613
H2O Metabolite chebi:15377
PIKfyve Protein uniprot:Q9Y2I7
PLCH1 Protein uniprot:Q4KWH8
Phosphate Metabolite chebi:43474
PI3K-C2α Protein uniprot:O00443
PTEN Protein uniprot:P60484
PLCG1 Protein uniprot:P19174
MTM1 Protein uniprot:Q13496
OCRL Protein uniprot:Q01968
PLCB1 Protein uniprot:Q9NQ66
PIK3CG Protein uniprot:P48736
PtdIns(4,5)P2 Metabolite chebi:58456
PI-3 kinase I Protein eccode:2.7.1.137
PIP4P1 Protein uniprot:Q86T03
SHIP (1) Protein uniprot:Q92835
PIP-5 kinase gamma Protein uniprot:O60331
PIP4K2A Protein uniprot:P48426
PIP4K2C Protein uniprot:Q8TBX8
PIP4K2B Protein uniprot:P78356
PtdIns(3,5)P2 Metabolite chebi:57923
PtdIns Metabolite chebi:57880
PtdIns(3)P Metabolite chebi:58088
PtdIns(3,4)P2 Metabolite chebi:57658
PtdIns(4)P Metabolite chebi:58178
PtdIns(3,4,5)P3 Metabolite chebi:57836
Ins(1,4,5)P3 Metabolite chebi:203600
PIP4P2 Protein uniprot:Q8N4L2
PIP-5 kinase beta Protein uniprot:O14986
PIK3CB Protein uniprot:P42338
PIK3CA Protein uniprot:P42336
PIK3CD Protein uniprot:O00329
Phospholipase C Protein eccode:3.1.4.11
PLCB3 Protein uniprot:Q01970
PLCB4 Protein uniprot:Q15147
PLCG2 Protein uniprot:P16885
PLCE1 Protein uniprot:Q9P212
PLCD1 Protein uniprot:P51178
PLCD3 Protein uniprot:Q8N3E9
PLCD4 Protein uniprot:Q9BRC7
PLCH2 Protein uniprot:O75038
PLCZ1 Protein uniprot:Q86YW0
PIK3CG Protein uniprot:P48736
PI-3 kinase I Protein eccode:2.7.1.137
PIK3CB Protein uniprot:P42338
PIK3CA Protein uniprot:P42336
PIK3CD Protein uniprot:O00329
PIP-5 kinase alpha Protein uniprot:Q99755
PIP-5 kinase gamma Protein uniprot:O60331
PIP-5 kinase beta Protein uniprot:O14986
4-phosphatase Protein eccode:3.1.3.78
PIP4P1 Protein uniprot:Q86T03
PIP4P2 Protein uniprot:Q8N4L2
PIP-4 kinase Protein eccode:2.7.1.149
PIP4K2A Protein uniprot:P48426
PIP4K2C Protein uniprot:Q8TBX8
PIP4K2B Protein uniprot:P78356
MTMR10 Protein uniprot:Q9NXD2
MTMR11 Protein uniprot:A4FU01
MTMR12 Protein uniprot:Q9C0I1
MTMR2 Protein uniprot:Q13614
MTMR3 Protein uniprot:Q13615
MTMR4 Protein uniprot:Q9NYA4
MTMR6 Protein uniprot:Q9Y217
MTMR7 Protein uniprot:Q9Y216
MTMR8 Protein uniprot:Q96EF0
MTMR9 Protein uniprot:Q96QG7
SBF2 Protein uniprot:Q86WG5
SBF1 Protein uniprot:O95248
PIK3CG Protein uniprot:P48736
PI-3 kinase I Protein eccode:2.7.1.137
PIK3CB Protein uniprot:P42338
PIK3CA Protein uniprot:P42336
PIK3CD Protein uniprot:O00329
PI-3 kinase II Protein eccode:2.7.1.154
PI3K-C2β Protein uniprot:O00750
PI3K-C2γ Protein uniprot:O75747
PIK3C3 Protein uniprot:Q8NEB9
PIK3R4 Protein uniprot:Q99570
ADP Metabolite chebi:456216
H+ Metabolite chebi:15378
MTM1 Protein uniprot:Q13496

References

  1. Laporte J, Hu LJ, Kretz C, Mandel JL, Kioschis P, Coy JF, et al. A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. Nat Genet. 1996 Jun;13(2):175–82. PubMed Europe PMC Scholia
  2. Rameh LE, Tolias KF, Duckworth BC, Cantley LC. A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate. Nature. 1997 Nov 13;390(6656):192–6. PubMed Europe PMC Scholia
  3. Rohrschneider LR, Fuller JF, Wolf I, Liu Y, Lucas DM. Structure, function, and biology of SHIP proteins. Genes Dev. 2000 Mar 1;14(5):505–20. PubMed Europe PMC Scholia
  4. Bolino A, Muglia M, Conforti FL, LeGuern E, Salih MA, Georgiou DM, et al. Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Nat Genet. 2000 May;25(1):17–9. PubMed Europe PMC Scholia
  5. Li S, Tiab L, Jiao X, Munier FL, Zografos L, Frueh BE, et al. Mutations in PIP5K3 are associated with François-Neetens mouchetée fleck corneal dystrophy. Am J Hum Genet. 2005 Jul;77(1):54–63. PubMed Europe PMC Scholia
  6. Ungewickell A, Hugge C, Kisseleva M, Chang S-C, Zou J, Feng Y, et al. The identification and characterization of two phosphatidylinositol-4,5-bisphosphate 4-phosphatases. Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18854–9. PubMed Europe PMC Scholia
  7. Rusten TE, Stenmark H. Analyzing phosphoinositides and their interacting proteins. Nat Methods. 2006 Apr;3(4):251–8. PubMed Europe PMC Scholia
  8. Backer JM. The regulation and function of Class III PI3Ks: novel roles for Vps34. Biochem J. 2008 Feb 15;410(1):1–17. PubMed Europe PMC Scholia
  9. Malek M, Kielkowska A, Chessa T, Anderson KE, Barneda D, Pir P, et al. PTEN Regulates PI(3,4)P2 Signaling Downstream of Class I PI3K. Mol Cell. 2017 Nov 2;68(3):566-580.e10. PubMed Europe PMC Scholia