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MetaCyc Pathway: D-myo-inositol-5-phosphate metabolism
Inferred from experiment

Enzyme View:

Pathway diagram: D-myo-inositol-5-phosphate metabolism

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisFatty Acid and Lipid BiosynthesisPhospholipid Biosynthesis
BiosynthesisSecondary Metabolites BiosynthesisSugar Derivatives BiosynthesisCyclitols Biosynthesis

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Homo sapiens, Rattus norvegicus, Saccharomyces cerevisiae

Expected Taxonomic Range: Eukaryota

General Background

myo-Inositol-containing phospholipids play an important role in the control of cellular functions within eukaryotic cells, being part of the intracellular signal transductions pathways from various regulators, including hormones, neurotransmitters, growth factors, and serum [Michell75]. When these regulators interact with their receptors in cell membranes, they induce the hydrolysis of certain phosphoinositides to produce second messenger molecules.

phosphatidylinositol 5-phosphate was discovered in 1997 in mammalian fibroblasts as a source for phosphatidylinositol 4,5-bisphosphate [Rameh97], and is still considered the least-characterized member of the phosphoinositol family. It is believed to play a role as a regulator of membrane trafficking [Lecompte08].

The best established pathway for the synthesis of phosphatidylinositol 5-phosphate is the dephosphorylation of 1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate, catalyzed by a number of myotubularin-related phosphatases, such as MTMR3 [Walker01] and MTMR14 [Tosch06]. Another source for the compound is the removal of the 4-phosphate group from a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate by either of two dedicated phsphatases, encoded by TMEM55A and TMEM55B [Ungewickell05].

It has been shown that phosphatidylinositol 5-phosphate is phosphorylated to a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate by phosphatidylinositol-5-phosphate 4-kinase, encoded by PIP4K2A [Rameh97]. However, the concentration of phosphatidylinositol 5-phosphate in the cell is very low (about 2% of phosphatidylinositol 4-phosphate), and thus it is unlikely that its main role is as a source of a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthesis. However, the exact role of this compound in the cell is still unknown.

Superpathways: superpathway of inositol phosphate compounds

Created 26-Oct-2009 by Caspi R, SRI International


Carricaburu03: Carricaburu V, Lamia KA, Lo E, Favereaux L, Payrastre B, Cantley LC, Rameh LE (2003). "The phosphatidylinositol (PI)-5-phosphate 4-kinase type II enzyme controls insulin signaling by regulating PI-3,4,5-trisphosphate degradation." Proc Natl Acad Sci U S A 100(17);9867-72. PMID: 12897244

Clarke01: Clarke JH, Letcher AJ, D'santos CS, Halstead JR, Irvine RF, Divecha N (2001). "Inositol lipids are regulated during cell cycle progression in the nuclei of murine erythroleukaemia cells." Biochem J 357(Pt 3);905-10. PMID: 11463365

Gozani03: Gozani O, Karuman P, Jones DR, Ivanov D, Cha J, Lugovskoy AA, Baird CL, Zhu H, Field SJ, Lessnick SL, Villasenor J, Mehrotra B, Chen J, Rao VR, Brugge JS, Ferguson CG, Payrastre B, Myszka DG, Cantley LC, Wagner G, Divecha N, Prestwich GD, Yuan J (2003). "The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor." Cell 114(1);99-111. PMID: 12859901

Lecompte08: Lecompte O, Poch O, Laporte J (2008). "PtdIns5P regulation through evolution: roles in membrane trafficking?." Trends Biochem Sci 33(10);453-60. PMID: 18774718

Meijer01: Meijer HJ, Berrie CP, Iurisci C, Divecha N, Musgrave A, Munnik T (2001). "Identification of a new polyphosphoinositide in plants, phosphatidylinositol 5-monophosphate (PtdIns5P), and its accumulation upon osmotic stress." Biochem J 360(Pt 2);491-8. PMID: 11716778

Michell75: Michell RH (1975). "Inositol phospholipids and cell surface receptor function." Biochim Biophys Acta 415(1);81-47. PMID: 164246

Morris00: Morris JB, Hinchliffe KA, Ciruela A, Letcher AJ, Irvine RF (2000). "Thrombin stimulation of platelets causes an increase in phosphatidylinositol 5-phosphate revealed by mass assay." FEBS Lett 475(1);57-60. PMID: 10854858

Pagliarini04: Pagliarini DJ, Worby CA, Dixon JE (2004). "A PTEN-like phosphatase with a novel substrate specificity." J Biol Chem 279(37);38590-6. PMID: 15247229

Rameh97: Rameh LE, Tolias KF, Duckworth BC, Cantley LC (1997). "A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate." Nature 390(6656);192-6. PMID: 9367159

Rohde02: Rohde G, Wenzel D, Haucke V (2002). "A phosphatidylinositol (4,5)-bisphosphate binding site within mu2-adaptin regulates clathrin-mediated endocytosis." J Cell Biol 158(2);209-14. PMID: 12119359

Schaletzky03: Schaletzky J, Dove SK, Short B, Lorenzo O, Clague MJ, Barr FA (2003). "Phosphatidylinositol-5-phosphate activation and conserved substrate specificity of the myotubularin phosphatidylinositol 3-phosphatases." Curr Biol 13(6);504-9. PMID: 12646134

Tosch06: Tosch V, Rohde HM, Tronchere H, Zanoteli E, Monroy N, Kretz C, Dondaine N, Payrastre B, Mandel JL, Laporte J (2006). "A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy." Hum Mol Genet 15(21);3098-106. PMID: 17008356

Ungewickell05: Ungewickell A, Hugge C, Kisseleva M, Chang SC, Zou J, Feng Y, Galyov EE, Wilson M, Majerus PW (2005). "The identification and characterization of two phosphatidylinositol-4,5-bisphosphate 4-phosphatases." Proc Natl Acad Sci U S A 102(52);18854-9. PMID: 16365287

Walker01: Walker DM, Urbe S, Dove SK, Tenza D, Raposo G, Clague MJ (2001). "Characterization of MTMR3. an inositol lipid 3-phosphatase with novel substrate specificity." Curr Biol 11(20);1600-5. PMID: 11676921

Zhang07b: Zhang Y, Zolov SN, Chow CY, Slutsky SG, Richardson SC, Piper RC, Yang B, Nau JJ, Westrick RJ, Morrison SJ, Meisler MH, Weisman LS (2007). "Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice." Proc Natl Acad Sci U S A 104(44);17518-23. PMID: 17956977

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Barr02: Barr AJ, Marjoram R, Xu J, Snyderman R (2002). "Phospholipase C-beta 2 interacts with mitogen-activated protein kinase kinase 3." Biochem Biophys Res Commun 293(1);647-52. PMID: 12054652

Bazenet90: Bazenet CE, Ruano AR, Brockman JL, Anderson RA (1990). "The human erythrocyte contains two forms of phosphatidylinositol-4-phosphate 5-kinase which are differentially active toward membranes." J Biol Chem 265(29);18012-22. PMID: 2170402

Bertagnolo02: Bertagnolo V, Marchisio M, Pierpaoli S, Colamussi ML, Brugnoli F, Visani G, Zauli G, Capitani S (2002). "Selective up-regulation of phospholipase C-beta2 during granulocytic differentiation of normal and leukemic hematopoietic progenitors." J Leukoc Biol 71(6);957-65. PMID: 12050180

Boronenkov95: Boronenkov IV, Anderson RA (1995). "The sequence of phosphatidylinositol-4-phosphate 5-kinase defines a novel family of lipid kinases." J Biol Chem 270(7);2881-4. PMID: 7852364

Buck02: Buck E, Schatz P, Scarlata S, Iyengar R (2002). "Role of dynamic interactions in effective signal transfer for Gbeta stimulation of phospholipase C-beta 2." J Biol Chem 277(51);49707-15. PMID: 12388553

Cheng95: Cheng HF, Jiang MJ, Chen CL, Liu SM, Wong LP, Lomasney JW, King K (1995). "Cloning and identification of amino acid residues of human phospholipase C delta 1 essential for catalysis." J Biol Chem 270(10);5495-505. PMID: 7890667

Divecha95: Divecha N, Truong O, Hsuan JJ, Hinchliffe KA, Irvine RF (1995). "The cloning and sequence of the C isoform of PtdIns4P 5-kinase." Biochem J 309 ( Pt 3);715-9. PMID: 7639683

Evellin02: Evellin S, Nolte J, Tysack K, vom Dorp F, Thiel M, Weernink PA, Jakobs KH, Webb EJ, Lomasney JW, Schmidt M (2002). "Stimulation of phospholipase C-epsilon by the M3 muscarinic acetylcholine receptor mediated by cyclic AMP and the GTPase Rap2B." J Biol Chem 277(19);16805-13. PMID: 11877431

Hernandez94: Hernandez D, Egan SE, Yulug IG, Fisher EM (1994). "Mapping the gene that encodes phosphatidylinositol-specific phospholipase C-gamma 2 in the human and the mouse." Genomics 23(2);504-7. PMID: 7835906

Hinchliffe96: Hinchliffe KA, Irvine RF, Divecha N (1996). "Aggregation-dependent, integrin-mediated increases in cytoskeletally associated PtdInsP2 (4,5) levels in human platelets are controlled by translocation of PtdIns 4-P 5-kinase C to the cytoskeleton." EMBO J 15(23);6516-24. PMID: 8978678

Hirayama95: Hirayama T, Ohto C, Mizoguchi T, Shinozaki K (1995). "A gene encoding a phosphatidylinositol-specific phospholipase C is induced by dehydration and salt stress in Arabidopsis thaliana." Proc Natl Acad Sci U S A 1995;92(9);3903-7. PMID: 7732004

Ishikawa97: Ishikawa S, Takahashi T, Ogawa M, Nakamura Y (1997). "Genomic structure of the human PLCD1 (phospholipase C delta 1) locus on 3p22-->p21.3." Cytogenet Cell Genet 78(1);58-60. PMID: 9345909

Keshamouni02: Keshamouni VG, Mattingly RR, Reddy KB (2002). "Mechanism of 17-beta-estradiol-induced Erk1/2 activation in breast cancer cells. A role for HER2 AND PKC-delta." J Biol Chem 277(25);22558-65. PMID: 11960991

Laporte02: Laporte J, Liaubet L, Blondeau F, Tronchere H, Mandel JL, Payrastre B (2002). "Functional redundancy in the myotubularin family." Biochem Biophys Res Commun 291(2);305-12. PMID: 11846405

Laporte98: Laporte J, Blondeau F, Buj-Bello A, Tentler D, Kretz C, Dahl N, Mandel JL (1998). "Characterization of the myotubularin dual specificity phosphatase gene family from yeast to human." Hum Mol Genet 7(11);1703-12. PMID: 9736772

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Ling89: Ling LE, Schulz JT, Cantley LC (1989). "Characterization and purification of membrane-associated phosphatidylinositol-4-phosphate kinase from human red blood cells." J Biol Chem 264(9);5080-8. PMID: 2538472

Lopez01: Lopez I, Mak EC, Ding J, Hamm HE, Lomasney JW (2001). "A novel bifunctional phospholipase c that is regulated by Galpha 12 and stimulates the Ras/mitogen-activated protein kinase pathway." J Biol Chem 276(4);2758-65. PMID: 11022047

Melin92: Melin PM, Pical C, Jergil B, Sommarin M (1992). "Polyphosphoinositide phospholipase C in wheat root plasma membranes. Partial purification and characterization." Biochim Biophys Acta 1123(2);163-9. PMID: 1310875

Niebuhr00: Niebuhr K, Jouihri N, Allaoui A, Gounon P, Sansonetti PJ, Parsot C (2000). "IpgD, a protein secreted by the type III secretion machinery of Shigella flexneri, is chaperoned by IpgE and implicated in entry focus formation." Mol Microbiol 38(1);8-19. PMID: 11029686

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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