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:||Biosynthesis → Secondary Metabolites Biosynthesis → Sugar Derivatives Biosynthesis → Cyclitols Biosynthesis|
Expected Taxonomic Range: Eukaryota
D-myo-inositol (1,4,5)-trisphosphate is a secondary messenger molecule used in signal transduction and lipid signaling in eukaryotic cells. It mediates the biological response of a large number of hormones and neurotransmitters in target cells by regulating calcium release from intracellular stores. D-myo-inositol (1,4,5)-trisphosphate is synthesized by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the plasma membrane, by the action of phospholipase C, as described in D-myo-inositol (1,4,5)-trisphosphate biosynthesis.
Once formed, the levels of D-myo-inositol (1,4,5)-trisphosphate are tightly regulated by two mechanisms.
In the first mechanism, which is described in this pathway, the compound is dephosphorylated in three successive steps, via D-myo-inositol (1,4)-bisphosphate and 1D-myo-inositol 4-monophosphate [Downes82, Storey84], providing myo-inositol that can be recycled to the plasma membrane as posphatidylinositol.
In the second mechanism, D-myo-inositol (1,4,5)-trisphosphate is phosphorylated further to generate additional phosphoinositol compounds, many of which play key roles in various cellular processes (see D-myo-inositol (1,3,4)-trisphosphate biosynthesis).
Irvine86: Irvine RF, Letcher AJ, Heslop JP, Berridge MJ (1986). "The inositol tris/tetrakisphosphate pathway - demonstration of Ins(1,4,5)P3 3-kinase activity in animal tissues." Nature 320(6063);631-4. PMID: 3010126
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
Zhong04: Zhong R, Ye ZH (2004). "Molecular and biochemical characterization of three WD-repeat-domain-containing inositol polyphosphate 5-phosphatases in Arabidopsis thaliana." Plant Cell Physiol 45(11);1720-8. PMID: 15574849
Ananieva08: Ananieva EA, Gillaspy GE, Ely A, Burnette RN, Erickson FL (2008). "Interaction of the WD40 domain of a myoinositol polyphosphate 5-phosphatase with SnRK1 links inositol, sugar, and stress signaling." Plant Physiol 148(4);1868-82. PMID: 18931139
Arai07: Arai R, Ito K, Ohnishi T, Ohba H, Akasaka R, Bessho Y, Hanawa-Suetsugu K, Yoshikawa T, Shirouzu M, Yokoyama S (2007). "Crystal structure of human myo-inositol monophosphatase 2, the product of the putative susceptibility gene for bipolar disorder, schizophrenia, and febrile seizures." Proteins 67(3);732-42. PMID: 17340635
Attree92: Attree O, Olivos IM, Okabe I, Bailey LC, Nelson DL, Lewis RA, McInnes RR, Nussbaum RL (1992). "The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase." Nature 358(6383);239-42. PMID: 1321346
Berdy01: Berdy SE, Kudla J, Gruissem W, Gillaspy GE (2001). "Molecular characterization of At5PTase1, an inositol phosphatase capable of terminating inositol trisphosphate signaling." Plant Physiol 126(2);801-10. PMID: 11402208
Bone94: Bone R, Frank L, Springer JP, Atack JR (1994). "Structural studies of metal binding by inositol monophosphatase: evidence for two-metal ion catalysis." Biochemistry 33(32);9468-76. PMID: 8068621
Cremona00: Cremona O, Nimmakayalu M, Haffner C, Bray-Ward P, Ward DC, De Camilli P (2000). "Assignment of SYNJ1 to human chromosome 21q22.2 and Synj12 to the murine homologous region on chromosome 16C3-4 by in situ hybridization." Cytogenet Cell Genet 88(1-2);89-90. PMID: 10773674
De94b: De Smedt F, Verjans B, Mailleux P, Erneux C (1994). "Cloning and expression of human brain type I inositol 1,4,5-trisphosphate 5-phosphatase. High levels of mRNA in cerebellar Purkinje cells." FEBS Lett 347(1);69-72. PMID: 8013665
De96b: De Smedt F, Boom A, Pesesse X, Schiffmann SN, Erneux C (1996). "Post-translational modification of human brain type I inositol-1,4,5-trisphosphate 5-phosphatase by farnesylation." J Biol Chem 271(17);10419-24. PMID: 8626616
Ganzhorn96: Ganzhorn AJ, Lepage P, Pelton PD, Strasser F, Vincendon P, Rondeau JM (1996). "The contribution of lysine-36 to catalysis by human myo-inositol monophosphatase." Biochemistry 35(33);10957-66. PMID: 8718889
Haffner97: Haffner C, Takei K, Chen H, Ringstad N, Hudson A, Butler MH, Salcini AE, Di Fiore PP, De Camilli P (1997). "Synaptojanin 1: localization on coated endocytic intermediates in nerve terminals and interaction of its 170 kDa isoform with Eps15." FEBS Lett 419(2-3);175-80. PMID: 9428629
Ijuin00: Ijuin T, Mochizuki Y, Fukami K, Funaki M, Asano T, Takenawa T (2000). "Identification and characterization of a novel inositol polyphosphate 5-phosphatase." J Biol Chem 275(15);10870-5. PMID: 10753883
Jackson95a: Jackson SP, Schoenwaelder SM, Matzaris M, Brown S, Mitchell CA (1995). "Phosphatidylinositol 3,4,5-trisphosphate is a substrate for the 75 kDa inositol polyphosphate 5-phosphatase and a novel 5-phosphatase which forms a complex with the p85/p110 form of phosphoinositide 3-kinase." EMBO J 14(18);4490-500. PMID: 7556092
Jefferson97: Jefferson AB, Auethavekiat V, Pot DA, Williams LT, Majerus PW (1997). "Signaling inositol polyphosphate-5-phosphatase. Characterization of activity and effect of GRB2 association." J Biol Chem 272(9);5983-8. PMID: 9038219
Kaye11: Kaye Y, Golani Y, Singer Y, Leshem Y, Cohen G, Ercetin M, Gillaspy G, Levine A (2011). "Inositol polyphosphate 5-phosphatase7 regulates the production of reactive oxygen species and salt tolerance in Arabidopsis." Plant Physiol 157(1);229-41. PMID: 21677096
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