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 the compound is dephosphorylated to D-myo-inositol (1,4)-bisphosphate [Downes82, Storey84], initiating a pathway that recycles the inositol moiety to the plasma membrane as phosphatidylinositols.
In the second mechanism, it is phosphorylated by inositol 1,4,5-trisphosphate 3-kinase to D-myo-inositol (1,3,4,5)-tetrakisphosphate. This compound has been suggested to have roles in controlling calcium homeostasis, transferring calcium between intracellular stores, and/or regulating calcium entry across the plasma membrane [Irvine91]. It may also play a role in regulating cross-talk between the calcium and other signaling pathways. A D-myo-inositol (1,3,4,5)-tetrakisphosphate-binding protein has been identified that can stimulate the GTPase activity of the ras and rap small GTP binding proteins [Cullen95a, Soriano97].
D-myo-inositol (1,3,4,5)-tetrakisphosphate can be cleaved to D-myo-inositol (1,3,4)-trisphosphate [Irvine86], or it could be phosphorylated further to D-myo-inositol 1,3,4,5,6-pentakisphosphate and eventually I1D-myo-inositol 1,2,3,4,5,6-hexakisphosphate [Berridge89, Shears89], as described in 1D-myo-inositol hexakisphosphate biosynthesis I (from Ins(1,4,5)P3).
D-myo-inositol (1,3,4)-trisphosphate links the degree and duration of receptor-dependent phospholipase C activation to the generation of D-myo-inositol (3,4,5,6)-tetrakisphosphate, a cellular signal that regulates the ionic conductance of Cl-channels [Xie98, Yang99c, Shears98].
Cullen95a: Cullen PJ, Hsuan JJ, Truong O, Letcher AJ, Jackson TR, Dawson AP, Irvine RF (1995). "Identification of a specific Ins(1,3,4,5)P4-binding protein as a member of the GAP1 family." Nature 376(6540);527-30. PMID: 7637787
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
Xie98: Xie W, Solomons KR, Freeman S, Kaetzel MA, Bruzik KS, Nelson DJ, Shears SB (1998). "Regulation of Ca2+-dependent Cl- conductance in a human colonic epithelial cell line (T84): cross-talk between Ins(3,4,5,6)P4 and protein phosphatases." J Physiol 510 ( Pt 3);661-73. PMID: 9660883
Yang99c: Yang X, Rudolf M, Carew MA, Yoshida M, Nerreter V, Riley AM, Chung SK, Bruzik KS, Potter BV, Schultz C, Shears SB (1999). "Inositol 1,3,4-trisphosphate acts in vivo as a specific regulator of cellular signaling by inositol 3,4,5,6-tetrakisphosphate." J Biol Chem 274(27);18973-80. PMID: 10383396
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
Caffrey99: Caffrey JJ, Hidaka K, Matsuda M, Hirata M, Shears SB (1999). "The human and rat forms of multiple inositol polyphosphate phosphatase: functional homology with a histidine acid phosphatase up-regulated during endochondral ossification." FEBS Lett 442(1);99-104. PMID: 9923613
Chang02: Chang SC, Miller AL, Feng Y, Wente SR, Majerus PW (2002). "The human homolog of the rat inositol phosphate multikinase is an inositol 1,3,4,6-tetrakisphosphate 5-kinase." J Biol Chem 277(46);43836-43. PMID: 12223481
Chi99: Chi H, Tiller GE, Dasouki MJ, Romano PR, Wang J, O'keefe RJ, Puzas JE, Rosier RN, Reynolds PR (1999). "Multiple inositol polyphosphate phosphatase: evolution as a distinct group within the histidine phosphatase family and chromosomal localization of the human and mouse genes to chromosomes 10q23 and 19." Genomics 56(3);324-36. PMID: 10087200
Cho08: Cho J, King JS, Qian X, Harwood AJ, Shears SB (2008). "Dephosphorylation of 2,3-bisphosphoglycerate by MIPP expands the regulatory capacity of the Rapoport-Luebering glycolytic shunt." Proc Natl Acad Sci U S A 105(16);5998-6003. PMID: 18413611
Craxton97: Craxton A, Caffrey JJ, Burkhart W, Safrany ST, Shears SB (1997). "Molecular cloning and expression of a rat hepatic multiple inositol polyphosphate phosphatase." Biochem J 328 ( Pt 1);75-81. PMID: 9359836
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
Cullen94: Cullen PJ, Patel Y, Kakkar VV, Irvine RF, Authi KS (1994). "Specific binding sites for inositol 1,3,4,5-tetrakisphosphate are located predominantly in the plasma membranes of human platelets." Biochem J 298 Pt 3;739-42. PMID: 8141791
Cullen95: Cullen PJ, Chung SK, Chang YT, Dawson AP, Irvine RF (1995). "Specificity of the purified inositol (1,3,4,5) tetrakisphosphate-binding protein from porcine platelets." FEBS Lett 358(3);240-2. PMID: 7843408
Damen96: Damen JE, Liu L, Rosten P, Humphries RK, Jefferson AB, Majerus PW, Krystal G (1996). "The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-triphosphate 5-phosphatase." Proc Natl Acad Sci U S A 93(4);1689-93. PMID: 8643691
De94: 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
De96: 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
Dewaste00: Dewaste V, Pouillon V, Moreau C, Shears S, Takazawa K, Erneux C (2000). "Cloning and expression of a cDNA encoding human inositol 1,4,5-trisphosphate 3-kinase C." Biochem J 352 Pt 2;343-51. PMID: 11085927
Dewaste02: Dewaste V, Roymans D, Moreau C, Erneux C (2002). "Cloning and expression of a full-length cDNA encoding human inositol 1,4,5-trisphosphate 3-kinase B." Biochem Biophys Res Commun 291(2);400-5. PMID: 11846419
Drayer96: Drayer AL, Pesesse X, De Smedt F, Woscholski R, Parker P, Erneux C (1996). "Cloning and expression of a human placenta inositol 1,3,4,5-tetrakisphosphate and phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase." Biochem Biophys Res Commun 225(1);243-9. PMID: 8769125
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