The Enzyme Database

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EC 2.7.1.68     
Accepted name: 1-phosphatidylinositol-4-phosphate 5-kinase
Reaction: ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
For diagram of 1-phosphatidyl-myo-inositol metabolism (part 2), click here
Glossary: 1-phosphatidyl-1D-myo-inositol = PtdIns
1-phosphatidyl-1D-myo-inositol 3-phosphate = PtdIns3P
1-phosphatidyl-1D-myo-inositol 4-phosphate = PtdIns4P
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate = PtdIns(3,4)P2
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = PtdIns(4,5)P2
Other name(s): diphosphoinositide kinase; PIP kinase; phosphatidylinositol 4-phosphate kinase; phosphatidylinositol-4-phosphate 5-kinase; type I PIP kinase
Systematic name: ATP:1-phosphatidyl-1D-myo-inositol-4-phosphate 5-phosphotransferase
Comments: This enzyme can also phosphorylate PtdIns3P in the 4-position, and PtdIns, PtdIns3P and PtdIns(3,4)P2 in the 5-position in vitro, but to a lesser extent. The last of these reactions occurs in vivo and is physiologically relevant. Three different isoforms are known.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 104645-76-3
References:
1.  Kai, M., Salway, J.G. and Hawthorne, J.N. The diphosphoinositide kinase of rat brain. Biochem. J. 106 (1968) 791–801. [PMID: 4295336]
2.  Kai, M., Salway, J.G., Michell, R.H. and Hawthorne, J.N. The biosynthesis of triphosphoinositide by rat brain in vitro. Biochem. Biophys. Res. Commun. 22 (1966) 370–375.
3.  Rameh, L.E., Tolias, K.F., Duckworth, B.C. and Cantley, L.C. A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate. Nature 390 (1997) 192–196. [DOI] [PMID: 9367159]
[EC 2.7.1.68 created 1972, modified 1980, modified 1982, modified 2002]
 
 
EC 2.7.1.153     
Accepted name: phosphatidylinositol-4,5-bisphosphate 3-kinase
Reaction: ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
For diagram of 1-phosphatidyl-myo-inositol metabolism (part 2), click here
Glossary: 1-phosphatidyl-1D-myo-inositol = PtdIns
1-phosphatidyl-1D-myo-inositol 3-phosphate = PtdIns3P
1-phosphatidyl-1D-myo-inositol 4-phosphate = PtdIns4P
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate = PtdIns(3,4)P2
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = PtdIns(4,5)P2
1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate = PtdIns(3,4,5)P3
Other name(s): type I phosphoinositide 3-kinase
Systematic name: ATP:1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 3-phosphotransferase
Comments: This enzyme also catalyses the phosphorylation of PtdIns4P to PtdIns(3,4)P2, and of PtdIns to PtdIns3P. Four mammalian isoforms are known to exist.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 103843-30-7
References:
1.  Vanhaesebroeck, B., Leevers, S.J., Ahmadi, K., Timms, J., Katso, R., Driscoll, P.C., Woscholski, R., Parker, P.J. and Waterfield, M.D. Synthesis and function of 3-phosphorylated inositol lipids. Annu. Rev. Biochem. 70 (2001) 535–602. [DOI] [PMID: 11395417]
[EC 2.7.1.153 created 2002]
 
 
EC 2.7.1.154     
Accepted name: phosphatidylinositol-4-phosphate 3-kinase
Reaction: ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
For diagram of 1-phosphatidyl-myo-inositol metabolism, click here
Glossary: 1-phosphatidyl-1D-myo-inositol = PtdIns
1-phosphatidyl-1D-myo-inositol 3-phosphate = PtdIns3P
1-phosphatidyl-1D-myo-inositol 4-phosphate = PtdIns4P
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate = PtdIns(3,4)P2
Other name(s): type II phosphoinositide 3-kinase; C2-domain-containing phosphoinositide 3-kinase; phosphoinositide 3-kinase
Systematic name: ATP:1-phosphatidyl-1D-myo-inositol-4-phosphate 3-phosphotransferase
Comments: This enzyme also phosphorylates PtdIns to PtdIns3P. Three mammalian isoforms have been found to date.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 141176-94-5
References:
1.  Vanhaesebroeck, B., Leevers, S.J., Ahmadi, K., Timms, J., Katso, R., Driscoll, P.C., Woscholski, R., Parker, P.J. and Waterfield, M.D. Synthesis and function of 3-phosphorylated inositol lipids. Annu. Rev. Biochem. 70 (2001) 535–602. [DOI] [PMID: 11395417]
[EC 2.7.1.154 created 2002]
 
 
EC 3.1.3.78     
Accepted name: phosphatidylinositol-4,5-bisphosphate 4-phosphatase
Reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 5-phosphate + phosphate
Glossary: 1-phosphatidyl-1D-myo-inositol 3-phosphate = PtdIns3P
1-phosphatidyl-1D-myo-inositol 4-phosphate = PtdIns4P
1-phosphatidyl-1D-myo-inositol 5-phosphate = PtdIns5P
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate = PtdIns(3,4)P2
1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate = PtdIns(3,5)P2
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = PtdIns(4,5)P2
1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate = PtdIns(3,4,5)P3
Other name(s): phosphatidylinositol-4,5-bisphosphate 4-phosphatase I; phosphatidylinositol-4,5-bisphosphate 4-phosphatase II; type I PtdIns-4,5-P2 4-Ptase; type II PtdIns-4,5-P2 4-Ptase; IpgD; PtdIns-4,5-P2 4-phosphatase type I; PtdIns-4,5-P2 4-phosphatase type II; type I phosphatidylinositol-4,5-bisphosphate 4-phosphatase; type 1 4-phosphatase
Systematic name: 1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 4-phosphohydrolase
Comments: 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 and the other by EC 3.1.3.36, phosphoinositide 5-phosphatase, where the product is PtdIns4P. 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]. It can control nuclear levels of PtdIns5P and thereby control p53-dependent apoptosis [3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Niebuhr, K., Giuriato, S., Pedron, T., Philpott, D.J., Gaits, F., Sable, J., Sheetz, M.P., Parsot, C., Sansonetti, P.J. and Payrastre, B. Conversion of PtdIns(4,5)P2 into PtdIns(5)P by the S. flexneri effector IpgD reorganizes host cell morphology. EMBO J. 21 (2002) 5069–5078. [DOI] [PMID: 12356723]
2.  Ungewickell, A., Hugge, C., Kisseleva, M., Chang, S.C., Zou, J., Feng, Y., Galyov, E.E., Wilson, M. and Majerus, P.W. The identification and characterization of two phosphatidylinositol-4,5-bisphosphate 4-phosphatases. Proc. Natl. Acad. Sci. USA 102 (2005) 18854–18859. [DOI] [PMID: 16365287]
3.  Zou, J., Marjanovic, J., Kisseleva, M.V., Wilson, M. and Majerus, P.W. Type I phosphatidylinositol-4,5-bisphosphate 4-phosphatase regulates stress-induced apoptosis. Proc. Natl. Acad. Sci. USA 104 (2007) 16834–16839. [DOI] [PMID: 17940011]
4.  Mason, D., Mallo, G.V., Terebiznik, M.R., Payrastre, B., Finlay, B.B., Brumell, J.H., Rameh, L. and Grinstein, S. Alteration of epithelial structure and function associated with PtdIns(4,5)P2 degradation by a bacterial phosphatase. J. Gen. Physiol. 129 (2007) 267–283. [DOI] [PMID: 17389247]
[EC 3.1.3.78 created 2008]
 
 
EC 3.1.3.86     
Accepted name: phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase
Reaction: 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + phosphate
For diagram of 1-phosphatidyl-myo-inositol metabolism, click here
Glossary: 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate = PtdIns(3,4)P2
1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate = PtdIns(3,4,5)P3
1-phosphatidyl-1D-myo-inositol 1,3,4,5-trisphosphate = PtdIns(1,3,4,5)P4
Other name(s): SHIP1; SHIP2; SHIP; p150Ship
Systematic name: 1-phosphatidyl-1D-myo-inositol-3,4,5-trisphosphate 5-phosphohydrolase
Comments: This enzyme hydrolyses 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. The enzyme also shows activity toward (PtdIns(1,3,4,5)P4) [5]. The enzyme is involved in several signal transduction pathways in the immune system leading to an adverse range of effects.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Lioubin, M.N., Algate, P.A., Tsai, S., Carlberg, K., Aebersold, A. and Rohrschneider, L.R. p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity. Genes Dev. 10 (1996) 1084–1095. [DOI] [PMID: 8654924]
2.  Damen, J.E., Liu, L., Rosten, P., Humphries, R.K., Jefferson, A.B., Majerus, P.W. and Krystal, G. 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. USA 93 (1996) 1689–1693. [DOI] [PMID: 8643691]
3.  Giuriato, S., Payrastre, B., Drayer, A.L., Plantavid, M., Woscholski, R., Parker, P., Erneux, C. and Chap, H. Tyrosine phosphorylation and relocation of SHIP are integrin-mediated in thrombin-stimulated human blood platelets. J. Biol. Chem. 272 (1997) 26857–26863. [DOI] [PMID: 9341117]
4.  Drayer, A.L., Pesesse, X., De Smedt, F., Woscholski, R., Parker, P. and Erneux, C. 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 (1996) 243–249. [DOI] [PMID: 8769125]
5.  Pesesse, X., Moreau, C., Drayer, A.L., Woscholski, R., Parker, P. and Erneux, C. The SH2 domain containing inositol 5-phosphatase SHIP2 displays phosphatidylinositol 3,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate 5-phosphatase activity. FEBS Lett. 437 (1998) 301–303. [DOI] [PMID: 9824312]
[EC 3.1.3.86 created 2011]
 
 


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