MetaCyc Enzyme: type IV inositol polyphosphate 5-phosphatase

Gene: INPP5E Accession Number: HS09270 (MetaCyc)

Synonyms: KIAA0123, inositol polyphosphate-5-phosphatase, 72kDa

Species: Homo sapiens

General Background

The signalling activities of both D-myo-inositol (1,4,5)-trisphosphate and D-myo-inositol (1,3,4,5)-tetrakisphosphate are terminated by hydrolysis of their 5-phosphate groups. The inositol polyphosphate 5-phosphatases have been subdivided into four subgroups based on their size and substrate specificity [Jefferson97, Erneux98].

Type I enzymes hydrolyze only the water soluble D-myo-inositol (1,4,5)-trisphosphate and D-myo-inositol (1,3,4,5)-tetrakisphosphate [Verjans94, Laxminarayan94].

Type II enzymes also accept the insoluble phospholipids 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate and a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate as substrates [Jefferson95, Jackson95].

Type III enzymes hydrolyze only phosphoinositides and inositol polyphosphates that have a 3-position phosphate group, such as 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate [Jackson95].

Type IV enzymes hydrolyze 1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate, 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate, and a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate D-myo-inositol (1,3,4,5)-tetrakisphosphate [Jefferson97]. They do not accept water soluble cyclitols [Kisseleva00].

About This Protein

INPP5E encodes a type IV inositol polyphosphate 5-phosphatase. An EST from human infant brain was identified by searching for conserved 5-phosphatase motifs. The EST was used to screen a human fetal brain cDNA library, and the full sequence was obtained. The enzyme was overexpressed in cultured insect cells using the Bac-to-Bac expression system, and a His-tagged version was purified [Kisseleva00].

The enzyme hydrolyzes only lipid substrates, 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate and a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate. It is a highly basic protein (pI = 8.8) and has the greatest affinity toward phosphatidylinositol 3,4,5-trisphosphate of known 5-phosphatases. The protein was found to be highly expressed in the human brain. mRNA was detected in many tissues and cell lines.

Map Position: [130,994,603 -> 131,007,700]

Molecular Weight of Polypeptide: 70.205 kD (from nucleotide sequence)

pI: 8.8 [Kisseleva00]

Unification Links: ArrayExpress:Q9NRR6 , Entrez-Nucleotide:AF187891 , PhosphoSite:Q9NRR6 , PhylomeDB:Q9NRR6 , Pride:Q9NRR6 , Protein Model Portal:Q9NRR6 , SMR:Q9NRR6 , String:9606.ENSP00000360777 , UniProt:Q9NRR6

Relationship Links: InterPro:IN-FAMILY:IPR000300 , InterPro:IN-FAMILY:IPR005135 , PDB:Structure:2XSW , Pfam:IN-FAMILY:PF03372 , Smart:IN-FAMILY:SM00128

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Created 27-Oct-2009 by Caspi R , SRI International

Enzymatic reaction of: phosphatidylinositol-4,5-bisphosphate 5-phosphatase (type IV inositol polyphosphate 5-phosphatase)

EC Number:

a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O <=> a 1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

In Pathways: 3-phosphoinositide degradation

Enzymatic reaction of: phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase (type IV inositol polyphosphate 5-phosphatase)

EC Number:

1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate + H2O <=> a 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + phosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

In Pathways: 3-phosphoinositide degradation

Kinetic Parameters:

Km (μM)
1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate


Schematic showing introns, exons and/or isoforms of INPP5E


Erneux98: Erneux C, Govaerts C, Communi D, Pesesse X (1998). "The diversity and possible functions of the inositol polyphosphate 5-phosphatases." Biochim Biophys Acta 1436(1-2);185-99. PMID: 9838104

Jackson95: 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

Jefferson95: Jefferson AB, Majerus PW (1995). "Properties of type II inositol polyphosphate 5-phosphatase." J Biol Chem 270(16);9370-7. PMID: 7721860

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

Kisseleva00: Kisseleva MV, Wilson MP, Majerus PW (2000). "The isolation and characterization of a cDNA encoding phospholipid-specific inositol polyphosphate 5-phosphatase." J Biol Chem 275(26);20110-6. PMID: 10764818

Laxminarayan94: Laxminarayan KM, Chan BK, Tetaz T, Bird PI, Mitchell CA (1994). "Characterization of a cDNA encoding the 43-kDa membrane-associated inositol-polyphosphate 5-phosphatase." J Biol Chem 269(25);17305-10. PMID: 8006039

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

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

Verjans94: Verjans B, De Smedt F, Lecocq R, Vanweyenberg V, Moreau C, Erneux C (1994). "Cloning and expression in Escherichia coli of a dog thyroid cDNA encoding a novel inositol 1,4,5-trisphosphate 5-phosphatase." Biochem J 300 ( Pt 1);85-90. PMID: 8198557

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

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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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