The protein deficient in Lowe syndrome is a phosphatidylinositol-4,5-bisphosphate 5-phosphatase

Proc Natl Acad Sci U S A. 1995 May 23;92(11):4853-6. doi: 10.1073/pnas.92.11.4853.


Lowe syndrome, also known as oculocerebrorenal syndrome, is caused by mutations in the X chromosome-encoded OCRL gene. The OCRL protein is 51% identical to inositol polyphosphate 5-phosphatase II (5-phosphatase II) from human platelets over a span of 744 aa, suggesting that OCRL may be a similar enzyme. We engineered a construct of the OCRL cDNA that encodes amino acids homologous to the platelet 5-phosphatase for expression in baculovirus-infected Sf9 insect cells. This cDNA encodes aa 264-968 of the OCRL protein. The recombinant protein was found to catalyze the reactions also carried out by platelet 5-phosphatase II. Thus OCRL converts inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate, and it converts inositol 1,3,4,5-tetrakisphosphate to inositol 1,3,4-trisphosphate. Most important, the enzyme converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate. The relative ability of OCRL to catalyze the three reactions is different from that of 5-phosphatase II and from that of another 5-phosphatase isoenzyme from platelets, 5-phosphatase I. The recombinant OCRL protein hydrolyzes the phospholipid substrate 10- to 30-fold better than 5-phosphatase II, and 5-phosphatase I does not cleave the lipid at all. We also show that OCRL functions as a phosphatidylinositol 4,5-bisphosphate 5-phosphatase in OCRL-expressing Sf9 cells. These results suggest that OCRL is mainly a lipid phosphatase that may control cellular levels of a critical metabolite, phosphatidylinositol 4,5-bisphosphate. Deficiency of this enzyme apparently causes the protean manifestations of Lowe syndrome.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blood Platelets / enzymology
  • Chromatography, High Pressure Liquid
  • DNA Primers
  • Humans
  • Isoenzymes / metabolism
  • Kinetics
  • Molecular Sequence Data
  • Oculocerebrorenal Syndrome / enzymology*
  • Oculocerebrorenal Syndrome / genetics*
  • Phosphoric Monoester Hydrolases / deficiency*
  • Phosphoric Monoester Hydrolases / genetics*
  • Phosphoric Monoester Hydrolases / metabolism
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • Proteins / genetics*
  • Proteins / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Spodoptera
  • Transfection
  • X Chromosome*


  • DNA Primers
  • Isoenzymes
  • Proteins
  • Recombinant Proteins
  • Phosphoric Monoester Hydrolases
  • OCRL protein, human
  • phosphoinositide 5-phosphatase