OCRL explained

Inositol polyphosphate 5-phosphatase OCRL-1, also known as Lowe oculocerebrorenal syndrome protein, is an enzyme encoded by the OCRL gene located on the X chromosome in humans.^[1]

This gene encodes an inositol polyphosphate 5-phosphatase. The responsible gene locus is at Xq26.1. This phosphatase enzyme is in part responsible for regulating membrane trafficking actin polymerization, and is located in several subcellular parts of the trans-Golgi network.

Deficiencies in OCRL-1 may cause with oculocerebrorenal syndrome^[2] and also have been linked to Dent's disease.^[3]

Further reading

• Ross MT, Grafham DV, Coffey AJ, etal . The DNA sequence of the human X chromosome. . Nature . 434 . 7031 . 325–37 . 2005 . 15772651 . 10.1038/nature03440 . 2665286. 2005Natur.434..325R .
• Erdmann KS, Mao Y, McCrea HJ, etal . A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway. . Dev. Cell . 13 . 3 . 377–90 . 2007 . 17765681 . 10.1016/j.devcel.2007.08.004 . 2025683.
• Hyvola N, Diao A, McKenzie E, etal . Membrane targeting and activation of the Lowe syndrome protein OCRL1 by rab GTPases. . EMBO J. . 25 . 16 . 3750–61 . 2006 . 16902405 . 10.1038/sj.emboj.7601274 . 1553191.
• Mao Y, Balkin DM, Zoncu R, etal . A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism. . EMBO J. . 28 . 13 . 1831–42 . 2009 . 19536138 . 10.1038/emboj.2009.155 . 2711190.
• Suchy SF, Cronin JC, Nussbaum RL . Abnormal bradykinin signalling in fibroblasts deficient in the PIP(2) 5-phosphatase, ocrl1. . J. Inherit. Metab. Dis. . 32 . 2 . 280–8 . 2009 . 19172411 . 10.1007/s10545-009-1058-3 . 31583330 .
• Wu F, Reed AA, Williams SE, etal . Mutational analysis of CLC-5, cofilin and CLC-4 in patients with Dent's disease. . Nephron Physiol . 112 . 4 . 53–62 . 2009 . 19546591 . 10.1159/000225944 . 24946606 .
• Coon BG, Mukherjee D, Hanna CB, etal . Lowe syndrome patient fibroblasts display Ocrl1-specific cell migration defects that cannot be rescued by the homologous Inpp5b phosphatase. . Hum. Mol. Genet. . 18 . 23 . 4478–91 . 2009 . 19700499 . 10.1093/hmg/ddp407 . 7289333 . free .
• Tosetto E, Addis M, Caridi G, etal . Locus heterogeneity of Dent's disease: OCRL1 and TMEM27 genes in patients with no CLCN5 mutations. . Pediatr. Nephrol. . 24 . 10 . 1967–73 . 2009 . 19582483 . 10.1007/s00467-009-1228-4 . 25741167 .
• Faucherre A, Desbois P, Nagano F, etal . Lowe syndrome protein Ocrl1 is translocated to membrane ruffles upon Rac GTPase activation: a new perspective on Lowe syndrome pathophysiology. . Hum. Mol. Genet. . 14 . 11 . 1441–8 . 2005 . 15829501 . 10.1093/hmg/ddi153 . free .
• Shrimpton AE, Hoopes RR, Knohl SJ, etal . OCRL1 mutations in Dent 2 patients suggest a mechanism for phenotypic variability. . Nephron Physiol . 112 . 2 . 27–36 . 2009 . 19390221 . 10.1159/000213506 . 21834343 .
• Sekine T, Nozu K, Iyengar R, etal . OCRL1 mutations in patients with Dent disease phenotype in Japan. . Pediatr. Nephrol. . 22 . 7 . 975–80 . 2007 . 17384968 . 10.1007/s00467-007-0454-x . 20047399 .
• Chabaâ L, Monnier N, Dahri S . [Oculo-cerebro-renal Lowe syndrome: clinical, biochemical and molecular studies in a Moroccan patient] . Ann. Biol. Clin. (Paris) . 64 . 1 . 53–9 . 2006. 16420990 . etal.
• Choudhury R, Diao A, Zhang F, etal . Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network. . Mol. Biol. Cell . 16 . 8 . 3467–79 . 2005 . 15917292 . 10.1091/mbc.E05-02-0120 . 1182289.
• Sethi SK, Bagga A, Gulati A, etal . Mutations in OCRL1 gene in Indian children with Lowe syndrome. . Clin. Exp. Nephrol. . 12 . 5 . 358–62 . 2008 . 18500547 . 10.1007/s10157-008-0059-0 . 3458176 .
• Cui S, Guerriero CJ, Szalinski CM, etal . OCRL1 function in renal epithelial membrane traffic. . Am. J. Physiol. Renal Physiol. . 298 . 2 . F335-45 . 2010 . 19940034 . 10.1152/ajprenal.00453.2009 . 2822509.
• McCrea HJ, Paradise S, Tomasini L, etal . All known patient mutations in the ASH-RhoGAP domains of OCRL affect targeting and APPL1 binding. . Biochem. Biophys. Res. Commun. . 369 . 2 . 493–9 . 2008 . 18307981 . 10.1016/j.bbrc.2008.02.067 . 2442618.
• Hoopes RR, Shrimpton AE, Knohl SJ, etal . Dent Disease with mutations in OCRL1. . Am. J. Hum. Genet. . 76 . 2 . 260–7 . 2005 . 15627218 . 10.1086/427887 . 1196371.
• Levtchenko EN, Monnens LA, Bökenkamp A, Knoers NV . [From gene to disease; Dent's disease caused by abnormalities in the CLCN5 and OCRL1 genes] . Ned Tijdschr Geneeskd . 151 . 43 . 2377–80 . 2007 . 18019214 .
• Choudhury R, Noakes CJ, McKenzie E, etal . Differential clathrin binding and subcellular localization of OCRL1 splice isoforms. . J. Biol. Chem. . 284 . 15 . 9965–73 . 2009 . 19211563 . 10.1074/jbc.M807442200 . 2665120. free .
• Swan LE, Tomasini L, Pirruccello M, etal . Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1. . Proc. Natl. Acad. Sci. U.S.A. . 107 . 8 . 3511–6 . 2010 . 20133602 . 10.1073/pnas.0914658107 . 2840420. 2010PNAS..107.3511S . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Lowe Syndrome
  • PDBe-KB provides an overview of all the structure information available in the PDB for Human Inositol polyphosphate 5-phosphatase OCRL-1

Notes and References

1. Web site: Entrez Gene: oculocerebrorenal syndrome of Lowe.
2. Kawano T, Indo Y, Nakazato H, Shimadzu M, Matsuda I . Oculocerebrorenal syndrome of Lowe: three mutations in the OCRL1 gene derived from three patients with different phenotypes . Am. J. Med. Genet. . 77 . 5 . 348–55 . June 1998 . 9632163 . 10.1002/(SICI)1096-8628(19980605)77:5<348::AID-AJMG2>3.0.CO;2-J.
3. Hoopes RR, Shrimpton AE, Knohl SJ, etal . Dent Disease with mutations in OCRL1 . Am. J. Hum. Genet. . 76 . 2 . 260–7 . February 2005 . 15627218 . 1196371 . 10.1086/427887 .