OCRL

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.[5]

OCRL
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4CMN, 2KIE, 2QV2, 3QBT, 3QIS
Identifiers
Aliases	OCRL, LOCR, NPHL2, OCRL-1, OCRL1, oculocerebrorenal syndrome of Lowe, inositol polyphosphate-5-phosphatase, OCRL inositol polyphosphate-5-phosphatase, INPP5F, Dent-2
External IDs	OMIM: 300535 MGI: 109589 HomoloGene: 233 GeneCards: OCRL
Gene location (Human) Chr. X chromosome (human)[1] Band Xq26.1 Start 129,539,849 bp[1] End 129,592,561 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X|X A5 Start 47,912,387 bp[2] End 47,965,868 bp[2]
Gene ontology Molecular function • Rac GTPase binding • phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity • GO:0001948 protein binding • hydrolase activity • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity • inositol-1,4,5-trisphosphate 5-phosphatase activity • inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity • phosphatidylinositol phosphate 4-phosphatase activity • phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity • inositol phosphate phosphatase activity Cellular component • cytoplasm • cytosol • endosome • phagocytic vesicle membrane • Golgi apparatus • cell projection • early endosome membrane • membrane • cell membrane • cilium • Golgi-associated vesicle • trans-Golgi network • early endosome • Golgi stack • clathrin-coated pit • cytoplasmic vesicle • cell nucleus • clathrin-coated vesicle • photoreceptor outer segment Biological process • lipid metabolism • GO:0043087, GO:0032313, GO:0032319, GO:0032314, GO:0043088 regulation of GTPase activity • in utero embryonic development • inositol phosphate metabolic process • cell projection organization • phosphatidylinositol dephosphorylation • phosphatidylinositol biosynthetic process • regulation of small GTPase mediated signal transduction • signal transduction • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • phosphatidylinositol-3-phosphate biosynthetic process • cilium morphogenesis • membrane organization • inositol phosphate dephosphorylation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4952	320634
Ensembl	ENSG00000122126	ENSMUSG00000001173
UniProt	Q01968	Q6NVF0
RefSeq (mRNA)	NM_000276 NM_001587 NM_001318784	NM_177215
RefSeq (protein)	NP_000267 NP_001305713 NP_001578	NP_796189
Location (UCSC)	Chr X: 129.54 – 129.59 Mb	Chr X: 47.91 – 47.97 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

This gene encodes a phosphatase enzyme involved in actin polymerization, and is found in the trans-Golgi network.[5]

Mutation in this gene are associated with oculocerebrorenal syndrome[6] and also with Dent's disease.[7][8]

References

1. GRCh38: Ensembl release 89: ENSG00000122126 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000001173 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: oculocerebrorenal syndrome of Lowe".
6. Kawano T, Indo Y, Nakazato H, Shimadzu M, Matsuda I (June 1998). "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. doi:10.1002/(SICI)1096-8628(19980605)77:5<348::AID-AJMG2>3.0.CO;2-J. PMID 9632163.
7. Online Mendelian Inheritance in Man (OMIM): 300555
8. Hoopes RR, Shrimpton AE, Knohl SJ, et al. (February 2005). "Dent Disease with mutations in OCRL1". Am. J. Hum. Genet. 76 (2): 260–7. doi:10.1086/427887. PMC 1196371. PMID 15627218.

Further reading

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

External links

• GeneReviews/NCBI/NIH/UW entry on Lowe Syndrome
• OCRL+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• PDBe-KB provides an overview of all the structure information available in the PDB for Human Inositol polyphosphate 5-phosphatase OCRL-1