2qv2: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2qv2.gif|left|200px]]
- {{Structure
+==A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway==
-|PDB= 2qv2 |SIZE=350|CAPTION= <scene name='initialview01'>2qv2</scene>, resolution 2.40&Aring;
+<StructureSection load='2qv2' size='340' side='right'caption='[[2qv2]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND=
+<table><tr><td colspan='2'>[[2qv2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QV2 FirstGlance]. <br>
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoinositide_5-phosphatase Phosphoinositide 5-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.36 3.1.3.36] </span>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-|GENE= OCRL, INPP5F, OCRL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qv2 OCA], [https://pdbe.org/2qv2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qv2 RCSB], [https://www.ebi.ac.uk/pdbsum/2qv2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qv2 ProSAT]</span></td></tr>
-|DOMAIN=
+</table>
-|RELATEDENTRY=
+== Disease ==
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qv2 OCA], [http://www.ebi.ac.uk/pdbsum/2qv2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qv2 RCSB]</span>
+[https://www.uniprot.org/uniprot/OCRL_HUMAN OCRL_HUMAN] Defects in OCRL are the cause of Lowe oculocerebrorenal syndrome (OCRL) [MIM:[https://omim.org/entry/309000 309000]. It is an X-linked multisystem disorder affecting eyes, nervous system, and kidney. It is characterized by hydrophthalmia, cataract, mental retardation, vitamin D-resistant rickets, aminoaciduria, and reduced ammonia production by the kidney. Ocular abnormalities include cataract, glaucoma, microphthalmos, and decreased visual acuity. Developmental delay, hypotonia, behavior abnormalities, and areflexia are also present. Renal tubular involvement is characterized by impaired reabsorption of bicarbonate, amino acids, and phosphate. Musculoskeletal abnormalities such as joint hypermobility, dislocated hips, and fractures may develop as consequences of renal tubular acidosis and hypophosphatemia. Cataract is the only significant manifestation in carriers and is detected by slit-lamp examination.<ref>PMID:20133602</ref> <ref>PMID:21233288</ref> <ref>PMID:9199559</ref> <ref>PMID:9682219</ref> <ref>PMID:9632163</ref> <ref>PMID:9788721</ref> <ref>PMID:10923037</ref> <ref>PMID:10767176</ref> <ref>PMID:19168822</ref> <ref>PMID:21031565</ref>   Defects in OCRL are the cause of Dent disease type 2 (DD2) [MIM:[https://omim.org/entry/300555 300555]. DD2 is a renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Characteristic abnormalities include low-molecular-weight proteinuria and other features of Fanconi syndrome, such as glycosuria, aminoaciduria, and phosphaturia, but typically do not include proximal renal tubular acidosis. Progressive renal failure is common, as are nephrocalcinosis and kidney stones.<ref>PMID:21031565</ref> <ref>PMID:15627218</ref> <ref>PMID:17384968</ref>
-}}
+== Function ==
+[https://www.uniprot.org/uniprot/OCRL_HUMAN OCRL_HUMAN] Converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate. Also converts inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate and inositol 1,3,4,5-tetrakisphosphate to inositol 1,3,4-trisphosphate. May function in lysosomal membrane trafficking by regulating the specific pool of phosphatidylinositol 4,5-bisphosphate that is associated with lysosomes. Involved in primary cilia assembly.<ref>PMID:22543976</ref> <ref>PMID:22228094</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qv/2qv2_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2qv2 ConSurf].
+<div style="clear:both"></div>
-'''A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway'''
+==See Also==
+*[[3D structures of inositol polyphosphate 5-phosphatase OCRL|3D structures of inositol polyphosphate 5-phosphatase OCRL]]
+== References ==
-==Overview==
+<references/>
-Mutations in the inositol 5-phosphatase OCRL are responsible for Lowe syndrome, whose manifestations include mental retardation and renal Fanconi syndrome. OCRL has been implicated in membrane trafficking, but disease mechanisms remain unclear. We show that OCRL visits late-stage, endocytic clathrin-coated pits and binds the Rab5 effector APPL1 on peripheral early endosomes. The interaction with APPL1, which is mediated by the ASH-RhoGAP-like domains of OCRL and is abolished by disease mutations, provides a link to protein networks implicated in the reabsorptive function of the kidney and in the trafficking and signaling of growth factor receptors in the brain. Crystallographic studies reveal a role of the ASH-RhoGAP-like domains in positioning the phosphatase domain at the membrane interface and a clathrin box protruding from the RhoGAP-like domain. Our results support a role of OCRL in the early endocytic pathway, consistent with the predominant localization of its preferred substrates, PI(4,5)P(2) and PI(3,4,5)P(3), at the cell surface.
+__TOC__
+</StructureSection>
-==About this Structure==
-QV2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QV2 OCA].
-==Reference==
-A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway., Erdmann KS, Mao Y, McCrea HJ, Zoncu R, Lee S, Paradise S, Modregger J, Biemesderfer D, Toomre D, De Camilli P, Dev Cell. 2007 Sep;13(3):377-90. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17765681 17765681]
 [[Category: Homo sapiens]]
-[[Category: Phosphoinositide 5-phosphatase]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: De Camilli P]]
-[[Category: Camilli, P De.]]
+[[Category: Erdman KS]]
-[[Category: Erdman, K S.]]
+[[Category: Mao Y]]
-[[Category: Mao, Y.]]
+[[Category: McCrea HJ]]
-[[Category: McCrea, H J.]]
-[[Category: appl1]]
-[[Category: ash]]
-[[Category: clathrin]]
-[[Category: endocytosis]]
-[[Category: hydrolase]]
-[[Category: phosphoinositide]]
-[[Category: rhogap]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:53:39 2008''