2kie

From Proteopedia

(Difference between revisions)

Current revision

A PH domain within OCRL bridges clathrin mediated membrane trafficking to phosphoinositide metabolis

Structural highlights

2kie is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 20 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

OCRL_HUMAN Defects in OCRL are the cause of Lowe oculocerebrorenal syndrome (OCRL) [MIM: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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] Defects in OCRL are the cause of Dent disease type 2 (DD2) [MIM: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.^[11] ^[12] ^[13]

Function

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.^[14] ^[15]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

OCRL, whose mutations are responsible for Lowe syndrome and Dent disease, and INPP5B are two similar proteins comprising a central inositol 5-phosphatase domain followed by an ASH and a RhoGAP-like domain. Their divergent NH2-terminal portions remain uncharacterized. We show that the NH2-terminal region of OCRL, but not of INPP5B, binds clathrin heavy chain. OCRL, which in contrast to INPP5B visits late stage endocytic clathrin-coated pits, was earlier shown to contain another binding site for clathrin in its COOH-terminal region. NMR structure determination further reveals that despite their primary sequence dissimilarity, the NH2-terminal portions of both OCRL and INPP5B contain a PH domain. The novel clathrin-binding site in OCRL maps to an unusual clathrin-box motif located in a loop of the PH domain, whose mutations reduce recruitment efficiency of OCRL to coated pits. These findings suggest an evolutionary pressure for a specialized function of OCRL in bridging phosphoinositide metabolism to clathrin-dependent membrane trafficking.

A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism.,Mao Y, Balkin DM, Zoncu R, Erdmann KS, Tomasini L, Hu F, Jin MM, Hodsdon ME, De Camilli P EMBO J. 2009 Jul 8;28(13):1831-42. Epub 2009 Jun 18. PMID:19536138^[16]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Swan LE, Tomasini L, Pirruccello M, Lunardi J, De Camilli P. Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1. Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3511-6. doi:, 10.1073/pnas.0914658107. Epub 2010 Feb 2. PMID:20133602 doi:10.1073/pnas.0914658107
↑ Noakes CJ, Lee G, Lowe M. The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway. Mol Biol Cell. 2011 Mar 1;22(5):606-23. doi: 10.1091/mbc.E10-08-0730. Epub 2011, Jan 13. PMID:21233288 doi:10.1091/mbc.E10-08-0730
↑ Lin T, Orrison BM, Leahey AM, Suchy SF, Bernard DJ, Lewis RA, Nussbaum RL. Spectrum of mutations in the OCRL1 gene in the Lowe oculocerebrorenal syndrome. Am J Hum Genet. 1997 Jun;60(6):1384-8. PMID:9199559 doi:10.1086/515471
↑ Lin T, Orrison BM, Suchy SF, Lewis RA, Nussbaum RL. Mutations are not uniformly distributed throughout the OCRL1 gene in Lowe syndrome patients. Mol Genet Metab. 1998 May;64(1):58-61. PMID:9682219 doi:S1096-7192(98)92687-7
↑ 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. 1998 Jun 5;77(5):348-55. PMID:9632163
↑ Kubota T, Sakurai A, Arakawa K, Shimazu M, Wakui K, Furihata K, Fukushima Y. Identification of two novel mutations in the OCRL1 gene in Japanese families with Lowe syndrome. Clin Genet. 1998 Sep;54(3):199-202. PMID:9788721
↑ Monnier N, Satre V, Lerouge E, Berthoin F, Lunardi J. OCRL1 mutation analysis in French Lowe syndrome patients: implications for molecular diagnosis strategy and genetic counseling. Hum Mutat. 2000;16(2):157-65. PMID:10923037 doi:<157::AID-HUMU8>3.0.CO;2-9 10.1002/1098-1004(200008)16:2<157::AID-HUMU8>3.0.CO;2-9
↑ Roschinger W, Muntau AC, Rudolph G, Roscher AA, Kammerer S. Carrier assessment in families with lowe oculocerebrorenal syndrome: novel mutations in the OCRL1 gene and correlation of direct DNA diagnosis with ocular examination. Mol Genet Metab. 2000 Mar;69(3):213-22. PMID:10767176 doi:10.1006/mgme.1999.2955
↑ Yuksel A, Karaca E, Albayram MS. Magnetic resonance imaging, magnetic resonance spectroscopy, and facial dysmorphism in a case of Lowe syndrome with novel OCRL1 gene mutation. J Child Neurol. 2009 Jan;24(1):93-6. doi: 10.1177/0883073808321047. PMID:19168822 doi:10.1177/0883073808321047
↑ Hichri H, Rendu J, Monnier N, Coutton C, Dorseuil O, Poussou RV, Baujat G, Blanchard A, Nobili F, Ranchin B, Remesy M, Salomon R, Satre V, Lunardi J. From Lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes. Hum Mutat. 2011 Apr;32(4):379-88. doi: 10.1002/humu.21391. Epub 2011 Mar 10. PMID:21031565 doi:10.1002/humu.21391
↑ Hichri H, Rendu J, Monnier N, Coutton C, Dorseuil O, Poussou RV, Baujat G, Blanchard A, Nobili F, Ranchin B, Remesy M, Salomon R, Satre V, Lunardi J. From Lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes. Hum Mutat. 2011 Apr;32(4):379-88. doi: 10.1002/humu.21391. Epub 2011 Mar 10. PMID:21031565 doi:10.1002/humu.21391
↑ Hoopes RR Jr, Shrimpton AE, Knohl SJ, Hueber P, Hoppe B, Matyus J, Simckes A, Tasic V, Toenshoff B, Suchy SF, Nussbaum RL, Scheinman SJ. Dent Disease with mutations in OCRL1. Am J Hum Genet. 2005 Feb;76(2):260-7. Epub 2004 Dec 30. PMID:15627218 doi:10.1086/427887
↑ Sekine T, Nozu K, Iyengar R, Fu XJ, Matsuo M, Tanaka R, Iijima K, Matsui E, Harita Y, Inatomi J, Igarashi T. OCRL1 mutations in patients with Dent disease phenotype in Japan. Pediatr Nephrol. 2007 Jul;22(7):975-80. Epub 2007 Mar 24. PMID:17384968 doi:10.1007/s00467-007-0454-x
↑ Luo N, West CC, Murga-Zamalloa CA, Sun L, Anderson RM, Wells CD, Weinreb RN, Travers JB, Khanna H, Sun Y. OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome. Hum Mol Genet. 2012 Aug 1;21(15):3333-44. doi: 10.1093/hmg/dds163. Epub 2012 Apr , 27. PMID:22543976 doi:10.1093/hmg/dds163
↑ Coon BG, Hernandez V, Madhivanan K, Mukherjee D, Hanna CB, Barinaga-Rementeria Ramirez I, Lowe M, Beales PL, Aguilar RC. The Lowe syndrome protein OCRL1 is involved in primary cilia assembly. Hum Mol Genet. 2012 Apr 15;21(8):1835-47. doi: 10.1093/hmg/ddr615. Epub 2012 Jan , 6. PMID:22228094 doi:10.1093/hmg/ddr615
↑ Mao Y, Balkin DM, Zoncu R, Erdmann KS, Tomasini L, Hu F, Jin MM, Hodsdon ME, De Camilli P. A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism. EMBO J. 2009 Jul 8;28(13):1831-42. Epub 2009 Jun 18. PMID:19536138 doi:10.1038/emboj.2009.155

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2kie"

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:2kie.jpg|left|200px]]
-<!--
+==A PH domain within OCRL bridges clathrin mediated membrane trafficking to phosphoinositide metabolis==
-The line below this paragraph, containing "STRUCTURE_2kie", creates the "Structure Box" on the page.
+<StructureSection load='2kie' size='340' side='right'caption='[[2kie]]' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2kie]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KIE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KIE FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
--->
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kie OCA], [https://pdbe.org/2kie PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kie RCSB], [https://www.ebi.ac.uk/pdbsum/2kie PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kie ProSAT]</span></td></tr>
-{{STRUCTURE_2kie|  PDB=2kie  |  SCENE=  }}
+</table>
+== Disease ==
+[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/ki/2kie_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2kie ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+OCRL, whose mutations are responsible for Lowe syndrome and Dent disease, and INPP5B are two similar proteins comprising a central inositol 5-phosphatase domain followed by an ASH and a RhoGAP-like domain. Their divergent NH2-terminal portions remain uncharacterized. We show that the NH2-terminal region of OCRL, but not of INPP5B, binds clathrin heavy chain. OCRL, which in contrast to INPP5B visits late stage endocytic clathrin-coated pits, was earlier shown to contain another binding site for clathrin in its COOH-terminal region. NMR structure determination further reveals that despite their primary sequence dissimilarity, the NH2-terminal portions of both OCRL and INPP5B contain a PH domain. The novel clathrin-binding site in OCRL maps to an unusual clathrin-box motif located in a loop of the PH domain, whose mutations reduce recruitment efficiency of OCRL to coated pits. These findings suggest an evolutionary pressure for a specialized function of OCRL in bridging phosphoinositide metabolism to clathrin-dependent membrane trafficking.
-===A PH domain within OCRL bridges clathrin mediated membrane trafficking to phosphoinositide metabolis===
+A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism.,Mao Y, Balkin DM, Zoncu R, Erdmann KS, Tomasini L, Hu F, Jin MM, Hodsdon ME, De Camilli P EMBO J. 2009 Jul 8;28(13):1831-42. Epub 2009 Jun 18. PMID:19536138<ref>PMID:19536138</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2kie" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_19536138}}, adds the Publication Abstract to the page
+*[[Inositol polyphosphate 5-phosphatase OCRL|Inositol polyphosphate 5-phosphatase OCRL]]
-(as it appears on PubMed at http://www.pubmed.gov), where 19536138 is the PubMed ID number.
+*[[3D structures of inositol polyphosphate 5-phosphatase OCRL|3D structures of inositol polyphosphate 5-phosphatase OCRL]]
--->
+== References ==
-{{ABSTRACT_PUBMED_19536138}}
+<references/>
+__TOC__
-==About this Structure==
+</StructureSection>
-KIE is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KIE OCA].
-==Reference==
-<ref group="xtra">PMID:19536138</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Phosphoinositide 5-phosphatase]]
+[[Category: Large Structures]]
-[[Category: Balkin, D M.]]
+[[Category: Balkin DM]]
-[[Category: Camilli, P De.]]
+[[Category: De Camilli P]]
-[[Category: Erdmann, K.]]
+[[Category: Erdmann K]]
-[[Category: Hodsdon, M E.]]
+[[Category: Hodsdon ME]]
-[[Category: Hu, F.]]
+[[Category: Hu F]]
-[[Category: Jin, M M.]]
+[[Category: Jin MM]]
-[[Category: Mao, Y.]]
+[[Category: Mao Y]]
-[[Category: Tomasini, L.]]
+[[Category: Tomasini L]]
-[[Category: Zoncu, R.]]
+[[Category: Zoncu R]]
-[[Category: Alternative splicing]]
-[[Category: Cataract]]
-[[Category: Clathrin]]
-[[Category: Disease mutation]]
-[[Category: Endocytosis]]
-[[Category: Hydrolase]]
-[[Category: Inpp5b]]
-[[Category: Ocrl]]
-[[Category: Ph]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 22 20:28:49 2009''

2kie

From Proteopedia

Current revision

A PH domain within OCRL bridges clathrin mediated membrane trafficking to phosphoinositide metabolis

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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Proteopedia Page Contributors and Editors (what is this?)

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