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From Proteopedia
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| + | ==See Also== | ||
| + | *[[Inositol polyphosphate 5-phosphatase OCRL|Inositol polyphosphate 5-phosphatase OCRL]] | ||
| + | *[[3D structures of inositol polyphosphate 5-phosphatase OCRL|3D structures of inositol polyphosphate 5-phosphatase OCRL]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 06:38, 16 March 2022
A PH domain within OCRL bridges clathrin mediated membrane trafficking to phosphoinositide metabolis
Structural highlights
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 PubMedOCRL, 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. See Also
References
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Categories: Human | Large Structures | Phosphoinositide 5-phosphatase | Balkin, D M | Camilli, P De | Erdmann, K | Hodsdon, M E | Hu, F | Jin, M M | Mao, Y | Tomasini, L | Zoncu, R | Alternative splicing | Cataract | Clathrin | Disease mutation | Endocytosis | Hydrolase | Inpp5b | Ocrl | Ph
