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PDBsum entry 2kig
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Endocytosis, hydrolase
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PDB id
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2kig
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Enzyme class:
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E.C.3.1.3.36
- phosphoinositide 5-phosphatase.
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Pathway:
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1-Phosphatidyl-myo-inositol Metabolism
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Reaction:
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a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + phosphate
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1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate)
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+
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H2O
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=
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1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate)
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+
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phosphate
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Embo J
28:1831-1842
(2009)
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PubMed id:
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A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism.
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Y.Mao,
D.M.Balkin,
R.Zoncu,
K.S.Erdmann,
L.Tomasini,
F.Hu,
M.M.Jin,
M.E.Hodsdon,
P.De Camilli.
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ABSTRACT
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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.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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H.Hichri,
J.Rendu,
N.Monnier,
C.Coutton,
O.Dorseuil,
R.V.Poussou,
G.Baujat,
A.Blanchard,
F.Nobili,
B.Ranchin,
M.Remesy,
R.Salomon,
V.Satre,
and
J.Lunardi
(2011).
From Lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes.
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Hum Mutat,
32,
379-388.
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M.Pirruccello,
L.E.Swan,
E.Folta-Stogniew,
and
P.De Camilli
(2011).
Recognition of the F&H motif by the Lowe syndrome protein OCRL.
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Nat Struct Mol Biol,
18,
789-795.
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PDB code:
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X.Hou,
N.Hagemann,
S.Schoebel,
W.Blankenfeldt,
R.S.Goody,
K.S.Erdmann,
and
A.Itzen
(2011).
A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1.
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EMBO J,
30,
1659-1670.
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PDB code:
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F.Nakatsu,
R.M.Perera,
L.Lucast,
R.Zoncu,
J.Domin,
F.B.Gertler,
D.Toomre,
and
P.De Camilli
(2010).
The inositol 5-phosphatase SHIP2 regulates endocytic clathrin-coated pit dynamics.
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J Cell Biol,
190,
307-315.
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L.E.Swan,
L.Tomasini,
M.Pirruccello,
J.Lunardi,
and
P.De Camilli
(2010).
Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.
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Proc Natl Acad Sci U S A,
107,
3511-3516.
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S.P.Bothwell,
L.W.Farber,
A.Hoagland,
and
R.L.Nussbaum
(2010).
Species-specific difference in expression and splice-site choice in Inpp5b, an inositol polyphosphate 5-phosphatase paralogous to the enzyme deficient in Lowe Syndrome.
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Mamm Genome,
21,
458-466.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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}
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