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PDBsum entry 1a12
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Guanine nucleotide exchange factor
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PDB id
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1a12
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Contents |
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* Residue conservation analysis
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DOI no:
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Nature
392:97
(1998)
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PubMed id:
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The 1.7 A crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller.
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L.Renault,
N.Nassar,
I.Vetter,
J.Becker,
C.Klebe,
M.Roth,
A.Wittinghofer.
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ABSTRACT
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The gene encoding the regulator of chromosome condensation (RCC1) was cloned by
virtue of its ability to complement the temperature-sensitive phenotype of the
hamster cell line tsBN2, which undergoes premature chromosome condensation or
arrest in the G1 phase of the cell cycle at non-permissive temperatures. RCC1
homologues have been identified in many eukaryotes, including budding and
fission yeast. Mutations in the gene affect pre-messenger RNA processing and
transport, mating, initiation of mitosis and chromatin decondensation,
suggesting that RCC1 is important in the control of nucleo-cytoplasmic transport
and the cell cycle. Biochemically, RCC1 is a guanine-nucleotide-exchange factor
for the nuclear Ras homologue Ran; it increases the dissociation of Ran-bound
GDP by 10(5)-fold. It may also bind to DNAvia a protein-protein complex. Here we
show that the structure of human RCC1, solved to 1.7-A resolution by X-ray
crystallography, consists of a seven-bladed propeller formed from internal
repeats of 51-68 residues per blade. The sequence and structure of the repeats
differ from those of WD40-domain proteins, which also form seven-bladed
propellers and include the beta-subunits of G proteins. The nature of the
structure explains the consequences of a wide range of known mutations. The
region of the protein that is involved in guanine-nucleotide exchange is located
opposite the region that is thought to be involved in chromosome binding.
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Selected figure(s)
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Figure 1.
Figure 1 Overall three-dimensional structure of RCC1. Ribbon
diagram of the RCC1 propeller structure as viewed along (a) or
perpendicular to (b) the central shaft. The blades (a) are
numbered (B1-B7) along the sequence. Semiconserved histidines
that connect the blades and invariant residues believed to be
important for the interaction with Ran are shown as
ball-and-stick representations.
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Figure 2.
Figure 2 Primary- and secondary-structure alignment. Sequence
alignment, obtained using the GCG program (adjusted manually) of
five RCC1 homologues (from top to bottom: human, hamster,
Drosophila, Schizosaccharomyces pombe and Saccharomyces
cerevisiae) and the protein product, RPGR/RP3 of the X-linked
retinitis pigmentosa gene, along with the secondary structure of
human RCC1. The seven blades are coloured as in Fig. 1. Residues
highly conserved in seven RCC1 homologues (including Xenopus and
Caenorhabditis albicans RCC1) are boxed; invariant residues are
also shown in bold. The structurally conserved residues among
different repeats of RCC1 and RPGR/RP3 are shaded brown. Alanine
mutations that perturb the GEF activity14 are shown in blue
(human); the mutation responsible for the tsBN2 (refs 1, 2)
phenotype is shown in pink (hamster); and RCC1 mutations in S.
cerevisiae and S. pombe^3-7,13 are shown in red. Asterisks
indicate truncated sequences.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(1998,
392,
97-0)
copyright 1998.
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Figures were
selected
by an automated process.
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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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D.Wu,
Q.Hu,
Z.Yan,
W.Chen,
C.Yan,
X.Huang,
J.Zhang,
P.Yang,
H.Deng,
J.Wang,
X.Deng,
and
Y.Shi
(2012).
Structural basis of ultraviolet-B perception by UVR8.
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Nature,
484,
214-219.
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PDB codes:
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E.Glaus,
F.Schmid,
R.Da Costa,
W.Berger,
and
J.Neidhardt
(2011).
Gene therapeutic approach using mutation-adapted U1 snRNA to correct a RPGR splice defect in patient-derived cells.
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Mol Ther,
19,
936-941.
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F.Wu,
Y.Liu,
Z.Zhu,
H.Huang,
B.Ding,
J.Wu,
and
Y.Shi
(2011).
The 1.9Å crystal structure of Prp20p from Saccharomyces cerevisiae and its binding properties to Gsp1p and histones.
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J Struct Biol,
174,
213-222.
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PDB code:
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J.Heo
(2011).
Redox control of GTPases: from molecular mechanisms to functional significance in health and disease.
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Antioxid Redox Signal,
14,
689-724.
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L.Mathieu,
S.Marsy,
Y.Saint-Georges,
C.Jacq,
and
G.Dujardin
(2011).
A transcriptome screen in yeast identifies a novel assembly factor for the mitochondrial complex III.
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Mitochondrion,
11,
391-396.
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L.Rizzini,
J.J.Favory,
C.Cloix,
D.Faggionato,
A.O'Hara,
E.Kaiserli,
R.Baumeister,
E.Schäfer,
F.Nagy,
G.I.Jenkins,
and
R.Ulm
(2011).
Perception of UV-B by the Arabidopsis UVR8 protein.
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Science,
332,
103-106.
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S.Tan,
and
C.A.Davey
(2011).
Nucleosome structural studies.
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Curr Opin Struct Biol,
21,
128-136.
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B.G.Fuller
(2010).
Self-organization of intracellular gradients during mitosis.
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Cell Div,
5,
5.
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E.Hitakomate,
F.E.Hood,
H.S.Sanderson,
and
P.R.Clarke
(2010).
The methylated N-terminal tail of RCC1 is required for stabilisation of its interaction with chromatin by Ran in live cells.
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BMC Cell Biol,
11,
43.
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E.Wywial,
and
S.M.Singh
(2010).
Identification and structural characterization of FYVE domain-containing proteins of Arabidopsis thaliana.
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BMC Plant Biol,
10,
157.
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H.Wang
(2010).
Characterization of zebrafish Esrom (Myc-binding protein 2) RCC1-like domain splice variants.
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Mol Cell Biochem,
339,
191-199.
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J.R.England,
J.Huang,
M.J.Jennings,
R.D.Makde,
and
S.Tan
(2010).
RCC1 uses a conformationally diverse loop region to interact with the nucleosome: a model for the RCC1-nucleosome complex.
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J Mol Biol,
398,
518-529.
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M.Hatayama,
and
J.Aruga
(2010).
Characterization of the tandem CWCH2 sequence motif: a hallmark of inter-zinc finger interactions.
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BMC Evol Biol,
10,
53.
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R.D.Makde,
J.R.England,
H.P.Yennawar,
and
S.Tan
(2010).
Structure of RCC1 chromatin factor bound to the nucleosome core particle.
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Nature,
467,
562-566.
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PDB code:
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X.Shu,
Z.Zeng,
P.Gautier,
A.Lennon,
M.Gakovic,
E.E.Patton,
and
A.F.Wright
(2010).
Zebrafish Rpgr is required for normal retinal development and plays a role in dynein-based retrograde transport processes.
|
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Hum Mol Genet,
19,
657-670.
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C.Lai,
C.Xie,
H.Shim,
J.Chandran,
B.W.Howell,
and
H.Cai
(2009).
Regulation of endosomal motility and degradation by amyotrophic lateral sclerosis 2/alsin.
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Mol Brain,
2,
23.
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D.A.Bonsor,
O.Hecht,
M.Vankemmelbeke,
A.Sharma,
A.M.Krachler,
N.G.Housden,
K.J.Lilly,
R.James,
G.R.Moore,
and
C.Kleanthous
(2009).
Allosteric beta-propeller signalling in TolB and its manipulation by translocating colicins.
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EMBO J,
28,
2846-2857.
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PDB code:
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D.C.Soares,
P.N.Barlow,
D.J.Porteous,
and
R.S.Devon
(2009).
An interrupted beta-propeller and protein disorder: structural bioinformatics insights into the N-terminus of alsin.
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J Mol Model,
15,
113-122.
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G.I.Jenkins
(2009).
Signal transduction in responses to UV-B radiation.
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Annu Rev Plant Biol,
60,
407-431.
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J.J.Favory,
A.Stec,
H.Gruber,
L.Rizzini,
A.Oravecz,
M.Funk,
A.Albert,
C.Cloix,
G.I.Jenkins,
E.J.Oakeley,
H.K.Seidlitz,
F.Nagy,
and
R.Ulm
(2009).
Interaction of COP1 and UVR8 regulates UV-B-induced photomorphogenesis and stress acclimation in Arabidopsis.
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EMBO J,
28,
591-601.
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J.Pei,
P.J.Lupardus,
K.C.Garcia,
and
N.V.Grishin
(2009).
CPDadh: a new peptidase family homologous to the cysteine protease domain in bacterial MARTX toxins.
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Protein Sci,
18,
856-862.
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K.Lui,
and
Y.Huang
(2009).
RanGTPase: A Key Regulator of Nucleocytoplasmic Trafficking.
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Mol Cell Pharmacol,
1,
148-156.
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M.B.Frankel,
and
L.J.Knoll
(2009).
The ins and outs of nuclear trafficking: unusual aspects in apicomplexan parasites.
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DNA Cell Biol,
28,
277-284.
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P.Zhou,
F.Tian,
F.Lv,
and
Z.Shang
(2009).
Geometric characteristics of hydrogen bonds involving sulfur atoms in proteins.
|
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Proteins,
76,
151-163.
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W.Jonkers,
and
M.Rep
(2009).
Lessons from fungal F-box proteins.
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Eukaryot Cell,
8,
677-695.
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H.Cai,
H.Shim,
C.Lai,
C.Xie,
X.Lin,
W.J.Yang,
and
J.Chandran
(2008).
ALS2/alsin knockout mice and motor neuron diseases.
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Neurodegener Dis,
5,
359-366.
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I.Chaudhuri,
J.Söding,
and
A.N.Lupas
(2008).
Evolution of the beta-propeller fold.
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Proteins,
71,
795-803.
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M.B.Frankel,
and
L.J.Knoll
(2008).
Functional analysis of key nuclear trafficking components reveals an atypical Ran network required for parasite pathogenesis.
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Mol Microbiol,
70,
410-420.
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T.J.Stevens,
and
M.Paoli
(2008).
RCC1-like repeat proteins: a pangenomic, structurally diverse new superfamily of beta-propeller domains.
|
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Proteins,
70,
378-387.
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X.Shu,
E.McDowall,
A.F.Brown,
and
A.F.Wright
(2008).
The human retinitis pigmentosa GTPase regulator gene variant database.
|
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Hum Mutat,
29,
605-608.
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Y.Hao,
and
I.G.Macara
(2008).
Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1.
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J Cell Biol,
182,
827-836.
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A.Cook,
F.Bono,
M.Jinek,
and
E.Conti
(2007).
Structural biology of nucleocytoplasmic transport.
|
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Annu Rev Biochem,
76,
647-671.
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A.Young
(2007).
Structural insights into the clathrin coat.
|
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Semin Cell Dev Biol,
18,
448-458.
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B.Grill,
W.V.Bienvenut,
H.M.Brown,
B.D.Ackley,
M.Quadroni,
and
Y.Jin
(2007).
C. elegans RPM-1 regulates axon termination and synaptogenesis through the Rab GEF GLO-4 and the Rab GTPase GLO-1.
|
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Neuron,
55,
587-601.
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C.D.Krause,
Z.H.Yang,
Y.S.Kim,
J.H.Lee,
J.R.Cook,
and
S.Pestka
(2007).
Protein arginine methyltransferases: evolution and assessment of their pharmacological and therapeutic potential.
|
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Pharmacol Ther,
113,
50-87.
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J.Bosch,
T.Tamura,
N.Tamura,
W.Baumeister,
and
L.O.Essen
(2007).
The beta-propeller domain of the trilobed protease from Pyrococcus furiosus reveals an open Velcro topology.
|
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Acta Crystallogr D Biol Crystallogr,
63,
179-187.
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PDB code:
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J.Chandran,
J.Ding,
and
H.Cai
(2007).
Alsin and the molecular pathways of amyotrophic lateral sclerosis.
|
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Mol Neurobiol,
36,
224-231.
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J.Neidhardt,
E.Glaus,
D.Barthelmes,
C.Zeitz,
J.Fleischhauer,
and
W.Berger
(2007).
Identification and characterization of a novel RPGR isoform in human retina.
|
| |
Hum Mutat,
28,
797-807.
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M.B.Frankel,
D.G.Mordue,
and
L.J.Knoll
(2007).
Discovery of parasite virulence genes reveals a unique regulator of chromosome condensation 1 ortholog critical for efficient nuclear trafficking.
|
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Proc Natl Acad Sci U S A,
104,
10181-10186.
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M.Scheffner,
and
O.Staub
(2007).
HECT E3s and human disease.
|
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BMC Biochem,
8,
S6.
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P.R.Clarke
(2007).
Anchoring RCC1 by the tail.
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Nat Cell Biol,
9,
485-487.
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S.Escusa,
D.Laporte,
A.Massoni,
H.Boucherie,
A.Dautant,
and
B.Daignan-Fornier
(2007).
Skp1-Cullin-F-box-dependent degradation of Aah1p requires its interaction with the F-box protein Saf1p.
|
| |
J Biol Chem,
282,
20097-20103.
|
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X.Shu,
G.C.Black,
J.M.Rice,
N.Hart-Holden,
A.Jones,
A.O'Grady,
S.Ramsden,
and
A.F.Wright
(2007).
RPGR mutation analysis and disease: an update.
|
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Hum Mutat,
28,
322-328.
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A.S.Madrid,
and
K.Weis
(2006).
Nuclear transport is becoming crystal clear.
|
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Chromosoma,
115,
98.
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B.Friedrich,
C.Quensel,
T.Sommer,
E.Hartmann,
and
M.Köhler
(2006).
Nuclear localization signal and protein context both mediate importin alpha specificity of nuclear import substrates.
|
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Mol Cell Biol,
26,
8697-8709.
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E.Hirose,
M.Mukai,
A.Shimada,
H.Nishitani,
Y.Shibata,
and
T.Nishimoto
(2006).
Loss of RanGEF/Pim1 activity abolishes the orchestration of Ran-mediated mitotic cellular events in S. pombe.
|
| |
Genes Cells,
11,
29-46.
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T.Li,
X.Chen,
K.C.Garbutt,
P.Zhou,
and
N.Zheng
(2006).
Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase.
|
| |
Cell,
124,
105-117.
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PDB codes:
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B.Padmanabhan,
M.Scharlock,
K.I.Tong,
Y.Nakamura,
M.I.Kang,
A.Kobayashi,
T.Matsumoto,
A.Tanaka,
M.Yamamoto,
and
S.Yokoyama
(2005).
Purification, crystallization and preliminary X-ray diffraction analysis of the Kelch-like motif region of mouse Keap1.
|
| |
Acta Crystallogr Sect F Struct Biol Cryst Commun,
61,
153-155.
|
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|
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|
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D.Gogendeau,
A.M.Keller,
A.Yanagi,
J.Cohen,
and
F.Koll
(2005).
Nd6p, a novel protein with RCC1-like domains involved in exocytosis in Paramecium tetraurelia.
|
| |
Eukaryot Cell,
4,
2129-2139.
|
|
|
|
|
|
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P.A.Ferreira
(2005).
Insights into X-linked retinitis pigmentosa type 3, allied diseases and underlying pathomechanisms.
|
| |
Hum Mol Genet,
14,
R259-R267.
|
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A.Komuro,
Y.Masuda,
K.Kobayashi,
R.Babbitt,
M.Gunel,
R.A.Flavell,
and
V.T.Marchesi
(2004).
The AHNAKs are a class of giant propeller-like proteins that associate with calcium channel proteins of cardiomyocytes and other cells.
|
| |
Proc Natl Acad Sci U S A,
101,
4053-4058.
|
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J.D.Topp,
N.W.Gray,
R.D.Gerard,
and
B.F.Horazdovsky
(2004).
Alsin is a Rab5 and Rac1 guanine nucleotide exchange factor.
|
| |
J Biol Chem,
279,
24612-24623.
|
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|
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J.Dai,
J.Liu,
Y.Deng,
T.M.Smith,
and
M.Lu
(2004).
Structure and protein design of a human platelet function inhibitor.
|
| |
Cell,
116,
649-659.
|
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PDB codes:
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J.Ma,
H.Plesken,
J.E.Treisman,
I.Edelman-Novemsky,
and
M.Ren
(2004).
Lightoid and Claret: a rab GTPase and its putative guanine nucleotide exchange factor in biogenesis of Drosophila eye pigment granules.
|
| |
Proc Natl Acad Sci U S A,
101,
11652-11657.
|
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J.R.Hutchins,
W.J.Moore,
F.E.Hood,
J.S.Wilson,
P.D.Andrews,
J.R.Swedlow,
and
P.R.Clarke
(2004).
Phosphorylation regulates the dynamic interaction of RCC1 with chromosomes during mitosis.
|
| |
Curr Biol,
14,
1099-1104.
|
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|
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S.Y.Reddy,
and
T.C.Bruice
(2004).
Determination of enzyme mechanisms by molecular dynamics: studies on quinoproteins, methanol dehydrogenase, and soluble glucose dehydrogenase.
|
| |
Protein Sci,
13,
1965-1978.
|
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|
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Y.Zheng
(2004).
G protein control of microtubule assembly.
|
| |
Annu Rev Cell Dev Biol,
20,
867-894.
|
|
|
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|
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H.M.Loovers,
K.Veenstra,
H.Snippe,
X.Pesesse,
C.Erneux,
and
P.J.van Haastert
(2003).
A diverse family of inositol 5-phosphatases playing a role in growth and development in Dictyostelium discoideum.
|
| |
J Biol Chem,
278,
5652-5658.
|
|
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|
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|
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S.Prag,
and
J.C.Adams
(2003).
Molecular phylogeny of the kelch-repeat superfamily reveals an expansion of BTB/kelch proteins in animals.
|
| |
BMC Bioinformatics,
4,
42.
|
|
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|
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W.K.Wang,
V.Tereshko,
P.Boccuni,
D.MacGrogan,
S.D.Nimer,
and
D.J.Patel
(2003).
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D.K.Breuer,
B.M.Yashar,
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M.A.Musarella,
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Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE.
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EMBO J,
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PDB code:
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H.Neitzel,
L.M.Neumann,
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Nercc1, a mammalian NIMA-family kinase, binds the Ran GTPase and regulates mitotic progression.
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Genes Dev,
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Purification, cloning, and characterization of Nek8, a novel NIMA-related kinase, and its candidate substrate Bicd2.
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Crystal structure and kinetic analysis of beta-lactamase inhibitor protein-II in complex with TEM-1 beta-lactamase.
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Nat Struct Biol,
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PDB codes:
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I.G.Macara
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Microbiol Mol Biol Rev,
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Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1).
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Cell,
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PDB code:
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S.Hadano,
C.K.Hand,
H.Osuga,
Y.Yanagisawa,
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A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2.
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A streamlined process to phenotypically profile heterologous cDNAs in parallel using yeast cell-based assays.
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rpm-1, a conserved neuronal gene that regulates targeting and synaptogenesis in C. elegans.
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Mutations in conserved regions of the predicted RAG2 kelch repeats block initiation of V(D)J recombination and result in primary immunodeficiencies.
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Mol Cell Biol,
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Random mutagenesis and functional analysis of the Ran-binding protein, RanBP1.
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J Biol Chem,
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D.R.McCarty,
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Conservation and innovation in plant signaling pathways.
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Cell,
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Highwire regulates synaptic growth in Drosophila.
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Neuron,
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J.Adams,
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The kelch repeat superfamily of proteins: propellers of cell function.
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Trends Cell Biol,
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M.E.Nemergut,
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Nuclear import of the ran exchange factor, RCC1, is mediated by at least two distinct mechanisms.
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J Cell Biol,
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M.Zhen,
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Regulation of presynaptic terminal organization by C. elegans RPM-1, a putative guanine nucleotide exchanger with a RING-H2 finger domain.
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Neuron,
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S.S.Mahajan,
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Mutations in host cell factor 1 separate its role in cell proliferation from recruitment of VP16 and LZIP.
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Mol Cell Biol,
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T.Nishimoto
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Upstream and downstream of ran GTPase.
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Biol Chem,
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Curr Opin Cell Biol,
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Structural view of the Ran-Importin beta interaction at 2.3 A resolution.
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| |
Cell,
97,
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PDB code:
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J.Cherfils,
and
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(1999).
GEFs: structural basis for their activation of small GTP-binding proteins.
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Trends Biochem Sci,
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J.M.Pérez,
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The solution structure of the guanine nucleotide exchange domain of human elongation factor 1beta reveals a striking resemblance to that of EF-Ts from Escherichia coli.
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Structure,
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PDB code:
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K.Welch,
J.Franke,
M.Köhler,
and
I.G.Macara
(1999).
RanBP3 contains an unusual nuclear localization signal that is imported preferentially by importin-alpha3.
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Mol Cell Biol,
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L.Renault,
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Crystallization and preliminary X-ray analysis of human RCC1, the regulator of chromosome condensation.
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Acta Crystallogr D Biol Crystallogr,
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M.Linari,
M.Ueffing,
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The retinitis pigmentosa GTPase regulator, RPGR, interacts with the delta subunit of rod cyclic GMP phosphodiesterase.
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Proc Natl Acad Sci U S A,
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A.Wittinghofer,
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(1999).
The crystal structure of rna1p: a new fold for a GTPase-activating protein.
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Mol Cell,
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PDB code:
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R.Grossberger,
C.Gieffers,
W.Zachariae,
A.V.Podtelejnikov,
A.Schleiffer,
K.Nasmyth,
M.Mann,
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(1999).
Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex.
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S.J.Gamblin,
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Nuclear transport: what a kary-on!
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Structure,
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V.Fülöp,
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Beta propellers: structural rigidity and functional diversity.
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M.Stewart,
I.Vetter,
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Pictures in cell biology. Structures of nuclear-transport components.
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Trends Cell Biol,
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A very large protein with diverse functional motifs is deficient in rjs (runty, jerky, sterile) mice.
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Proc Natl Acad Sci U S A,
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PDB code:
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B.Aghazadeh,
K.Zhu,
T.J.Kubiseski,
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T.Pawson,
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Structure and mutagenesis of the Dbl homology domain.
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PDB code:
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D.Yan,
P.K.Swain,
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Biochemical characterization and subcellular localization of the mouse retinitis pigmentosa GTPase regulator (mRpgr).
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Atomic structure of clathrin: a beta propeller terminal domain joins an alpha zigzag linker.
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PDB code:
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J.Goldberg
(1998).
Structural basis for activation of ARF GTPase: mechanisms of guanine nucleotide exchange and GTP-myristoyl switching.
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Ran and nuclear transport.
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A glutamic finger in the guanine nucleotide exchange factor ARNO displaces Mg2+ and the beta-phosphate to destabilize GDP on ARF1.
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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
codes are
shown on the right.
|
|
Links
