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242 a.a.
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165 a.a.
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44 a.a.
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* Residue conservation analysis
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PDB id:
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RNA binding protein
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Title:
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Crystal structure of the RNA-binding domain of the mRNA export factor tap
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Structure:
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Tip associating protein. Chain: a, b, c, d, e. Fragment: residues 42-312. Synonym: tap. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Biol. unit:
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Decamer (from
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Resolution:
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3.15Å
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R-factor:
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0.303
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R-free:
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0.303
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Authors:
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E.Liker,E.Fernandez,E.Izaurralde,E.Conti
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Key ref:
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E.Liker
et al.
(2000).
The structure of the mRNA export factor TAP reveals a cis arrangement of a non-canonical RNP domain and an LRR domain.
EMBO J,
19,
5587-5598.
PubMed id:
DOI:
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Date:
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12-Sep-00
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Release date:
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11-Dec-00
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PROCHECK
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Headers
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References
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Q9UBU9
(NXF1_HUMAN) -
Nuclear RNA export factor 1 from Homo sapiens
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Seq:
Struc:
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619 a.a.
242 a.a.*
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Enzyme class:
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Chains A, B, C, D, E:
E.C.?
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DOI no:
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EMBO J
19:5587-5598
(2000)
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PubMed id:
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The structure of the mRNA export factor TAP reveals a cis arrangement of a non-canonical RNP domain and an LRR domain.
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E.Liker,
E.Fernandez,
E.Izaurralde,
E.Conti.
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ABSTRACT
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Human TAP is implicated in mRNA nuclear export and is used by simian type D
retroviruses to export their unspliced genomic RNA to the cytoplasm of the host
cell. We have determined the crystal structure of the minimal TAP fragment that
binds the constitutive transport element (CTE) of retroviral RNAs. Unexpectedly,
we find the fragment consists of a ribonucleoprotein (RNP) domain, which is not
identifiable by its sequence, and a leucine-rich repeat (LRR) domain. The
non-canonical RNP domain functions as the general RNA-binding portion of the
fragment. The LRR domain is required in cis to the RNP domain for CTE RNA
binding. The structural and biochemical properties of the domains point to a
remarkable similarity with the U2B"(RNP)-U2A'(LRR) spliceosomal
heterodimer. Our in vitro and in vivo functional studies using structure-based
mutants suggest that a phylogenetically conserved surface of the LRR domain of
TAP may have different roles in the export of viral and cellular RNAs.
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Selected figure(s)
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Figure 1.
Figure 1 Domain structure of human TAP. The N-terminal region of
the molecule includes the minimal CTE RNA-binding fragment
(residues 102–372) (Braun et al., 1999). The domain boundaries
of the RNP and the LRR domains (shaded in gray) are as
identified from this work. The domain mapping of the C-terminal
region is as previously described (Bachi et al., 2000; Suyama et
al., 2000).
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Figure 6.
Figure 6 Identification of putative macromolecular interaction
surfaces. (A) Ribbon diagram of the RNP domain in green with the
side chains of mutated residues in pink (see Figure 2C).
Residues that are essential for CTE binding are boxed. (B)
Surface representation of the RNP domain in a similar
orientation to (A). The surface is colored according to
electrostatic potential, with blue indicating positively charged
areas and red indicating negatively charged areas. (C) Structure
of the LRR domain viewed towards the convex  -helical
surface. Residues at this surface that have been mutated are
shown in pink (see Figure 3E). The molecule has been rotated
180° with respect to the view in Figure 3A. (D)
Electrostatic surface of the convex outer surface of the LRR
domain viewed as in (A), and colored as in (B). Residues whose
function is discussed in the text are labeled, and boxed when
essential.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2000,
19,
5587-5598)
copyright 2000.
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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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A.G.Murachelli,
J.Ebert,
C.Basquin,
H.Le Hir,
and
E.Conti
(2012).
The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex.
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Nat Struct Mol Biol,
19,
378-386.
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PDB codes:
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H.Zhao,
Y.Yang,
and
Y.Zhou
(2011).
Structure-based prediction of RNA-binding domains and RNA-binding sites and application to structural genomics targets.
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Nucleic Acids Res,
39,
3017-3025.
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M.Teplova,
L.Wohlbold,
N.W.Khin,
E.Izaurralde,
and
D.J.Patel
(2011).
Structure-function studies of nucleocytoplasmic transport of retroviral genomic RNA by mRNA export factor TAP.
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Nat Struct Mol Biol,
18,
990-998.
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PDB codes:
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J.M.Doolittle,
and
S.M.Gomez
(2010).
Structural similarity-based predictions of protein interactions between HIV-1 and Homo sapiens.
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Virol J,
7,
82.
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L.J.Colwell,
M.P.Brenner,
and
K.Ribbeck
(2010).
Charge as a selection criterion for translocation through the nuclear pore complex.
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PLoS Comput Biol,
6,
e1000747.
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M.Stewart
(2010).
Nuclear export of mRNA.
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Trends Biochem Sci,
35,
609-617.
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J.Katahira,
H.Inoue,
E.Hurt,
and
Y.Yoneda
(2009).
Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNA.
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EMBO J,
28,
556-567.
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K.L.Hindle,
J.Bella,
and
S.C.Lovell
(2009).
Quantitative analysis and prediction of curvature in leucine-rich repeat proteins.
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Proteins,
77,
342-358.
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F.Gabel,
B.Simon,
M.Nilges,
M.Petoukhov,
D.Svergun,
and
M.Sattler
(2008).
A structure refinement protocol combining NMR residual dipolar couplings and small angle scattering restraints.
|
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J Biomol NMR,
41,
199-208.
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G.M.Hautbergue,
M.L.Hung,
A.P.Golovanov,
L.Y.Lian,
and
S.A.Wilson
(2008).
Mutually exclusive interactions drive handover of mRNA from export adaptors to TAP.
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Proc Natl Acad Sci U S A,
105,
5154-5159.
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L.H.Matzat,
S.Berberoglu,
and
L.Lévesque
(2008).
Formation of a Tap/NXF1 Homotypic Complex Is Mediated through the Amino-Terminal Domain of Tap and Enhances Interaction with Nucleoporins.
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Mol Biol Cell,
19,
327-338.
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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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|
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M.Hobeika,
C.Brockmann,
N.Iglesias,
C.Gwizdek,
D.Neuhaus,
F.Stutz,
M.Stewart,
G.Divita,
and
C.Dargemont
(2007).
Coordination of Hpr1 and ubiquitin binding by the UBA domain of the mRNA export factor Mex67.
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Mol Biol Cell,
18,
2561-2568.
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PDB code:
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N.Matsushima,
T.Tanaka,
P.Enkhbayar,
T.Mikami,
M.Taga,
K.Yamada,
and
Y.Kuroki
(2007).
Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors.
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BMC Genomics,
8,
124.
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T.Huyton,
and
C.Wolberger
(2007).
The crystal structure of the tumor suppressor protein pp32 (Anp32a): structural insights into Anp32 family of proteins.
|
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Protein Sci,
16,
1308-1315.
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PDB codes:
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G.Pimienta,
F.Gabel,
K.Zanier,
E.Conti,
and
M.Sattler
(2006).
Chemical shift backbone assignments of TAP-N, the 31 kDa cargo-binding region of the protein TAP.
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J Biomol NMR,
36,
23.
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L.Lévesque,
Y.C.Bor,
L.H.Matzat,
L.Jin,
S.Berberoglu,
D.Rekosh,
M.L.Hammarskjöld,
and
B.M.Paschal
(2006).
Mutations in tap uncouple RNA export activity from translocation through the nuclear pore complex.
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Mol Biol Cell,
17,
931-943.
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P.Lischka,
Z.Toth,
M.Thomas,
R.Mueller,
and
T.Stamminger
(2006).
The UL69 transactivator protein of human cytomegalovirus interacts with DEXD/H-Box RNA helicase UAP56 to promote cytoplasmic accumulation of unspliced RNA.
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Mol Cell Biol,
26,
1631-1643.
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U.Schmidt,
K.Richter,
A.B.Berger,
and
P.Lichter
(2006).
In vivo BiFC analysis of Y14 and NXF1 mRNA export complexes: preferential localization within and around SC35 domains.
|
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J Cell Biol,
172,
373-381.
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C.Maris,
C.Dominguez,
and
F.H.Allain
(2005).
The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression.
|
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FEBS J,
272,
2118-2131.
|
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W.Tan,
A.S.Zolotukhin,
I.Tretyakova,
J.Bear,
S.Lindtner,
S.V.Smulevitch,
and
B.K.Felber
(2005).
Identification and characterization of the mouse nuclear export factor (Nxf) family members.
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Nucleic Acids Res,
33,
3855-3865.
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Y.Zhang,
and
J.T.Barbieri
(2005).
A leucine-rich motif targets Pseudomonas aeruginosa ExoS within mammalian cells.
|
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Infect Immun,
73,
7938-7945.
|
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K.B.Murray,
W.R.Taylor,
and
J.M.Thornton
(2004).
Toward the detection and validation of repeats in protein structure.
|
| |
Proteins,
57,
365-380.
|
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|
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L.B.Clark,
P.Viswanathan,
G.Quigley,
Y.C.Chiang,
J.S.McMahon,
G.Yao,
J.Chen,
A.Nelsbach,
and
C.L.Denis
(2004).
Systematic mutagenesis of the leucine-rich repeat (LRR) domain of CCR4 reveals specific sites for binding to CAF1 and a separate critical role for the LRR in CCR4 deadenylase activity.
|
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J Biol Chem,
279,
13616-13623.
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L.Jeffery,
and
S.Nakielny
(2004).
Components of the DNA methylation system of chromatin control are RNA-binding proteins.
|
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J Biol Chem,
279,
49479-49487.
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P.Enkhbayar,
M.Kamiya,
M.Osaki,
T.Matsumoto,
and
N.Matsushima
(2004).
Structural principles of leucine-rich repeat (LRR) proteins.
|
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Proteins,
54,
394-403.
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C.K.Lau,
M.D.Diem,
G.Dreyfuss,
and
G.D.Van Duyne
(2003).
Structure of the Y14-Magoh core of the exon junction complex.
|
| |
Curr Biol,
13,
933-941.
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PDB code:
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G.C.Pérez-Alvarado,
M.Martínez-Yamout,
M.M.Allen,
R.Grosschedl,
H.J.Dyson,
and
P.E.Wright
(2003).
Structure of the nuclear factor ALY: insights into post-transcriptional regulatory and mRNA nuclear export processes.
|
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Biochemistry,
42,
7348-7357.
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PDB code:
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M.B.Blevins,
A.M.Smith,
E.M.Phillips,
and
M.A.Powers
(2003).
Complex formation among the RNA export proteins Nup98, Rae1/Gle2, and TAP.
|
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J Biol Chem,
278,
20979-20988.
|
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P.Viswanathan,
J.Chen,
Y.C.Chiang,
and
C.L.Denis
(2003).
Identification of multiple RNA features that influence CCR4 deadenylation activity.
|
| |
J Biol Chem,
278,
14949-14955.
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S.Fribourg,
and
E.Conti
(2003).
Structural similarity in the absence of sequence homology of the messenger RNA export factors Mtr2 and p15.
|
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EMBO Rep,
4,
699-703.
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PDB code:
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A.Calapez,
H.M.Pereira,
A.Calado,
J.Braga,
J.Rino,
C.Carvalho,
J.P.Tavanez,
E.Wahle,
A.C.Rosa,
and
M.Carmo-Fonseca
(2002).
The intranuclear mobility of messenger RNA binding proteins is ATP dependent and temperature sensitive.
|
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J Cell Biol,
159,
795-805.
|
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A.S.Zolotukhin,
W.Tan,
J.Bear,
S.Smulevitch,
and
B.K.Felber
(2002).
U2AF participates in the binding of TAP (NXF1) to mRNA.
|
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J Biol Chem,
277,
3935-3942.
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A.V.Kajava,
and
B.Kobe
(2002).
Assessment of the ability to model proteins with leucine-rich repeats in light of the latest structural information.
|
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Protein Sci,
11,
1082-1090.
|
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D.N.Ho,
G.A.Coburn,
Y.Kang,
B.R.Cullen,
and
M.M.Georgiadis
(2002).
The crystal structure and mutational analysis of a novel RNA-binding domain found in the human Tap nuclear mRNA export factor.
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Proc Natl Acad Sci U S A,
99,
1888-1893.
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PDB codes:
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I.C.Braun,
A.Herold,
M.Rode,
and
E.Izaurralde
(2002).
Nuclear export of mRNA by TAP/NXF1 requires two nucleoporin-binding sites but not p15.
|
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Mol Cell Biol,
22,
5405-5418.
|
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J.Katahira,
K.Straesser,
T.Saiwaki,
Y.Yoneda,
and
E.Hurt
(2002).
Complex formation between Tap and p15 affects binding to FG-repeat nucleoporins and nucleocytoplasmic shuttling.
|
| |
J Biol Chem,
277,
9242-9246.
|
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J.P.Siebrasse,
E.Coutavas,
and
R.Peters
(2002).
Reconstitution of nuclear protein export in isolated nuclear envelopes.
|
| |
J Cell Biol,
158,
849-854.
|
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|
|
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M.Mondragón-Palomino,
B.C.Meyers,
R.W.Michelmore,
and
B.S.Gaut
(2002).
Patterns of positive selection in the complete NBS-LRR gene family of Arabidopsis thaliana.
|
| |
Genome Res,
12,
1305-1315.
|
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R.P.Grant,
E.Hurt,
D.Neuhaus,
and
M.Stewart
(2002).
Structure of the C-terminal FG-nucleoporin binding domain of Tap/NXF1.
|
| |
Nat Struct Biol,
9,
247-251.
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PDB code:
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S.Lindtner,
B.K.Felber,
and
J.Kjems
(2002).
An element in the 3' untranslated region of human LINE-1 retrotransposon mRNA binds NXF1(TAP) and can function as a nuclear export element.
|
| |
RNA,
8,
345-356.
|
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|
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|
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A.Herold,
T.Klymenko,
and
E.Izaurralde
(2001).
NXF1/p15 heterodimers are essential for mRNA nuclear export in Drosophila.
|
| |
RNA,
7,
1768-1780.
|
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C.A.Korey,
G.Wilkie,
I.Davis,
and
D.Van Vactor
(2001).
small bristles is required for the morphogenesis of multiple tissues during Drosophila development.
|
| |
Genetics,
159,
1659-1670.
|
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E.Conti,
and
E.Izaurralde
(2001).
Nucleocytoplasmic transport enters the atomic age.
|
| |
Curr Opin Cell Biol,
13,
310-319.
|
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G.A.Coburn,
H.L.Wiegand,
Y.Kang,
D.N.Ho,
M.M.Georgiadis,
and
B.R.Cullen
(2001).
Using viral species specificity to define a critical protein/RNA interaction surface.
|
| |
Genes Dev,
15,
1194-1205.
|
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G.S.Wilkie,
V.Zimyanin,
R.Kirby,
C.Korey,
H.Francis-Lang,
D.Van Vactor,
and
I.Davis
(2001).
Small bristles, the Drosophila ortholog of NXF-1, is essential for mRNA export throughout development.
|
| |
RNA,
7,
1781-1792.
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I.G.Macara
(2001).
Transport into and out of the nucleus.
|
| |
Microbiol Mol Biol Rev,
65,
570.
|
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J.Yang,
H.P.Bogerd,
P.J.Wang,
D.C.Page,
and
B.R.Cullen
(2001).
Two closely related human nuclear export factors utilize entirely distinct export pathways.
|
| |
Mol Cell,
8,
397-406.
|
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L.Jun,
S.Frints,
H.Duhamel,
A.Herold,
J.Abad-Rodrigues,
C.Dotti,
E.Izaurralde,
P.Marynen,
and
G.Froyen
(2001).
NXF5, a novel member of the nuclear RNA export factor family, is lost in a male patient with a syndromic form of mental retardation.
|
| |
Curr Biol,
11,
1381-1391.
|
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|
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|
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S.Fribourg,
I.C.Braun,
E.Izaurralde,
and
E.Conti
(2001).
Structural basis for the recognition of a nucleoporin FG repeat by the NTF2-like domain of the TAP/p15 mRNA nuclear export factor.
|
| |
Mol Cell,
8,
645-656.
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PDB codes:
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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.
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Links
