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PDBsum entry 1nfa
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Transcription regulation
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PDB id
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1nfa
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Contents |
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* Residue conservation analysis
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PDB id:
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Transcription regulation
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Title:
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Human transcription factor nfatc DNA binding domain, nmr, 10 structures
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Structure:
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Human transcription factor nfatc1. Chain: a. Fragment: DNA-binding domain, residues 416 - 591. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Cellular_location: cytoplasm until dephosphorylated. Gene: nfatc1. Expressed in: escherichia coli. Expression_system_taxid: 562.
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NMR struc:
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10 models
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Authors:
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S.A.Wolfe,P.Zhou,V.Dotsch,L.Chen,A.You,S.N.Ho,G.R.Crabtree,G.Wagner, G.L.Verdine
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Key ref:
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S.A.Wolfe
et al.
(1997).
Unusual Rel-like architecture in the DNA-binding domain of the transcription factor NFATc.
Nature,
385,
172-176.
PubMed id:
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Date:
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18-Jan-97
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Release date:
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01-Apr-97
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PROCHECK
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Headers
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References
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O95644
(NFAC1_HUMAN) -
Nuclear factor of activated T-cells, cytoplasmic 1 from Homo sapiens
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Seq:
Struc:
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943 a.a.
178 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
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Nature
385:172-176
(1997)
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PubMed id:
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Unusual Rel-like architecture in the DNA-binding domain of the transcription factor NFATc.
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S.A.Wolfe,
P.Zhou,
V.Dötsch,
L.Chen,
A.You,
S.N.Ho,
G.R.Crabtree,
G.Wagner,
G.L.Verdine.
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ABSTRACT
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Transcription factors of the NFAT family regulate the production of effector
proteins that coordinate the immune response. The immunosuppressive drugs FK506
and cyclosporin A (CsA) act by blocking a Ca2+-mediated signalling pathway
leading to NFAT. Although FK506 and CsA have enabled human organs to be
transplanted routinely, the toxic side-effects of these drugs limit their usage.
This toxicity might be absent in antagonists that target NFAT directly. As a
first step in the structure-based search for NFAT antagonists, we now report the
identification and solution structure of a 20K domain of NFATc (NFATc-DBD) that
is both necessary and sufficient to bind DNA and activate transcription
cooperatively. Although the overall fold of the NFATc DNA-binding domain is
related to that of NF-kappaB p50 (refs 2, 3), the two proteins use significantly
different strategies for DNA recognition. On the basis of these results, we
present a model for the cooperative complex formed between NFAT and the
mitogenic transcription factor AP-1 on the interleukin-2 enhancer.
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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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M.Y.Lee,
S.M.Garvey,
A.S.Baras,
J.A.Lemmon,
M.F.Gomez,
P.D.Schoppee Bortz,
G.Daum,
R.C.LeBoeuf,
and
B.R.Wamhoff
(2010).
Integrative genomics identifies DSCR1 (RCAN1) as a novel NFAT-dependent mediator of phenotypic modulation in vascular smooth muscle cells.
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Hum Mol Genet,
19,
468-479.
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T.Shen,
Y.Liu,
M.Contreras,
E.O.Hernández-Ochoa,
W.R.Randall,
and
M.F.Schneider
(2010).
DNA binding sites target nuclear NFATc1 to heterochromatin regions in adult skeletal muscle fibers.
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Histochem Cell Biol,
134,
387-402.
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B.Schweighofer,
J.Testori,
C.Sturtzel,
S.Sattler,
H.Mayer,
O.Wagner,
M.Bilban,
and
E.Hofer
(2009).
The VEGF-induced transcriptional response comprises gene clusters at the crossroad of angiogenesis and inflammation.
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Thromb Haemost,
102,
544-554.
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H.Wu,
A.Peisley,
I.A.Graef,
and
G.R.Crabtree
(2007).
NFAT signaling and the invention of vertebrates.
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Trends Cell Biol,
17,
251-260.
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K.Takeuchi,
M.H.Roehrl,
Z.Y.Sun,
and
G.Wagner
(2007).
Structure of the calcineurin-NFAT complex: defining a T cell activation switch using solution NMR and crystal coordinates.
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Structure,
15,
587-597.
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PDB code:
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T.T.Yang,
P.M.Ung,
M.Rincón,
and
C.W.Chow
(2006).
Role of the CCAAT/enhancer-binding protein NFATc2 transcription factor cascade in the induction of secretory phospholipase A2.
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J Biol Chem,
281,
11541-11552.
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C.P.Chang,
J.R.Neilson,
J.H.Bayle,
J.E.Gestwicki,
A.Kuo,
K.Stankunas,
I.A.Graef,
and
G.R.Crabtree
(2004).
A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis.
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Cell,
118,
649-663.
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E.Serfling,
F.Berberich-Siebelt,
A.Avots,
S.Chuvpilo,
S.Klein-Hessling,
M.K.Jha,
E.Kondo,
P.Pagel,
J.Schulze-Luehrmann,
and
A.Palmetshofer
(2004).
NFAT and NF-kappaB factors-the distant relatives.
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Int J Biochem Cell Biol,
36,
1166-1170.
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G.Ghosh,
D.B.Huang,
and
T.Huxford
(2004).
Molecular mimicry of the NF-kappaB DNA target site by a selected RNA aptamer.
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Curr Opin Struct Biol,
14,
21-27.
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G.R.Crabtree,
and
E.N.Olson
(2002).
NFAT signaling: choreographing the social lives of cells.
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Cell,
109,
S67-S79.
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A.Behrens,
K.Sabapathy,
I.Graef,
M.Cleary,
G.R.Crabtree,
and
E.F.Wagner
(2001).
Jun N-terminal kinase 2 modulates thymocyte apoptosis and T cell activation through c-Jun and nuclear factor of activated T cell (NF-AT).
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Proc Natl Acad Sci U S A,
98,
1769-1774.
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I.A.Graef,
F.Chen,
and
G.R.Crabtree
(2001).
NFAT signaling in vertebrate development.
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Curr Opin Genet Dev,
11,
505-512.
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I.A.Graef,
J.M.Gastier,
U.Francke,
and
G.R.Crabtree
(2001).
Evolutionary relationships among Rel domains indicate functional diversification by recombination.
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Proc Natl Acad Sci U S A,
98,
5740-5745.
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M.T.Tosteson,
J.B.Kim,
D.J.Goldstein,
and
D.C.Tosteson
(2001).
Ion channels formed by transcription factors recognize consensus DNA sequences.
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Biochim Biophys Acta,
1510,
209-218.
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E.Serfling,
F.Berberich-Siebelt,
S.Chuvpilo,
E.Jankevics,
S.Klein-Hessling,
T.Twardzik,
and
A.Avots
(2000).
The role of NF-AT transcription factors in T cell activation and differentiation.
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Biochim Biophys Acta,
1498,
1.
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F.Macián,
C.García-Rodríguez,
and
A.Rao
(2000).
Gene expression elicited by NFAT in the presence or absence of cooperative recruitment of Fos and Jun.
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EMBO J,
19,
4783-4795.
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K.Tokoyoda,
Y.Takemoto,
T.Nakayama,
T.Arai,
and
M.Kubo
(2000).
Synergism between the calmodulin-binding and autoinhibitory domains on calcineurin is essential for the induction of their phosphatase activity.
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J Biol Chem,
275,
11728-11734.
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S.Matsuda,
F.Shibasaki,
K.Takehana,
H.Mori,
E.Nishida,
and
S.Koyasu
(2000).
Two distinct action mechanisms of immunophilin-ligand complexes for the blockade of T-cell activation.
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EMBO Rep,
1,
428-434.
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H.Miyakawa,
S.K.Woo,
S.C.Dahl,
J.S.Handler,
and
H.M.Kwon
(1999).
Tonicity-responsive enhancer binding protein, a rel-like protein that stimulates transcription in response to hypertonicity.
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Proc Natl Acad Sci U S A,
96,
2538-2542.
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K.Stankunas,
I.A.Graef,
J.R.Neilson,
S.H.Park,
and
G.R.Crabtree
(1999).
Signaling through calcium, calcineurin, and NF-AT in lymphocyte activation and development.
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Cold Spring Harb Symp Quant Biol,
64,
505-516.
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L.Chen,
A.Rao,
and
S.C.Harrison
(1999).
Signal integration by transcription-factor assemblies: interactions of NF-AT1 and AP-1 on the IL-2 promoter.
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Cold Spring Harb Symp Quant Biol,
64,
527-531.
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T.Huxford,
S.Malek,
and
G.Ghosh
(1999).
Structure and mechanism in NF-kappa B/I kappa B signaling.
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Cold Spring Harb Symp Quant Biol,
64,
533-540.
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U.Fürstenau,
M.Schwaninger,
R.Blume,
E.M.Jendrusch,
and
W.Knepel
(1999).
Characterization of a novel calcium response element in the glucagon gene.
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J Biol Chem,
274,
5851-5860.
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V.Nadkarni,
K.H.Gabbay,
K.M.Bohren,
and
D.Sheikh-Hamad
(1999).
Osmotic response element enhancer activity. Regulation through p38 kinase and mitogen-activated extracellular signal-regulated kinase kinase.
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J Biol Chem,
274,
20185-20190.
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A.M.Baranger
(1998).
Accessory factor-bZIP-DNA interactions.
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Curr Opin Chem Biol,
2,
18-23.
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E.S.Masuda,
R.Imamura,
Y.Amasaki,
K.Arai,
and
N.Arai
(1998).
Signalling into the T-cell nucleus: NFAT regulation.
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Cell Signal,
10,
599-611.
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I.Rahman,
and
W.MacNee
(1998).
Role of transcription factors in inflammatory lung diseases.
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Thorax,
53,
601-612.
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J.D.Molkentin,
J.R.Lu,
C.L.Antos,
B.Markham,
J.Richardson,
J.Robbins,
S.R.Grant,
and
E.N.Olson
(1998).
A calcineurin-dependent transcriptional pathway for cardiac hypertrophy.
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Cell,
93,
215-228.
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K.Schuh,
B.Kneitz,
J.Heyer,
U.Bommhardt,
E.Jankevics,
F.Berberich-Siebelt,
K.Pfeffer,
H.K.Müller-Hermelink,
A.Schimpl,
and
E.Serfling
(1998).
Retarded thymic involution and massive germinal center formation in NF-ATp-deficient mice.
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Eur J Immunol,
28,
2456-2466.
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K.Schuh,
T.Twardzik,
B.Kneitz,
J.Heyer,
A.Schimpl,
and
E.Serfling
(1998).
The interleukin 2 receptor alpha chain/CD25 promoter is a target for nuclear factor of activated T cells.
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J Exp Med,
188,
1369-1373.
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L.J.Holsinger,
I.A.Graef,
W.Swat,
T.Chi,
D.M.Bautista,
L.Davidson,
R.S.Lewis,
F.W.Alt,
and
G.R.Crabtree
(1998).
Defects in actin-cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction.
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Curr Biol,
8,
563-572.
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P.Zhou,
L.J.Sun,
V.Dötsch,
G.Wagner,
and
G.L.Verdine
(1998).
Solution structure of the core NFATC1/DNA complex.
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Cell,
92,
687-696.
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PDB code:
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S.Ghosh,
M.J.May,
and
E.B.Kopp
(1998).
NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses.
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Annu Rev Immunol,
16,
225-260.
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S.Tan,
and
T.J.Richmond
(1998).
Eukaryotic transcription factors.
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Curr Opin Struct Biol,
8,
41-48.
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T.J.Gibson,
C.Ramu,
C.Gemünd,
and
R.Aasland
(1998).
The APECED polyglandular autoimmune syndrome protein, AIRE-1, contains the SAND domain and is probably a transcription factor.
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Trends Biochem Sci,
23,
242-244.
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P.Cramer,
C.J.Larson,
G.L.Verdine,
and
C.W.Müller
(1997).
Structure of the human NF-kappaB p52 homodimer-DNA complex at 2.1 A resolution.
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EMBO J,
16,
7078-7090.
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PDB code:
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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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Links
