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* Residue conservation analysis
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Enzyme class:
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E.C.2.7.11.1
- Non-specific serine/threonine protein kinase.
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Reaction:
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ATP + a protein = ADP + a phosphoprotein
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ATP
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+
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protein
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=
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ADP
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+
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phosphoprotein
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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J Mol Biol
294:1041-1049
(1999)
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PubMed id:
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Structure and function of a new phosphopeptide-binding domain containing the FHA2 of Rad53.
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H.Liao,
I.J.Byeon,
M.D.Tsai.
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ABSTRACT
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The forkhead-associated (FHA) domain is a 55-75 amino acid residue module found
in >20 proteins from yeast to human. It has been suggested to participate in
signal transduction pathways, perhaps via protein-protein interactions involving
recognition of phosphopeptides. Neither the structure nor the ligand of FHA is
known. Yeast Rad53, a checkpoint protein involved in DNA damage response,
contains two FHA domains, FHA1 (residues 66-116) and FHA2 (residues 601-664),
the second of which recognizes phosphorylated Rad9. We herein report the
solution structure of an "FHA2-containing domain" of Rad53 (residues
573-730). The structure consists of a beta-sandwich containing two antiparallel
beta-sheets and a short, C-terminal alpha-helix. Binding experiments suggested
that the FHA2-containing domain specifically recognizes pTyr and a
pTyr-containing peptide from Rad9, and that the binding site involves residues
highly conserved across FHA domains. The results, along with other recent
reports, suggest that FHA domains could have pTyr and pSer/Thr dual specificity.
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Selected figure(s)
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Figure 1.
Figure 1. (a) Sequence alignments of FHA motifs. The first two lines are for FHA2 and FHA1, respectively, of
Rad53. (b) Sequence of the FHA2-containing domain of Rad53 (residues 573 to 730). The secondary structures were
identified based on the NMR data.
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Figure 6.
Figure 6. Comparison of the potential phosphate binding site of FHA2 with that of SH2 domain (Eck et al., 1993)
and 14-3-3 protein (Yaffe et al., 1997).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1999,
294,
1041-1049)
copyright 1999.
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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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X.Duan,
and
Z.G.He
(2011).
Characterization of the specific interaction between archaeal FHA domain-containing protein and the promoter of a flagellar-like gene-cluster and its regulation by phosphorylation.
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Biochem Biophys Res Commun, 407,
242-247.
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D.Chevalier,
E.R.Morris,
and
J.C.Walker
(2009).
14-3-3 and FHA domains mediate phosphoprotein interactions.
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Annu Rev Plant Biol, 60,
67-91.
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M.A.Brooks,
A.Dziembowski,
S.Quevillon-Cheruel,
V.Henriot,
C.Faux,
H.van Tilbeurgh,
and
B.Séraphin
(2009).
Structure of the yeast Pml1 splicing factor and its integration into the RES complex.
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Nucleic Acids Res, 37,
129-143.
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PDB code:
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M.Gupta,
A.Sajid,
G.Arora,
V.Tandon,
and
Y.Singh
(2009).
Forkhead-associated domain-containing protein Rv0019c and polyketide-associated protein PapA5, from substrates of serine/threonine protein kinase PknB to interacting proteins of Mycobacterium tuberculosis.
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J Biol Chem, 284,
34723-34734.
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S.So,
A.J.Davis,
and
D.J.Chen
(2009).
Autophosphorylation at serine 1981 stabilizes ATM at DNA damage sites.
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J Cell Biol, 187,
977-990.
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S.Pennell,
and
S.J.Smerdon
(2008).
Pellino proteins splitting up the FHAmily!
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Structure, 16,
1752-1754.
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V.Plans,
M.Guerra-Rebollo,
and
T.M.Thomson
(2008).
Regulation of mitotic exit by the RNF8 ubiquitin ligase.
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Oncogene, 27,
1355-1365.
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K.C.Roche,
S.Rocha,
C.P.Bracken,
and
N.D.Perkins
(2007).
Regulation of ATR-dependent pathways by the FHA domain containing protein SNIP1.
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Oncogene, 26,
4523-4530.
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Y.Tanaka,
M.Kuroda,
Y.Yasutake,
M.Yao,
K.Tsumoto,
N.Watanabe,
T.Ohta,
and
I.Tanaka
(2007).
Crystal structure analysis reveals a novel forkhead-associated domain of ESAT-6 secretion system C protein in Staphylococcus aureus.
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Proteins, 69,
659-664.
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PDB code:
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V.Plans,
J.Scheper,
M.Soler,
N.Loukili,
Y.Okano,
and
T.M.Thomson
(2006).
The RING finger protein RNF8 recruits UBC13 for lysine 63-based self polyubiquitylation.
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J Cell Biochem, 97,
572-582.
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I.J.Byeon,
H.Li,
H.Song,
A.M.Gronenborn,
and
M.D.Tsai
(2005).
Sequential phosphorylation and multisite interactions characterize specific target recognition by the FHA domain of Ki67.
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Nat Struct Mol Biol, 12,
987-993.
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PDB code:
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R.I.Dmitriev,
N.B.Pestov,
T.V.Korneenko,
A.V.Gerasimova,
K.h.Zhao,
N.N.Modianov,
M.B.Kostina,
and
M.I.Shakhparonov
(2005).
[Tissue specificity of alternative splicing products of mouse mRNA encoding new protein hampin homologous to the Drosophila MSL-1 protein]
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Bioorg Khim, 31,
363-371.
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Z.Ding,
G.I.Lee,
X.Liang,
F.Gallazzi,
A.Arunima,
and
S.R.Van Doren
(2005).
PhosphoThr peptide binding globally rigidifies much of the FHA domain from Arabidopsis receptor kinase-associated protein phosphatase.
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Biochemistry, 44,
10119-10134.
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K.Tanaka,
and
P.Russell
(2004).
Cds1 phosphorylation by Rad3-Rad26 kinase is mediated by forkhead-associated domain interaction with Mrc1.
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J Biol Chem, 279,
32079-32086.
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M.B.Yaffe,
and
S.J.Smerdon
(2004).
The use of in vitro peptide-library screens in the analysis of phosphoserine/threonine-binding domain structure and function.
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Annu Rev Biophys Biomol Struct, 33,
225-244.
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B.L.Pike,
S.Yongkiettrakul,
M.D.Tsai,
and
J.Heierhorst
(2003).
Diverse but overlapping functions of the two forkhead-associated (FHA) domains in Rad53 checkpoint kinase activation.
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J Biol Chem, 278,
30421-30424.
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B.Y.Qin,
C.Liu,
S.S.Lam,
H.Srinath,
R.Delston,
J.J.Correia,
R.Derynck,
and
K.Lin
(2003).
Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation.
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Nat Struct Biol, 10,
913-921.
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PDB code:
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C.Leroy,
S.E.Lee,
M.B.Vaze,
F.Ochsenbien,
R.Guerois,
J.E.Haber,
and
M.C.Marsolier-Kergoat
(2003).
PP2C phosphatases Ptc2 and Ptc3 are required for DNA checkpoint inactivation after a double-strand break.
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Mol Cell, 11,
827-835.
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D.Reynolds,
B.J.Shi,
C.McLean,
F.Katsis,
B.Kemp,
and
S.Dalton
(2003).
Recruitment of Thr 319-phosphorylated Ndd1p to the FHA domain of Fkh2p requires Clb kinase activity: a mechanism for CLB cluster gene activation.
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Genes Dev, 17,
1789-1802.
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G.I.Lee,
Z.Ding,
J.C.Walker,
and
S.R.Van Doren
(2003).
NMR structure of the forkhead-associated domain from the Arabidopsis receptor kinase-associated protein phosphatase.
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Proc Natl Acad Sci U S A, 100,
11261-11266.
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PDB codes:
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H.A.Kemp,
and
G.F.Sprague
(2003).
Far3 and five interacting proteins prevent premature recovery from pheromone arrest in the budding yeast Saccharomyces cerevisiae.
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Mol Cell Biol, 23,
1750-1763.
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A.Hammet,
B.L.Pike,
and
J.Heierhorst
(2002).
Posttranscriptional regulation of the RAD5 DNA repair gene by the Dun1 kinase and the Pan2-Pan3 poly(A)-nuclease complex contributes to survival of replication blocks.
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J Biol Chem, 277,
22469-22474.
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B.P.Duncker,
K.Shimada,
M.Tsai-Pflugfelder,
P.Pasero,
and
S.M.Gasser
(2002).
An N-terminal domain of Dbf4p mediates interaction with both origin recognition complex (ORC) and Rad53p and can deregulate late origin firing.
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Proc Natl Acad Sci U S A, 99,
16087-16092.
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E.S.Stavridi,
Y.Huyen,
I.R.Loreto,
D.M.Scolnick,
T.D.Halazonetis,
N.P.Pavletich,
and
P.D.Jeffrey
(2002).
Crystal structure of the FHA domain of the Chfr mitotic checkpoint protein and its complex with tungstate.
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Structure, 10,
891-899.
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PDB codes:
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J.Ahn,
and
C.Prives
(2002).
Checkpoint kinase 2 (Chk2) monomers or dimers phosphorylate Cdc25C after DNA damage regardless of threonine 68 phosphorylation.
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J Biol Chem, 277,
48418-48426.
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M.D.Tsai
(2002).
FHA: a signal transduction domain with diverse specificity and function.
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Structure, 10,
887-888.
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M.Pallen,
R.Chaudhuri,
and
A.Khan
(2002).
Bacterial FHA domains: neglected players in the phospho-threonine signalling game?
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Trends Microbiol, 10,
556-563.
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S.Souchelnytskyi,
A.Moustakas,
and
C.H.Heldin
(2002).
TGF-beta signaling from a three-dimensional perspective: insight into selection of partners.
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Trends Cell Biol, 12,
304-307.
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X.Xu,
L.M.Tsvetkov,
and
D.F.Stern
(2002).
Chk2 activation and phosphorylation-dependent oligomerization.
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Mol Cell Biol, 22,
4419-4432.
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B.Y.Qin,
B.M.Chacko,
S.S.Lam,
M.P.de Caestecker,
J.J.Correia,
and
K.Lin
(2001).
Structural basis of Smad1 activation by receptor kinase phosphorylation.
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Mol Cell, 8,
1303-1312.
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PDB code:
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H.Blanchard,
M.R.Fontes,
A.Hammet,
B.L.Pike,
T.Teh,
T.Gleichmann,
P.R.Gooley,
B.Kobe,
and
J.Heierhorst
(2001).
Crystallization and preliminary X-ray diffraction studies of FHA domains of Dun1 and Rad53 protein kinases.
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Acta Crystallogr D Biol Crystallogr, 57,
459-461.
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M.B.Yaffe,
and
A.E.Elia
(2001).
Phosphoserine/threonine-binding domains.
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Curr Opin Cell Biol, 13,
131-138.
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M.Huse,
T.W.Muir,
L.Xu,
Y.G.Chen,
J.Kuriyan,
and
J.Massagué
(2001).
The TGF beta receptor activation process: an inhibitor- to substrate-binding switch.
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Mol Cell, 8,
671-682.
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PDB code:
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S.W.Vetter,
and
E.Leclerc
(2001).
Phosphorylation of serine residues affects the conformation of the calmodulin binding domain of human protein 4.1.
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Eur J Biochem, 268,
4292-4299.
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D.Durocher,
I.A.Taylor,
D.Sarbassova,
L.F.Haire,
S.L.Westcott,
S.P.Jackson,
S.J.Smerdon,
and
M.B.Yaffe
(2000).
The molecular basis of FHA domain:phosphopeptide binding specificity and implications for phospho-dependent signaling mechanisms.
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Mol Cell, 6,
1169-1182.
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PDB code:
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D.Durocher,
S.J.Smerdon,
M.B.Yaffe,
and
S.P.Jackson
(2000).
The FHA domain in DNA repair and checkpoint signaling.
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Cold Spring Harb Symp Quant Biol, 65,
423-431.
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M.Huang,
and
S.J.Elledge
(2000).
The FHA domain, a phosphoamino acid binding domain involved in the DNA damage response pathway.
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Cold Spring Harb Symp Quant Biol, 65,
413-421.
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P.A.Dalby,
R.H.Hoess,
and
W.F.DeGrado
(2000).
Evolution of binding affinity in a WW domain probed by phage display.
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Protein Sci, 9,
2366-2376.
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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
