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PDBsum entry 4qut
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Signaling protein
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PDB id
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4qut
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PDB id:
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| Name: |
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Signaling protein
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Title:
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Structure of the bromodomain of human atpase family aaa domain- containing protein 2 (atad2) complexed with histone h4-k(ac)12
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Structure:
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Atpase family aaa domain-containing protein 2. Chain: a. Fragment: bromodomain (residues 981-1108). Synonym: aaa nuclear coregulator cancer-associated protein, ancca. Engineered: yes. Histone h4. Chain: b. Fragment: histone h4 tail. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: atad2, l16, pro2000. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence occurs naturally in humans
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Resolution:
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1.70Å
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R-factor:
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0.163
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R-free:
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0.180
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Authors:
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A.Chaikuad,I.Felletar,F.Von Delft,C.H.Arrowsmith,A.M.Edwards, C.Bountra,S.Knapp,Structural Genomics Consortium (Sgc)
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Key ref:
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Y.Morozumi
et al.
(2016).
Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
J Mol Cell Biol,
8,
349-362.
PubMed id:
DOI:
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Date:
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12-Jul-14
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Release date:
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30-Jul-14
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PROCHECK
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Headers
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References
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Q6PL18
(ATAD2_HUMAN) -
ATPase family AAA domain-containing protein 2 from Homo sapiens
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Seq:
Struc:
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1390 a.a.
130 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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DOI no:
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J Mol Cell Biol
8:349-362
(2016)
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PubMed id:
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Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
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Y.Morozumi,
F.Boussouar,
M.Tan,
A.Chaikuad,
M.Jamshidikia,
G.Colak,
H.He,
L.Nie,
C.Petosa,
M.de Dieuleveult,
S.Curtet,
A.L.Vitte,
C.Rabatel,
A.Debernardi,
F.L.Cosset,
E.Verhoeyen,
A.Emadali,
N.Schweifer,
D.Gianni,
M.Gut,
P.Guardiola,
S.Rousseaux,
M.Gérard,
S.Knapp,
Y.Zhao,
S.Khochbin.
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ABSTRACT
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Although the conserved AAA ATPase and bromodomain factor, ATAD2, has been
described as a transcriptional co-activator upregulated in many cancers, its
function remains poorly understood. Here, using a combination of ChIP-seq,
ChIP-proteomics, and RNA-seq experiments in embryonic stem cells where Atad2 is
normally highly expressed, we found that Atad2 is an abundant nucleosome-bound
protein present on active genes, associated with chromatin remodelling, DNA
replication, and DNA repair factors. A structural analysis of its bromodomain
and subsequent investigations demonstrate that histone acetylation guides ATAD2
to chromatin, resulting in an overall increase of chromatin accessibility and
histone dynamics, which is required for the proper activity of the highly
expressed gene fraction of the genome. While in exponentially growing cells
Atad2 appears dispensable for cell growth, in differentiating ES cells Atad2
becomes critical in sustaining specific gene expression programmes, controlling
proliferation and differentiation. Altogether, this work defines Atad2 as a
facilitator of general chromatin-templated activities such as transcription.
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