2j6w

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[[Image:2j6w.png|left|200px]]
 
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{{STRUCTURE_2j6w| PDB=2j6w | SCENE= }}
{{STRUCTURE_2j6w| PDB=2j6w | SCENE= }}
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===R164N MUTANT OF THE RUNX1 RUNT DOMAIN===
===R164N MUTANT OF THE RUNX1 RUNT DOMAIN===
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{{ABSTRACT_PUBMED_17059830}}
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==Disease==
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[[http://www.uniprot.org/uniprot/RUNX1_MOUSE RUNX1_MOUSE]] Note=Mice with an Runx1 lacking the DNA-binding region are found to die between embryonic days 11.5 to 12.5 due to hemorrhaging in the central nervous system. This hemorrhaging is preceded by necrosis and hematopoiesis is blocked.
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==Function==
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[[http://www.uniprot.org/uniprot/RUNX1_MOUSE RUNX1_MOUSE]] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL-3 and GM-CSF promoters. Essential for the development of normal hematopoiesis. Isoform 4 shows higher binding activities for target genes and binds TCR-beta-E2 and RAG-1 target site with threefold higher affinity than other isoforms. It is less effective in the context of neutrophil terminal differentiation. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the BLK promoter. Inhibits KAT6B-dependent transcriptional activation (By similarity).<ref>PMID:8565077</ref><ref>PMID:8622955</ref>
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(as it appears on PubMed at http://www.pubmed.gov), where 17059830 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17059830}}
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==About this Structure==
==About this Structure==
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==Reference==
==Reference==
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<ref group="xtra">PMID:017059830</ref><references group="xtra"/>
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<ref group="xtra">PMID:017059830</ref><references group="xtra"/><references/>
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Bielnicka, I.]]
[[Category: Bielnicka, I.]]

Revision as of 02:55, 25 March 2013

Template:STRUCTURE 2j6w

Contents

R164N MUTANT OF THE RUNX1 RUNT DOMAIN

Template:ABSTRACT PUBMED 17059830

Disease

[RUNX1_MOUSE] Note=Mice with an Runx1 lacking the DNA-binding region are found to die between embryonic days 11.5 to 12.5 due to hemorrhaging in the central nervous system. This hemorrhaging is preceded by necrosis and hematopoiesis is blocked.

Function

[RUNX1_MOUSE] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL-3 and GM-CSF promoters. Essential for the development of normal hematopoiesis. Isoform 4 shows higher binding activities for target genes and binds TCR-beta-E2 and RAG-1 target site with threefold higher affinity than other isoforms. It is less effective in the context of neutrophil terminal differentiation. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the BLK promoter. Inhibits KAT6B-dependent transcriptional activation (By similarity).[1][2]

About this Structure

2j6w is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

  • Li Z, Lukasik SM, Liu Y, Grembecka J, Bielnicka I, Bushweller JH, Speck NA. A mutation in the S-switch region of the Runt domain alters the dynamics of an allosteric network responsible for CBFbeta regulation. J Mol Biol. 2006 Dec 15;364(5):1073-83. Epub 2006 Oct 4. PMID:17059830 doi:10.1016/j.jmb.2006.10.002
  1. Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell. 1996 Jan 26;84(2):321-30. PMID:8565077
  2. Wang Q, Stacy T, Binder M, Marin-Padilla M, Sharpe AH, Speck NA. Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3444-9. PMID:8622955

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