Evidence map›Paper›PMID 12626758›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2003

Mutations that affect the ability of the vnd/NK-2 homeoprotein to regulate gene expression: transgenic alterations and tertiary structure.

Keita Koizumi, Carla Lintas, Marshall Nirenberg, Jin-Soo Maeng, Jeong-Ho Ju, James W Mack, James M Gruschus, Ward F Odenwald, James A Ferretti

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. How the Dorsal gradient works: insights from postgenome technologies.Proceedings of the National Academy of Sciences of the United States of America · 2008
    Review
  8. NOBOX homeobox mutation causes premature ovarian failure.American journal of human genetics · 2007
    Article
  9. Article
  10. Article
  11. Review
  12. Identification and analysis of vnd/NK-2 homeodomain binding sites in genomic DNA.Proceedings of the National Academy of Sciences of the United States of America · 2005
    Article
  13. Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Keita KoizumiNeural Cell-Fate Determinants Section, National Institute of Neurological Diseases and Stroke, Building 36, Room 3C17, National Institutes of Health, Bethesda, MD 20892-4130, USA.
Carla Lintas
Marshall Nirenberg
Jin-Soo Maeng
Jeong-Ho Ju
James W Mack
James M Gruschus
Ward F Odenwald
James A Ferretti
National Heart Lung and Blood Institute · US

Funding

The Howard University SCORE Program Supplemental GrantS06GM008016 · NIGMS · HOWARD UNIVERSITY · PI TIZABI, YOUSEF · 1989 to 2009
$16.1M
Three-dimensional Structures Of Biological MacromoleculesZIAHL001027 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI BROOKS, BERNARD R · 2009 to 2025
$8.1M
Analysis of Neural Precursor Cell cis-Regulatory EnhancersZIANS002820 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI ODENWALD, WARD F · 2010 to 2017
$5.3M
CELL RECOGNITION AND SYNAPSE FORMATIONZ01HL000009 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI NIRENBERG, MARSHALL WARREN · 1985 to 2008
$4.5M
Cell Recognition And Synapse FormationZIAHL000009 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI NIRENBERG, MARSHALL WARREN · 2009 to 2010
$4.4M
Gene Regulatory Networks Controlling CNS DevelopmentZ01NS002820 · NINDS · NEUROLOGICAL DISORDERS AND STROKE · PI ODENWALD, WARD F · 1990 to 2008
$2.5M
Analysis Of Gene Expression Regulatory Networks Controlling CNS DevelopmentZIHNS002820 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI ODENWALD, WARD F · 2009 to 2009
$1.2M
THREE-DIMENSIONAL STRUCTURES OF BIOLOGICAL MACROMOLECULESZ01HL001027 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI BROOKS, BERNARD R · 1985 to 2008
$617k
NIGMS NIH HHS GM 08016NIGMS NIH HHS S06 GM008016
6 · The paper itself

Abstract

The importance in downstream target regulation of tertiary structure and DNA binding specificity of the protein encoded by the vndNK-2 homeobox gene is analyzed. The ectopic expression patterns of WT and four mutant vndNK-2 genes are analyzed together with expression of two downstream target genes, ind and msh, which are down-regulated by vndNK-2. Three mutants are deletions of conserved regions (i.e., tinman motif, acidic motif, and NK-2 box), and the fourth, Y54M vndNK-2, corresponds to a single amino acid residue replacement in the homeodomain. Of the four ectopically expressed mutant genes examined, only the Y54M mutation inactivates the ability of the vndNK-2 homeodomain protein to repress ind and msh. The acidic motif deletion mutant slightly reduced the ability of the protein to repress ind and msh. By contrast, both tinman and NK-2 box deletion mutants behaved as functional vndNK-2 genes in their ability to repress ind and msh. The NMR-determined tertiary structures of the Y54M vndNK-2 homeodomain, both free and bound to DNA, are compared with the WT analog. The only structural difference observed for the mutant homeodomain is in the complex with DNA and involved closer interaction of the methionine-54 with A2, rather than with C3 of the (-) strand of the DNA. This subtle change in the homeodomain-DNA complex resulted in modifications of binding affinities to DNA. These changes resulting from a single amino acid residue replacement constitute the molecular basis for the phenotypic alterations observed on ectopic expression of the Y54M vndNK-2 gene during embryogenesis.

Indexed as

Amino Acid SubstitutionAnimalsAnimals, Genetically ModifiedBase SequenceBinding SitesDNADrosophila melanogasterDrosophila ProteinsGene Expression Regulation, DevelopmentalGenes, HomeoboxGenes, InsectHomeodomain ProteinsModels, MolecularMutationPhenotypeProtein Structure, TertiaryDNADrosophila ProteinsHomeodomain ProteinsTranscription Factorsvnd protein, Drosophila

Identifiers

PMID12626758
PMCPMC152256
OpenAlexW2020627925

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.