Homeodomain revisited: a lesson from disease-causing mutations. Hum Genet 2005 May;116(6):433-44
Date
02/24/2005Pubmed ID
15726414Pubmed Central ID
PMC1579204DOI
10.1007/s00439-004-1252-1Scopus ID
2-s2.0-21444446875 (requires institutional sign-in at Scopus site) 61 CitationsAbstract
The homeodomain is a highly conserved DNA-binding motif that is found in numerous transcription factors throughout a large variety of species from yeast to humans. These gene-specific transcription factors play critical roles in development and adult homeostasis, and therefore, any germline mutations associated with these proteins can lead to a number of congenital abnormalities. Although much has been revealed concerning the molecular architecture and the mechanism of homeodomain-DNA interactions, the study of disease-causing mutations can further provide us with instructive information as to the role of particular residues in a conserved mode of action. In this paper, I have compiled the homeodomain missense mutations found in various human diseases and re-examined the functional role of the mutational "hot spot" residues in light of the structures obtained from crystallography. These findings should be useful in understanding the essential components of the homeodomain and in attempts to design agonist or antagonists to modulate their activity and to reverse the effects caused by the mutations.
Author List
Chi YIAuthor
Young-In Chi PhD Assistant Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceConserved Sequence
Genetic Diseases, Inborn
Homeodomain Proteins
Humans
Models, Molecular
Molecular Sequence Data
Mutation
Transcription Factors
