REVIEW - BORDERS, PATTERNS, AND DISTINCTIVE FAMILIES OF HOMEODOMAINS

Purpose: Homeotic proteins function as transcription factors in early embryogenesis of many organisms. To date, hundreds of distinctive homo eproteins have been identified, including 84 human homeodomains. Howev er further progress in understanding functional relationships between particular homeoproteins and other embryonic regulators requires a com prehensive structural classification of these proteins. Results: The m ost probable borders and conservative amino acid positions inside the homeodomain region have been established using a statistical analysis of variabilities of amino acid occurrences at various positions outsid e and inside the domain. A new format for a homeodomain sequence prese ntation and regular amino acid patterns which are strongly representat ive of distinctive homeodomain groups are proposed. Using the establis hed patterns, 33 families of closely related homeodomains have been di stinguished and classified. The total list of 297 homeodomain amino ac id sequences is presented in the Appendix. Conclusion: The structural classification of homeodomains has been proposed. It can be useful for both the identification (or prediction) of new homeotic genes/protein s and the recognition of possible PCR-induced sequence errors. This sy stematics will also have an impact on understanding functional relatio nships among homeotic proteins and other genetic regulators of develop mental processes.