HHrep:: de novo protein repeat detection and the origin of TIM barrels

HHrep is a web server for the de novo identification of repeats in protein sequences, which is based on the pairwise comparison of profile hidden Markov models (HMMs). Its main strength is its sensitivity, allowing it to detect highly divergent repeat units in protein sequences whose repeats could as yet only be detected from their structures. Examples include sequences with beta-propellor fold, ferredoxin-like fold, double psi barrels or (beta a)(8) (TIM) barrels. We illustrate this with proteins from four superfamilies of TIM barrels by revealing a clear 4- and 8- fold symmetry, which we detect solely from their sequences. This symmetry might be the trace of an ancient origin through duplication of a beta a beta a or beta a unit. HHrep can be accessed at http://hhrep. tuebingen.mpg.de.