Release 8.2

Looking for Titin

"I am looking for Titine" Charlie Chaplin sang in Modern Times. While for many people Titin brings back memories about this song, for the scientific community the meaning is completely different. Titin is a giant sarcomeric protein of roughly 35'000 aa. Protein analysis programs used to crash when encountering huge proteins, and the size limit of a protein to be integrated into UniProtKB/Swiss-Prot used to be under 10'000 aa long. Modern times finally arrived and bioinformatics has improved by leaps and bounds. Programs are now able to deal with huge proteins and titin has finally been integrated into UniProtKB/Swiss-Prot.

Titin is a long (up to 1 micron), slender and flexible strand, frequently with a large globule at one end. It has a complex modular structure that varies depending on the splicing events. In its longest form it may contain up to 132 fibronectin type-III domains, 152 Ig-like domains, 9 Kelch, 17 RCC1, 14 TPR, 15 WD and 31 PEVK repeats and 1 protein kinase domain. Titin functions as a mechanical sensor through its interaction with many other proteins, such as myomesins, tropomyosins, myosins, actins, myopalladin, etc. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere and thus to muscle extensibility. In non-muscle cells, it seems to play a role in chromosome condensation and segregation during mitosis.

Needless to say, the titin-seeking of Charlie Chaplin was a legitimate demand, because all human beings need titin in their life.