Xdv. Biophys., Vol. 33, pp. 13-25 (1996) cDNA SEQUENCE OF RABBIT CARDIAC TITIN/ CONNECTIN M.L. GREASER,*’ M.G. SEBESTYEN,** J.D. FRITZ,**~*” AND J.A. WOLFF*2 *I Muscle Biology Laboratory and Department of Anatomy, Uni- versity of Wisconsin-Madison, Madison, WI 53706 and b2 De- partments of Pediatrics and Medical Genetics, Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, U.S.A. Titin (I), also known as connectin (Z), has the largest polypeptide chain length of proteins studied to date. A key step in the understanding of a protein’s function is the determination of its amino acid sequence. The tedious approach of amino acid sequencing a protein of titin’s size is not feasible (the sequence contains more than 25,000 residues), and even ob- taining full sequence information from cDNA is a daunting task. In this review we summarize studies conducted on the cDNA sequence of rabbit cardiac titin. Also, since most of the published titin cDNA work has re- ported sequences from only a single tissue or species, we will summarize comparative results in the regions where this information is available. Titin is believed to extend from the M line to the Z line in each half sarcomere (Fig. 1). The figure also summarizes the approximate sarcomere locations of published titin cDNA sequences at the time of this review. I. .4 BAND CARDIAC TITIN CLONES 1. Initial Clones The first cDNA sequence for titin was reported by Labeit et al. (3). They *’ Current address: Department of Pharmacology, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232, U.S.A. 13