Titin

4UOW, 1BPV, 1G1C, 1NCT, 1NCU, 1TIT, 1TIU, 1TKI, 1TNM, 1TNN, 1WAA, 1YA5, 2A38, 2BK8, 2F8V, 2ILL, 2J8H, 2J8O, 2NZI, 2RQ8, 2WP3, 2WWK, 2WWM, 2Y9R, 3KNB, 3LCY, 3LPW, 3PUC, 3Q5O, 3QP3, 4C4K, 4JNW, 4O00, 4QEG, 5BS0727322138ENSG00000155657ENSMUSG00000051747Q8WZ42A2ASS6NM_133432NM_133437NM_011652NM_028004NP_597676NP_597681NP_035782NP_082280Titin /ˈtaɪtɪn/, also known as connectin, is a protein that, in humans, is encoded by the TTN gene. Titin is a giant protein, greater than 1 µm in length, that functions as a molecular spring which is responsible for the passive elasticity of muscle. It comprises 244 individually folded protein domains connected by unstructured peptide sequences. These domains unfold when the protein is stretched and refold when the tension is removed.1bpv: TITIN MODULE A71 FROM HUMAN CARDIAC MUSCLE, NMR, 50 STRUCTURES1g1c: I1 DOMAIN FROM TITIN1h8b: EF-HANDS 3,4 FROM ALPHA-ACTININ / Z-REPEAT 7 FROM TITIN1nct: TITIN MODULE M5, N-TERMINALLY EXTENDED, NMR1ncu: Titin Module M5, N-terminally Extended, NMR1tit: TITIN, IG REPEAT 27, NMR, MINIMIZED AVERAGE STRUCTURE1tiu: TITIN, IG REPEAT 27, NMR, 24 STRUCTURES1tki: AUTOINHIBITED SERINE KINASE DOMAIN OF THE GIANT MUSCLE PROTEIN TITIN1tnm: TERTIARY STRUCTURE OF AN IMMUNOGLOBULIN-LIKE DOMAIN FROM THE GIANT MUSCLE PROTEIN TITIN: A NEW MEMBER OF THE I SET1tnn: Tertiary structure of an immunoglobulin-like domain from the giant muscle protein titin: a new member of the I set1waa: IG27 PROTEIN DOMAIN1ya5: Crystal structure of the titin domains z1z2 in complex with telethonin2a38: Crystal structure of the N-Terminus of titin2bk8: M1 DOMAIN FROM TITIN2f8v: Structure of full length telethonin in complex with the N-terminus of titin2ill: Anomalous substructure of Titin-A1681692nzi: Crystal structure of domains A168-A170 from titin Titin /ˈtaɪtɪn/, also known as connectin, is a protein that, in humans, is encoded by the TTN gene. Titin is a giant protein, greater than 1 µm in length, that functions as a molecular spring which is responsible for the passive elasticity of muscle. It comprises 244 individually folded protein domains connected by unstructured peptide sequences. These domains unfold when the protein is stretched and refold when the tension is removed. Titin is important in the contraction of striated muscle tissues. It connects the Z line to the M line in the sarcomere. The protein contributes to force transmission at the Z line and resting tension in the I band region. It limits the range of motion of the sarcomere in tension, thus contributing to the passive stiffness of muscle. Variations in the sequence of titin between different types of muscle (e.g., cardiac or skeletal) have been correlated with differences in the mechanical properties of these muscles. Titin is the third most abundant protein in muscle (after myosin and actin), and an adult human contains approximately 0.5 kg of titin. With its length of ~27,000 to ~33,000 amino acids (depending on the splice isoform), titin is the largest known protein. Furthermore, the gene for titin contains the largest number of exons (363) discovered in any single gene, as well as the longest single exon (17,106 bp). Reiji Natori in 1954 was the first to propose an elastic structure in muscle fiber to account for the return to the resting state when muscles are stretched and then released. In 1977, Koscak Maruyama and coworkers isolated an elastic protein from muscle fiber, which they called connectin. Two years later, Kuan Wang and coworkers identified a doublet band on electrophoresis gel corresponding to a high molecular weight elastic protein, which they named titin. Siegfried Labeit in 1990 isolated a partial cDNA clone of titin. In 1995, Labeit and Bernhard Kolmerer determined the cDNA sequence of human cardiac titin. Labeit and colleagues in 2001 determined the complete sequence of the human titin gene. The human gene encoding for titin is located on the long arm of chromosome 2 and contains 363 exons, which together code for 38,138 residues (4200 kDa). Within the gene are found a large number of PEVK (proline-glutamate-valine-lysine -abundant structural motifs) exons 84 to 99 nucleotides in length which code for conserved 28- to 33-residue motifs which may represent structural units of the titin PEVK spring. The number of PEVK motifs in the titin gene appears to have increased during evolution, apparently modifying the genomic region responsible for titin’s spring properties. A number of titin isoforms are produced in different striated muscle tissues as a result of alternative splicing. All but one of these isoforms are in the range of ~27,000 to ~36,000 amino acid residues in length. The exception is the small cardiac novex-3 isoform, which is only 5,604 amino acid residues in length. The following table lists the known titin isoforms: Titin is the largest known protein; its human variant consists of 34,350 amino acids, with the molecular weight of the mature 'canonical' isoform of the protein being approximately 3,816,188.13 Da. Its mouse homologue is even larger, comprising 35,213 amino acids with a MW of 3,906,487.6 Da. It has a theoretical isoelectric point of 6.01. The protein's empirical chemical formula is C169,719H270,466N45,688O52,238S911. It has a theoretical instability index (II) of 42.41, classifying the protein as unstable. The protein's in vivo half-life, the time it takes for half of the amount of protein in a cell to break down after its synthesis in the cell, is predicted to be approximately 30 hours (in mammalian reticulocytes). The titin protein is located between the myosin thick filament and the Z disk. Titin consists primarily of a linear array of two types of modules, also referred to as protein domains (244 copies in total): type I fibronectin type III domain (132 copies) and type II immunoglobulin domain (112 copies). However, the exact number of these domains is different in different species. This linear array is further organized into two regions: