Abstract
Titin and twitchin are giant proteins expressed in muscle. They are mainly composed of domains belonging to the fibronectin class III and immunoglobulin c2 families, repeated many times. In addition, both proteins have a protein kinase domain near the C-terminus. This paper explores the evolution of these and related muscle proteins in an attempt to determine the order of events that gave rise to the different repeat patterns and the order of appearance of the proteins. Despite their great similarity at the level of sequence organization, titin and twitchin diverged from each other at least as early as the divergence between vertebrates and nematodes. Most of the repeating units in titin and twitchin were estimated to derive from three original domains. Chicken smooth-muscle myosin light-chain kinase (smMLCK) also has a kinase domain, several immunoglobulin domains, and a fibronectin domain. From a comparison of the kinase domains, titin is predicted to have appeared first during the evolution of the family, followed by twitchin and with the vertebrate MLCKs last to appear. The so-called C-protein from chicken is also a member of this family but has no kinase domain. Its origin remains unclear but it most probably pre-dates the titin/twitchin duplication.
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References
Ayme-Southgate A, Vigoreaux J, Benian G, Pardue, ML (1991) Drosophila has a twitchin/titin-related gene that appears to encode projectin. Proc Natl Acad Sci USA 88:7973–7977
Bairoch A, Boeckmann B (1992) The SWISS-PROT protein sequence data bank. Nucleic Acids Res 20:2019–2022
Benian GM, Kiff JE, Neckelmann N, Moerman DG, Waterston RH (1989) Sequence of an unusually large protein implicated in regulation of myosin activity in C. elegans. Nature 342:45–50
Bork P, Doolittle RF (1992) Proposed acquisition of an animal protein domain by bacteria. Proc Natl Acad Sci USA 89:8990–8994
Dayhoff MO (1978) Survey of new data and computer methods of analysis. In: Dayhoff MO (ed) Atlas of protein sequence and structure, vol 5, suppl 3. National Biomedical Research Foundation, Washington, DC, pp 1–8
Einheber S, Fischman DA (1990) Isolation and characterisation of a cDNA clone encoding avian skeletal muscle C-protein: an intracellular member of the immunoglobulin superfamily. Proc Natl Acad Sci USA 87:2157–2161
Felsenstein J (1985) Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39:783–791
Felsenstein J (1989) PHYLIP: phylogeny inference package (version 3.2). Cladistics 5:164–166
Fyrberg CC, Labeit S, Bullard B, Leonard K, Fyrberg E (1992) Drosophila projectin: relatedness to titin and twitchin and correlation with lethal (4)102 CDa and bent-dominant. Proc R Soc Lond B 249:33–40
Fürst DO, Osborn M, Weber K (1989) Myogenesis in mouse embryo: differential onset of myogenic proteins and the involvement of titin in myofibril assembly. J Cell Biol 109:517–527
Gibson TJ, Higgins DG (1992) Myosin light-chain kinase: no end in sight. Submitted to J DNA Seq Map
Hanks SK, Quinn AM, Hunter T (1988) The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241:42–52
Herring BP, Stull JT, Gallagher PJ (1990) Domain characterisation of rabbit skeletal muscle myosin light-chain kinase. J Biol Chem 265:1724–1730
Higgins DG, Bleasby AJ, Fuchs R (1992) Clustal V: improved software for multiple sequence alignment. Comput Appl Biosci 8:189–191
Higgins DG, Fuchs R, Stoehr PJ, Cameron GN (1992) The EMBL data library. Nucleic Acids Res 20:2071–2074
Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, Cambridge
Kornblihtt AR, Umezawa K, Vibe-Pedersen K, Baralle FE (1985) Primary structure of human fibronectin: differential splicing may generate at least 10 polypeptides from a single gene. EMBO J 4:1755–1759
Kurzban GP, Wang K (1988) Giant polypeptides of skeletal muscle titin: sedimentation equilibrium in guanidine hydrochloride. Biochem Biophys Res Commun 155:1155–1161
Labeit S, Barlow DP, Gautel M, Gibson T, Holt J, Hsieh CL, Francke U, Leonard K, Wardale J, Whiting A, Trinick J (1990) A regular pattern of two types of 100-residue motif in the sequence of titin. Nature 345:273–276
Labeit S, Gautel M, Lakey A, Trinick J (1992) Towards a molecular understanding of titin. EMBO J 11:1711–1716
Lakey A, Ferguson C, Labeit S, Reedy M, Larkins A, Butcher G, Leonard K, Bullard B (1990) Identification and localisation of high molecular weight proteins in insect flight and leg muscles. EMBO J 9:3459–3467
Locker RH, Wild DJC (1986) A comparative study of high molecular weight proteins in various types of muscle across the animal kingdom. J Biochem 99:1473–1484
Maruyama K, Kimura S, Yoshidomi H, Sawada H, Kikuchi M (1984) Molecular size and shape of beta-connectin, an elastic protein of striated muscle. J Biochem 95:1423–1493
Olson NJ, Pearson RB, Needleman DS, Hurwitz MY, Kemp BE, Means AR (1990) Regulatory and structural motifs of chicken gizzard myosin light-chain kinase. Proc Natl Acad Sci USA87:2284–2288
Roush CL, Kennelly PJ, Glaccum MB, Helfman DM, Scott JD, Krebs EG (1988) Isolation of the cDNA encoding rat skeletal muscle myosin light-chain kinase. J Biol Chem 263:10510–10516
Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425
Shoemaker MO, Lau W, Shattuck RL, Kwiatkowski AP, Matrisian PE, Guerra-Santos L, Wilson E, Lukas TJ, van Eldik LJ, Watterson DM (1990) Use of DNA sequence and mutant analyses and antisense deoxynucleotides to examine the molecular basis of nonmuscle myosin light-chain kinase autoinhibition, calmodulin recognition, and activity. J Cell Biol 111:1107–1125
Tan JL, Spudich JA (1991) Characterisation and bacterial expression of the Dictyostelium myosin light-chain kinase cDNA: identification of an autoinhibitory domain. J Biol Chem 266:16044–16049
Whiting A, Wardale J, Trinick J (1989) Does titin regulate the length of thick filaments? J Mol Biol 205:263–268
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Correspondence to: D.G. Higgins
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Higgins, D.G., Labeit, S., Gautel, M. et al. The evolution of titin and related giant muscle proteins. J Mol Evol 38, 395–404 (1994). https://doi.org/10.1007/BF00163156
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DOI: https://doi.org/10.1007/BF00163156