Not to be confused with Tintin.
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Titin
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| PDB rendering based on 1bpv. |
| Available structures: 1bpv, 1g1c, 1h8b, 1nct, 1ncu, 1tit, 1tiu, 1tki, 1tnm, 1tnn, 1waa, 1ya5, 2a38, 2bk8, 2f8v, 2ill, 2nzi |
| Identifiers |
| Symbols |
TTN; CMD1G; CMH9; CMPD4; DKFZp451N061; FLJ26020; FLJ26409; FLJ32040; FLJ34413; FLJ39564; FLJ43066; HMERF; LGMD2J; TMD |
| External IDs |
OMIM: 188840 MGI: 98864 HomoloGene: 26418 |
| EC number |
2.7.11.1 |
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| RNA expression pattern |
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More reference expression data
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| Orthologs |
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Human |
Mouse |
| Entrez |
7273 |
22138 |
| Ensembl |
ENSG00000155657 |
ENSMUSG00000051747 |
| Uniprot |
Q8WZ42 |
n/a |
| Refseq |
NM_003319 (mRNA)
NP_003310 (protein) |
NM_011652 (mRNA)
NP_035782 (protein) |
| Location |
Chr 2: 179.1 - 179.38 Mb |
Chr 2: 76.51 - 76.64 Mb |
| Pubmed search |
[1] |
[2] |
Titin, also known as connectin is a protein that is important in the contraction of striated muscle tissues.[1][2]
Structure
Sliding filament model of muscle contraction. (Titin labeled at upper right.)
Titin is the largest known protein, consisting of 34,350 amino acids. The molecular weight of the mature protein is approximately 2,993,442.763 u[3], and it has a theoretical pI of 6.01[4] The protein's empirical chemical formula is C132983H211861N36149O40883S693. It has a theoretical instability index (II) of 39.69, indicating that it would be stable in a test tube. The protein's in vivo half-life, the time it takes for half of the amount of protein in a cell to disappear after its synthesis in the cell, is predicted to be approximately 30 hours (in mammalian reticulocytes).[5]
Linguistic significance
As the largest known protein, titin also has the longest IUPAC name. The full chemical name, containing 189,819 letters, is sometimes stated to be the longest word in the English language.[6] However, professional dictionary writers regard generic names of chemical compounds as verbal formulae rather than as English words.[7]
Function
Titin is a large abundant protein of striated muscle. The protein is divided into two regions:
- N-terminal I-band – is the elastic part of the molecule, contains two regions of tandem immunoglobulin domains on either side of a PEVK region that is rich in proline, glutamate, valine and lysine
- C-terminal A-band – thought to act as a protein-ruler, contains a mixture of immunoglobulin and fibronectin repeats, and possesses kinase activity.
A N-terminal Z-disc region and a C-terminal M-line region bind to the Z-line and M-line of the sarcomere respectively so that a single titin molecule spans half the length of a sarcomere. Titin also contains binding sites for muscle associated proteins so it serves as an adhesion template for the assembly of contractile machinery in muscle cells. It has also been identified as a structural protein for chromosomes. Considerable variability exists in the I-band, the M-line and the Z-disc regions of titin. Variability in the I-band region contributes to the differences in elasticity of different titin isoforms and, therefore, to the differences in elasticity of different muscle types. Of the many titin variants identified, five for which complete transcript information is available are described.[2][8]
Titin interacts with many sarcomeric proteins including:[9]
Disease linkage
Mutations in this gene are associated with familial hypertrophic cardiomyopathy 9[10][11] and tibial muscular dystrophy.[12] Autoantibodies to titin are produced in patients with the autoimmune disease scleroderma.[13]
References
- ^ Online 'Mendelian Inheritance in Man' (OMIM) 188840
- ^ a b "Entrez Gene: TTN titin".
- ^ Result of Molecular Weight Calculation
- ^ "ExPASy-calculated pI for titin". Retrieved on 2007-08-26.
- ^ "Swiss-Prot Protein knowledgebase, main entry". Retrieved on 2006-05-04.
- ^ Othyr. "Othyr". othyr.com. Retrieved on 2008-05-27.
- ^ Oxford Word and Language Service team. "Ask the experts - What is the longest English word?". AskOxford.com / Oxford University Press. Retrieved on 2008-01-13.
- ^ Labeit S, Barlow DP, Gautel M, Gibson T, Holt J, Hsieh CL, Francke U, Leonard K, Wardale J, Whiting A, Trinick J (May 1990). "A regular pattern of two types of 100-residue motif in the sequence of titin". Nature 345 (6272): 273–6. doi:10.1038/345273a0. PMID 2129545.
- ^ Bang ML, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, Witt CC, Labeit D, Gregorio CC, Granzier H, Labeit S (November 2001). "The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system". Circ. Res. 89 (11): 1065–72. PMID 11717165.
- ^ Siu BL, Niimura H, Osborne JA, Fatkin D, MacRae C, Solomon S, Benson DW, Seidman JG, Seidman CE (March 1999). "Familial dilated cardiomyopathy locus maps to chromosome 2q31". Circulation 99 (8): 1022–6. PMID 10051295.
- ^ Itoh-Satoh M, Hayashi T, Nishi H, Koga Y, Arimura T, Koyanagi T, Takahashi M, Hohda S, Ueda K, Nouchi T, Hiroe M, Marumo F, Imaizumi T, Yasunami M, Kimura A (February 2002). "Titin mutations as the molecular basis for dilated cardiomyopathy". Biochem. Biophys. Res. Commun. 291 (2): 385–93. doi:10.1006/bbrc.2002.6448. PMID 11846417.
- ^ Hackman P, Vihola A, Haravuori H, Marchand S, Sarparanta J, De Seze J, Labeit S, Witt C, Peltonen L, Richard I, Udd B (September 2002). "Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin". Am. J. Hum. Genet. 71 (3): 492–500. doi:10.1086/342380. PMID 12145747.
- ^ Machado C, Sunkel CE, Andrew DJ (April 1998). "Human autoantibodies reveal titin as a chromosomal protein". J. Cell Biol. 141 (2): 321–33. doi:10.1083/jcb.141.2.321. PMID 9548712.
Further reading
- Kinbara K, Sorimachi H, Ishiura S, Suzuki K (1998). "Skeletal muscle-specific calpain, p49: structure and physiological function". Biochem. Pharmacol. 56 (4): 415–20. PMID 9763216.
- Kolmerer B, Witt CC, Freiburg A, et al. (1999). "The titin cDNA sequence and partial genomic sequences: insights into the molecular genetics, cell biology and physiology of the titin filament system". Rev. Physiol. Biochem. Pharmacol. 138: 19–55. doi:10.1007/BF02346659. PMID 10396137.
- Trinick J, Tskhovrebova L (1999). "Titin: a molecular control freak". Trends Cell Biol. 9 (10): 377–80. doi:10.1016/S0962-8924(99)01641-4. PMID 10481174.
- Sorimachi H, Ono Y, Suzuki K (2000). "Skeletal muscle-specific calpain, p94, and connectin/titin: their physiological functions and relationship to limb-girdle muscular dystrophy type 2A". Adv. Exp. Med. Biol. 481: 383–95; discussion 395–7. PMID 10987085.
- Tskhovrebova L, Trinick J (2002). "Role of titin in vertebrate striated muscle". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 357 (1418): 199–206. doi:10.1098/rstb.2001.1028. PMID 11911777.
- Sela BA (2002). "[Titin: some aspects of the largest protein in the body]". Harefuah 141 (7): 631–5, 665. PMID 12187564.
- Wu Y, Labeit S, Lewinter MM, Granzier H (2003). "Titin: an endosarcomeric protein that modulates myocardial stiffness in DCM". J. Card. Fail. 8 (6 Suppl): S276–86. doi:10.1054/jcaf.2002.129278. PMID 12555133.
- Tskhovrebova L, Trinick J (2004). "Properties of titin immunoglobulin and fibronectin-3 domains". J. Biol. Chem. 279 (45): 46351–4. doi:10.1074/jbc.R400023200. PMID 15322090.
External links
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Histology: muscle tissue |
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| skeletal muscle/general |
epimysium, fascicle, perimysium, endomysium, muscle fiber ( intrafusal, extrafusal), myofibril
sarcomere (a, i, and h bands; z and m lines), myofilaments (thin filament/actin, thick filament/myosin, elastic filament/titin, nebulin), tropomyosin, troponin (T, C, I)
costamere (dystrophin, a,ß-dystrobrevin, syncoilin, synemin/desmuslin, dysbindin, sarcoglycan, dystroglycan, sarcospan), desmin
neuromuscular junction, motor unit, muscle spindle, excitation-contraction coupling, sliding filament mechanism
myoblast, satellite cell, sarcoplasm, sarcolemma, sarcoplasmic reticulum, T-tubule
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| cardiac muscle |
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| smooth muscle |
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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