Titin (TTN)
The protein contains 34350 amino acids for an estimated molecular weight of 3816030 Da.
Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The size and extensibility of the cross-links are the main determinants of sarcomere extensibility properties of muscle. In non-muscle cells, seems to play a role in chromosome condensation and chromosome segregation during mitosis. Might link the lamina network to chromatin or nuclear actin, or both during interphase. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Actin filament organization
Blood coagulation
Cardiac muscle contraction
Cardiac muscle fiber development
Cardiac muscle hypertrophy
Cardiac muscle tissue morphogenesis
Cardiac myofibril assembly
Detection of muscle stretch
Mitotic chromosome condensation
Muscle contraction
Muscle filament sliding
Peptidyl-tyrosine phosphorylation
Platelet activation
Platelet degranulation
Positive regulation of gene expression
Positive regulation of protein secretion
Protein kinase A signaling
Regulation of catalytic activity
Regulation of protein kinase activity
Response to calcium ion
Sarcomere organization
Sarcomerogenesis
Skeletal muscle myosin thick filament assembly
Skeletal muscle thin filament assembly
Striated muscle contraction
Striated muscle myosin thick filament assembly
Cellular Component
Condensed nuclear chromosome
Cytosol
Extracellular exosome
Extracellular region
I band
M band
Muscle myosin complex
Sarcomere
Striated muscle thin filament
Z disc
Molecular Function
Actin filament binding
Actinin binding
ATP binding
Calcium ion binding
Calmodulin binding
Enzyme binding
Identical protein binding
Muscle alpha-actinin binding
Protease binding
Protein kinase binding
Protein self-association
Protein serine kinase activity
Protein serine/threonine kinase activity
Protein threonine kinase activity
Protein tyrosine kinase activity
Structural constituent of muscle
Structural molecule activity conferring elasticity
Telethonin binding
The reference OMIM entry for this protein is 188840
Titin; ttn
Connectin
DESCRIPTION
Titin, or connectin, is a giant muscle protein expressed in the cardiac and skeletal muscles that spans half of the sarcomere from Z line to M line. Titin plays a key role in muscle assembly, force transmission at the Z line, and maintenance of resting tension in the I band region (Itoh-Satoh et al., 2002).CLONING
Labeit et al. (1990) showed that partial titin cDNAs encode a regular pattern of 2 types of 100-residue motif, each of which probably folds into a separate domain type. Such motifs are present in several evolutionarily divergent proteins, all of which are likely to interact with myosin. Labeit and Kolmerer (1995) determined the cDNA sequence of human cardiac titin. The 82-kb cDNA predicted a 26,926-amino acid protein with a molecular mass of 2,993 kD. Ninety percent of the mass is contained in a repetitive structure composed of 244 copies of 100-residue repeats that encode 112 immunoglobulin-like and 132 fibronectin type III domains. Alternative splicing accounts for tissue-specific titin isoforms. In the central part of I band titin, cardiac and skeletal titins branch into distinct isoforms; in heart, differential splicing includes about 3.5 kb of cDNA within the I band region of titin, whereas in skeletal muscle, 22.5 kb of cDNA is included. In addition, a sequence element rich in proline (P), glutamic acid (E), lysine (K), and valine (V) residues, referred to as the PEVK domain, comprises 163 residues in cardiac titin and 2,174 residues in skeletal titin. Bang et al. (2001) determined that the complete sequence of human titin encodes a 38,138-amino acid protein with a molecular mass of 4,200 kD.GENE STRUCTURE
Bang et al. (2001) determined that titin has 363 exons. Titin contains 6 M band-encoding exons at the C terminus, exons 358 to 363, referred to as Mex1 to Mex6. These exons are constitutively expressed in both skeletal and cardiac muscle (Carmignac et al., 2007).GENE FUNCTION
Labeit et al. (1990) suggested that the I band of titin makes elastic connections between the thick filament and the Z line within the sarcomere. The A band of titin appears to bind to the thick filament, where it may regulate filament length and assembly. The architecture of sequences in the A band region of titin suggested to Labeit and Kolmerer (1995) why thick filament structure is conserved among vertebrates. In the I band region, comparison of titin sequences from muscles of different passive tension identified 2 elements that correlate with tissue stiffness, suggesting that titin may act as 2 springs in series. The differential expression of the springs provides a molecular explanation for the diversity of sarcomere length and resting tension in vertebrate striated muscles. Ma and Wang (2002) presented evidence that the PEVK segment of titin, which contains numerous SH3-binding motifs, and the Z line protein myopalladin (MYPN; 608517) may play signaling roles in targeting and orienting nebulin (NEB; 161650) to the Z line during sarcomere assembly. The I band region of titin contains tandem arrays of immunoglobulin domains. Immunoglobulin domain-27 (I27) unfolds through an intermediate under force in which the A-strand is detached. The lengthening of I27 without unfolding forms a stable intermediate that is believed to be an important component of titin elasticity (Marszalek et al., 1999). Williams et al. (2003) used mutant titins to study the role of the partly unfolded intermediate ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 188840 was added.