TTN

This gene encodes a large abundant protein of striated muscle. The product of this gene is divided into two regions, a N-terminal I-band and a C-terminal A-band. The I-band, which 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. The A-band, which is 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. Mutations in this gene are associated with familial hypertrophic cardiomyopathy 9 and autoantibodies to titin are produced in patients with the autoimmune disease scleroderma. [provided by RefSeq]

titin

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.

Biological Process cardiac muscle cell development Source:BHF-UCL1 Publication
Biological Process cardiac muscle contraction Source:BHF-UCL1 Publication
Biological Process cardiac muscle hypertrophy Source:BHF-UCL1 Publication
Biological Process cardiac muscle tissue morphogenesis Source:BHF-UCL1 Publication
Biological Process cardiac myofibril assembly Source:BHF-UCL2 Publications
Biological Process detection of muscle stretch Source:MGI1 Publication
Biological Process mitotic chromosome condensation Source:BHF-UCL1 Publication
Biological Process muscle contraction Source:UniProtKB1 Publication
Biological Process positive regulation of gene expression Source:CAFA1 Publication
Biological Process positive regulation of protein secretion Source:CAFA1 Publication
Biological Process protein kinase A signaling Source:CAFA1 Publication
Biological Process regulation of catalytic activity Source:BHF-UCL1 Publication
Biological Process regulation of protein kinase activity Source:BHF-UCL1 Publication
Biological Process response to calcium ion Source:BHF-UCL1 Publication
Biological Process sarcomere organization Source:BHF-UCL2 Publications
Biological Process sarcomerogenesis Source:BHF-UCL1 Publication
Biological Process skeletal muscle myosin thick filament assembly Source:BHF-UCL1 Publication
Biological Process skeletal muscle thin filament assembly Source:BHF-UCL1 Publication
Biological Process striated muscle contraction Source:UniProtKB1 Publication

Cytoplasm
Nucleus

Myopathy, myofibrillar, 9, with early respiratory failure (MFM9):
An autosomal dominant myopathy characterized by adulthood onset of weakness in proximal, distal, axial and respiratory muscles. Pelvic girdle weakness, foot drop and neck weakness are the main symptoms at onset, but ultimately the weakness usually involves the proximal compartment of both upper and lower limbs. Additional features include variable degrees of Achilles tendon contractures, spinal rigidity and muscle hypertrophy. Respiratory involvement often leads to requirement for non-invasive ventilation support.
Cardiomyopathy, familial hypertrophic 9 (CMH9):
A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
Cardiomyopathy, dilated 1G (CMD1G):
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Tardive tibial muscular dystrophy (TMD):
Autosomal dominant, late-onset distal myopathy. Muscle weakness and atrophy are usually confined to the anterior compartment of the lower leg, in particular the tibialis anterior muscle. Clinical symptoms usually occur at age 35-45 years or much later.
Muscular dystrophy, limb-girdle, autosomal recessive 10 (LGMDR10):
An autosomal recessive degenerative myopathy characterized by progressive weakness of the pelvic and shoulder girdle muscles. Severe disability is observed within 20 years of onset.
Salih myopathy (SALMY):
An autosomal recessive, early-onset muscular disorder characterized by dilated cardiomyopathy, delayed motor development with generalized muscle weakness predominantly affecting proximal and distal lower limbs. Skeletal muscle biopsies show minicore-like lesions with mitochondrial depletion and sarcomere disorganization, centralized nuclei, and type 1 fiber predominance. Dystrophic changes become apparent in the second decade. Cardiac muscle biopsies show disruption of myocardial architecture, nuclear hypertrophy, and endomysial fibrosis. Sudden death may occurr due to cardiomyopathy.

Autophosphorylated.