InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TTN

Summary

InnateDB Protein

IDBP-76107.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TTN

Protein Name

titin

Synonyms

CMD1G; CMH9; CMPD4; EOMFC; HMERF; LGMD2J; MYLK5; TMD;

Species

Homo sapiens

Ensembl Protein

ENSP00000354117

InnateDB Gene

IDBG-76091 (TTN)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:9804419}.

Subcellular Localization

Cytoplasm {ECO:0000305PubMed:16410549}. Nucleus {ECO:0000269PubMed:16410549}.

Disease Associations

Hereditary myopathy with early respiratory failure (HMERF) [MIM:603689]: Autosomal dominant, adult-onset myopathy with early respiratory muscle involvement. {ECO:0000269PubMed:15802564}. Note=The disease is caused by mutations affecting the gene represented in this entry.Cardiomyopathy, familial hypertrophic 9 (CMH9) [MIM:613765]: 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. {ECO:0000269PubMed:10462489}. Note=The disease is caused by mutations affecting the gene represented in this entry.Cardiomyopathy, dilated 1G (CMD1G) [MIM:604145]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269PubMed:11788824, ECO:0000269PubMed:11846417, ECO:0000269PubMed:16465475}. Note=The disease is caused by mutations affecting the gene represented in this entry.Tardive tibial muscular dystrophy (TMD) [MIM:600334]: 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. {ECO:0000269PubMed:12145747, ECO:0000269PubMed:12891679}. Note=The disease is caused by mutations affecting the gene represented in this entry.Limb-girdle muscular dystrophy 2J (LGMD2J) [MIM:608807]: 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. Note=The disease is caused by mutations affecting the gene represented in this entry.Early-onset myopathy with fatal cardiomyopathy (EOMFC) [MIM:611705]: Early-onset myopathies are inherited muscle disorders that manifest typically from birth or infancy with hypotonia, muscle weakness, and delayed motor development. EOMFC is a titinopathy that, in contrast with the previously described examples, involves both heart and skeletal muscle, has a congenital onset, and is purely recessive. This phenotype is due to homozygous out-of-frame TTN deletions, which lead to a total absence of titin's C-terminal end from striated muscles and to secondary CAPN3 depletion. {ECO:0000269PubMed:17444505}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Isoforms 3, 7 and 8 are expressed in cardiac muscle. Isoform 4 is expressed in vertebrate skeletal muscle. Isoform 6 is expressed in skeletal muscle (at protein level). {ECO:0000269PubMed:11717165, ECO:0000269PubMed:7819249}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 70 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	70 [view]
Protein-Protein	70 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002020	protease binding
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0005516	calmodulin binding
GO:0005524	ATP binding
GO:0008307	structural constituent of muscle
GO:0019899	enzyme binding
GO:0019901	protein kinase binding
GO:0031433	telethonin binding
GO:0042802	identical protein binding
GO:0042805	actinin binding
GO:0043621	protein self-association
GO:0051015	actin filament binding
GO:0051371	muscle alpha-actinin binding
GO:0097493	structural molecule activity conferring elasticity

Biological Process

GO:0002576	platelet degranulation
GO:0003300	cardiac muscle hypertrophy
GO:0006936	muscle contraction
GO:0006941	striated muscle contraction
GO:0007076	mitotic chromosome condensation
GO:0007596	blood coagulation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030049	muscle filament sliding
GO:0030168	platelet activation
GO:0030240	skeletal muscle thin filament assembly
GO:0030241	skeletal muscle myosin thick filament assembly
GO:0035995	detection of muscle stretch
GO:0045214	sarcomere organization
GO:0045859	regulation of protein kinase activity
GO:0048739	cardiac muscle fiber development
GO:0048769	sarcomerogenesis
GO:0050790	regulation of catalytic activity
GO:0051592	response to calcium ion
GO:0055003	cardiac myofibril assembly
GO:0055008	cardiac muscle tissue morphogenesis
GO:0060048	cardiac muscle contraction

Cellular Component

GO:0000794	condensed nuclear chromosome
GO:0005576	extracellular region
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0005865	striated muscle thin filament
GO:0030018	Z disc
GO:0031430	M band
GO:0031674	I band
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR003598 Immunoglobulin subtype 2
IPR003599 Immunoglobulin subtype
IPR007110 Immunoglobulin-like domain
IPR013098 Immunoglobulin I-set
IPR013151 Immunoglobulin
IPR015129 Titin Z

PFAM

PF07679
PF00047
PF09042

PRINTS

PIRSF

SMART

SM00408
SM00409

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q8WZ42