Gene content    
TTN (-- by HUGO)
titin ----- (Previous names: cardiomyopathy, dilated 1G (autosomal dominant) ) (Previous
Cardiomyopathy, Dilated 1G (Autosomal Dominant)
Rhabdomyosarcoma Antigen MU-RMS-40.14
NCBI: 2q31    Ensembl: 2q31.2
TITIN_HUMANSize: 34350 amino acidsMass: 3816030 Da

  • Subcellular location: Cytoplasm (Probable). Nucleus Miscellaneous: In some isoforms, after the PEVK repeat region there is a long PEVK duplicated region. On account of this region, it has been very difficult to sequence the whole protein. The length of this region (ranging fro
  • Subunit: Interacts with MYOM1, MYOM2, tropomyosin and myosin. Interacts with actin, primarily via the PEVK domains and with MYPN (By similarity). Interacts with FHL2, NEB, CRYAB, LMNA/lamin-A and LMNB/lamin-B. Interacts with TCAP/telethonin and/or ANK1 isoform Mu17/ank1.5, via the first two N-terminal immunoglobulin domains. Interacts with TRIM63 and TRIM55, through several domains including immunoglobulin domains 141 and 142. Interacts with ANKRD1, ANKRD2 and ANKRD23, via the region between immunoglobulin domains 77 and 78 and interacts with CAPN3, via immunoglobulin domain 79. Interacts with NBR1 through the protein kinase domain. Interacts with CALM/calmodulin. Isoform 6 interacts with OBSCN isoform 3. Interacts with CMYA5
  • 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)
  • Similarity:
    Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family
    Contains 132 fibronectin type-III domains
    Contains 152 Ig-like (immunoglobulin-like) domains
    Contains 19 Kelch repeats
    Contains 1 protein kinase domain
    Contains 17 RCC1 rep
  • Protein Domain/Family    
    Source ID Domain Name Type
    InterProIPR002290Ser/Thr_dual-sp_kinase_domSerine/threonine protein kinaseDomain
    IPR003598Ig_sub2Immunoglobulin C2 typeDomain
    IPR003599Ig_subImmunoglobulin subtypeDomain
    IPR003961Fibronectin_type3Fibronectin, type IIIDomain
    BlocksIPB003598Immunoglobulin C-2 typeImmunoglobulin C-2 type
    IPB008266Tyrosine protein kinaseTyrosine protein kinase, active site

    Disorder & Mutation    
    Source Disease
    SWISS-PROTDefects in TTN are the cause of 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
    SWISS-PROTDefects in TTN are the cause of cardiomyopathy dilated type 1G (CMD1G) [MIM:604145]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death
    SWISS-PROTDefects in TTN are the cause of tardive tibial muscular dystrophy (TMD) [MIM:600334]; also known as Udd myopathy. TMD is an 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
    SWISS-PROTDefects in TTN are the cause of limb-girdle muscular dystrophy type 2J (LGMD2J) [MIM:608807]. LGMD2J is 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
    SWISS-PROTDefects in TTN are the cause of hereditary myopathy with early respiratory failure (HMERF) [MIM:603689]; also known as Edstrom myopathy. HMERF is an autosomal dominant, adult-onset myopathy with early respiratory muscle involvement
    SWISS-PROTDefects in TTN are the cause of familial hypertrophic cardiomyopathy type 9 (CMH9) [MIM:613765]. Familial hypertrophic cardiomyopathy is 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

    TTN cross reference    
    PubMed Entrez Gene NCKU SNP Nucleotide UniProt Genome Data Viewer HomoloGene