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FLASH GENE
Symbol TTN contributors: mct/npt/pgu - updated : 04-03-2015
HGNC name titin
HGNC id 12403
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal I band forming the elastic part end
  • a PEVK (pro-Glu-Val-Lys) rich region
  • five regions of tandem repeats of the Ig type, binding to ACTA1
  • a N2A domain, putative binding site for CAPN3
  • the A band acting as a protein ruber containing a mixture of Ig and FBN repeats and possessing kinase activity
    • HOMOLOGY
    interspecies homolog to murine Ttn
    Homologene
    FAMILY
  • protein kinase superfamily
  • CAMK Ser/Thr protein kinase family
    • CATEGORY enzyme , structural protein
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    text giant sarcomeric protein, extending from the Z line to the M line of striated muscle sarcomere, myofibrils
    basic FUNCTION
  • essential in the temporal and spatial control of the assembly of the highly ordered sarcomeres of striated muscles
  • responsible for the elasticity of relaxed striated muscle
  • playing a CAPN3-dependent role through the N2A domain in the dynamics of muscle contraction
  • in striated muscle, titin provides elasticity and support functions for the sarcomere
  • titin filaments play important roles in sarcomere assembly, stability, and passive tension, as well as in stretch sensing, protein turnover, and gene regulation through interactions with other proteins including ACTN1
  • transient TTN-calcium interaction may serve a protective function in muscle, which could preclude costly unfolding of select domains when muscles elongate to great lengths
  • determinant of a resting tension of the sarcomere and crucial role in diastolic function
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text muscular
    PATHWAY
    metabolism
    signaling
    a component
  • complex between the muscle proteins titin and telethonin forms a highly directed molecular bond
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • calmodulin binding
  • obscurin
  • interacting with CAPN3, through N2A domain
  • interacting with ACTN1 (through N-terminal domains of titin to provide a structural linkage crucial for the integrity of the sarcomere)
  • interacting with TCAP (anchored in the Z-disk by telethonin, TCAP)
  • head-to-tail interaction of the C-terminus of titin and the N-terminus of obscurin-like-1(OBSL1)
  • RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing
  • FHL1 as a novel negative regulator of titin N2B levels and phosphorylation-mediated mechanics
  • titin can be phosphoryalated by CAMK2D, and titin molecular spring region that determines diastolic stiffness is a target of CAMK2D
    • cell & other
    REGULATION
    Phosphorylated by CAMK2D, and titin molecular spring region that determines diastolic stiffness is a target of CAMK2D
    ASSOCIATED DISORDERS
    corresponding disease(s) CMD1G , CMH9 , TMDT , LGMD2J , MPRM , EOMFC , RCM4
    related resource FHC Mutation Database
    Susceptibility
  • to autoimmune scleroderma (antibodies in patients)
  • to autoimmune form of rippling muscle disease with myasthenia gravis (ARMD)
  • to atrial fibrillation (AF)
    • Variant & Polymorphism other
  • specific reaction of ARMD patient sera with the titin domain portion of the fusion protein GST-RMMG6
    • Candidate gene
  • strong biological candidate gene at the 2q31 locus for atrial fibrillation because of its role in maintaining the structural integrity of the sarcomere and its involvement in muscle elasticity and force transmission
    • Marker
    Therapy target
    ANIMAL & CELL MODELS
    Mdm mouse