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Symbol TTN contributors: mct/npt/pgu - updated : 04-03-2015
HGNC name titin
HGNC id 12403
Corresponding disease
CMD1G cardiomyopathy, dilated 1G
CMH9 cardiomyopathy, familial, hypertrophic, 9
EOMFC early-onset myopathy with fatal cardiomyopathy
LGMD2J limb-girdle muscular dystrophy type 2J
MPRM myopathy, proximal, with early respiratory muscle involvement
RCM4 restrictive cardiomyopathy 4, familial
TMDT tibial muscular dystrophy, onset in the early 40 years
Location 2q31.2      Physical location : 179.390.719 - 179.672.150
Synonym name
  • connectin
  • rhabdomyosarcoma antigen MU-RMS-40.14
  • giant skeletal muscle protein
  • Synonym symbol(s) FLJ26020, FLJ26409, FLJ32040, FLJ34413, FLJ39564, FLJ43066, HMERF, CMPD4, CONNECTIN, TMD, CMD1G, CMH9, CMPD4, EOMFC, HMERF, LGMD2J, MYLK5
    TYPE anonymous DNA segment
    SPECIAL FEATURE arranged in tandem
    STRUCTURE 281.44 kb     313 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D2S335 - TTN - D2S324 - D2S364 - D2S384 - D2S350 - D2S118 - D2S72 - qter
    Authors LDB (99)
    TRANSCRIPTS type messenger
    text likely several (? or many) isoforms contributing to myofibrillar elastic diversity
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    312 - 101519 3800 33423 major in the muscle 2002 11812150
    also called TTN2A or N2-A
    191 splicing 82028 2970 26926 cardiac muscle 2002 11812150
  • also called TTN2B or N2-B
  • phosphorylation of the N2-B unique sequence (N2BUS) by cGMP-dependent protein kinase (PKG) or cAMP-dependent protein kinase (PKA) decreases titin stiffness (PMID: 23764881)
  • lacking some repeats of the PEVK region excluding 101 exons
  • FHL1 directly interferes with ERK2-mediated TTN-N2B phosphorylation (PMID: 22778266)
  • 192 - 82403 3025 27051 cardiac isoform 2002 11812150
    also called novex-1
    192 - 82604 3980 27118 cardiac and skeletal muscle 2002 11812150
    also called novex-2
    46 - 17306 616 5604 all striated muscle 2002 11812150
  • also called novex-3
  • lacking the PEVK region truncated
  • - - - 2000 - smooth muscles 2002 11812150
  • also called sm-titin or smitin
  • interacts with C-terminal EF hand region and central rod R2-R3 spectrin-like repeat region sites in ACTN1
  • having a Zq domain that may bind to the ACTN1 R2-R3 central rod domain as well as Z-repeat domains that bind to the EF hand region
  • 3 - - 24.1 214 - 2002 11812150
  • encompassing 90p100 exon 248, 100p100 exon 249 and 23.4p100 exon 250
  • 100p100 identity with a region of titin N2-A
  • fused with GST to form glutathione-S-transferase fusion protein (GST-RMMG6) with a predicted size of 51.1 kDa
  • 273 - 109224 - 35991 - 2002 11812150
    313 - 104301 - 34350 - 2002 11812150
  • variant N2BA
  • cardiac titin-isoform
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestivepharynx   highly
    Respiratoryrespiratory tractlarynx  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
  • 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
    interspecies homolog to murine Ttn
  • protein kinase superfamily
  • CAMK Ser/Thr protein kinase family
  • CATEGORY enzyme , structural protein
    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
    text muscular
    a component
  • complex between the muscle proteins titin and telethonin forms a highly directed molecular bond
    small molecule
  • 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
    Phosphorylated by CAMK2D, and titin molecular spring region that determines diastolic stiffness is a target of CAMK2D
    corresponding disease(s) CMD1G , CMH9 , TMDT , LGMD2J , MPRM , EOMFC , RCM4
    related resource FHC Mutation Database
  • 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
    Mdm mouse