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FLASH GENE
Symbol TNNI3 contributors: SGE/npt - updated : 27-12-2016
HGNC name troponin I type 3 (cardiac)
HGNC id 11947
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • has a unique 31-AAs N-terminal region that binds cardiac troponin C (TNNC1) to increase the calcium sensitivity of the sarcomere
  • C-terminal end segment of TNNI3 participates in the Ca(2+) regulation of muscle thin filament through interaction with tropomyosin
    • conjugated PhosphoP , Other
    HOMOLOGY
    interspecies homolog to murine Tnni3 (93.3pc)
    homolog to rattus Tnni3 (93.3pc)
    Homologene
    FAMILY
  • troponin I family
    • CATEGORY motor/contractile , regulatory , structural protein
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    basic FUNCTION
  • involved in the regulation of heart
  • involved in the regulation of muscle contraction
  • calcium channel inhibitory activity
  • blocking actin-myosin interactions and thereby mediating striated muscle relaxation
  • participates in proper stabilization of tropomyosin in the Ca2+-activated state (Galinska 2010)
  • inhibitory subunit of the troponin complex in the sarcomeric thin filament of striated muscle and plays a central role in the calcium regulation of contraction and relaxation
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text muscle development
    PATHWAY
    metabolism
    signaling
    a component
  • inhibitory subunit of the troponin complex of the thin filaments of striated muscle
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to actin-tropomyosin
  • interactng with TRIM63
  • binding to DSCR1L2 (Canaider 2006)
  • CAMK2A-dependent TNNI3 phosphorylation is involved in frequency-dependent myofilament Ca(2+) desensitization (FDMCD) and the consequent frequency-dependent acceleration of relaxation (FDAR) and CAMK2A inhibition removes this mechanism and thus induces diastolic dysfunction
    • cell & other
    REGULATION
    Phosphorylated by STK4 (You 2009)
    Other phosphorylation of the PRKACA sites (Ser(23)/Ser(24)) of TNNI3 results in a decrease in myofilament Ca(2+) sensitivity and an increase in the rate of relaxation
    phosphorylation by PRKAG1 may represent a novel mechanism of regulation of cardiac function
    ASSOCIATED DISORDERS
    corresponding disease(s) CMH7 , CMD1FF
    related resource FHCMutationDatabase
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • two novel missense mutations (Lys36Gln, Asn185Lys) causing autosomal dominant dilated cardiomyopathy (Carballo 2009)
  • combination of elevated CRP and TNNI3 increase the risk of adverse cardiac events (Huang 2009)
  • elevated TNNI3 levels are significantly associated with short- and long-term mortality in ESRD patients with sepsis (Kang 2009)
    • Marker
  • NPPB and TNNI3 are useful markers for identifying patients at risk for clinical deteriorations, and combined measurements of these biomarkers further improves the prognostic value of increased cardiovascular events in hypertrophic cardiomyopathy (HCM)
    • Therapy target
    SystemTypeDisorderPubmed
    cardiovascularaquired 
    may be a useful tool in identifying patients with heart failure who are at increased risk for progressive ventricular dysfunction and death
    ANIMAL & CELL MODELS