TNNI3

1J1D, 1J1E, 1LXF, 1MXL, 1OZS, 2KGB, 2KRD, 2L1R, 2MZP, 4Y99713721954ENSG00000129991ENSMUSG00000035458P19429Q6FGX2P48787NM_000363NM_009406NP_000354NP_000354.4NP_033432Troponin I, cardiac muscle is a protein that in humans is encoded by the TNNI3 gene.It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex.1j1d: Crystal structure of the 46kDa domain of human cardiac troponin in the Ca2+ saturated form1j1e: Crystal structure of the 52kDa domain of human cardiac troponin in the Ca2+ saturated form Troponin I, cardiac muscle is a protein that in humans is encoded by the TNNI3 gene.It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex. The TNNI3 gene encoding cardiac troponin I (cTnI) is located at 19q13.4 in the human chromosomal genome. Human cTnI is a 24 kDa protein consisting of 210 amino acids with isoelectric point (pI) of 9.87. cTnI is exclusively expressed in adult cardiac muscle. cTnI has diverged from the skeletal muscle isoforms of TnI (slow TnI and fast TnI) mainly with a unique N-terminal extension. The amino acid sequence of cTnI is strongly conserved among mammalian species (Fig. 1). On the other hand, the N-terminal extension of cTnI has significantly different structures among mammal, amphibian and fish. TNNI3 is expressed as a heart specific gene. Early embryonic heart expresses solely slow skeletal muscle TnI. cTnI begins to express in mouse heart at approximately embryonic day 10, and the level gradually increases to one-half of the total amount of TnI in the cardiac muscle at birth. cTnI completely replaces slow TnI in the mouse heart approximately 14 days after birth Based on in vitrostructure-function relationship studies, the structure of cTnI can be divided into six functional segments: a) a cardiac-specific N-terminal extension (residue 1–30) that is not present in fast TnI and slow TnI; b)an N-terminal region (residue 42–79) that binds the C domain of TnC; c) a TnT-binding region (residue 80–136); d) the inhibitory peptide (residue 128–147) that interacts with TnC and actin–tropomyosin; e) the switch or triggering region (residue 148–163) that binds the N domain of TnC; and f) the C-terminal mobile domain (residue 164–210) that binds actin–tropomyosin and is the most conserved segment highly similar among isoforms and across species. Partially crystal structure of human troponin has been determined. Multiple mutations in cTnI have been found to cause cardiomyopathies. cTnI mutations account for approximately 5% of familial hypertrophic cardiomyopathy cases and to date, more than 20 myopathic mutations of cTnI have been characterized. The half-life of cTnI in adult cardiomyocytes is estimated to be ~3.2 days and there is a pool of unassembled cardiac TnI in the cytoplasm. Cardiac TnI is exclusively expressed in the myocardium and is thus a highly specific diagnostic marker for cardiac muscle injuries, and cTnI has been universally used as indicator for myocardial infarction. An increased level of serum cTnI also independently predicts poor prognosis of critically ill patients in the absence of acute coronary syndrome.