Troponin I, cardiac muscle is a protein that in humans is encoded by the TNNI3 gene. [5] [6] 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. [7] [8]
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. [8]
TNNI3 is expressed as a heart specific gene. [8] 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. [9] cTnI completely replaces slow TnI in the mouse heart approximately 14 days after birth [10]
Based on in vitro structure-function relationship studies, the structure of cTnI can be divided into six functional segments: [11] 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. [12]
Multiple mutations in cTnI have been found to cause cardiomyopathies. [31] [32] cTnI mutations account for approximately 5% of familial hypertrophic cardiomyopathy cases and to date, more than 20 myopathic mutations of cTnI have been characterized. [15]
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. [33] 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. [34] An increased level of serum cTnI also independently predicts poor prognosis of critically ill patients in the absence of acute coronary syndrome. [35] [36]
The 2015 version of this article was updated by an external expert under a dual publication model. The corresponding academic peer reviewed article was published in Gene and can be cited as: Juan-Juan Sheng; Jian-Ping Jin (22 October 2015). "TNNI1, TNNI2 and TNNI3: Evolution, regulation, and protein structure-function relationships". Gene . 576 (1 Pt 3): 385–394. doi:10.1016/J.GENE.2015.10.052. PMC 5798203 . PMID 26526134. |