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.
TNNI3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | TNNI3, CMD1FF, CMD2A, CMH7, RCM1, TNNC1, cTnI, troponin I3, cardiac type | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 191044 MGI: 98783 HomoloGene: 309 GeneCards: TNNI3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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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. |