Table 1.

The N-terminal hypervariable region of mammalian and avian TnT

Features	References
Exons alternatively spliced under physiological conditions:
A fetal exon in mammalian embryonic fast TnT	31,59
Exons 4, 5, 6, 7 and 8 in avian and mammalian fast TnT	31,40,61
P exons (up to 7) in avian fast TnT (encoding the Tx segment)	61,62,63
Exons w and y in avian fast TnT	64
Exon 5 in avian and mammalian cardiac TnT	37,38
Exon 4 in mammalian cardiac TnT	39,41
Exon 5 in mammalian slow TnT	42,66
Alternative acceptor sites in intron 5 of mouse and intron 4 of chicken slow TnT genes	42,43
Developmental regulations:
Alternative splicing of exon 5 in cardiac TnT results in isoform switch in heart	58
Alternative splicing of exons 4, 6, 7, 8 and fetal in fast TnT results in isoform     switches in skeletal muscles	31,59
Postnatal inclusion of P exons in avian pectoral muscle fast TnT	60,62,63
Posttranslational modifications:
Constitutive phosphorylation of Ser2 at the N terminus	10,116
Selective removal of the N-terminal variable region by restrictive proteolysis     for adaptation to stress conditions	121,122
Functional significance
Variable N-terminal negative charges determine the overall charge of TnT	31
N-terminal structures modulate the conformation and function     of the middle and C-terminal regions of TnT	33,34,35,36
TnT N-terminal variation alters thin filament Ca2+-sensitivity and force production	69,72,79,125
N-terminal acidic residues of TnT provide a binding capacity for Ca2+	104
Deletion of the N-terminal variable region of cardiac TnT increases heart efficiency	121,122
Pathological relevance:
Exclusion of exon 4 in adult cardiac TnT in human heart failure	81,82
Increased exclusion of exon 4 in adult cardiac TnT in diabetic or hypertrophic     rat hearts	83,84
Exclusion of exon 8 in cardiac TnT in turkey dilated cardiomyopathy	79
Exclusion of exon 7 in cardiac TnT in dog dilated cardiomyopathy	80
Inclusion of exon 5 in adult cardiac TnT in dog dilated cardiomyopathy	80
Increased exclusion of exon 5 in slow TnT in type 1 Charcot-Marie-Tooth disease	32