Calponin 1

Protein sequence alignment shows that calponin 1 is highly conserved in mammals but more diverged among lower vertebrates.

The expression of CNN1 is specific to differentiated mature smooth muscle cells, suggesting a role in contractile functions.

This feature is consistent with the hypothesis that the second actin-binding site plays a regulatory role in the binding of calponin to the actin filament.

The variable lengths and amino acid sequences of the C-terminal segment produce the size and charge differences among the calponin isoforms.

Deletion of the C-terminal tail strongly enhanced the actin-binding and bundling activities of all three isoforms of calponin.

[24] Numerous in vitro experimental data indicate that calponin 1 functions as an inhibitory regulator of smooth muscle contractility through inhibiting actomyosin interactions.

[6][25][26] In this regulation, binding of Ca2+-calmodulin and PKC phosphorylation dissociate calponin 1 from the actin filament and facilitate smooth muscle contraction.

While aortic smooth muscle of adult Wistar Kyoto rats, which naturally lacks calponin 1, is fully contractile, it has a decreased sensitivity to norepinephrine activation.

[30] Vas deferens smooth muscle from calponin 1 knockout mice showed faster maximum shortening velocity.

Figure 1 : Evolutionary lineage of vertebrate CNN1 .
Figure 2. Structural and functional domains of calponin. The linear structural map summarized primarily from studies of chicken calponin 1 illustrates the structural and functional domains of calponin. The CH domain, two actin-binding sites, three repeating sequence motifs, and the C-terminal variable region are outlined. The CH domain overlaps with the ERK signaling binding region. Amino acid sequences of the two actin-binding sites in the three isoforms and the three repeating motifs of calponin 1 are shown in the insets. The regulatory phosphorylation sites Ser 175 and Thr 184 are located in the second actin-binding site that overlaps with the first repeating motif. Potentially phosphorylatable serine residues corresponding to Ser 175 are conserved in repeats 2 and 3, while a Thr 184 equivalent is conserved in repeat 2. Different from calponin 1 and calponin 3, calponin 2 has a potentially phosphorylatable additional serine at position 177.