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QuickView for Gap junction alpha-1 protein (Cx43), alpha helix domain superfamily (biogroup)
- Description:
- Gap junction alpha-1 protein (also called connexin43, or Cx43) is a connexinof 381 amino acid residues (human isoform) that is widely expressed inseveral organs and cell types, and is the principal gap junction protein ofthe heart. Characterisation of genetically-engineered mice that lack Cx43,and also of human patients that have spontaneously-occurring mutations inthe gene encoding it (GJA1), suggest Cx43 is essential for the developmentof normal cardiac architecture and ventricular conduction. Mice lacking Cx43survive to term but die shortly after birth. They have cardiac malformationsthat lead to the obstruction of the pulmonary artery, leading to neonatalcyanosis, and subsequent death. This phenotype is reminiscent of some formsof stenosis of the pulmonary artery. Human subjects with visceroatrialheterotaxia (a heart disorder characterised by arterial defects), have beenfound to have points mutations in the Cx43-encoding gene, as a result of which a potential phosphorylation site within the C terminus is disrupted. Consequently, although these mutant Cx43 molecules still form functional gapjunction channels, their response to protein kinase activation is impaired.Regulation of cell-cell communication by the gap junction protein connexin43 can be modulated by a variety of connexin-associating proteins. In particular, c-Src can disrupt the connexin43 (Cx43)-zonula occludens-1 (ZO-1) interaction, leading to down-regulation of gap junction intercellular communication. The connexin43 carboxyl-terminal domain (Cx43CT) exists primarily as an elongated random coil, with two regions of alpha-helical structure. The alpha-helical domains has two hypothetical roles. The first one is to allow the formation of a higher order structure necessary to regulate channel behavior during chemical gating and the second is to act as a conduit for a cross-talk between different Cx43 binding partners.
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