Three novel collagen VI chains with high homology to the α3 chain

Here we describe three novel collagen VI chains, alpha 4, alpha 5, and alpha 6. The corresponding genes are arranged in tandem on mouse chromosome 9. The new chains structurally resemble the collagen VI alpha 3 chain. Each chain consists of sevenvon Willebrand factor A domains followed by a collagenous domain, two C-terminal von Willebrand factor A domains, and a unique domain. In addition, the collagen VI alpha 4 chain carries a Kunitz domain at the C terminus, whereas the collagen VI alpha 5 chain contains an additional von Willebrand factor A domain and a unique domain. The size of the collagenous domains and the position of the structurally important cysteine residues within these domains are identical between the collagen VI alpha 3, alpha 4, alpha 5, and alpha 6 chains. In mouse, the new chains are found in or close to basement membranes. Collagen VI alpha 1 chain-deficient mice lack expression of the new collagen VI chains implicating that the new chains may substitute for the alpha 3 chain, probably forming alpha 1 alpha 2 alpha 4, alpha 1 alpha 2 alpha 5, or alpha 1 alpha 2 alpha 6 heterotrimers. Due to a large scale pericentric inversion, the human COL6A4 gene on chromosome 3 was broken into two pieces and became a non-processed pseudogene. Recently COL6A5 was linked to atopic dermatitis and designated COL29A1. The identification of novel collagen VI chains carries implications for the etiology of atopic dermatitis as well as Bethlem myopathy and Ullrich congenital muscular dystrophy.