Collagen alpha-3(VI) chain is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''COL6A3''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
This protein is an alpha chain of type VI collagen that aids in microfibril formation.
As part of type VI collagen, this protein has been implicated in Bethlem myopathy,
Ullrich congenital muscular dystrophy
Ullrich congenital muscular dystrophy is a form of congenital muscular dystrophy. It is associated with variants of type VI collagen, it is commonly associated with muscle weakness and respiratory problems, though cardiac issues are not associated ...
(UCMD), and other diseases related to muscle and connective tissue.
Structure
This gene encodes the alpha 3 chain, one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The alpha 3 chain of type VI collagen is much larger than the alpha 1 and 2 chains. This difference in size is largely due to an increase in the number of subdomains, similar to von Willebrand Factor type A domains, found in the amino terminal globular domain of all the alpha chains. In addition to the full length transcript, four transcript variants have been identified that encode proteins with N-terminal globular domains of varying sizes.
Function
The alpha 3 type VI chain has been shown to bind extracellular matrix proteins, an interaction that explains the importance of this collagen in organizing matrix components.
Microfibril formation has been traced to interactions between its
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
subdomain N5 and its
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
C5 domain in adjacent type VI collagen monomers.
Clinical significance
Mutations in the type VI collagen genes are associated with Bethlem myopathy and
Ullrich congenital muscular dystrophy
Ullrich congenital muscular dystrophy is a form of congenital muscular dystrophy. It is associated with variants of type VI collagen, it is commonly associated with muscle weakness and respiratory problems, though cardiac issues are not associated ...
(UCMD).
Typically, both Bethlem myopathy and autosomal recessive UCMD patients are heterozygous for mutations in the three type VI collagen alpha chains, but only the former exhibit symptoms. Of the three alpha chains, COL6A3 mutations contribute to only 18% of the Bethlem myopathy and UCMD cases.
A study on UCMD mutations by Zhang et al found only one non-pathogenic mutation in COL6A3.
Nonetheless, knockdown of mutant COL6A3 in patient fibroblast cells using siRNA has successfully improved cellular deposition of type VI collagen in autosomal dominant UCMD, and may become a promising treatment for it.
Though high expression levels of COL6A3 have been correlated with obesity and diabetes in mice, this relationship was not observed in humans.
Other disorders involving muscle and connective tissue include weakness, joint laxity and contractures, and abnormal skin.
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Congenital Muscular Dystrophy Overview
{{Fibrous proteins
Collagens