User:Cysteine22/Collagen, type VII, alpha 1

Lead
Collagen alpha-1(VII) chain is a protein that in humans is encoded by the COL7A1 gene. It is composed of a triple helical, collagenous domain flanked by two non-collagenous domains, and functions as an anchoring fibril between the dermal-epidermal junction in the basement membrane. Mutations in COL7A1 cause all types of dystrophic epidermolysis bullosa, and the exact mutations vary based on the specific type or subtype. It has been shown that interactions between the NC-1 domain of collagen VII and several other proteins, including Laminin-5 and collagen IV, contribute greatly to the overall stability of the basement membrane.

Structure
Type VII collagen is composed of three main domains in the following order: a non-collagenous domain, abbreviated NC-1; a collagenous domain; and a second non-collagenous domain, NC-2. The NC-1 domain has a cartilage matrix protein (CMP), nine fibronectin III (FNIII)-like subdomains, and a von Willebrand Factor A-like subdomain (VWFA1); a notable segment in the NC-2 domain is analogous to a Kunitz protease inhibitor molecule.

Clinical significance
The inherited disease, dystrophic epidermolysis bullosa, is caused by recessive or dominant mutations in COL7A1. Recessive dystrophic epidermolysis bullosa, the most severe type of epidermolysis bullosa, has two subtypes, generalized intermediate and generalized severe, which have been linked to different mutations in the COL7A1 gene. Recessive dystrophic epidermolysis bullosa, generalized intermediate, is caused primarily by missense, in-frame, and splice-site mutations on one allele. The generalized severe subtype may be caused by premature termination codons in both alleles. These mutations cause little to no expression of collagen VII, which manifests primarily as generalized blistering in the skin and mucosal membranes. This blistering may also lead to several other complications, such as eye abrasions, esophageal stricture, deformity of the hands and feet, and squamous cell carcinoma, among others.

Dominant dystrophic epidermolysis bullosa is most often caused by missense mutations, especially glycine substitutions in the collagenous domain. The symptoms of dominant dystrophic epidermolysis bullosa are less severe than those of the recessive types, with mild blistering and loss of nails.

Epidermolysis bullosa acquisita involves an autoimmune reaction to this form of collagen.

Interactions
Collagen, type VII, alpha 1 forms a complex network with several other proteins in the basement membrane. It has been shown to interact with laminin 5 and fibronectin, as well as collagen IV, by binding these proteins in the NC-1 domain. The stability of the basement membrane and dermal-epidermal junction is thought to be due to these interactions.