COL7A1

What is COL7A1 protein?

COL7A1 gene (collagen type VII alpha 1 chain) is a protein coding gene which situated on the short arm of chromosome 3 at locus 3p21. This gene encodes the alpha chain of type VII collagen. The type VII collagen fibril, composed of three identical alpha collagen chains, is restricted to the basement zone beneath stratified squamous epithelia. It functions as an anchoring fibril between the external epithelia and the underlying stroma. Mutations in this gene are associated with all forms of dystrophic epidermolysis bullosa. In the absence of mutations, however, an acquired form of this disease can result from an autoimmune response made to type VII collagen. The COL7A1 protein is consisted of 2944 amino acids and COL7A1 molecular weight is approximately 295.2 kDa.

What is the function of COL7A1 protein?

COL7A1 protein plays a crucial role in the structural integrity of the skin and other tissues. It is a major component of the extracellular matrix and is involved in the formation of anchoring fibrils, which serve as a connection between the external epithelial cells and the underlying stroma. This function is critical for the organization and adherence of the epithelial basement membrane, and it contributes to the overall stability of tissues. Additionally, research indicates that COL7A1 mRNA expression levels have potential as a prognostic biomarker and are associated with immune cell infiltration in pancreatic cancer, suggesting its broader implications in disease processes and immune responses.

COL7A1 Related Signaling Pathway

COL7A1 is associated with the ERK signaling pathway, which plays an important role in cell proliferation and differentiation. COL7A1 is also associated with the Focal Adhesion Kinase 1 (FAK1) signaling pathway, which is commonly associated with cell adhesion and migration. The GnRH (Gonadotropin-releasing hormone) signaling pathway is associated with COL7A1, which may be related to the function of the reproductive system. COL7A1 is associated with the ILK (Integrin-linked kinase) signaling pathway, which is involved in cell-extracellular matrix interactions. In addition, COL7A1 can be identified as an immediate early response gene for transforming growth factor β (TGF-β) /SMAD, a signaling pathway that plays a central role in cell proliferation, differentiation, and extracellular matrix synthesis.

COL7A1 Related Diseases

COL7A1 gene mutations are associated with a group of genetic skin disorders collectively known as dystrophic epidermolysis bullosa (DEB) . DEB is characterized by skin fragility and the formation of blisters and wounds due to minor trauma or friction. In addition to the various forms of DEB, there are other related phenotypes that can be caused by COL7A1 mutations. For instance, COL7A1 is associated with epidermolysis bullosa pruriginosa, a subtype of DEB characterized by intense itching and nodular skin lesions. Furthermore, research has indicated that certain mutations in COL7A1 may also be linked to conditions such as transient bullous dermolysis of the newborn, a self-limiting skin disorder that resolves within the first months or years of life.

Bioapplications of COL7A1

One of the most significant bioapplications is the development of the gene therapy product VYJUVEKTM (beremagene geperpavec, B-VEC), which is a replication-defective herpes simplex virus type 1 (HSV-1) vector designed to deliver a functional copy of the COL7A1 gene to patients' cells. This therapy has shown promising results in clinical trials, with a significant rate of wound healing in patients with recessive dystrophic epidermolysis bullosa (RDEB). Additionally, research is being conducted on the use of COL7A1 antibodies for diagnostic and potentially therapeutic purposes. These antibodies can be used in immunohistochemistry, Western blot, and other scientific applications to detect the presence of COL7A1. Furthermore, the development of Col7a1 knockout (KO) mice models has been crucial for the study of DEB pathogenesis and for the evaluation of potential therapies.

Case Study 1: Stefan Hainzl, 2017

Designer nucleases allow specific and precise genomic modifications and represent versatile molecular tools for the correction of disease-associated mutations. In this study, researchers have exploited an ex vivo CRISPR/Cas9-mediated homology-directed repair approach for the correction of a frequent inherited mutation in exon 80 of COL7A1, which impairs type VII collagen expression, causing the severe blistering skin disease recessive dystrophic epidermolysis bullosa. Upon CRISPR/Cas9 treatment of patient-derived keratinocytes, using either the wild-type Cas9 or D10A nickase, corrected single-cell clones expressed and secreted similar levels of type VII collagen as control keratinocytes. Transplantation of skin equivalents grown from corrected keratinocytes onto immunodeficient mice showed phenotypic reversion with normal localization of type VII collagen at the basement membrane zone, compared with uncorrected keratinocytes, as well as fully stratified and differentiated skin layers without indication of blister development.

Fig1. PCR amplification of the COL7A1-targeting region.

Fig2. Western blot analysis on total cell lysates and supernatants of the repaired single-cell clone spCas9-C44.

Case Study 2: Araksya Izmiryan, 2018

Recessive dystrophic epidermolysis bullosa is a rare and severe genetic skin disease resulting in blistering of the skin and mucosa. Recessive dystrophic epidermolysis bullosa (RDEB) is caused by a wide variety of mutations in COL7A1-encoding type VII collagen, which is essential for dermal-epidermal adhesion. Here researchers demonstrate the feasibility of ex vivo COL7A1 editing in primary RDEB cells and in grafted 3D skin equivalents through CRISPR/Cas9-mediated homology-directed repair. They designed five guide RNAs to correct a RDEB causative null mutation in exon 2. Among the site-specific guide RNAs tested, one showed significant cleavage activity in primary RDEB keratinocytes and in fibroblasts when delivered as integration-deficient lentivirus. Genetic correction was detected in transduced keratinocytes and fibroblasts by allele-specific highly sensitive TaqMan-droplet digital PCR (ddPCR), resulting in 11% and 15.7% of corrected COL7A1 mRNA expression, respectively, without antibiotic selection.

Fig3. Genomic PCR analysis of the edited COL7A1 locus.

Fig4. The fractional abundance plot shows the percentage of frequency of the corrected COL7A1 on the mutated COL7A1 background.

COL7A1 has several biochemical functions, for example, identical protein binding,peptidase inhibitor activity,serine-type endopeptidase inhibitor activity. Some of the functions are cooperated with other proteins, some of the functions could acted by COL7A1 itself. We selected most functions COL7A1 had, and list some proteins which have the same functions with COL7A1. You can find most of the proteins on our site.

COL7A1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with COL7A1 here. Most of them are supplied by our site. Hope this information will be useful for your research of COL7A1.

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