Type IV collagens support extracellular matrix function by forming a cross-linking network in the basement membrane zone. There are six different type IV collagens that are encoded by the following genes: COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, and COL4A6. Among them, COL4A1 and COL4A2 are the most common collagens found in the basement membrane, and are usually used as a marker of the basement membrane dynamic stability. The type IV collagen fiber exists as a trimeric complex composed of two molecules of COL4A1 and one molecule of COL4A2. The N-terminal 7S domains of the protein function on intermolecular cross-linking, and C-terminal non-collagenous domains are responsible for heterotrimer assembly. The trimeric fiber further associates to form a cross-linked sheet structure by NCI/NCI and 7S/7S interaction. COL4A1 plays a critical role in maintaining basement membrane integrity for normal tissue functions. Genetic mutations of COL4A1 and COL4A2 have been linked to cardiovascular disease, cerebral small vessel disease, and glomerulocystic kidney disease.
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