Types I (COL1s), II (COL2s), and III (COL3s) collagen, the so-called interstitial collagens, are in many ways distinct from basement membrane collagen (COL4s). Type IV collagen (COL4s) does not form ordered fibrillar structures; rather, a meshwork is formed by 4 molecules held together at the ends.
Both disulfide and typical lysyl-derived collagen crosslinks are involved. Type IV procollagen contains 2 distinct chains. The collagen IV molecule (COL4s) is a heterotrimer of 2 alpha-1 chains (COL4A1) and 1 alpha-2 chain. The alpha-2 chain is encoded at a distinct locus (COL4A2) (MIM.120090).
Type IV collagen is associated with laminin, entactin, and heparan sulfate proteoglycans to form the sheetlike basement membranes that separate epithelium from connective tissue.
The dispersion of the other collagen genes helps to avoid unequal crossing-over. Because the alpha-1 (COL4A1) and alpha-2 (COL4A2) chains of type IV collagen are highly divergent, close proximity on chromosome 13 carries less hazard of a disruptive event than might otherwise be the case. On the other hand, their coordinate regulation may be enhanced by the close situation.
Type IV collagens (COL4s)
| COL4A1 | COL4A2 | COL4A3 | COL4A4 | COL4A5 | COL4A6 |
Pathology
COL4As : germline mutations in Alport syndromes
- COL4A1 : Target for auto-antibodies in Goodpasture disease
- COL4A3 : mutations in autosomal recessive Alport syndrome
- COL4A3 : mutations in benign familial hematuria (MIM.141200)
- COL4A4 : mutations in autosomal recessive Alport syndrome
- COL4A5 : mutations in X-linked Alport syndrome
- COL4A6 : deletions in diffuse leiomyomatosis (MIM.308940) with X-linked Alport syndrome