FUNCTION Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.FUNCTION Arresten, comprising the C-terminal NC1 domain, inhibits angiogenesis and tumor formation. The C-terminal half is found to possess the anti-angiogenic activity. Specifically inhibits endothelial cell proliferation, migration and tube formation.SUBUNIT There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network. Interacts with EFEMP2 (PubMed:17324935).SUBCELLULAR LOCATION Detected in the basement membrane of the cornea (at protein level).DOMAIN Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain. NC1 domain mediates hexamerization of alpha chains of type IV collagen (PubMed:22842973).PTM Lysines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated. The modified lysines can be O-glycosylated.PTM Contains 4-hydroxyproline. Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.PTM Contains 3-hydroxyproline. This modification occurs on the first proline residue in the sequence motif Gly-Pro-Hyp, where Hyp is 4-hydroxyproline.PTM Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.PTM The trimeric structure of the NC1 domains is stabilized by covalent bonds (sulfilimine cross-links) between Lys and Met residues. These cross-links are important for the mechanical stability of the basement membrane (PubMed:22842973, PubMed:28424209). Sulfilimine cross-link is catalyzed by PXDN (PubMed:22842973).PTM Proteolytic processing produces the C-terminal NC1 peptide, arresten.DISRUPTION PHENOTYPE Mice develop perinatal cerebral hemorrhage and porencephaly. The mutant protein inhibits the secretion of mutant and normal proteins into the basement membrane of embryonic origin. The mutation is semidominant.SIMILARITY Belongs to the type IV collagen family.SEQUENCE CAUTION Insertion sequence.
This website requires cookies and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice.
