Col4a1

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).

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.

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.

Post-translational modifications

Lysines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated. The modified lysines can be O-glycosylated.

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.

Contains 3-hydroxyproline. This modification occurs on the first proline residue in the sequence motif Gly-Pro-Hyp, where Hyp is 4-hydroxyproline.

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.

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).

Proteolytic processing produces the C-terminal NC1 peptide, arresten.

Sequence Similarities

Belongs to the type IV collagen family.

Tissue Specificity

Detected in the basement membrane of the cornea (at protein level).

Cellular localization

• Secreted
• Extracellular space
• Extracellular matrix
• Basement membrane

Alternative names

Collagen alpha-1(IV) chain, Col4a1

Database links

swissprot:P02463 swissprot:P08122 swissprot:Q9QZR9 swissprot:Q9QZS0 entrezGene:12826 entrezGene:12827 entrezGene:12828 entrezGene:12829 entrezGene:12830

Other research areas

• Cardiovascular