collagen 4 alpha-2; contains: canstatin (COL4A2)
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Function
- type 4 collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans & entactin/nidogen
- proteolytic processing produces the C-terminal NC1 peptide, canstatin:
- has both anti-angiogenic & anti-tumor cell activity
- inhibits proliferation & migration of endothelial cells,
- reduces mitochondrial membrane potential
- induces apoptosis
- specifically induces Fas-dependent apoptosis
- activates procaspase-8 & procaspase-9 activity
- ligand for integrin alpha-5/beta-3 & integrin alpha-5/beta-5
- Pro at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains
- type 4 collagen contains numerous Cys which are involved in intermolecular & intramolecular disulfide bonding
- 12 of these, located in the NC1 domain, are conserved in all known type 4 collagen
- the trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys & Met residues (putative)
- there are six type 4 collagen isoforms, each of which can form a triple helix structure with 2 other chains to generate type 4 collagen network
Structure
- alpha chains of type 4 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)
- short N-terminal triple-helical 7S domain
- belongs to the type 4 collagen family
- contains 1 collagen 4 NC1 (C-terminal non-collagenous) domain
Compartment
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Component of
References
- ↑ UniProt http://www.uniprot.org/uniprot/P08572.html
- ↑ Molecular Cell Biology (2nd ed) Darnell J; Lodish H & Baltimore D (eds), Scientific American Books, WH Freeman, NY 1990, pg 906
- ↑ OMIM https://mirror.omim.org/entry/120090
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1284