collagen 4 alpha-1; contains: arresten (COL4A1)

Function

• collagen type 4 is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans & entactin/nidogen
• arresten, comprising the C-terminal NC1 domain, inhibits angiogenesis & tumor formation
• the C-terminal half has anti-angiogenic activity
• specifically inhibits endothelial cell proliferation, migration & tube formation
• inhibits expression of hypoxia-inducible factor 1-alpha & ERK1/2 & p38 MAPK activation
• ligand for integrin alpha-1/beta-1
• Lys at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in all cases & bind carbohydrates
• 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 bonds
  • 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
• proteolytic processing produces the C-terminal NC1 peptide, arresten
• there are six type 4 collagen isoforms, alpha 1(IV) ... alpha 6(IV), each of which can form a triple helix 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)
  • a 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

• secreted, extracellular space
• extracellular matrix, basement membrane

Alternative splicing

named isoforms=2

Expression

highly expressed in placenta

Pathology

• defects in COL4A1 are a cause of
  • brain small vessel disease with hemorrhage
  • familial porencephaly
• defects in COL4A1 are the cause of hereditary angiopathy with nephropathy, aneurysms & muscle cramps

More general terms

• collagen subunit

Component of

• collagen type-4

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1282
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1282
• OMIM: https://mirror.omim.org/entry/120130
• OMIM: https://mirror.omim.org/entry/175780
• OMIM: https://mirror.omim.org/entry/607595
• OMIM: https://mirror.omim.org/entry/611773
• UniProt: http://www.uniprot.org/uniprot/P02462.html