collagen 4 alpha-4 (COL4A4)

Function

• type 4 collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen
• 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
• the COL4A3 chain forms a triple helical protomer with COL4A4 & COL4A5
  • this triple helical structure dimerizes through NC1-NC1 domain interactions such that the COL4A3, COL4A4 & COL4A5 of one protomer connect with the COL4A5, COL4A4 & COL4A3 of the opposite protomer, respectively
• associates with LAMB2 at the neuromuscular junction & in GBM (putative)

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 (putative)
• colocalizes with COL4A4 & COL4A5 in
  • GBM
  • tubular basement membrane
  • synaptic basal lamina (putative)

Expression

• collagen 4 alpha-3 & collagen 4 alpha-4 are colocalized & present in kidney, eye, basement membranes of lens capsule, cochlea, lung, skeletal muscle, aorta, synaptic fibers, fetal kidney & fetal lung
• highest levels of expression of COL4A4 detected in kidney, calvaria, neuroretina & cardiac muscle
• lower levels of expression are observed in brain, lung & thymus,
• no expression is detected in choroid plexus, liver, adrenal, pancreas, ileum or skin

Pathology

• defects in COL4A4 are associated with
  • hereditary nephritis
  • thin glomerular basement membrane disease
• defects in COL4A4 are a cause of
  • Alport syndrome (autosomal recessive)
  • benign familial hematuria

More general terms

• collagen subunit
• phosphoprotein

Additional terms

• Alport syndrome; hereditary nephropathy
• thin glomerular basement membrane disease; benign familial hematuria

Component of

• collagen type-4

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1286
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1286
• OMIM: https://mirror.omim.org/entry/120131
• OMIM: https://mirror.omim.org/entry/141200
• OMIM: https://mirror.omim.org/entry/203780
• UniProt: http://www.uniprot.org/uniprot/P53420.html