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

General

collagen subunit

Properties

SIZE: entity length = 1669 aa MW = 161 kD MOTIF: signal sequence {1-27} N-glycosylation site {N126} Triple-helical region {173-1440} Collagen IV NC1 {1445-1669} MOTIF: cysteine residue {C1460} MODIFICATION: cysteine residue {C1551} cysteine residue {C1493} MODIFICATION: cysteine residue {C1548} cysteine residue {C1505} MODIFICATION: cysteine residue {C1511} cysteine residue {C1511} MODIFICATION: cysteine residue {C1505} cysteine residue {C1548} MODIFICATION: cysteine residue {C1493} cysteine residue {C1551} MODIFICATION: cysteine residue {C1460} cysteine residue {C1570} MODIFICATION: cysteine residue {C1665} cysteine residue {C1604} MODIFICATION: cysteine residue {C1662} cysteine residue {C1616} MODIFICATION: cysteine residue {C1622} cysteine residue {C1622} MODIFICATION: cysteine residue {C1616} cysteine residue {C1662} MODIFICATION: cysteine residue {C1604} cysteine residue {C1665} MODIFICATION: cysteine residue {C1570}

Database Correlations

OMIM correlations MORBIDMAP 120130 UniProt P02462 PFAM correlations Entrez Gene 1282 Kegg hsa:1282

References

  1. UniProt :accession P02462
  2. Molecular Cell Biology (2nd ed) Darnell J; Lodish H & Baltimore D (eds), Scientific American Books, WH Freeman, NY 1990, pg 906
  3. OMIM :accession 120130
  4. Entrez Gene :accession 1282

Component-of

collagen type-4