Collagen IV (ColIV or Col4) is a type of
collagen found primarily in the
basal lamina. The
collagen IV C4 domain at the C-terminus is not removed in post-translational processing, and the fibers link head-to-head, rather than in parallel. Also, collagen IV lacks the regular
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...
in every third residue necessary for the tight,
collagen helix. This makes the overall arrangement more sloppy with kinks. These two features cause the collagen to form in a sheet, the form of the basal lamina. Collagen IV is the more common usage, as opposed to the older terminology of "type-IV collagen". Collagen IV exists in all
metazoa
Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage ...
n phyla, to whom they served as an evolutionary stepping stone to
multicellularity.
There are six human genes associated with it:
*
COL4A1,
COL4A2,
COL4A3,
COL4A4,
COL4A5,
COL4A6
Clinical significance
The alpha-3 subunit (COL4A3) of collagen IV is thought to be the antigen implicated in
Goodpasture syndrome
Goodpasture syndrome (GPS), also known as anti–glomerular basement membrane disease, is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs, glomerulonephritis, ...
, wherein the immune system attacks the
basement membrane
The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tissues including mesothelium and ...
s of the
glomeruli and the
alveoli upon the antigenic site on the alpha-3 subunit becomes unsequestered due to environmental exposures.
Goodpasture syndrome
Goodpasture syndrome (GPS), also known as anti–glomerular basement membrane disease, is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs, glomerulonephritis, ...
presents with
nephritic syndrome and
hemoptysis
Hemoptysis is the coughing up of blood or blood-stained mucus from the bronchi, larynx, trachea, or lungs. In other words, it is the airway bleeding. This can occur with lung cancer, infections such as tuberculosis, bronchitis, or pneumonia ...
. Microscopic evaluation of biopsied renal tissue will reveal linear deposits of
Immunoglobulin G
Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...
by
immunofluorescence. This is classically in young adult males.
Mutations to the genes coding for collagen IV lead to
Alport syndrome. This will cause thinning and splitting of the
glomerular basement membrane. It will present as isolated
hematuria,
sensorineural hearing loss, and ocular disturbances and is passed on genetically, usually in an
X-linked manner, although there are rarer autosomal forms.
Liver fibrosis and
cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
are associated with the deposition of collagen IV in the liver. Serum Collagen IV concentrations correlate with hepatic tissue levels of collagen IV in subjects with
alcoholic liver disease and
hepatitis C and fall following successful therapy.
Mutations in ''COL4A1'' exons 24 and 25 are associated with HANAC (
autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...
hereditary
angiopathy with
nephropathy,
aneurysms, and
muscle cramps).
It has also been confirmed that mutations in the ''COL4A1'' gene occur in some patients with
porencephaly and
schizencephaly.
In humans, a novel mutation of the COL4A1 gene coding for collagen type IV was found to be associated with autosomal dominant congenital cataract in a Chinese family. This mutation was not found in unaffected family members or in 200 unrelated controls. In this study, sequence analysis confirmed that the Gly782 amino acid residue was highly conserved.
This report of a new mutation in the COL4A1 gene is the first report of a non-syndromic autosomal dominant congenital cataract that highlights an important role for collagen type IV in the physiological and optical properties of the lens.
Additionally, in the cardiovascular field, the COL4A1 and COL4A2 regions on chromosome 13q34 are a highly replicated locus for coronary artery disease. In a normal wall of arteries, collagen type IV acts to inhibit smooth muscle cell proliferation. Accordingly, it was demonstrated that protein expression of collagen type IV in human vascular smooth muscle cells is regulated by both SMAD3 protein and TGFβ mediated stimulation of mRNA.
Altogether, it was concluded that the pathogenesis of coronary artery disease may be regulated by COL4A1 and COL4A2 genes.
An autosomal recessive encephalopathy associated with mutations in this gene has also been reported.
[Yaramis A, Lochmüller H, Töpf A, Sonmezler E, Yilmaz E, Hiz S, Yis U, Gungor S, Ipek Polat A, Edem P, Beltran S, Laurie S, Yaramis A, Horvath R, Oktay Y (2020) COL4A1-related autosomal recessive encephalopathy in 2 Turkish children. Neurol Genet 6(1):e392]
Increased glomerular and mesangial deposition of collagen IV occurs in
diabetic nephropathy and increased urinary levels are associated with the extent of renal injury.
See also
*
Spongin, a variant of this collagen type found in some animals
References
External links
*
Collagens
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