Recombinant Human Collagen alpha-3 (IV) chain (COL4A3), partial

Function

Tumstatin, a cleavage fragment corresponding to the collagen alpha 3(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity; these two anti-tumor properties may be regulated via RGD-independent ITGB3-mediated mechanisms

Subcellular Location

Secreted, extracellular space, extracellular matrix, basement membrane

Disease Association

[Autoantibodies against the NC1 domain of alpha 3(IV) are found in Goodpasture syndrome, an autoimmune disease of lung and kidney] | Hematuria, benign familial, 2 (BFH2) : An autosomal dominant condition characterized by non-progressive isolated microscopic hematuria that does not result in renal failure. It is characterized pathologically by thinning of the glomerular basement membrane. [The disease is caused by variants affecting the gene represented in this entry] | Alport syndrome 3A, autosomal dominant (ATS3A) : A form of Alport syndrome, a syndrome characterized by progressive glomerulonephritis, glomerular basement membrane defects, renal failure, sensorineural deafness and specific eye abnormalities (lenticonous and macular flecks). The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness. [The disease is caused by variants affecting the gene represented in this entry] | Alport syndrome 3B, autosomal recessive (ATS3B) : A form of Alport syndrome, a syndrome characterized by progressive glomerulonephritis, glomerular basement membrane defects, renal failure, sensorineural deafness and specific eye abnormalities (lenticonous and macular flecks). The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Alpha 3 and alpha 4 type IV collagens are colocalized and present in kidney, eye, basement membranes of lens capsule, cochlea, lung, skeletal muscle, aorta, synaptic fibers, fetal kidney and fetal lung. PubMed:8083201 reports similar levels of expression of alpha 3 and alpha 4 type IV collagens in kidney, but PubMed:7523402 reports that in kidney levels of alpha 3 type IV collagen are significantly lower than those of alpha 4 type IV collagen. According to PubMed:8083201, alpha 3 type IV collagen is not detected in heart, brain, placenta, liver, pancreas, extrasynaptic muscle fibers, endoneurial and perineurial nerves, fetal brain, fetal heart and fetal liver. According to PubMed:7523402, alpha 3 type IV collagen is strongly expressed in pancreas, neuroretina and calvaria and not expressed in adrenal, ileum and skin. Isoform 1 and isoform 3 are strongly expressed in kidney, lung, suprarenal capsule, muscle and spleen, in each of these tissues isoform 1 is more abundant than isoform 3. Isoform 1 and isoform 3 are expressed at low levels in artery, fat, pericardium and peripherical nerve, but not in placenta, mesangium, skin, pleura and cultured umbilical endothelial cells

Subunit

There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network. The alpha 3(IV) chain forms a triple helical protomer with alpha 4(IV) and alpha 5(IV); this triple helical structure dimerizes through NC1-NC1 domain interactions such that the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains of one protomer connect with the alpha 5(IV), alpha 4(IV) and alpha 3(IV) chains of the opposite promoter, respectively (PubMed:12193605). Interacts with ITGB3 (PubMed:12682293). Associates with LAMB2 at the neuromuscular junction and in GBM (By similarity)

• Mariyama M. et al. Complete primary structure of the human alpha 3(IV) collagen chain. Coexpression of the alpha 3(IV) and alpha 4(IV) collagen chains in human tissues. — J. Biol. Chem. (1994)
• Leinonen A. et al. PubMed: CI-27U21AELEG01T (OCT-)
• Heidet L. et al. Structure of the human type IV collagen gene COL4A3 and mutations in autosomal Alport syndrome. — J. Am. Soc. Nephrol. (2001)
• Hillier L.W. et al. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. — Nature (2005)
• Momota R. et al. Two genes, COL4A3 and COL4A4 coding for the human alpha3(IV) and alpha4(IV) collagen chains are arranged head-to-head on chromosome 2q36. — FEBS Lett. (1998)
• Turner N. et al. Molecular cloning of the human Goodpasture antigen demonstrates it to be the alpha 3 chain of type IV collagen. — J. Clin. Invest. (1992)
• Quinones S. et al. Exon/intron structure of the human alpha 3(IV) gene encompassing the Goodpasture antigen (alpha 3(IV)NC1). Identification of a potentially antigenic region at the triple helix/NC1 domain junction. — J. Biol. Chem. (1992)
• Quinones S. et al. PubMed: 8006044 — J. Biol. Chem. (1994)