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Gene Review

Col4a3  -  collagen, type IV, alpha 3

Mus musculus

Synonyms: Collagen alpha-3(IV) chain, alpha3(IV), tumstatin
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Disease relevance of Col4a3


High impact information on Col4a3


Chemical compound and disease context of Col4a3

  • We evaluated the effectiveness of gene therapy, that is, intramuscular delivery of plasmid DNA encoding tumstatin (pSecTag2B-tum), combined with gemcitabine administration in vitro and in vivo, using colon carcinoma (CT26) and Lewis lung carcinoma (LLC) murine models [7].
  • Collectively, our results demonstrate that tumstatin or its C-terminal antitumor fragment, Tum 183-232, inhibits in vivo melanoma progression by triggering an intracellular transduction pathway, which involves a cyclic AMP (cAMP)-dependent mechanism [8].

Biological context of Col4a3


Anatomical context of Col4a3


Associations of Col4a3 with chemical compounds


Other interactions of Col4a3

  • In (129 x B6)F1 Col4a3(-/-) mice, the amount of alpha5/6(IV) collagen in the GBM was inherited in a mother-to-son manner, suggesting that it is controlled by one or more X-linked loci, possibly Col4a6 itself [1].
  • Gelatinase B-deficient mice were bred with Col4a3-/- mice, a model for Alport syndrome, to determine whether gelB influences the progression of glomerulonephritis [12].
  • Recently, we reported that tumstatin (the NC1 domain of alpha 3 chain of type IV collagen) and its deletion mutant tum-5 possess anti-angiogenic activity [13].
  • NGR Enhanced the Anti-Angiogenic Activity of tum-5 [14].

Analytical, diagnostic and therapeutic context of Col4a3


  1. Loss of {alpha}3/{alpha}4(IV) Collagen from the Glomerular Basement Membrane Induces a Strain-Dependent Isoform Switch to {alpha}5{alpha}6(IV) Collagen Associated with Longer Renal Survival in Col4a3-/- Alport Mice. Kang, J.S., Wang, X.P., Miner, J.H., Morello, R., Sado, Y., Abrahamson, D.R., Borza, D.B. J. Am. Soc. Nephrol. (2006) [Pubmed]
  2. Insertional mutation of the collagen genes Col4a3 and Col4a4 in a mouse model of Alport syndrome. Lu, W., Phillips, C.L., Killen, P.D., Hlaing, T., Harrison, W.R., Elder, F.F., Miner, J.H., Overbeek, P.A., Meisler, M.H. Genomics (1999) [Pubmed]
  3. Antiangiogenic endostatin peptide ameliorates renal alterations in the early stage of a type 1 diabetic nephropathy model. Ichinose, K., Maeshima, Y., Yamamoto, Y., Kitayama, H., Takazawa, Y., Hirokoshi, K., Sugiyama, H., Yamasaki, Y., Eguchi, K., Makino, H. Diabetes (2005) [Pubmed]
  4. Tumstatin peptide, an inhibitor of angiogenesis, prevents glomerular hypertrophy in the early stage of diabetic nephropathy. Yamamoto, Y., Maeshima, Y., Kitayama, H., Kitamura, S., Takazawa, Y., Sugiyama, H., Yamasaki, Y., Makino, H. Diabetes (2004) [Pubmed]
  5. Function of endogenous inhibitors of angiogenesis as endothelium-specific tumor suppressors. Sund, M., Hamano, Y., Sugimoto, H., Sudhakar, A., Soubasakos, M., Yerramalla, U., Benjamin, L.E., Lawler, J., Kieran, M., Shah, A., Kalluri, R. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. Quantitative trait loci influence renal disease progression in a mouse model of Alport syndrome. Andrews, K.L., Mudd, J.L., Li, C., Miner, J.H. Am. J. Pathol. (2002) [Pubmed]
  7. Enhanced antitumor effect of the combination of tumstatin gene therapy and gemcitabine in murine models. Yao, B., He, Q.M., Tian, L., Xiao, F., Jiang, Y., Zhang, R., Li, G., Zhang, L., Hou, J.M., Wang, L., Cheng, X.C., Wen, Y.J., Kan, B., Li, J., Zhao, X., Hu, B., Zhou, Q., Zhang, L., Wei, Y.Q. Hum. Gene Ther. (2005) [Pubmed]
  8. In vivo overexpression of tumstatin domains by tumor cells inhibits their invasive properties in a mouse melanoma model. Pasco, S., Ramont, L., Venteo, L., Pluot, M., Maquart, F.X., Monboisse, J.C. Exp. Cell Res. (2004) [Pubmed]
  9. Implication of tumstatin in tumor progression of human bronchopulmonary carcinomas. Caudroy, S., Cucherousset, J., Lorenzato, M., Zahm, J.M., Martinella-Catusse, C., Polette, M., Birembaut, P. Hum. Pathol. (2004) [Pubmed]
  10. Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. Hamano, Y., Zeisberg, M., Sugimoto, H., Lively, J.C., Maeshima, Y., Yang, C., Hynes, R.O., Werb, Z., Sudhakar, A., Kalluri, R. Cancer Cell (2003) [Pubmed]
  11. Expression, purification, and bioactivity of human tumstatin from Escherichia coli. Gu, Q., Zhang, T., Luo, J., Wang, F. Protein Expr. Purif. (2006) [Pubmed]
  12. Gelatinase B (MMP-9) is not essential in the normal kidney and does not influence progression of renal disease in a mouse model of Alport syndrome. Andrews, K.L., Betsuyaku, T., Rogers, S., Shipley, J.M., Senior, R.M., Miner, J.H. Am. J. Pathol. (2000) [Pubmed]
  13. Extracellular matrix-derived peptide binds to alpha(v)beta(3) integrin and inhibits angiogenesis. Maeshima, Y., Yerramalla, U.L., Dhanabal, M., Holthaus, K.A., Barbashov, S., Kharbanda, S., Reimer, C., Manfredi, M., Dickerson, W.M., Kalluri, R. J. Biol. Chem. (2001) [Pubmed]
  14. NGR Enhanced the Anti-Angiogenic Activity of tum-5. Meng, J., Ma, N., Yan, Z., Han, W., Zhang, Y. J. Biochem. (2006) [Pubmed]
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