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Gene Review

A2m  -  alpha-2-macroglobulin

Rattus norvegicus

Synonyms: A2MAC1, A2m1, A2maa, Alpha-2-M, Alpha-2-macroglobulin, ...
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Disease relevance of A2m


Psychiatry related information on A2m

  • Results of this study indicate that the accumulation and activation of alpha 2M with inflammatory neuropathologies such as Alzheimer's disease can inhibit synaptic plasticity, which might partly account for the memory deficits seen in these patients [5].

High impact information on A2m


Chemical compound and disease context of A2m


Biological context of A2m


Anatomical context of A2m

  • Very high concentrations of alpha 2-macroglobulin mRNA originating from both start sites were also found in the uterus but not in the liver of pregnant females [19].
  • In addition, alpha 2-macroglobulin mRNA was detected in brain, spinal cord and eye [10].
  • It was inhibited by the variant alpha 1-antitrypsin Pittsburgh (Met358 to Arg358; K0.5 = 100 nM) but not by other related proteins normally co-secreted with albumin from hepatocytes, namely alpha 1-antitrypsin M, alpha 2-macroglobulin, or antithrombin III [20].
  • Insulin stimulates receptor-mediated uptake of apoE-enriched lipoproteins and activated alpha 2-macroglobulin in adipocytes [21].
  • Native and activated forms of alpha 2-macroglobulin increase expression of platelet-derived growth factor alpha-receptor in vascular smooth muscle cells. Evidence for autocrine transforming growth factor-beta activity [22].

Associations of A2m with chemical compounds


Physical interactions of A2m

  • In summary, results demonstrated that alpha 2M-MA enhanced TGF-beta 1-induced growth responses and that this effect was dependent on alpha 2M-MA binding to alpha 2M receptor/LRP [25].
  • The increase in the binding of alpha 2-macroglobulin-protease complex parallelled an increase in the incorporation of glucosamine, although the latter did not increase to the same extent [26].

Regulatory relationships of A2m


Other interactions of A2m


Analytical, diagnostic and therapeutic context of A2m


  1. Direct injection and expression in vivo of full-length cDNA of the cardiac isoform of alpha-2 macroglobulin induces cardiac hypertrophy in the rat heart. Rajan, S., Radhakrishnan, J., Rajamanickam, C. Basic Res. Cardiol. (2003) [Pubmed]
  2. No association of three polymorphisms in the alpha-2-macroglobulin and lipoprotein related receptor genes with multiple sclerosis. Schweer, D., Jacobsen, M., Ziegler, A., Jäkel, S., Oertel, W.H., Sommer, N., Hemmer, B. J. Neuroimmunol. (2001) [Pubmed]
  3. Acute-phase reaction induces a specific complex between hepatic nuclear proteins and the interleukin 6 response element of the rat alpha 2-macroglobulin gene. Hattori, M., Abraham, L.J., Northemann, W., Fey, G.H. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  4. Localization of alpha 2-macroglobulin protein and messenger RNA in rat liver fibrosis: evidence for the synthesis of alpha 2-macroglobulin within Schistosoma mansoni egg granulomas. Tiggelman, A.M., Boers, W., Moorman, A.F., de Boer, P.A., Van der Loos, C.M., Rotmans, J.P., Chamuleau, R.A. Hepatology (1996) [Pubmed]
  5. Inhibition of long-term potentiation development in rat hippocampal slice by alpha 2-macroglobulin, an acute-phase protein in the brain. Cavuş, I., Koo, P.H., Teyler, T.J. J. Neurosci. Res. (1996) [Pubmed]
  6. The mannose 6-phosphate receptor and the biogenesis of lysosomes. Griffiths, G., Hoflack, B., Simons, K., Mellman, I., Kornfeld, S. Cell (1988) [Pubmed]
  7. Transglutaminase is essential in receptor-mediated endocytosis of alpha 2-macroglobulin and polypeptide hormones. Davies, P.J., Davies, D.R., Levitzki, A., Maxfield, F.R., Milhaud, P., Willingham, M.C., Pastan, I.H. Nature (1980) [Pubmed]
  8. Acute-phase response factor, increased binding, and target gene transcription during liver regeneration. Trautwein, C., Rakemann, T., Niehof, M., Rose-John, S., Manns, M.P. Gastroenterology (1996) [Pubmed]
  9. Filipin-sensitive caveolae-mediated transport in endothelium: reduced transcytosis, scavenger endocytosis, and capillary permeability of select macromolecules. Schnitzer, J.E., Oh, P., Pinney, E., Allard, J. J. Cell Biol. (1994) [Pubmed]
  10. Alpha 2-macroglobulin gene expression during rat development studied by in situ hybridization. Kodelja, V., Heisig, M., Northemann, W., Heinrich, P.C., Zimmermann, W. EMBO J. (1986) [Pubmed]
  11. Inhibition of cell surface receptor-bound plasmin by alpha 2-antiplasmin and alpha 2-macroglobulin. Hall, S.W., Humphries, J.E., Gonias, S.L. J. Biol. Chem. (1991) [Pubmed]
  12. Inhibition of the nuclear entry of 3,3',5'-triiodo-L-thyronine by monodansylcadaverine in GH3 cells. Horiuchi, R., Cheng, S.Y., Willingham, M., Pastan, I. J. Biol. Chem. (1982) [Pubmed]
  13. Interaction of a 39 kDa protein with the low-density-lipoprotein-receptor-related protein (LRP) on rat hepatoma cells. Iadonato, S.P., Bu, G., Maksymovitch, E.A., Schwartz, A.L. Biochem. J. (1993) [Pubmed]
  14. Endotoxaemia and cytokine production in experimental colitis. Neilly, P.J., Gardiner, K.R., Kirk, S.J., Jennings, G., Anderson, N.H., Elia, M., Rowlands, B.J. The British journal of surgery. (1995) [Pubmed]
  15. Influence of an established acute phase response on the severity of experimental nephritis. Karkar, A.M., Rees, A.J. Clin. Exp. Immunol. (1994) [Pubmed]
  16. Sequence of rat liver alpha 2-macroglobulin and acute phase control of its messenger RNA. Gehring, M.R., Shiels, B.R., Northemann, W., de Bruijn, M.H., Kan, C.C., Chain, A.C., Noonan, D.J., Fey, G.H. J. Biol. Chem. (1987) [Pubmed]
  17. Molecular cloning of cDNA sequences for rat alpha 2-macroglobulin and measurement of its transcription during experimental inflammation. Northemann, W., Heisig, M., Kunz, D., Heinrich, P.C. J. Biol. Chem. (1985) [Pubmed]
  18. Identification of the promoter sequences involved in the interleukin-6 dependent expression of the rat alpha 2-macroglobulin gene. Kunz, D., Zimmermann, R., Heisig, M., Heinrich, P.C. Nucleic Acids Res. (1989) [Pubmed]
  19. Structure and acute-phase regulation of the rat alpha 2-macroglobulin gene. Northemann, W., Shiels, B.R., Braciak, T.A., Hanson, R.W., Heinrich, P.C., Fey, G.H. Biochemistry (1988) [Pubmed]
  20. Proalbumin to albumin conversion by a proinsulin processing endopeptidase of insulin secretory granules. Rhodes, C.J., Brennan, S.O., Hutton, J.C. J. Biol. Chem. (1989) [Pubmed]
  21. Insulin stimulates receptor-mediated uptake of apoE-enriched lipoproteins and activated alpha 2-macroglobulin in adipocytes. Descamps, O., Bilheimer, D., Herz, J. J. Biol. Chem. (1993) [Pubmed]
  22. Native and activated forms of alpha 2-macroglobulin increase expression of platelet-derived growth factor alpha-receptor in vascular smooth muscle cells. Evidence for autocrine transforming growth factor-beta activity. Weaver, A.M., Owens, G.K., Gonias, S.L. J. Biol. Chem. (1995) [Pubmed]
  23. alpha 2-Macroglobulin exposure reduces calcium responses to N-methyl-D-aspartate via low density lipoprotein receptor-related protein in cultured hippocampal neurons. Qiu, Z., Strickland, D.K., Hyman, B.T., Rebeck, G.W. J. Biol. Chem. (2002) [Pubmed]
  24. Evidence for participation of transglutaminase in receptor-mediated endocytosis. Levitzki, A., Willingham, M., Pastan, I. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  25. Activated alpha 2-macroglobulin and transforming growth factor-beta 1 induce a synergistic smooth muscle cell proliferative response. Stouffer, G.A., LaMarre, J., Gonias, S.L., Owens, G.K. J. Biol. Chem. (1993) [Pubmed]
  26. In vivo inflammatory stimulation induces a transient change in the binding of thrombin to rat peritoneal macrophages. Fisker, S., Kudahl, K., Sonne, O. Exp. Cell Res. (1992) [Pubmed]
  27. Protease administration decreases enhanced transforming growth factor-beta 1 content in isolated glomeruli of diabetic rats. Paczek, L., Gaciong, Z., Bartlomiejczyk, I., Sebekova, K., Birkenmeier, G., Heidland, A. Drugs under experimental and clinical research. (2001) [Pubmed]
  28. Regulation of Sertoli cell alpha 2-macroglobulin and clusterin (SGP-2) secretion by peritubular myoid cells. Zwain, I.H., Grima, J., Stahler, M.S., Saso, L., Cailleau, J., Verhoeven, G., Bardin, C.W., Cheng, C.Y. Biol. Reprod. (1993) [Pubmed]
  29. Transforming growth factor-alpha's effects on astroglial-cholinergic cell interactions in the medial septal area in vitro are mediated by alpha 2-macroglobulin. Mazzoni, I.E., Kenigsberg, R.L. Neuroscience (1997) [Pubmed]
  30. Alteration of dopamine release by rat caudate putamen tissues superfused with alpha 2-macroglobulin. Hu, Y.Q., Liu, B.J., Dluzen, D.E., Koo, P.H. J. Neurosci. Res. (1996) [Pubmed]
  31. Characterization of the IL-6 responsive elements in the gamma fibrinogen gene promoter. Zhang, Z., Fuentes, N.L., Fuller, G.M. J. Biol. Chem. (1995) [Pubmed]
  32. Low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor is an hepatic receptor for tissue-type plasminogen activator. Bu, G., Williams, S., Strickland, D.K., Schwartz, A.L. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  33. Nuclear factors interacting with an interleukin-6 responsive element of rat alpha 2-macroglobulin gene. Ito, T., Tanahashi, H., Misumi, Y., Sakaki, Y. Nucleic Acids Res. (1989) [Pubmed]
  34. Prolactin induction of the alpha 2-Macroglobulin gene in rat ovarian granulosa cells: stat 5 activation and binding to the interleukin-6 response element. Dajee, M., Kazansky, A.V., Raught, B., Hocke, G.M., Fey, G.H., Richards, J.S. Mol. Endocrinol. (1996) [Pubmed]
  35. Molecular cloning of DNA complementary to rat alpha 2-macroglobulin mRNA. Hayashida, K., Okubo, H., Noguchi, M., Yoshida, H., Kangawa, K., Matsuo, H., Sakaki, Y. J. Biol. Chem. (1985) [Pubmed]
  36. Sequence analysis of the putative regulatory region of rat alpha 2-macroglobulin gene. Tsuchiya, Y., Hattori, M., Hayashida, K., Ishibashi, H., Okubo, H., Sakaki, Y. Gene (1987) [Pubmed]
  37. Antiproteinase chemotherapy of acute experimental pancreatitis using the low molecular weight oligopeptide aldehyde leupeptin. Jones, P.A., Hermon-Taylor, J., Grant, D.A. Gut (1982) [Pubmed]
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