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Gene Review

Ahsg  -  alpha-2-HS-glycoprotein

Mus musculus

Synonyms: Alpha-2-HS-glycoprotein, Countertrypin, Fetua, Fetuin-A, fetuin-A
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Disease relevance of Ahsg

  • Using the Multiple intestinal neoplasia/+ (Min/+) mouse model of intestinal tumorigenesis, we found twice as many intestinal polyps overall, twice as many large polyps (>3 mm diameter), and more progression to invasive adenocarcinoma in Min/+ Ahsg-/- mice than in littermates expressing Ahsg [1].
  • Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene [2].
  • Our results suggest that Ahsg may be useful for prevention of the heterotopic ossification and the regulation of osteoinductive effects of BMP used with grafts [3].
  • Using reporter gene assays in hepatoma cells combined with electrophoretic mobility shift assays we determined that dexamethasone up-regulates hepatic Ahsg [4].
  • Similarly, intrasplenic injection of LLC cells resulted in rapid colonization of the liver with metastasis to the lungs within 2 weeks in the WT but not fetuin-A null mice [5].

High impact information on Ahsg


Chemical compound and disease context of Ahsg

  • Here, we explore insulin signaling, glucose homeostasis, and the effect of a high-fat diet on weight gain, body fat composition, and glucose disposal in mice carrying two null alleles for the gene encoding fetuin, Ahsg (B6, 129-Ahsg(tm1Mbl)) [2].

Biological context of Ahsg


Anatomical context of Ahsg


Associations of Ahsg with chemical compounds

  • A high degree of sequence identity in mouse, rat and human Ahsg promoters suggests that the promoter is similarly up-regulated by dexamethasone in all three species [4].
  • A steroid response unit at position -146/-119 within the mouse Ahsg promoter mediates the glucocorticoid-induced increase of Ahsg mRNA [4].
  • alpha2-HS glycoprotein (AHSG), also known as fetuin-A, inhibits insulin receptor autophosphorylation and tyrosine kinase activity in vitro and in vivo [11].

Other interactions of Ahsg

  • Bone formation in response to implanted BMP cytokine extended further from the implant in Ahsg(-/-) compared with Ahsg(+/+) mice, confirming the interaction between ASHG and TGF-beta/BMP cytokines in vivo [7].

Analytical, diagnostic and therapeutic context of Ahsg


  1. alpha2HS-glycoprotein, an antagonist of transforming growth factor beta in vivo, inhibits intestinal tumor progression. Swallow, C.J., Partridge, E.A., Macmillan, J.C., Tajirian, T., DiGuglielmo, G.M., Hay, K., Szweras, M., Jahnen-Dechent, W., Wrana, J.L., Redston, M., Gallinger, S., Dennis, J.W. Cancer Res. (2004) [Pubmed]
  2. Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Mathews, S.T., Singh, G.P., Ranalletta, M., Cintron, V.J., Qiang, X., Goustin, A.S., Jen, K.L., Charron, M.J., Jahnen-Dechent, W., Grunberger, G. Diabetes (2002) [Pubmed]
  3. Regulation of BMP-induced ectopic bone formation by Ahsg. Rittenberg, B., Partridge, E., Baker, G., Clokie, C., Zohar, R., Dennis, J.W., Tenenbaum, H.C. J. Orthop. Res. (2005) [Pubmed]
  4. CCAAT enhancer binding protein beta and hepatocyte nuclear factor 3beta are necessary and sufficient to mediate dexamethasone-induced up-regulation of alpha2HS-glycoprotein/fetuin-A gene expression. Wöltje, M., Tschöke, B., von Bülow, V., Westenfeld, R., Denecke, B., Gräber, S., Jahnen-Dechent, W. J. Mol. Endocrinol. (2006) [Pubmed]
  5. The serum glycoprotein fetuin-A promotes Lewis lung carcinoma tumorigenesis via adhesive-dependent and adhesive-independent mechanisms. Kundranda, M.N., Henderson, M., Carter, K.J., Gorden, L., Binhazim, A., Ray, S., Baptiste, T., Shokrani, M., Leite-Browning, M.L., Jahnen-Dechent, W., Matrisian, L.M., Ochieng, J. Cancer Res. (2005) [Pubmed]
  6. The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. Schafer, C., Heiss, A., Schwarz, A., Westenfeld, R., Ketteler, M., Floege, J., Muller-Esterl, W., Schinke, T., Jahnen-Dechent, W. J. Clin. Invest. (2003) [Pubmed]
  7. alpha 2-HS glycoprotein/fetuin, a transforming growth factor-beta/bone morphogenetic protein antagonist, regulates postnatal bone growth and remodeling. Szweras, M., Liu, D., Partridge, E.A., Pawling, J., Sukhu, B., Clokie, C., Jahnen-Dechent, W., Tenenbaum, H.C., Swallow, C.J., Grynpas, M.D., Dennis, J.W. J. Biol. Chem. (2002) [Pubmed]
  8. Genetic mapping and functional studies of a natural inhibitor of the insulin receptor tyrosine kinase: the mouse ortholog of human alpha2-HS glycoprotein. Cintrón, V.J., Ko, M.S., Chi, K.D., Gross, J.P., Srinivas, P.R., Goustin, A.S., Grunberger, G. Int. J. Exp. Diabetes Res. (2001) [Pubmed]
  9. Isolation and characterization of mouse countertrypin, a new trypsin inhibitor belonging to the mammalian fetuin family. Yamamoto, K., Sinohara, H. J. Biol. Chem. (1993) [Pubmed]
  10. Fetuin-A, a hepatocyte-specific protein that binds Plasmodium berghei thrombospondin-related adhesive protein: a potential role in infectivity. Jethwaney, D., Lepore, T., Hassan, S., Mello, K., Rangarajan, R., Jahnen-Dechent, W., Wirth, D., Sultan, A.A. Infect. Immun. (2005) [Pubmed]
  11. Fetuin-null mice are protected against obesity and insulin resistance associated with aging. Mathews, S.T., Rakhade, S., Zhou, X., Parker, G.C., Coscina, D.V., Grunberger, G. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  12. Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles. Heiss, A., DuChesne, A., Denecke, B., Grötzinger, J., Yamamoto, K., Renné, T., Jahnen-Dechent, W. J. Biol. Chem. (2003) [Pubmed]
  13. Alpha 2-HS glycoprotein (fetuin-A) modulates murine skin tumorigenesis. Leite-Browning, M.L., McCawley, L.J., Jahnen-Dechent, W., King, L.E., Matrisian, L.M., Ochieng, J. Int. J. Oncol. (2004) [Pubmed]
  14. Multifunctional roles for serum protein fetuin-a in inhibition of human vascular smooth muscle cell calcification. Reynolds, J.L., Skepper, J.N., McNair, R., Kasama, T., Gupta, K., Weissberg, P.L., Jahnen-Dechent, W., Shanahan, C.M. J. Am. Soc. Nephrol. (2005) [Pubmed]
  15. Molecular cloning and sequencing of cDNA encoding plasma countertrypin, a member of mammalian fetuin family, from the Mongolian gerbil, Meriones unguiculatus. Goto, K., Yoshida, K., Suzuki, Y., Yamamoto, K., Sinohara, H. J. Biochem. (1997) [Pubmed]
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