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Gene Review

Cubn  -  cubilin (intrinsic factor-cobalamin receptor)

Rattus norvegicus

Synonyms: 460 kDa receptor, Cubilin, GP280, Glycoprotein 280, IFCR, ...
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High impact information on Cubn

  • Both antibodies precipitated a single radiolabeled protein > 200 kD from cellular extract from [35S]methionine-labeled yolk sac epithelial cells, and antibody to gp280 inhibited the uptake and internalization of 125IF-Cbl [1].
  • Furthermore, antibodies raised to purified gp280 and IFCR inhibited the binding of IF-[57Co]Cbl complex to intestinal, renal, and yolk sac apical membranes and revealed a single identically sized protein on immunoblotting of the renal membranes [1].
  • Previous studies have identified two high-molecular weight (280 and 330 kd) glycoproteins expressed by coated pits of the proximal renal tubule and yolk sac and have further established that, in vivo, antibodies to gp280 but not to gp330 induce fetal malformations [2].
  • Synthesis and brush border expression of intrinsic factor-cobalamin receptor from rat renal cortex [3].
  • However, the membrane IFCR activity recovered to 100 or 75%, respectively, when the slices were cultured with intrinsic factor-cobalamin mixed with either leupeptin or chloroquine [3].

Biological context of Cubn

  • We have previously shown the close association with endocytosis of 2 glycoproteins, gp330 and gp280, expressed within the clathrin coated intermicrovillar areas of epithelial cells lining the proximal tubule and visceral layer of the yolk sac [4].
  • These observations suggest that gp280 and gp330, visualized by anti-gp280 and anti-gp330 antibodies coupled to gold particles, returned to the cell surface via dense apical tubules, whereas albumin gold particles dissociated from a potential binding protein in the early endocytic compartment and were subsequently accumulated in lysosomes [5].
  • While the IFCR activity declined in the visceral yolk sac membranes by 15-fold, it rose nearly 20-fold in the placental membranes from fourteen to nineteen days of gestation [6].

Anatomical context of Cubn

  • Furthermore, incubation of yolk sacs in the presence of colloidal gold-labeled antibodies to gp280 demonstrated that gp280, initially expressed on the cell membrane, was translocated into endocytic vacuoles and accumulated in dense apical tubules, whereas only a small fraction reached the lysosomes [5].
  • The present study analyzes the distribution, the internalization and intracellular trafficking of gp280 and gp330 in yolk sac epithelium by immunoultrastructural and cell surface labeling techniques [5].
  • Second, the fraction contains markers associated with intermicrovillar clefts: clathrin light chains, actin, glycoprotein gp280, and gp330, the "Heymann antigen." The presence of the brush border enzyme markers gamma-glutamyl transpeptidase and leucine aminopeptidase in > 99% of the heavy endosomes confirms that the vesicles are of apical origin [7].
  • Metabolic labeling studies with Tran 35S-label confirmed the presence of a 230-kDa IFCR in OK and LLC-PK1 cells [8].
  • Based on these results, we suggest that the IFCR activity, protein expression and mRNA levels in fetal membranes are regulated during pregnancy and may play an important role in the maternal-fetal transfer of cobalamin [6].

Associations of Cubn with chemical compounds

  • Antibodies to gp280 markedly altered development of the yolk sac and embryo, induced malformations, inhibited by 40% the uptake of [14C] sucrose and perturbed the intracellular traffic of internalized proteins [2].
  • This apical expression of IFCR in OK cells is inhibited by the microtubule-disruptive drugs, colchicine and nocodazole [8].
  • The binding of intrinsic factor-cyano[57Co]cobalamin complex to the visceral yolk sac membranes was inhibited by preincubation of these membranes with anti-serum to rat IFCR but not with anti-serum to rat asialoglycoprotein receptor or mannose or mannan or N-acetylglucosamine [6].

Analytical, diagnostic and therapeutic context of Cubn


  1. Identification of rat yolk sac target protein of teratogenic antibodies, gp280, as intrinsic factor-cobalamin receptor. Seetharam, B., Christensen, E.I., Moestrup, S.K., Hammond, T.G., Verroust, P.J. J. Clin. Invest. (1997) [Pubmed]
  2. Antibodies to the 280-kd coated pit protein, target of teratogenic antibodies, produce alterations in the traffic of internalized proteins. Le Panse, S., Ayani, E., Mulliez, N., Chatelet, F., Cywiner-Golenzer, C., Galceran, M., Citadelle, D., Roux, C., Ronco, P., Verroust, P. Am. J. Pathol. (1994) [Pubmed]
  3. Synthesis and brush border expression of intrinsic factor-cobalamin receptor from rat renal cortex. Seetharam, S., Ramanujam, K.S., Seetharam, B. J. Biol. Chem. (1992) [Pubmed]
  4. Unusual processing of GP280, a protein associated with the intermicrovillar areas of yolk sac epithelial cells: plasma membrane delivery of immature protein. Baricault, L., Galceran, M., Ronco, P.M., Trugnan, G., Verroust, P.J. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  5. Internalization and recycling of glycoprotein 280 in epithelial cells of yolk sac. Le Panse, S., Ayani, E., Nielsen, S., Ronco, P., Verroust, P., Christensen, E.I. Eur. J. Cell Biol. (1997) [Pubmed]
  6. Regulated expression of intrinsic factor-cobalamin receptor by rat visceral yolk sac and placental membranes. Ramanujam, K.S., Seetharam, S., Seetharam, B. Biochim. Biophys. Acta (1993) [Pubmed]
  7. Heavy endosomes isolated from the rat renal cortex show attributes of intermicrovillar clefts. Hammond, T.G., Verroust, P.J., Majewski, R.R., Muse, K.E., Oberley, T.D. Am. J. Physiol. (1994) [Pubmed]
  8. Functional expression of intrinsic factor-cobalamin receptor by renal proximal tubular epithelial cells. Ramanujam, K.S., Seetharam, S., Dahms, N.M., Seetharam, B. J. Biol. Chem. (1991) [Pubmed]
  9. Molecular dissection of the intrinsic factor-vitamin B12 receptor, cubilin, discloses regions important for membrane association and ligand binding. Kristiansen, M., Kozyraki, R., Jacobsen, C., Nexø, E., Verroust, P.J., Moestrup, S.K. J. Biol. Chem. (1999) [Pubmed]
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