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Gene Review

Fam89b  -  family with sequence similarity 89, member B

Mus musculus

Synonyms: 1110021A21Rik, C184L ORF2 protein, C184M protein, C184m, MMTV, ...
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Disease relevance of Mtvr2


Psychiatry related information on Mtvr2

  • Mouse mammary tumor virus (MMTV) is a B-type retrovirus which induces predominantly mammary carcinomas after a relatively long latency period [4].
  • In addition, no increase in the amount of proviral DNA was detected in tissues of IFN-alpha/betaR(0/0) and IFN-gammaR(0/0) mice, suggesting that interferons are not essential antiviral defense mechanisms during MMTV infection [5].
  • The binding of these anti-Id antibodies to the respective Id was specifically inhibited by prior incubation of the Id with MMTV and/or HuMTV antigens [6].

High impact information on Mtvr2

  • Upon MMTV infection, B cells present SAg to the appropriate T cell subset, which leads to a strong "cognate" T-B interaction [7].
  • Mouse mammary tumor virus (MMTV) is a milk-transmitted type B retrovirus that encodes a SAg in its 3' long terminal repeat [7].
  • In this way a stable MMTV infection is achieved that ultimately results in infection of the mammary gland and virus transmission via milk [7].
  • Because of their ability to stimulate very strong T cell responses in MHC-identical mice, minor lymphocyte stimulatory (Mls) antigens, discovered more than 20 years ago, are now known to be SAgs encoded by endogenous MMTV proviruses that have randomly integrated into germ cells [7].
  • The aim of this review is to combine the extensive biology of Mls SAgs with our current understanding of the life cycle of MMTV [7].

Chemical compound and disease context of Mtvr2


Biological context of Mtvr2

  • MMTV may use transferrin receptor 1, a membrane protein that is endocytosed via clathrin-coated pits and traffics through the acidic endosomes, to rapidly get to a compartment where acid pH triggers the conformational changes in envelope protein required for membrane fusion [2].
  • The critical Phe(40) residue is located on a surface of the MMTV RBD model that is distant from and may be structurally more rigid than the region of F-MLV RBD that contains its critical binding site residues [3].
  • Single substitution of one of the amino acids found in an h-MTV RBS variant in the RBD of MMTV, Phe(40) to Ser, did not alter species tropism but abolished both virus binding to cells and infectivity [3].
  • This suggests that, in contrast to other murine retroviruses, binding to its receptor may result in few or no changes in MMTV envelope protein conformation [3].
  • In light of these data and data published previously, gP130 is apparently a polyprotein containing juxtaposed components translated from the 5' and 3' end of the MMTV genome and protein components not previously identified as virus-specific [9].

Anatomical context of Mtvr2


Associations of Mtvr2 with chemical compounds

  • Neutralizing anti-SU monoclonal antibodies also recognized a glutathione S-transferase fusion protein that contained the five-amino-acid RBS region from MMTV [3].
  • In somatic cell hybrids between different MMTV TGr clones and mouse or hamster TK- cells, expression of constitutive levels of MMTV and responsiveness to dexamethasone induction is dominant [16].
  • Using monoclonal antibodies to the receptor we find that upon heat-activation the steroid-free glucocorticoid receptor present in rat liver cytosol binds specifically in vitro to the HRE of MMTV [17].
  • The promoter of the mouse mammary-tumour virus (MMTV) is packaged into a regular array of nucleosomes when it becomes stably integrated into mammalian chromosomes, and has been used to investigate the relationship between chromatin architecture and transcriptional activation by the hormone-bound glucocorticoid and progesterone receptors [18].
  • We have demonstrated the presence in S115 cells of MMTV-related sequences which are transcribed into RNA only in the long-term presence of androgen [19].

Regulatory relationships of Mtvr2

  • MMTV-resistant human cells that expressed mouse transferrin receptor 1 became susceptible to MMTV infection, and treatment of mouse cells with a monoclonal antibody that down-regulated cell surface expression of the receptor blocked infection [2].

Analytical, diagnostic and therapeutic context of Mtvr2


  1. A novel membrane protein is a mouse mammary tumor virus receptor. Golovkina, T.V., Dzuris, J., van den Hoogen, B., Jaffe, A.B., Wright, P.C., Cofer, S.M., Ross, S.R. J. Virol. (1998) [Pubmed]
  2. Mouse transferrin receptor 1 is the cell entry receptor for mouse mammary tumor virus. Ross, S.R., Schofield, J.J., Farr, C.J., Bucan, M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  3. Identification of the receptor binding domain of the mouse mammary tumor virus envelope protein. Zhang, Y., Rassa, J.C., deObaldia, M.E., Albritton, L.M., Ross, S.R. J. Virol. (2003) [Pubmed]
  4. Exogenous mouse mammary tumor virus proviral DNA isolated from a kidney adenocarcinoma cell line contains alterations in the U3 region of the long terminal repeat. Wellinger, R.J., Garcia, M., Vessaz, A., Diggelmann, H. J. Virol. (1986) [Pubmed]
  5. Immune response to mouse mammary tumor virus in mice lacking the alpha/beta interferon or the gamma interferon receptor. Maillard, I., Launois, P., Xenarios, I., Louis, J.A., Acha-Orbea, H., Diggelmann, H. J. Virol. (1998) [Pubmed]
  6. Towards an idiotype vaccine against mammary tumors. Induction of an immune response to breast cancer-associated antigens by anti-idiotypic antibodies. Smorodinsky, N.I., Ghendler, Y., Bakimer, R., Chaitchuk, S., Keydar, I., Shoenfeld, Y. Eur. J. Immunol. (1988) [Pubmed]
  7. Superantigens of mouse mammary tumor virus. Acha-Orbea, H., MacDonald, H.R. Annu. Rev. Immunol. (1995) [Pubmed]
  8. Dexamethasone-mediated induction of mouse mammary tumor virus RNA: a system for studying glucocorticoid action. Ringold, G.M., Yamamoto, K.R., Tomkins, G.M., Bishop, M., Varmus, H.E. Cell (1975) [Pubmed]
  9. A unique glycoprotein containing GR-mouse mammary tumor virus peptides and additional peptides unrelated to viral structural proteins. Anderson, S.J., Naso, R.B. Cell (1980) [Pubmed]
  10. Ubiquitous transcription factor OTF-1 mediates induction of the MMTV promoter through synergistic interaction with hormone receptors. Brüggemeier, U., Kalff, M., Franke, S., Scheidereit, C., Beato, M. Cell (1991) [Pubmed]
  11. DNA binding properties of glucocorticosteroid receptors bound to the steroid antagonist RU-486. Bourgeois, S., Pfahl, M., Baulieu, E.E. EMBO J. (1984) [Pubmed]
  12. Mineralocorticoid regulation of transcription of transfected mouse mammary tumor virus DNA in cultured kidney cells. Cato, A.C., Weinmann, J. J. Cell Biol. (1988) [Pubmed]
  13. Toll-like receptor 4-dependent activation of dendritic cells by a retrovirus. Burzyn, D., Rassa, J.C., Kim, D., Nepomnaschy, I., Ross, S.R., Piazzon, I. J. Virol. (2004) [Pubmed]
  14. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Muller, W.J., Sinn, E., Pattengale, P.K., Wallace, R., Leder, P. Cell (1988) [Pubmed]
  15. Infection of cultured rat hepatoma cells by mouse mammary tumor virus. Ringold, G.M., Cardiff, R.D., Varmus, H.E., Yamamoto, K.R. Cell (1977) [Pubmed]
  16. High frequency variation in mammary tumor virus expression in cell culture. Parks, W.P., Hubbell, E.S., Goldberg, R.J., O'Neill, F.J., Scolnick, E.M. Cell (1976) [Pubmed]
  17. Steroid-free glucocorticoid receptor binds specifically to mouse mammary tumour virus DNA. Willmann, T., Beato, M. Nature (1986) [Pubmed]
  18. Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex. Fryer, C.J., Archer, T.K. Nature (1998) [Pubmed]
  19. Androgen regulation of cell proliferation and expression of viral sequences in mouse mammary tumour cells. Darbre, P., Dickson, C., Peters, G., Page, M., Curtis, S., King, R.J. Nature (1983) [Pubmed]
  20. Mammary tumor induction loci in GR and DBAf mice contain one provirus of the mouse mammary tumor virus. Michalides, R., van Nie, R., Nusse, R., Hynes, N.E., Groner, B. Cell (1981) [Pubmed]
  21. A signaling pathway coupled to T cell receptor ligation by MMTV superantigen leading to transient activation and programmed cell death. Weber, G.F., Abromson-Leeman, S., Cantor, H. Immunity (1995) [Pubmed]
  22. Expression of a MHC class II transgene determines both superantigenicity and susceptibility to mammary tumor virus infection. Pucillo, C., Cepeda, R., Hodes, R.J. J. Exp. Med. (1993) [Pubmed]
  23. An exogenous mouse mammary tumor virus with properties of Mls-1a (Mtv-7). Held, W., Shakhov, A.N., Waanders, G., Scarpellino, L., Luethy, R., Kraehenbuhl, J.P., MacDonald, H.R., Acha-Orbea, H. J. Exp. Med. (1992) [Pubmed]
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