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Gene Review

ANTXR1  -  anthrax toxin receptor 1

Homo sapiens

Synonyms: ATR, Anthrax toxin receptor 1, FLJ10601, FLJ21776, GAPO, ...
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Disease relevance of ANTXR1

  • The anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA) toxin subunit from forming pores until exposure to low pH [1].
  • Notably, internalized LFn-Al and LFn-Lip protected cells that overexpressed anthrax receptor TEM8 from PA-induced, LF-independent toxicity, suggesting an independent mechanism for PA inhibition inside the cell [2].
  • In this work, we expressed the ATR/TEM8 VWA domain as a fusion protein in Escherichia coli [3].
  • TEM-7R (P = 0.05) and TEM-8 (P < 0.01) were significantly raised in breast cancer tissues compared with the levels detected in normal background tissues [4].
  • RESULTS: TEM-1 (P = 0.01), TEM-7 (P = 0.04), TEM-7R (P = 0.03), TEM-8 (P = 0.001) significantly raised in colon cancer tissues compared with the levels detected in normal background tissues [5].

Psychiatry related information on ANTXR1


High impact information on ANTXR1


Chemical compound and disease context of ANTXR1


Biological context of ANTXR1

  • Both tracers retained high affinity to PA/ANTXR complexes and were readily internalized via receptor-mediated endocytosis [2].
  • ATR-dependent phosphorylation of ATRIP in response to genotoxic stress [14].
  • The serine 68 and 72 residues are important for the phosphorylation in vivo and are required exclusively for direct modification by ATR in vitro [14].
  • METHODS: A ribozyme transgene (TEM-8) was cloned into a suitable mammalian expression vector (pc DNA 3.1-GFP-NT) and transfected into HECV cells [15].
  • PI-kinase-related protein kinase ATR forms a complex with ATRIP and plays pivotal roles in maintaining genome integrity [14].

Anatomical context of ANTXR1

  • The coordinate expression of TEM1, TEM5, and TEM8 on tumor endothelium in humans and mice makes these genes attractive targets for the development of antiangiogenic therapies [16].
  • Finally, we show that the epithelial cells lining the small intestine strongly express ATR/TEM8 isoforms [17].
  • Our results indicate that CMG2 transcripts are preferentially expressed over TEM8 transcripts in primary human and mouse macrophages as compared to immortalized cell lines [18].
  • In this communication, we examined the expression of mRNA transcripts of TEM8 and CMG2 in primary human and mouse macrophages and mouse tissues by standard and quantitative real-time RT-PCR [18].
  • Quantitative measurement of anthrax toxin receptor messenger RNA in primary mononuclear phagocytes [18].

Associations of ANTXR1 with chemical compounds

  • Previously it was shown that the MIDAS threonine is essential for PA interaction with ANTXR1, a result consistent with the requirement that the I domain of that receptor adopts an open conformation for PA-binding [1] [12].
  • The ATR/TEM8-PA interaction is mediated by the receptor's extracellular domain related to von Willebrand factor type A or integrin inserted domains (VWA/I domains) [19].
  • For TEM8-associated toxin, these events can occur at close to neutral pH values, and they show relatively low sensitivity to ammonium chloride treatment in cells [20].
  • UV transiently increased GSK-3beta activity, and this increase could be blocked by caffeine or by ATR small interfering RNA, indicating ATR-dependent activation of GSK-3beta. ser-114, located within the putative GSK-3beta target sequence, was phosphorylated by GSK-3beta upon UV exposure [21].
  • It was previously shown that ATR is critical to fragile-site stability and that ATR-deficient cells have greatly elevated fragile-site expression (A. M. Casper, P. Nghiem, M. F. Arlt, and T. W. Glover, Cell 111:779-789, 2002) [22].

Regulatory relationships of ANTXR1

  • Residues conserved between ANTXR2 and ANTXR1 that influence the ANTXR2-associated pH threshold of pore formation were also identified [1].

Other interactions of ANTXR1


Analytical, diagnostic and therapeutic context of ANTXR1

  • Anthrax toxin receptor ATR/TEM8 VWA domain is responsible for the binding of protective antigen (PA) of B. anthracis, and thus an attractive target for structure-based drug therapies [3].
  • The expression of TEMs (TEM-1 to TEM-8) was assessed using RT-PCR and their transcript levels were determined using real-time-quantitative PCR (Q-RT-PCR) [5].
  • Immunoprecipitation studies of recombinant ATR reveal that catalytic activity of this polypeptide is required for DNA-stimulated phosphorylation of p53 on serine-15 [25].
  • In the current study, the ATR protein was examined by gel filtration of protein extracts and was found to exist predominantly as part of a large protein complex [26].
  • A kinase-inactivated form of the ATR gene was prepared by site-directed mutagenesis and was used in transfection experiments to probe the function of this complex [26].


  1. Anthrax Toxin Receptor 2 Determinants that Dictate the pH Threshold of Toxin Pore Formation. Scobie, H.M., Marlett, J.M., Rainey, G.J., Lacy, D.B., Collier, R.J., Young, J.A. PLoS ONE (2007) [Pubmed]
  2. Inhibition of anthrax protective antigen outside and inside the cell. Backer, M.V., Patel, V., Jehning, B.T., Claffey, K.P., Karginov, V.A., Backer, J.M. Antimicrob. Agents Chemother. (2007) [Pubmed]
  3. Expression and purification of functional human anthrax toxin receptor (ATR/TEM8) binding domain from Escherichia coli. Ding, Z., Bradley, K.A., Amin Arnaout, M., Xiong, J.P. Protein Expr. Purif. (2006) [Pubmed]
  4. Levels of expression of endothelial markers specific to tumour-associated endothelial cells and their correlation with prognosis in patients with breast cancer. Davies, G., Cunnick, G.H., Mansel, R.E., Mason, M.D., Jiang, W.G. Clin. Exp. Metastasis (2004) [Pubmed]
  5. Prognostic values of tumor endothelial markers in patients with colorectal cancer. Rmali, K.A., Puntis, M.C., Jiang, W.G. World J. Gastroenterol. (2005) [Pubmed]
  6. Myopic astigmatism and presbyopia trial. Savage, H., Rothstein, M., Davuluri, G., El Ghormli, L., Zaetta, D.M. Am. J. Ophthalmol. (2003) [Pubmed]
  7. Interstitial deletion in 3q in a patient with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and microcephaly, mild mental retardation and growth delay: clinical report and review of the literature. de Ru, M.H., Gille, J.J., Nieuwint, A.W., Bijlsma, J.B., van der Blij, J.F., van Hagen, J.M. Am. J. Med. Genet. A (2005) [Pubmed]
  8. LRP6 holds the key to the entry of anthrax toxin. Bann, J.G., Cegelski, L., Hultgren, S.J. Cell (2006) [Pubmed]
  9. Identification of the cellular receptor for anthrax toxin. Bradley, K.A., Mogridge, J., Mourez, M., Collier, R.J., Young, J.A. Nature (2001) [Pubmed]
  10. ATR and ATRIP: partners in checkpoint signaling. Cortez, D., Guntuku, S., Qin, J., Elledge, S.J. Science (2001) [Pubmed]
  11. A role for ATR in the DNA damage-induced phosphorylation of p53. Tibbetts, R.S., Brumbaugh, K.M., Williams, J.M., Sarkaria, J.N., Cliby, W.A., Shieh, S.Y., Taya, Y., Prives, C., Abraham, R.T. Genes Dev. (1999) [Pubmed]
  12. Divalent metal ion coordination by residue t118 of anthrax toxin receptor 2 is not essential for protective antigen binding. Scobie, H.M., Young, J.A. PLoS ONE (2006) [Pubmed]
  13. Selection of Anthrax Toxin Protective Antigen Variants That Discriminate between the Cellular Receptors TEM8 and CMG2 and Achieve Targeting of Tumor Cells. Chen, K.H., Liu, S., Bankston, L.A., Liddington, R.C., Leppla, S.H. J. Biol. Chem. (2007) [Pubmed]
  14. ATR-dependent phosphorylation of ATRIP in response to genotoxic stress. Itakura, E., Umeda, K., Sekoguchi, E., Takata, H., Ohsumi, M., Matsuura, A. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  15. TEM-8 and tubule formation in endothelial cells, its potential role of its vW/TM domains. Rmali, K.A., Puntis, M.C., Jiang, W.G. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  16. Cell surface tumor endothelial markers are conserved in mice and humans. Carson-Walter, E.B., Watkins, D.N., Nanda, A., Vogelstein, B., Kinzler, K.W., St Croix, B. Cancer Res. (2001) [Pubmed]
  17. ATR/TEM8 is highly expressed in epithelial cells lining Bacillus anthracis' three sites of entry: implications for the pathogenesis of anthrax infection. Bonuccelli, G., Sotgia, F., Frank, P.G., Williams, T.M., de Almeida, C.J., Tanowitz, H.B., Scherer, P.E., Hotchkiss, K.A., Terman, B.I., Rollman, B., Alileche, A., Brojatsch, J., Lisanti, M.P. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
  18. Quantitative measurement of anthrax toxin receptor messenger RNA in primary mononuclear phagocytes. Premanandan, C., Lairmore, M.D., Fernandez, S., Phipps, A.J. Microb. Pathog. (2006) [Pubmed]
  19. Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Scobie, H.M., Rainey, G.J., Bradley, K.A., Young, J.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  20. Receptor-specific requirements for anthrax toxin delivery into cells. Rainey, G.J., Wigelsworth, D.J., Ryan, P.L., Scobie, H.M., Collier, R.J., Young, J.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  21. Glycogen Synthase Kinase 3{beta} Phosphorylates p21WAF1/CIP1 for Proteasomal Degradation after UV Irradiation. Lee, J.Y., Yu, S.J., Park, Y.G., Kim, J., Sohn, J. Mol. Cell. Biol. (2007) [Pubmed]
  22. BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function. Arlt, M.F., Xu, B., Durkin, S.G., Casper, A.M., Kastan, M.B., Glover, T.W. Mol. Cell. Biol. (2004) [Pubmed]
  23. Opposing effects of the UV lesion repair protein XPA and UV bypass polymerase eta on ATR checkpoint signaling. Bomgarden, R.D., Lupardus, P.J., Soni, D.V., Yee, M.C., Ford, J.M., Cimprich, K.A. EMBO J. (2006) [Pubmed]
  24. An ATR- and BRCA1-mediated Fanconi anemia pathway is required for activating the G2/M checkpoint and DNA damage repair upon rereplication. Zhu, W., Dutta, A. Mol. Cell. Biol. (2006) [Pubmed]
  25. The ataxia-telangiectasia related protein ATR mediates DNA-dependent phosphorylation of p53. Lakin, N.D., Hann, B.C., Jackson, S.P. Oncogene (1999) [Pubmed]
  26. Protein kinase mutants of human ATR increase sensitivity to UV and ionizing radiation and abrogate cell cycle checkpoint control. Wright, J.A., Keegan, K.S., Herendeen, D.R., Bentley, N.J., Carr, A.M., Hoekstra, M.F., Concannon, P. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
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