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Gene Review

MTX1  -  metaxin 1

Homo sapiens

Synonyms: MTX, MTXN, Metaxin-1, Mitochondrial outer membrane import complex protein 1
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Disease relevance of MTX1


Psychiatry related information on MTX1


High impact information on MTX1

  • In a multiple regression analysis of B-lineage ALL, blast MTX-PG was significantly related to MTX dose (or plasma MTX concentration), lymphoblast ploidy (hyperdiploid > nonhyperdiploid), and percentage S-phase [7].
  • Binding sites for MoAb 225.28S were more efficient for internalization of MTX than were those for the two polyclonal antibody preparations [2].
  • Of 478 previously untreated patients who subsequently achieved an initial marrow remission, 299 were randomised to receive 2400 rad craniospinal radiation therapy (RT) or 2400 rad cranial RT plus intrathecal methotrexate (i.t. MTX) while the remaining 179 patients were randomised between the same two regimens using a radiation dose of 1800 rad [8].
  • The presence of contiguous, highly homologous pseudogenes for both glucocerebrosidase and metaxin at the locus increases the likelihood of DNA rearrangements in this region [9].
  • Since the same amino acid mutation in humans is associated with mild type 1 Gaucher disease, we suggest that metaxin protein is likely to be essential for embryonic development in mice [10].

Chemical compound and disease context of MTX1


Biological context of MTX1


Anatomical context of MTX1

  • A recently described protein, metaxin 1, serves as a component of a preprotein import complex in the outer membrane of the mammalian mitochondrion [18].
  • The incidence of central nervous system (CNS) relapses following BM relapse was 19%, indicating that reprophylaxis to the CNS with IV/intrathecal (IT) MTX was insufficient [19].
  • The modulation of MTX cytotoxicity by purines has been studied in a number of mammalian cell lines [13].
  • During induced maturation of HL-60/LCV cells toward the granulocyte pathway, [3H]methotrexate (MTX) influx capacity and the amount of the affinity labeled transporter decreased rapidly in a parallel fashion [20].
  • The major proteoglycan species identified in HT-29 MTX cells showed less acidic behavior than the proteoglycan isolated from HT-29 cells [21].

Associations of MTX1 with chemical compounds

  • In the present paper, the utility of the combined solid-phase and solution approach is demonstrated by synthesizing muscarinic toxin 1 (MTX1) which binds to the muscarinic acetylcholine receptors [22].
  • Metaxin is rich in leucine (14.2%) and in basic (12.9%) and acidic (12.0%) amino acids [17].
  • It is also notable that only 2 (5%) of 39 patients who received the combination of methotrexate and cyclosporine (MTX/CSP) for the prevention of GVHD developed grade II acute GVHD, and none developed grades III to IV acute GVHD [23].
  • A marked increase in hepatotoxicity was observed in 20 patients administered CyA/MTX, compared with 67 historical control patients who received CyA/methylprednisolone (CyA/MP) for GVHD prophylaxis with all other treatment and support variables remaining constant [5].
  • During maintenance therapy the patients received daily oral thioguanine and biweekly intravenous (IV) MTX [19].

Other interactions of MTX1


Analytical, diagnostic and therapeutic context of MTX1


  1. A novel alteration in metaxin 1, F202L, is associated with N370S in Gaucher disease. LaMarca, M.E., Goldstein, M., Tayebi, N., Arcos-Burgos, M., Martin, B.M., Sidransky, E. J. Hum. Genet. (2004) [Pubmed]
  2. Uptake of methotrexate linked to polyclonal and monoclonal antimelanoma antibodies by a human melanoma cell line. Uadia, P., Blair, A.H., Ghose, T., Ferrone, S. J. Natl. Cancer Inst. (1985) [Pubmed]
  3. Mild preconditioning and low-level engraftment confer methotrexate resistance in mice transplanted with marrow expressing drug-resistant dihydrofolate reductase activity. James, R.I., Warlick, C.A., Diers, M.D., Gunther, R., McIvor, R.S. Blood (2000) [Pubmed]
  4. Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia. Muriel, F.S., Svarch, E., Pavlovsky, S., Eppinger-Helft, M., Braier, J., Vergara, B., Garay, G., Kvicala, R., Divito, J.M., Failace, R., Dibar, E., Jimenez, E. Blood (1983) [Pubmed]
  5. Marked increase in veno-occlusive disease of the liver associated with methotrexate use for graft-versus-host disease prophylaxis in patients receiving busulfan/cyclophosphamide. Essell, J.H., Thompson, J.M., Harman, G.S., Halvorson, R.D., Snyder, M.J., Johnson, R.A., Rubinsak, J.R. Blood (1992) [Pubmed]
  6. Rescue of combination therapy failures using infliximab, while maintaining the combination or monotherapy with methotrexate: results of an open trial. Ferraccioli, G.F., Assaloni, R., Di Poi, E., Gremese, E., De Marchi, G., Fabris, M. Rheumatology (Oxford, England) (2002) [Pubmed]
  7. Blast cell methotrexate-polyglutamate accumulation in vivo differs by lineage, ploidy, and methotrexate dose in acute lymphoblastic leukemia. Synold, T.W., Relling, M.V., Boyett, J.M., Rivera, G.K., Sandlund, J.T., Mahmoud, H., Crist, W.M., Pui, C.H., Evans, W.E. J. Clin. Invest. (1994) [Pubmed]
  8. Presymptomatic central nervous system therapy in previously untreated childhood acute lymphoblastic leukaemia: comparison of 1800 rad and 2400 rad. A report for Children's Cancer Study Group. Nesbit, M.E., Sather, H.N., Robison, L.L., Ortega, J., Littman, P.S., D'Angio, G.J., Hammond, G.D. Lancet (1981) [Pubmed]
  9. Reciprocal and nonreciprocal recombination at the glucocerebrosidase gene region: implications for complexity in Gaucher disease. Tayebi, N., Stubblefield, B.K., Park, J.K., Orvisky, E., Walker, J.M., LaMarca, M.E., Sidransky, E. Am. J. Hum. Genet. (2003) [Pubmed]
  10. Metaxin, a gene contiguous to both thrombospondin 3 and glucocerebrosidase, is required for embryonic development in the mouse: implications for Gaucher disease. Bornstein, P., McKinney, C.E., LaMarca, M.E., Winfield, S., Shingu, T., Devarayalu, S., Vos, H.L., Ginns, E.I. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  11. The effect of prior cisplatin therapy on the pharmacokinetics of high-dose methotrexate. Crom, W.R., Pratt, C.B., Green, A.A., Champion, J.E., Crom, D.B., Stewart, C.F., Evans, W.E. J. Clin. Oncol. (1984) [Pubmed]
  12. Risk of relapse in childhood acute lymphoblastic leukemia is related to RBC methotrexate and mercaptopurine metabolites during maintenance chemotherapy. Nordic Society for Pediatric Hematology and Oncology. Schmiegelow, K., Schrøder, H., Gustafsson, G., Kristinsson, J., Glomstein, A., Salmi, T., Wranne, L. J. Clin. Oncol. (1995) [Pubmed]
  13. Purine modulation of methotrexate cytotoxicity in mammalian cell lines. Taylor, I.W., Slowiaczek, P., Francis, P.R., Tattersall, M.H. Cancer Res. (1982) [Pubmed]
  14. Pharmacokinetics of tumor cell exposure to [14C]methotrexate after intracarotid administration without and with hyperosmotic opening of the blood-brain and blood-tumor barriers in rat brain tumors: a quantitative autoradiographic study. Shapiro, W.R., Voorhies, R.M., Hiesiger, E.M., Sher, P.B., Basler, G.A., Lipschutz, L.E. Cancer Res. (1988) [Pubmed]
  15. The zebrafish metaxin 3 gene (mtx3): cDNA and protein structure, and comparison to zebrafish metaxins 1 and 2. Adolph, K.W. Gene (2004) [Pubmed]
  16. Identification of three additional genes contiguous to the glucocerebrosidase locus on chromosome 1q21: implications for Gaucher disease. Winfield, S.L., Tayebi, N., Martin, B.M., Ginns, E.I., Sidransky, E. Genome Res. (1997) [Pubmed]
  17. Structure and organization of the human metaxin gene (MTX) and pseudogene. Long, G.L., Winfield, S., Adolph, K.W., Ginns, E.I., Bornstein, P. Genomics (1996) [Pubmed]
  18. Metaxin 1 interacts with metaxin 2, a novel related protein associated with the mammalian mitochondrial outer membrane. Armstrong, L.C., Saenz, A.J., Bornstein, P. J. Cell. Biochem. (1999) [Pubmed]
  19. Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group. Henze, G., Fengler, R., Hartmann, R., Kornhuber, B., Janka-Schaub, G., Niethammer, D., Riehm, H. Blood (1991) [Pubmed]
  20. Alteration of folate analogue transport inward after induced maturation of HL-60 leukemia cells. Molecular properties of the transporter in an overproducing variant and evidence for down-regulation of its synthesis in maturating cells. Yang, C.H., Pain, J., Sirotnak, F.M. J. Biol. Chem. (1992) [Pubmed]
  21. Characterization of mucins and proteoglycans synthesized by a mucin-secreting HT-29 cell subpopulation. Huet, G., Kim, I., de Bolos, C., Lo-Guidice, J.M., Moreau, O., Hemon, B., Richet, C., Delannoy, P., Real, F.X., Degand, P. J. Cell. Sci. (1995) [Pubmed]
  22. Combined solid-phase and solution approach for the synthesis of large peptides or proteins. Nishiuchi, Y., Nishio, H., Inui, T., Bódi, J., Kimura, T. J. Pept. Sci. (2000) [Pubmed]
  23. Low incidence of acute graft-versus-host disease by the administration of methotrexate and cyclosporine in Japanese leukemia patients after bone marrow transplantation from human leukocyte antigen compatible siblings; possible role of genetic homogeneity. The Nagoya Bone Marrow Transplantation Group. Morishima, Y., Morishita, Y., Tanimoto, M., Ohno, R., Saito, H., Horibe, K., Hamajima, N., Naito, K., Yamada, K., Yokomaku, S. Blood (1989) [Pubmed]
  24. The structure and cytochemistry of the neurosecretory cells in Ocypoda platytarsis Milne Edwards (Crustacea: Brachyura). Babu, D.E., Shyamasundari, K., Rao, K.H. Zeitschrift für mikroskopisch-anatomische Forschung. (1979) [Pubmed]
  25. Enzyme studies of methotrexate-resistant human leukemic cell (K562) subclones. Koizumi, S., Allegra, C.J. Leuk. Res. (1992) [Pubmed]
  26. Functional analysis of human metaxin in mitochondrial protein import in cultured cells and its relationship with the Tom complex. Abdul, K.M., Terada, K., Yano, M., Ryan, M.T., Streimann, I., Hoogenraad, N.J., Mori, M. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  27. The human thrombospondin 3 gene: analysis of transcription initiation and an alternatively spliced transcript. Adolph, K.W., Bornstein, P. Mol. Cell Biol. Res. Commun. (1999) [Pubmed]
  28. The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM Group Study NHL-BFM95. Woessmann, W., Seidemann, K., Mann, G., Zimmermann, M., Burkhardt, B., Oschlies, I., Ludwig, W.D., Klingebiel, T., Graf, N., Gruhn, B., Juergens, H., Niggli, F., Parwaresch, R., Gadner, H., Riehm, H., Schrappe, M., Reiter, A. Blood (2005) [Pubmed]
  29. The treatment of malignant histiocytosis. Tseng, A., Coleman, C.N., Cox, R.S., Colby, T.V., Turner, R.R., Horning, S.J., Rosenberg, S.A. Blood (1984) [Pubmed]
  30. The value of high-dose methotrexate-based neoadjuvant chemotherapy in malignant fibrous histiocytoma of bone. Ham, S.J., Hoekstra, H.J., van der Graaf, W.T., Kamps, W.A., Molenaar, W.M., Schraffordt Koops, H. J. Clin. Oncol. (1996) [Pubmed]
  31. Intensive oral methotrexate protects against lymphoid marrow relapse in childhood B-precursor acute lymphoblastic leukemia. Winick, N., Shuster, J.J., Bowman, W.P., Borowitz, M., Farrow, A., Jacaruso, D., Buchanan, G.R., Kamen, B.A. J. Clin. Oncol. (1996) [Pubmed]
  32. Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice. Waber, D.P., Tarbell, N.J., Fairclough, D., Atmore, K., Castro, R., Isquith, P., Lussier, F., Romero, I., Carpenter, P.J., Schiller, M. J. Clin. Oncol. (1995) [Pubmed]
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