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Gene Review

Slc7a1  -  solute carrier family 7 (cationic amino...

Mus musculus

Synonyms: 4831426K01Rik, AI447493, Atrc-1, Atrc1, CAT-1, ...
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Disease relevance of Slc7a1

  • Thus, mCAT-1 not only appears to be the sole receptor for a group of murine ecotropic retroviruses associated with hematological disease but also plays a critical role in both hematopoiesis and growth control during mouse development [1].
  • The product of the mouse Rec-1 locus is an integral membrane protein that determines susceptibility to infection by murine ecotropic retroviruses [2].
  • This sequence also exhibited 14 base changes compared with the sequence of ecotropic retrovirus receptor (ERR)/CAT-1 from rat hepatoma [3].
  • To analyze the ecotropic receptor, CAT1, in XC cells, a mouse CAT1 tagged with the influenza virus hemagglutinin epitope (mCAT1-HA)-expressing retroviral vector was inoculated into XC and NIH 3T3 cells [4].
  • Only the neutralizing MAbs specific for the receptor-binding pocket were able to block binding of purified SU and MuLV virions to cells expressing the ecotropic MuLV receptor, mCAT-1 [5].

Psychiatry related information on Slc7a1


High impact information on Slc7a1

  • The data are consistent with a model for receptor co-operativity in which binding to the targeted (Ram-1) receptor triggers conformational rearrangements of the envelope that lead to complete unmasking of the hidden Rec-1-binding domain, thereby facilitating its interaction with the viral (Rec-1) receptor which leads to optimal fusion triggering [7].
  • The mCAT-2 protein sequence is closely related to another cationic AA transporter (mCAT-1); these related proteins elicit virtually identical cationic AA transport in Xenopus oocytes [8].
  • The Tea gene is distinct from, but bears extensive amino acid and DNA sequence similarity with, the murine ecotropic retroviral receptor which is encoded by the Rec-1 gene [9].
  • These results suggest that Cat3 compensates for the loss of functional Cat1 in cells derived from Cat1 knockout mice and mediates the majority of high affinity arginine transport [10].
  • Even though Cat3 expression is normally limited to adult brain, there was a large increase in the amount of Cat3 protein present at the plasma membrane of Cat1(-/-) embryonic fibroblast cells [10].

Chemical compound and disease context of Slc7a1

  • CONCLUSIONS: Gentamicin may be used along with doxycycline when the classical combination is considered the first choice in the treatment of patients with brucellosis due to B. melitensis vaccine strain Rev 1 [11].
  • OBJECTIVES: The objective of the present study was to compare the efficacy of gentamicin given alone or combined with doxycycline with that of standard combination therapies in BALB/c mice experimentally infected with the Brucella melitensis vaccine strain Rev 1 [11].
  • Insertion of targeting domains into the envelope glycoprotein of Moloney murine leukemia virus (MoMLV)-based vectors modulates the route of mCAT-1-mediated viral entry [12].

Biological context of Slc7a1


Anatomical context of Slc7a1

  • In the present study, we raised a polyclonal antibody against CAT-1, and show using reciprocal co-immunoprecipitation protocols that eNOS and CAT-1 do indeed form a complex in BAECs (bovine aortic endothelial cells) [18].
  • Increased Cat3-mediated cationic amino acid transport functionally compensates in Cat1 knockout cell lines [10].
  • Our data establish CAT-1 as a major determinant of ecotropic retrovirus infection in rodent hepatocytes and suggest that CAT-2 is not a receptor for viruses in the amphotropic subgroup [19].
  • Because this serine residue is one of the critical amino acids that form the CAT-1 receptor binding site, and because M. dunni and hamster cells have variant CAT-1 receptors, these results suggest that syncytium formation as well as altered host range may be a consequence of altered interaction between virus and receptor [20].
  • CAT-1 was expressed in both cell types, whereas CAT-2B was only expressed in activated macrophages [21].

Associations of Slc7a1 with chemical compounds

  • Overexpression of CAT-1 in BAECs by adenoviral-mediated gene transfer results in significant increases in both L-arginine uptake and NO production by the cells [18].
  • However, whereas increased L-arginine transport is reversed completely by the CAT-1 inhibitor, L-lysine, increased NO release is unaltered, suggesting that NO production in this in vitro model is independent of CAT-1-mediated transport [18].
  • In vitro binding assays with GST (glutathione S-transferase)-CAT-1 fusion proteins and eNOS show that the two proteins interact directly and that no single CAT-1 intracellular domain is sufficient to mediate the interaction [18].
  • Bindings of ecotropic envelope glycoprotein gp7O to the accessible receptor sites on surfaces of mink cells expressing wild-type or mutant mCAT-1 were not significantly different in kinetics or in equilibrium affinities (i.e., K(D) approximately 3.7 X 10(-10) to 7.5 X 10(-10) M) [16].
  • The R(+) Env protein induced syncytia in XC cells expressing a mutant mCAT1 lacking both of two N glycosylation sites, and tunicamycin treatment suppressed syncytium formation by R(+) Env in those cells [4].

Regulatory relationships of Slc7a1

  • B. melitensis Rev 1 (2.2 x 10(5) c.f.u.) and B. suis strain 2 (1.2 x 10(7) c.f.u.) live vaccines but not the inactivated B. melitensis H38 vaccine conferred protection against B. ovis [22].

Other interactions of Slc7a1

  • In situ hybridization on brain sections revealed that CAT3 transcripts were localized predominantly along the midbrain-thalamus-hypothalamus axis, whereas neither CAT1 nor CAT2 transcripts demonstrated a similar localization [23].
  • SLC7A1/Cat1 is constitutively expressed, and is not modified by proliferating or activating agents [24].
  • The expression of CAT1, CAT3, y+ LAT1 and y+ LAT2 mRNAs supports the presence of each system [25].
  • AMOPRO viruses could not enter cells expressing only Rec-1 or only Ram-1 but could efficiently infect cells co-expressing both receptors [7].
  • Our data revealed that LPS co-induced iNOS, CAT-2, and CAT-2B expression, whereas CAT-1 and CAT-2A expression remained unaffected [26].

Analytical, diagnostic and therapeutic context of Slc7a1


  1. Anemia and perinatal death result from loss of the murine ecotropic retrovirus receptor mCAT-1. Perkins, C.P., Mar, V., Shutter, J.R., del Castillo, J., Danilenko, D.M., Medlock, E.S., Ponting, I.L., Graham, M., Stark, K.L., Zuo, Y., Cunningham, J.M., Bosselman, R.A. Genes Dev. (1997) [Pubmed]
  2. The human cationic amino acid transporter (ATRC1): physical and genetic mapping to 13q12-q14. Albritton, L.M., Bowcock, A.M., Eddy, R.L., Morton, C.C., Tseng, L., Farrer, L.A., Cavalli-Sforza, L.L., Shows, T.B., Cunningham, J.M. Genomics (1992) [Pubmed]
  3. Angiotensin II stimulates system y+ and cationic amino acid transporter gene expression in cultured vascular smooth muscle cells. Low, B.C., Grigor, M.R. J. Biol. Chem. (1995) [Pubmed]
  4. N-Linked glycosylation is required for XC cell-specific syncytium formation by the R peptide-containing envelope protein of ecotropic murine leukemia viruses. Kubo, Y., Ishimoto, A., Amanuma, H. J. Virol. (2003) [Pubmed]
  5. Distinct mechanisms of neutralization by monoclonal antibodies specific for sites in the N-terminal or C-terminal domain of murine leukemia virus SU. Burkhart, M.D., Kayman, S.C., He, Y., Pinter, A. J. Virol. (2003) [Pubmed]
  6. Stress differentially induces cationic amino acid transporter gene expression. Kakuda, D.K., Finley, K.D., Maruyama, M., MacLeod, C.L. Biochim. Biophys. Acta (1998) [Pubmed]
  7. Receptor co-operation in retrovirus entry: recruitment of an auxiliary entry mechanism after retargeted binding. Valsesia-Wittmann, S., Morling, F.J., Hatziioannou, T., Russell, S.J., Cosset, F.L. EMBO J. (1997) [Pubmed]
  8. A mammalian arginine/lysine transporter uses multiple promoters. Finley, K.D., Kakuda, D.K., Barrieux, A., Kleeman, J., Huynh, P.D., MacLeod, C.L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  9. Activated T cells express a novel gene on chromosome 8 that is closely related to the murine ecotropic retroviral receptor. MacLeod, C.L., Finley, K., Kakuda, D., Kozak, C.A., Wilkinson, M.F. Mol. Cell. Biol. (1990) [Pubmed]
  10. Increased Cat3-mediated cationic amino acid transport functionally compensates in Cat1 knockout cell lines. Nicholson, B., Sawamura, T., Masaki, T., MacLeod, C.L. J. Biol. Chem. (1998) [Pubmed]
  11. Efficacy of several antibiotic combinations against Brucella melitensis Rev 1 experimental infection in BALB/c mice. Grilló, M.J., De Miguel, M.J., Muñoz, P.M., Marín, C.M., Ariza, J., Blasco, J.M. J. Antimicrob. Chemother. (2006) [Pubmed]
  12. Insertion of targeting domains into the envelope glycoprotein of Moloney murine leukemia virus (MoMLV)-based vectors modulates the route of mCAT-1-mediated viral entry. Viejo-Borbolla, A., Pizzato, M., Blair, E.D., Schulz, T.F. Virus Res. (2005) [Pubmed]
  13. Genetic mapping of a cloned sequence responsible for susceptibility to ecotropic murine leukemia viruses. Kozak, C.A., Albritton, L.M., Cunningham, J. J. Virol. (1990) [Pubmed]
  14. Dexamethasone suppresses eNOS and CAT-1 and induces oxidative stress in mouse resistance arterioles. Schäfer, S.C., Wallerath, T., Closs, E.I., Schmidt, C., Schwarz, P.M., Förstermann, U., Lehr, H.A. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  15. Transient transfection of ecotropic retrovirus receptor permits stable gene transfer into non-rodent cells with murine retroviral vectors. Scholz, A., Beato, M. Nucleic Acids Res. (1996) [Pubmed]
  16. Modulation of ecotropic murine retroviruses by N-linked glycosylation of the cell surface receptor/amino acid transporter. Wang, H., Klamo, E., Kuhmann, S.E., Kozak, S.L., Kavanaugh, M.P., Kabat, D. J. Virol. (1996) [Pubmed]
  17. Importance of Receptor Usage, Fli1 Activation, and Mouse Strain for the Stem Cell Specificity of 10A1 Murine Leukemia Virus Leukemogenicity. Rodenburg, M., Fischer, M., Engelmann, A., Harbers, S.O., Ziegler, M., L??hler, J., Stocking, C. J. Virol. (2007) [Pubmed]
  18. Interaction of the endothelial nitric oxide synthase with the CAT-1 arginine transporter enhances NO release by a mechanism not involving arginine transport. Li, C., Huang, W., Harris, M.B., Goolsby, J.M., Venema, R.C. Biochem. J. (2005) [Pubmed]
  19. Retroviral infection and expression of cationic amino acid transporters in rodent hepatocytes. Closs, E.I., Borel Rinkes, I.H., Bader, A., Yarmush, M.L., Cunningham, J.M. J. Virol. (1993) [Pubmed]
  20. Novel host range and cytopathic variant of ecotropic Friend murine leukemia virus. Jung, Y.T., Wu, T., Kozak, C.A. J. Virol. (2004) [Pubmed]
  21. Substrate supply for nitric-oxide synthase in macrophages and endothelial cells: role of cationic amino acid transporters. Closs, E.I., Scheld, J.S., Sharafi, M., Förstermann, U. Mol. Pharmacol. (2000) [Pubmed]
  22. Evaluation of vaccines and of antigen therapy in a mouse model for Brucella ovis. Jiménez de Bagüés, M.P., Marín, C.M., Barberán, M., Blasco, J.M. Vaccine (1993) [Pubmed]
  23. A new member of the cationic amino acid transporter family is preferentially expressed in adult mouse brain. Ito, K., Groudine, M. J. Biol. Chem. (1997) [Pubmed]
  24. Macrophages require distinct arginine catabolism and transport systems for proliferation and for activation. Yeramian, A., Martin, L., Arpa, L., Bertran, J., Soler, C., McLeod, C., Modolell, M., Palacín, M., Lloberas, J., Celada, A. Eur. J. Immunol. (2006) [Pubmed]
  25. Y+ and y+ L arginine transporters in neuronal cells expressing tyrosine hydroxylase. Bae, S.Y., Xu, Q., Hutchinson, D., Colton, C.A. Biochim. Biophys. Acta (2005) [Pubmed]
  26. Catecholamines' enhancement of inducible nitric oxide synthase-induced nitric oxide biosynthesis involves CAT-1 and CAT-2A. Lin, W.C., Tsai, P.S., Huang, C.J. Anesth. Analg. (2005) [Pubmed]
  27. Protective properties of rifampin-resistant rough mutants of Brucella melitensis. Adone, R., Ciuchini, F., Marianelli, C., Tarantino, M., Pistoia, C., Marcon, G., Petrucci, P., Francia, M., Riccardi, G., Pasquali, P. Infect. Immun. (2005) [Pubmed]
  28. Distribution of ecotropic retrovirus receptor protein in rat brains detected by immunohistochemistry. Takase-Yoden, S., Watanabe, R. J. Gen. Virol. (2001) [Pubmed]
  29. Determinant for the inhibition of ecotropic murine leukemia virus infection by N-linked glycosylation of the rat receptor. Kubo, Y., Ishimoto, A., Ono, T., Yoshii, H., Tominaga, C., Mitani, C., Amanuma, H., Yamamoto, N. Virology (2004) [Pubmed]
  30. Changes in a murine leukemia virus (MLV) receptor encoded by an alphavirus vector during passage in cells expressing the MLV envelope. Kazachkov, Y., Long, D., Wang, C., Silver, J. Virology (2000) [Pubmed]
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