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Gene Review

SLC7A1  -  solute carrier family 7 (cationic amino...

Homo sapiens

Synonyms: ATRC1, CAT-1, CAT1, ERR, Ecotropic retroviral leukemia receptor homolog, ...
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Disease relevance of SLC7A1


High impact information on SLC7A1

  • The derepression requires binding of HuR, an AU-rich-element binding protein, to the 3'UTR of CAT-1 mRNA [5].
  • The derepression of CAT-1 mRNA is accompanied by its release from cytoplasmic processing bodies and its recruitment to polysomes [5].
  • The human cationic amino acid transporter hCAT-1 is almost ubiquitously expressed and probably the most important entity for supplying cells with extracellular arginine, lysine, and ornithine [1].
  • PKC did not phosphorylate hCAT-1 directly as evidenced by in vivo phosphorylation experiments and mutational analysis, indicating an indirect action of PKC on hCAT-1 [1].
  • Alanine scanning mutagenesis of highly conserved residues within HCAT identified one mutation (D893A) that destroyed enzyme activity but not the ability of the mutant subunit to form homodimers [6].

Biological context of SLC7A1


Anatomical context of SLC7A1

  • System y+ plays a minor role in arginine uptake by monocytes and the expression of system y+-related genes, SLC7A1 and SLC7A2, is not changed by IFNgamma [9].
  • We report here that the system y+ cationic amino acid transporter ATRC1 localized to clusters within the basolateral membrane of polarized Madin-Darby canine kidney and human embryonic kidney (HEK) cells, suggesting that the transporters are restricted to discrete membrane microdomains in epithelial cells [10].
  • In agreement with these findings, cytochalasin D reduced the amount of ATRC1 associated with the actin membrane cytoskeleton [10].
  • Based on solubility in nonionic detergents, two populations of ATRC1 molecules existed: approximately half of the total ATRC1 in HEK cells associated with the actin membrane cytoskeleton, whereas another one-fourth resided in detergent-resistant membranes (DRM) [10].
  • Although some ATRC1 clusters in HEK cells colocalized with caveolin, the majority of ATRC1 did not colocalize with this marker protein for a type of DRM called caveolae [10].

Associations of SLC7A1 with chemical compounds


Regulatory relationships of SLC7A1

  • AMT (100 microM) did not affect L-arginine transport studied by electrophysiological techniques in Xenopus laevis oocytes expressing either the human cationic amino acid transporter hCAT-1 or hCAT-2B [13].

Other interactions of SLC7A1

  • Increased expression of SLC7A2/CAT2B is detectable from 3 h of treatment, while SLC7A1 expression is inhibited at later times of incubation [14].
  • Immunohistochemistry and Western blotting confirmed the presence of 4F2hc and CAT1 protein in HPMEC [15].
  • In association with these biochemical indices, we observed a 38% reduction (P<0.05) in the mRNA expression of the cationic amino acid transporter CAT-1 in ventricular myocardial samples from patients with CHF compared with healthy unused donor myocardium, whereas myocardial NOS enzymatic activity and NOS protein were unchanged [16].
  • Pairwise linkage analysis established linkage between ATRC1 and ATP1AL1, D13S1, D13S6, D13S10, D13S11, D13S21, D13S22, D13S33, D13S36, and D13S37 [7].

Analytical, diagnostic and therapeutic context of SLC7A1

  • The cytoprotective effect of CAT-1-specific siRNA on ornithine cytotoxicity was measured using quantitative analysis of cellular adenosine triphosphate (ATP) at 24 hours after treatment with ornithine in OAT-deficient RPE cells [2].
  • Arginine transport activity, arginine transporter CAT1 mRNA and protein levels were measured with transport assay, Northern blot analysis, and Western blot analysis, respectively [17].
  • It suggests a particular temporal code patterning of single LD neuronal firing and its relationships to hippocampal EEG wave code in time series, the latter implies the LD neuronal encoding mechanisms of ATRC-induced epileptic electrical network in bilateral HPCi [18].


  1. Protein kinase C activation promotes the internalization of the human cationic amino acid transporter hCAT-1. A new regulatory mechanism for hCAT-1 activity. Rotmann, A., Strand, D., Martiné, U., Closs, E.I. J. Biol. Chem. (2004) [Pubmed]
  2. Ornithine transport via cationic amino Acid transporter-1 is involved in ornithine cytotoxicity in retinal pigment epithelial cells. Kaneko, S., Ando, A., Okuda-Ashitaka, E., Maeda, M., Furuta, K., Suzuki, M., Matsumura, M., Ito, S. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  3. Tissue-specific activity of heterologous viral promoters in primary rat hepatocytes and Hep G2 cells. Fang, X.J., Keating, A., de Villiers, J., Sherman, M. Hepatology (1989) [Pubmed]
  4. Bile acid malabsorption associated with Graves' disease. Raju, G.S., Dawson, B., Bardhan, K.D. J. Clin. Gastroenterol. (1994) [Pubmed]
  5. Relief of microRNA-mediated translational repression in human cells subjected to stress. Bhattacharyya, S.N., Habermacher, R., Martine, U., Closs, E.I., Filipowicz, W. Cell (2006) [Pubmed]
  6. Dominant negative mutations of the guanylyl cyclase-A receptor. Extracellular domain deletion and catalytic domain point mutations. Thompson, D.K., Garbers, D.L. J. Biol. Chem. (1995) [Pubmed]
  7. 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]
  8. New cluster of plasmid-located class 1 integrons in Vibrio cholerae O1 and a dfrA15 cassette-containing integron in Vibrio parahaemolyticus isolated in Angola. Ceccarelli, D., Salvia, A.M., Sami, J., Cappuccinelli, P., Colombo, M.M. Antimicrob. Agents Chemother. (2006) [Pubmed]
  9. INFgamma stimulates arginine transport through system y+L in human monocytes. Rotoli, B.M., Bussolati, O., Sala, R., Barilli, A., Talarico, E., Gazzola, G.C., Dall'Asta, V. FEBS Lett. (2004) [Pubmed]
  10. System y+ localizes to different membrane subdomains in the basolateral plasma membrane of epithelial cells. Kizhatil, K., Albritton, L.M. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  11. Augmented arginine uptake, through modulation of cationic amino acid transporter-1, increases GFR in diabetic rats. Schwartz, I.F., Iaina, A., Benedict, Y., Wollman, Y., Chernichovski, T., Brasowski, E., Misonzhnik, F., Ben-Dor, A., Blum, M., Levo, Y., Schwartz, D. Kidney Int. (2004) [Pubmed]
  12. Lysine uptake by cloned hCAT-2B: comparison with hCAT-1 and with trophoblast surface membranes. Furesz, T.C., Heath-Monnig, E., Kamath, S.G., Smith, C.H. J. Membr. Biol. (2002) [Pubmed]
  13. Inhibition of nitric oxide synthase abrogates lipopolysaccharides-induced up-regulation of L-arginine uptake in rat alveolar macrophages. Hammermann, R., Stichnote, C., Closs, E.I., Nawrath, H., Racké, K. Br. J. Pharmacol. (2001) [Pubmed]
  14. Two-way arginine transport in human endothelial cells: TNF-alpha stimulation is restricted to system y(+). Sala, R., Rotoli, B.M., Colla, E., Visigalli, R., Parolari, A., Bussolati, O., Gazzola, G.C., Dall'Asta, V. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  15. Characterization of cationic amino acid transporters and expression of endothelial nitric oxide synthase in human placental microvascular endothelial cells. Dye, J.F., Vause, S., Johnston, T., Clark, P., Firth, J.A., D'Souza, S.W., Sibley, C.P., Glazier, J.D. FASEB J. (2004) [Pubmed]
  16. Reduced myocardial and systemic L-arginine uptake in heart failure. Kaye, D.M., Parnell, M.M., Ahlers, B.A. Circ. Res. (2002) [Pubmed]
  17. Regulation of amino acid arginine transport by lipopolysaccharide and nitric oxide in intestinal epithelial IEC-6 cells. Meng, Q., Choudry, H.A., Souba, W.W., Karinch, A.M., Huang, J., Lin, C., Vary, T.C., Pan, M. J. Gastrointest. Surg. (2005) [Pubmed]
  18. Characteristic neuronal firing interspike intervals in laterodorsal thalamic nuclei induced by tetanization of rat caudate putamen: possible relations to hippocampal electroencephalogram changes. Liu, Q., Han, D., Wang, S., Zou, Z.Y. Sheng li xue bao [Acta physiologica Sinica]. (2005) [Pubmed]
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