Alternative titles; symbols
HGNC Approved Gene Symbol: SLC7A2
Cytogenetic location: 8p22 Genomic coordinates (GRCh38): 8:17,494,069-17,570,566 (from NCBI)
Hoshide et al. (1996) cloned the human cationic amino acid transporter-2 (CAT2) from an intestine cDNA library. The gene encodes a 658-amino acid polypeptide that is 60% similar to CAT1 (ATRC1; 104615). CAT1 and CAT2 are members of the APC family of transporters, the members of which are specific for amino acids, polyamines, and choline. Northern blot analysis revealed that CAT2 is expressed as a 9.0-kb transcript in a variety of tissues.
Cationic amino acid transport in mammalian cells is mediated by the cationic amino acid transporter (CAT) family (for review, see Closs (1996)). The 2 genes of the mouse CAT family, Cat1 and Cat2, encode 3 different proteins, Cat1, Cat2a, and Cat2b, that mediate transport of cationic amino acids when expressed in Xenopus oocytes. Closs et al. (1997) isolated cDNAs encoding human CAT2A and CAT2B from a liver cDNA library and a hepatoma cell line cDNA library, respectively. CAT2A and CAT2B are produced by alternative splicing. The deduced CAT2A and CAT2B proteins contain 657 and 658 amino acids, respectively, and both have 14 transmembrane domains and 2 putative N-glycosylation sites in extracellular loop 3. They differ from one another in 19 residues in the vicinity of transmembrane segments 8 and 9.
Both mouse Cat1 and Cat2b show characteristics consistent with system y+, the principal mechanism for cellular uptake of cationic amino acids (Kim et al., 1991; Kakuda et al., 1993). Closs et al. (1997) assayed Xenopus oocytes injected with human CAT2A and CAT2B cRNA and found that both proteins supported concentration-dependent transport of L-arginine and showed trans-stimulation, a property of y+ transporters. Compared with CAT1, CAT2A and CAT2B had a lower substrate affinity and a more narrow pH optimum, between pH 7 and 8.5.
Hoshide et al. (1996) used fluorescence in situ hybridization to map the CAT2 gene to human chromosome 8p21.3-p22. Using a cDNA containing the complete human CAT2B coding region, Lauteala et al. (1997) mapped the gene to 8p22 by fluorescence in situ hybridization.
Nitric oxide synthase (see NOS1; 163731) and arginase (see ARG1; 608313) metabolize arginine, and their reaction products, nitric oxide (NO) and ornithine, respectively, have been implicated in regulation of lung inflammation and airway tone. Rothenberg et al. (2006) found that Cat2-deficient mice, while grossly normal, showed spontaneous inflammation in lung. Marked eosinophilia was present in bronchoalveolar lavage fluid of juvenile mice, and the eosinophilia was gradually replaced by neutrophilia in adult mice. Despite the presence of activated alveolar macrophages in Cat2-deficient mice, NO production was compromised in these cells. Dendritic cell activation was increased in lungs of Cat2-deficient mice, and this process was accompanied by an increase in the number of memory T cells. Rothenberg et al. (2006) concluded that CAT2 regulates antiinflammatory processes in lungs.
Closs, E. I., Graf, P., Habermeier, A., Cunningham, J. M., Forstermann, U. Human cationic amino acid transporters hCAT-1, hCAT-2A, and hCAT-2B: three related carriers with distinct transport properties. Biochemistry 36: 6462-6468, 1997. [PubMed: 9174363] [Full Text: https://doi.org/10.1021/bi962829p]
Closs, E. CATs, a family of three distinct cationic amino acid transporters. Amino Acids 11: 193-208, 1996. [PubMed: 24178687] [Full Text: https://doi.org/10.1007/BF00813860]
Hoshide, R., Ikeda, Y., Karashima, S., Matsuura, T., Komaki, S., Kishino, T., Niikawa, N., Endo, F., Matsuda, I. Molecular cloning, tissue distribution, and chromosomal localization of human cationic amino acid transporter 2 (HCAT2). Genomics 38: 174-178, 1996. [PubMed: 8954799] [Full Text: https://doi.org/10.1006/geno.1996.0613]
Kakuda, D., Finley, K., Dionne, V., MacLeod, C. Two distinct gene products mediate y+-type cationic amino acid transport in Xenopus oocytes and show different tissue expression patterns. Transgene 1: 91-101, 1993.
Kim, J. W., Closs, E. I., Albritton, L. M., Cunningham, J. M. Transport of cationic amino acids by the mouse ecotropic retrovirus receptor. Nature 352: 725-728, 1991. [PubMed: 1652100] [Full Text: https://doi.org/10.1038/352725a0]
Lauteala, T., Horelli-Kuitunen, N., Closs, E., Savontaus, M.-L., Lukkarinen, M., Simell, O., Cunningham, J., Palotie, A., Aula, P. Human cationic amino acid transporter gene hCAT-2 is assigned to 8p22 but is not the causative gene in lysinuric protein intolerance. Hum. Genet. 100: 80-83, 1997. [PubMed: 9225973] [Full Text: https://doi.org/10.1007/s004390050469]
Rothenberg, M. E., Doepker, M. P., Lewkowich, I. P., Chiaramonte, M. G., Stringer, K. F., Finkelman, F. D., MacLeod, C. L., Ellies, L. G., Zimmermann, N. Cationic amino acid transporter 2 regulates inflammatory homeostasis in the lung. Proc. Nat. Acad. Sci. 103: 14895-14900, 2006. [PubMed: 17003120] [Full Text: https://doi.org/10.1073/pnas.0605478103]