* 109190

SOLUTE CARRIER FAMILY 1 (NEUTRAL AMINO ACID TRANSPORTER), MEMBER 5; SLC1A5


Alternative titles; symbols

NEUTRAL AMINO ACID TRANSPORTER-LIKE PROTEIN
BABOON M7 VIRUS RECEPTOR; M7V1; M7VS1
RD114 VIRUS RECEPTOR; RDRC
RD114 SENSITIVITY


HGNC Approved Gene Symbol: SLC1A5

Cytogenetic location: 19q13.32     Genomic coordinates (GRCh38): 19:46,774,883-46,788,594 (from NCBI)


TEXT

Description

The SLC1A5 gene encodes a sodium-dependent neutral amino acid transporter that can act as a receptor for RD114/type D retrovirus (Larriba et al., 2001).


Cloning and Expression

The transport of amino acids across the plasma membrane is mediated by a family of Na(+)-dependent amino acid transporters, each of which has distinct tissue distribution and pharmacologic and physiologic properties (Jones et al., 1994). These proteins are involved in the reuptake of neurotransmitters (such as glutamate from the synaptic cleft), an action essential for terminating the postsynaptic action of amino acid neurotransmitters, as well as dietary and cellular uptake of amino acids. By random partial sequencing of a human pancreatic islet cDNA library, Takeda et al. (1993) found a clone encoding an 83-amino acid segment of a protein having 75% and 81% sequence similarity to glutamate and neutral amino acid transporters, respectively. This cDNA was used to screen the human genomic library for the gene encoding this member of the Na(+)-dependent amino acid transporter superfamily.

A common cell surface receptor is used for cell entry by the RD114/simian type D retroviruses, which include the feline endogenous retrovirus RD114, all strains of simian immunosuppressive type D retroviruses, the avian reticuloendotheliosis group, including spleen necrosis virus, and baboon endogenous virus. Rasko et al. (1999) used a retroviral cDNA library approach, involving transfer and expression of cDNAs from highly infectable HeLa cells to nonpermissive NIH 3T3 mouse cells, to clone and identify this receptor. The cloned cDNA, which they denoted RDR (RD114/type D virus interference group), is an allele of the neutral amino acid transporter gene SLC1A5.


Gene Function

SLC1A5 serves as a retrovirus receptor, and Rasko et al. (1999) confirmed that RDR shows specific transport of neutral amino acids. Infection of cells with RD114/type D retroviruses resulted in an impaired amino acid transport, suggesting a mechanism for virus toxicity and immunosuppression. The identification and functional characterization of this retrovirus receptor provided insight into the retrovirus life cycle and pathogenesis and will be an important tool for optimizing gene therapy using vectors derived from RD114/type D retroviruses.


Gene Structure

Larriba et al. (2001) determined the genomic structure and exon/intron boundaries of the SLC1A5 gene. They identified 8 exons varying from 43 bp to 566 bp.


Mapping

The earliest reports that the determinant of entry of endogenous baboon virus was located on chromosome 19 were published by Brown et al. (1978, 1979). By study of mouse-human hybrid cells, Schnitzer et al. (1980) showed that the gene encoding the RD114 virus receptor (RDRC) is located on human chromosome 19. They showed that the receptor is independent of that for poliovirus, which is also encoded by a gene on chromosome 19, and that the feline and baboon endogenous type C retroviruses make use of the same receptor. Replication and integration of the baboon virus are dependent on chromosome 6 (see 109180); whether this is also true of the feline virus is not known (Schnitzer et al., 1980).

By analysis of human-mouse hybrid cells, Kaneda et al. (1987) assigned RDRC to 19q1.1-qter. Further localization to 19q13.1-q13.2 and exclusion of many candidate receptors came from exhaustive analyses performed by Sommerfelt and Weiss (1990) and Sommerfelt et al. (1990). Sommerfelt et al. (1990) used envelope glycoproteins from several of these viral strains to detect receptors expressed in human/rodent somatic cell hybrids segregating human chromosomes. The only human chromosome common to all the susceptible hybrids was chromosome 19. By using hybrids retaining different fragments of chromosome 19, they assigned the receptor gene to 19q13.1-q13.2.

By fluorescence in situ hybridization, Jones et al. (1994) localized the gene encoding the neutral amino acid transporter-like protein SLC1A5 to chromosome 19q13.3. Linkage analyses in CEPH families showed linkage between a polymorphic (GT)n repeat in the 3-prime untranslated region of the cDNA clone and markers in the 19q13 region and localized the gene close to the gene for glycogen synthase (GYS1; 138570) in the interval between D19S22 and D19S8.

By radiation hybrid mapping, Rasko et al. (1999) localized the RDR receptor to a 500-kb region on chromosome 19q13.3.

Rasko et al. (2000) examined whether genes could be precisely localized based on phenotypic assay of radiation cell lines. They assayed the susceptibility of each of the hybrid cell lines to transduction by retroviral vectors bearing different retroviral envelope proteins that recognize receptors present on human but not on hamster cells. Using this method, they mapped the RD114 gene to 19q13.3. After cloning of the receptor for this retrovirus, they found that its standard genotypic mapping by PCR gave results that were nearly identical to those from genotypic mapping. They mapped 2 other retroviruses by this method: xenotropic murine leukemia virus (MuLV) to 1q25.1, and type C feline leukemia virus (FeLV-C) to 1q32.1.

Using fine chromosomal mapping on radiation hybrid panels, Larriba et al. (2001) localized the SLC1A5 gene between STS SHGC-13875 (D19S995) and STS SHGC-6138 in 19q13.3. On the basis of its function and location within the region of chromosome 19 syntenic to the cystic fibrosis (CF; 219700) modifier locus 1 in mouse, the SLC1A5 gene was hypothesized a potential role in the intestinal phenotype of CF. Larriba et al. (2001) analyzed sequence changes in the SLC1A5 gene in CF patients, but none of the identified nucleotide changes seemed to be related to the intestinal phenotype of CF, as their frequencies were found to be similar in CF patients with and without meconium ileus.


REFERENCES

  1. Brown, S., Oie, H., Francke, U., Gazdar, A. F., Minna, J. D. Assignment of a gene required for infection with endogenous baboon virus to human chromosome 19. Cytogenet. Cell Genet. 22: 239-242, 1978. [PubMed: 222542, related citations] [Full Text]

  2. Brown, S., Oie, H. K., Gazdar, A. F., Minna, J. D., Francke, U. Requirement of human chromosomes 19, 6 and possibly 3 for infection of hamster x human hybrid cells with baboon M7 type C virus. Cell 18: 135-143, 1979. [PubMed: 228859, related citations] [Full Text]

  3. Jones, E. M. C., Menzel, S., Espinosa, R., III, Le Beau, M. M., Bell, G. I., Takeda, J. Localization of the gene encoding a neutral amino acid transporter-like protein to human chromosome band 19q13.3 and characterization of a simple sequence repeat DNA polymorphism. Genomics 23: 490-491, 1994. [PubMed: 7835902, related citations] [Full Text]

  4. Kaneda, Y., Hayes, H., Uchida, T., Yoshida, M. C., Okada, Y. Regional assignment of five genes on human chromosome 19. Chromosoma 95: 8-12, 1987. [PubMed: 3034518, related citations] [Full Text]

  5. Larriba, S., Sumoy, L., Ramos, M. D., Gimenez, J., Estivill, X., Casals, T., Nunes, V. ATB(0)/SLC1A5 gene: fine localisation and exclusion of association with the intestinal phenotype of cystic fibrosis. Europ. J. Hum. Genet. 9: 860-866, 2001. [PubMed: 11781704, related citations] [Full Text]

  6. Rasko, J. E. J., Battini, J.-L., Gottschalk, R. J., Mazo, I., Miller, A. D. The RD114/simian type D retrovirus receptor is a neutral amino acid transporter. Proc. Nat. Acad. Sci. 96: 2129-2134, 1999. [PubMed: 10051606, images, related citations] [Full Text]

  7. Rasko, J. E. J., Battini, J.-L., Kruglak, L., Cox, D. R., Miller, A. D. Precise gene localization by phenotypic assay of radiation hybrid cells. Proc. Nat. Acad. Sci. 97: 7388-7392, 2000. [PubMed: 10852967, images, related citations] [Full Text]

  8. Schnitzer, T. J., Weiss, R. A., Juricek, D. K., Ruddle, F. H. Use of vesicular stomatitis virus pseudotypes to map viral receptor genes: assignment of RD114 virus receptor gene to human chromosome 19. J. Virol. 35: 575-580, 1980. [PubMed: 6255197, related citations] [Full Text]

  9. Sommerfelt, M. A., Weiss, R. A. Receptor interference groups of 20 retroviruses plating on human cells. Virology 176: 58-69, 1990. [PubMed: 1691887, related citations] [Full Text]

  10. Sommerfelt, M. A., Williams, B. P., McKnight, A., Goodfellow, P. N., Weiss, R. A. Localization of the receptor gene for type D simian retroviruses on human chromosome 19. J. Virol. 64: 6214-6220, 1990. [PubMed: 2173788, related citations] [Full Text]

  11. Takeda, J., Yano, H., Eng, S., Zeng, Y., Bell, G. I. A molecular inventory of human pancreatic islets: sequence analysis of 1000 cDNA clones. Hum. Molec. Genet. 2: 1793-1798, 1993. [PubMed: 7506601, related citations] [Full Text]


Michael B. Petersen - updated : 9/3/2002
Victor A. McKusick - updated : 8/16/2000
Victor A. McKusick - updated : 3/23/1999
Creation Date:
Victor A. McKusick : 6/4/1986
terry : 01/12/2011
alopez : 5/21/2010
alopez : 9/3/2002
carol : 3/8/2002
terry : 3/8/2002
carol : 8/21/2000
terry : 8/16/2000
carol : 6/3/1999
terry : 3/23/1999
davew : 7/20/1994
supermim : 3/16/1992
carol : 6/11/1991
carol : 6/10/1991
supermim : 3/20/1990
ddp : 10/26/1989

* 109190

SOLUTE CARRIER FAMILY 1 (NEUTRAL AMINO ACID TRANSPORTER), MEMBER 5; SLC1A5


Alternative titles; symbols

NEUTRAL AMINO ACID TRANSPORTER-LIKE PROTEIN
BABOON M7 VIRUS RECEPTOR; M7V1; M7VS1
RD114 VIRUS RECEPTOR; RDRC
RD114 SENSITIVITY


HGNC Approved Gene Symbol: SLC1A5

Cytogenetic location: 19q13.32     Genomic coordinates (GRCh38): 19:46,774,883-46,788,594 (from NCBI)


TEXT

Description

The SLC1A5 gene encodes a sodium-dependent neutral amino acid transporter that can act as a receptor for RD114/type D retrovirus (Larriba et al., 2001).


Cloning and Expression

The transport of amino acids across the plasma membrane is mediated by a family of Na(+)-dependent amino acid transporters, each of which has distinct tissue distribution and pharmacologic and physiologic properties (Jones et al., 1994). These proteins are involved in the reuptake of neurotransmitters (such as glutamate from the synaptic cleft), an action essential for terminating the postsynaptic action of amino acid neurotransmitters, as well as dietary and cellular uptake of amino acids. By random partial sequencing of a human pancreatic islet cDNA library, Takeda et al. (1993) found a clone encoding an 83-amino acid segment of a protein having 75% and 81% sequence similarity to glutamate and neutral amino acid transporters, respectively. This cDNA was used to screen the human genomic library for the gene encoding this member of the Na(+)-dependent amino acid transporter superfamily.

A common cell surface receptor is used for cell entry by the RD114/simian type D retroviruses, which include the feline endogenous retrovirus RD114, all strains of simian immunosuppressive type D retroviruses, the avian reticuloendotheliosis group, including spleen necrosis virus, and baboon endogenous virus. Rasko et al. (1999) used a retroviral cDNA library approach, involving transfer and expression of cDNAs from highly infectable HeLa cells to nonpermissive NIH 3T3 mouse cells, to clone and identify this receptor. The cloned cDNA, which they denoted RDR (RD114/type D virus interference group), is an allele of the neutral amino acid transporter gene SLC1A5.


Gene Function

SLC1A5 serves as a retrovirus receptor, and Rasko et al. (1999) confirmed that RDR shows specific transport of neutral amino acids. Infection of cells with RD114/type D retroviruses resulted in an impaired amino acid transport, suggesting a mechanism for virus toxicity and immunosuppression. The identification and functional characterization of this retrovirus receptor provided insight into the retrovirus life cycle and pathogenesis and will be an important tool for optimizing gene therapy using vectors derived from RD114/type D retroviruses.


Gene Structure

Larriba et al. (2001) determined the genomic structure and exon/intron boundaries of the SLC1A5 gene. They identified 8 exons varying from 43 bp to 566 bp.


Mapping

The earliest reports that the determinant of entry of endogenous baboon virus was located on chromosome 19 were published by Brown et al. (1978, 1979). By study of mouse-human hybrid cells, Schnitzer et al. (1980) showed that the gene encoding the RD114 virus receptor (RDRC) is located on human chromosome 19. They showed that the receptor is independent of that for poliovirus, which is also encoded by a gene on chromosome 19, and that the feline and baboon endogenous type C retroviruses make use of the same receptor. Replication and integration of the baboon virus are dependent on chromosome 6 (see 109180); whether this is also true of the feline virus is not known (Schnitzer et al., 1980).

By analysis of human-mouse hybrid cells, Kaneda et al. (1987) assigned RDRC to 19q1.1-qter. Further localization to 19q13.1-q13.2 and exclusion of many candidate receptors came from exhaustive analyses performed by Sommerfelt and Weiss (1990) and Sommerfelt et al. (1990). Sommerfelt et al. (1990) used envelope glycoproteins from several of these viral strains to detect receptors expressed in human/rodent somatic cell hybrids segregating human chromosomes. The only human chromosome common to all the susceptible hybrids was chromosome 19. By using hybrids retaining different fragments of chromosome 19, they assigned the receptor gene to 19q13.1-q13.2.

By fluorescence in situ hybridization, Jones et al. (1994) localized the gene encoding the neutral amino acid transporter-like protein SLC1A5 to chromosome 19q13.3. Linkage analyses in CEPH families showed linkage between a polymorphic (GT)n repeat in the 3-prime untranslated region of the cDNA clone and markers in the 19q13 region and localized the gene close to the gene for glycogen synthase (GYS1; 138570) in the interval between D19S22 and D19S8.

By radiation hybrid mapping, Rasko et al. (1999) localized the RDR receptor to a 500-kb region on chromosome 19q13.3.

Rasko et al. (2000) examined whether genes could be precisely localized based on phenotypic assay of radiation cell lines. They assayed the susceptibility of each of the hybrid cell lines to transduction by retroviral vectors bearing different retroviral envelope proteins that recognize receptors present on human but not on hamster cells. Using this method, they mapped the RD114 gene to 19q13.3. After cloning of the receptor for this retrovirus, they found that its standard genotypic mapping by PCR gave results that were nearly identical to those from genotypic mapping. They mapped 2 other retroviruses by this method: xenotropic murine leukemia virus (MuLV) to 1q25.1, and type C feline leukemia virus (FeLV-C) to 1q32.1.

Using fine chromosomal mapping on radiation hybrid panels, Larriba et al. (2001) localized the SLC1A5 gene between STS SHGC-13875 (D19S995) and STS SHGC-6138 in 19q13.3. On the basis of its function and location within the region of chromosome 19 syntenic to the cystic fibrosis (CF; 219700) modifier locus 1 in mouse, the SLC1A5 gene was hypothesized a potential role in the intestinal phenotype of CF. Larriba et al. (2001) analyzed sequence changes in the SLC1A5 gene in CF patients, but none of the identified nucleotide changes seemed to be related to the intestinal phenotype of CF, as their frequencies were found to be similar in CF patients with and without meconium ileus.


REFERENCES

  1. Brown, S., Oie, H., Francke, U., Gazdar, A. F., Minna, J. D. Assignment of a gene required for infection with endogenous baboon virus to human chromosome 19. Cytogenet. Cell Genet. 22: 239-242, 1978. [PubMed: 222542] [Full Text: https://doi.org/10.1159/000130945]

  2. Brown, S., Oie, H. K., Gazdar, A. F., Minna, J. D., Francke, U. Requirement of human chromosomes 19, 6 and possibly 3 for infection of hamster x human hybrid cells with baboon M7 type C virus. Cell 18: 135-143, 1979. [PubMed: 228859] [Full Text: https://doi.org/10.1016/0092-8674(79)90362-3]

  3. Jones, E. M. C., Menzel, S., Espinosa, R., III, Le Beau, M. M., Bell, G. I., Takeda, J. Localization of the gene encoding a neutral amino acid transporter-like protein to human chromosome band 19q13.3 and characterization of a simple sequence repeat DNA polymorphism. Genomics 23: 490-491, 1994. [PubMed: 7835902] [Full Text: https://doi.org/10.1006/geno.1994.1529]

  4. Kaneda, Y., Hayes, H., Uchida, T., Yoshida, M. C., Okada, Y. Regional assignment of five genes on human chromosome 19. Chromosoma 95: 8-12, 1987. [PubMed: 3034518] [Full Text: https://doi.org/10.1007/BF00293835]

  5. Larriba, S., Sumoy, L., Ramos, M. D., Gimenez, J., Estivill, X., Casals, T., Nunes, V. ATB(0)/SLC1A5 gene: fine localisation and exclusion of association with the intestinal phenotype of cystic fibrosis. Europ. J. Hum. Genet. 9: 860-866, 2001. [PubMed: 11781704] [Full Text: https://doi.org/10.1038/sj.ejhg.5200726]

  6. Rasko, J. E. J., Battini, J.-L., Gottschalk, R. J., Mazo, I., Miller, A. D. The RD114/simian type D retrovirus receptor is a neutral amino acid transporter. Proc. Nat. Acad. Sci. 96: 2129-2134, 1999. [PubMed: 10051606] [Full Text: https://doi.org/10.1073/pnas.96.5.2129]

  7. Rasko, J. E. J., Battini, J.-L., Kruglak, L., Cox, D. R., Miller, A. D. Precise gene localization by phenotypic assay of radiation hybrid cells. Proc. Nat. Acad. Sci. 97: 7388-7392, 2000. [PubMed: 10852967] [Full Text: https://doi.org/10.1073/pnas.130200097]

  8. Schnitzer, T. J., Weiss, R. A., Juricek, D. K., Ruddle, F. H. Use of vesicular stomatitis virus pseudotypes to map viral receptor genes: assignment of RD114 virus receptor gene to human chromosome 19. J. Virol. 35: 575-580, 1980. [PubMed: 6255197] [Full Text: https://doi.org/10.1128/JVI.35.2.575-580.1980]

  9. Sommerfelt, M. A., Weiss, R. A. Receptor interference groups of 20 retroviruses plating on human cells. Virology 176: 58-69, 1990. [PubMed: 1691887] [Full Text: https://doi.org/10.1016/0042-6822(90)90230-o]

  10. Sommerfelt, M. A., Williams, B. P., McKnight, A., Goodfellow, P. N., Weiss, R. A. Localization of the receptor gene for type D simian retroviruses on human chromosome 19. J. Virol. 64: 6214-6220, 1990. [PubMed: 2173788] [Full Text: https://doi.org/10.1128/JVI.64.12.6214-6220.1990]

  11. Takeda, J., Yano, H., Eng, S., Zeng, Y., Bell, G. I. A molecular inventory of human pancreatic islets: sequence analysis of 1000 cDNA clones. Hum. Molec. Genet. 2: 1793-1798, 1993. [PubMed: 7506601] [Full Text: https://doi.org/10.1093/hmg/2.11.1793]


Contributors:
Michael B. Petersen - updated : 9/3/2002
Victor A. McKusick - updated : 8/16/2000
Victor A. McKusick - updated : 3/23/1999

Creation Date:
Victor A. McKusick : 6/4/1986

Edit History:
terry : 01/12/2011
alopez : 5/21/2010
alopez : 9/3/2002
carol : 3/8/2002
terry : 3/8/2002
carol : 8/21/2000
terry : 8/16/2000
carol : 6/3/1999
terry : 3/23/1999
davew : 7/20/1994
supermim : 3/16/1992
carol : 6/11/1991
carol : 6/10/1991
supermim : 3/20/1990
ddp : 10/26/1989