Alanine/serine/cysteine transporter subfamily | Transporters | IUPHAR/BPS Guide to IMMUNOPHARMACOLOGY

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SLC superfamily of solute carriers
SLC1 family of amino acid transporters
Alanine/serine/cysteine transporter subfamily

Alanine/serine/cysteine transporter subfamily C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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ASC transporters mediate Na⁺-dependent exchange of small neutral amino acids such as Ala, Ser, Cys and Thr and their structure is predicted to be similar to that of the glutamate transporters [2,12]. ASCT1 and ASCT2 also exhibit thermodynamically uncoupled chloride channel activity associated with substrate transport [1,4,13]. Whereas EAATs counter-transport K⁺ (see above) ASCTs do not and their function is independent of the intracellular concentration of K⁺ [1,13].

Transporters

Targets of relevance to immunopharmacology are highlighted in blue

ASCT1 (Alanine/serine/cysteine transporter 1 / SLC1A4) C Show summary »« Hide summary

Target Id	873
Nomenclature	Alanine/serine/cysteine transporter 1
Systematic nomenclature	SLC1A4
Common abbreviation	ASCT1
Previous and unofficial names	Neutral amino acid transporter A \| ASCT1 \| SATT \| alanine/serine/cysteine/threonine transporter \| solute carrier family 1 (glutamate/neutral amino acid transporter), member 4 \| solute carrier family 1 (glutamate/neutral amino acid transporter)
Genes	SLC1A4 (Hs), Slc1a4 (Mm), Slc1a4 (Rn)
Ensembl ID	ENSG00000115902 (Hs), ENSMUSG00000020142 (Mm), ENSRNOG00000005248 (Rn)
UniProtKB AC	P43007 (Hs), O35874 (Mm)
Bioparadigms SLC Tables	SLC1A4 (Hs)
RESOLUTE	SLC1A4 (Hs)
Endogenous substrates	L-cysteine > L-alanine = L-serine > L-threonine
Stoichiometry	1 Na⁺: 1 amino acid (in): 1 Na⁺: 1 amino acid (out); (homo-, or hetero-exchange; [14])

ASCT2 (Alanine/serine/cysteine transporter 2 / SLC1A5) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

874

Nomenclature

Alanine/serine/cysteine transporter 2

Systematic nomenclature

SLC1A5

Common abbreviation

ASCT2

Previous and unofficial names

Genes

SLC1A5 (Hs), Slc1a5 (Mm), Slc1a5 (Rn)

Ensembl ID

ENSG00000105281 (Hs), ENSMUSG00000001918 (Mm), ENSRNOG00000015948 (Rn)

UniProtKB AC

Q15758 (Hs), P51912 (Mm)

Bioparadigms SLC Tables

SLC1A5 (Hs)

RESOLUTE

SLC1A5 (Hs)

Endogenous substrates

L-alanine = L-serine = L-cysteine (low Vmax) = L-threonine = L-glutamine = L-asparagine >> L-methionine ≅ glycine ≅ L-leucine > L-valine > L-glutamic acid (enhanced at low pH)

Inhibitors

p-nitrophenyl glutamyl anilide pK_i 4.3 [5] - Rat

benzylcysteine pK_i 3.1 [6]

benzylserine pK_i 3.0 [6]

Stoichiometry

1 Na⁺: 1 amino acid (in): 1 Na⁺: 1 amino acid (out); (homo-, or hetero-exchange; [3])

Comment

Expression upregulated in lung cancers [7-8], so inhibiting ASCT2-mediated glutamine transport in this situation is predicted to starve tumours of this essential nutrient and diminish their proliferative capacity (or drive apoptosis).

Comments

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References

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1. Alexander SPH, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL et al.. (2019) THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters. Br J Pharmacol, 176 Suppl 1: S397-S493. [PMID:31710713]

2. Arriza JL, Kavanaugh MP, Fairman WA, Wu YN, Murdoch GH, North RA, Amara SG. (1993) Cloning and expression of a human neutral amino acid transporter with structural similarity to the glutamate transporter gene family. J Biol Chem, 268 (21): 15329-32. [PMID:8101838]

3. Bröer A, Brookes N, Ganapathy V, Dimmer KS, Wagner CA, Lang F, Bröer S. (1999) The astroglial ASCT2 amino acid transporter as a mediator of glutamine efflux. J Neurochem, 73 (5): 2184-94. [PMID:10537079]

4. Bröer A, Wagner C, Lang F, Bröer S. (2000) Neutral amino acid transporter ASCT2 displays substrate-induced Na+ exchange and a substrate-gated anion conductance. Biochem J, 346 Pt 3: 705-10. [PMID:10698697]

5. Esslinger CS, Cybulski KA, Rhoderick JF. (2005) Ngamma-aryl glutamine analogues as probes of the ASCT2 neutral amino acid transporter binding site. Bioorg Med Chem, 13 (4): 1111-8. [PMID:15670919]

6. Grewer C, Grabsch E. (2004) New inhibitors for the neutral amino acid transporter ASCT2 reveal its Na+-dependent anion leak. J Physiol (Lond.), 557 (Pt 3): 747-59. [PMID:15107471]

7. Hassanein M, Qian J, Hoeksema MD, Wang J, Jacobovitz M, Ji X, Harris FT, Harris BK, Boyd KL, Chen H et al.. (2015) Targeting SLC1a5-mediated glutamine dependence in non-small cell lung cancer. Int J Cancer, 137 (7): 1587-97. [PMID:25821004]

8. Lopes C, Pereira C, Medeiros R. (2021) ASCT2 and LAT1 Contribution to the Hallmarks of Cancer: From a Molecular Perspective to Clinical Translation. Cancers (Basel), 13 (2). [PMID:33429909]

9. Oppedisano F, Galluccio M, Indiveri C. (2010) Inactivation by Hg2+ and methylmercury of the glutamine/amino acid transporter (ASCT2) reconstituted in liposomes: Prediction of the involvement of a CXXC motif by homology modelling. Biochem Pharmacol, 80 (8): 1266-73. [PMID:20599776]

10. Pinilla-Tenas J, Barber A, Lostao MP. (2003) Transport of proline and hydroxyproline by the neutral amino-acid exchanger ASCT1. J Membr Biol, 195 (1): 27-32. [PMID:14502423]

11. Tamarappoo BK, McDonald KK, Kilberg MS. (1996) Expressed human hippocampal ASCT1 amino acid transporter exhibits a pH-dependent change in substrate specificity. Biochim Biophys Acta, 1279 (2): 131-6. [PMID:8603078]

12. Utsunomiya-Tate N, Endou H, Kanai Y. (1996) Cloning and functional characterization of a system ASC-like Na+-dependent neutral amino acid transporter. J Biol Chem, 271 (25): 14883-90. [PMID:8662767]

13. Zerangue N, Kavanaugh MP. (1996) ASCT-1 is a neutral amino acid exchanger with chloride channel activity. J Biol Chem, 271 (45): 27991-4. [PMID:8910405]

14. Zerangue N, Kavanaugh MP. (1996) Flux coupling in a neuronal glutamate transporter. Nature, 383 (6601): 634-7. [PMID:8857541]

How to cite this family page

Database page citation (select format):

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Transporters. Br J Pharmacol. 180 Suppl 2:S374-469.