SLC28 family | Transporters | IUPHAR/BPS Guide to IMMUNOPHARMACOLOGY

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SLC superfamily of solute carriers
SLC28 and SLC29 families of nucleoside transporters
SLC28 family

SLC28 family 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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SLC28 family membersappear to have 13 TM segments with cytoplasmic N-termini and extracellular C-termini, and function as concentrative nucleoside transporters.

Transporters

Targets of relevance to immunopharmacology are highlighted in blue

CNT1 (Sodium/nucleoside cotransporter 1 / SLC28A1) C Show summary »« Hide summary

Target Id

1114

Nomenclature

Sodium/nucleoside cotransporter 1

Systematic nomenclature

SLC28A1

Common abbreviation

CNT1

Previous and unofficial names

concentrative nucleoside transporter 1 | sodium-coupled nucleoside transporter 1 | solute carrier family 28 (sodium-coupled nucleoside transporter), member 1 | solute carrier family 28 (concentrative nucleoside transporter), member 1 | solute carrier family 28 (sodium-coupled nucleoside transporter)

Genes

SLC28A1 (Hs), Slc28a1 (Mm), Slc28a1 (Rn)

Ensembl ID

ENSG00000156222 (Hs), ENSMUSG00000025726 (Mm), ENSRNOG00000018940 (Rn)

UniProtKB AC

O00337 (Hs), Q62674 (Rn)

Bioparadigms SLC Tables

SLC28A1 (Hs)

RESOLUTE

SLC28A1 (Hs)

Endogenous substrates

adenosine

uridine

thymidine

cytidine

Substrates

gemcitabine [1]

zidovudine

zalcitabine

ribavirin [2]

Stoichiometry

1 Na⁺ : 1 nucleoside (in)

CNT2 (Sodium/nucleoside cotransporter 2 / SLC28A2) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

1115

Nomenclature

Sodium/nucleoside cotransporter 2

Systematic nomenclature

SLC28A2

Common abbreviation

CNT2

Previous and unofficial names

concentrative nucleoside transporter 2 | sodium-coupled nucleoside transporter 2 | sodium/purine nucleoside cotransporter | solute carrier family 28 (concentrative nucleoside transporter), member 2 | solute carrier family 28 (sodium-coupled nucleoside transporter) | solute carrier family 28 (sodium-coupled nucleoside transporter) member 2 | SPNT | SPNT1

Genes

SLC28A2 (Hs), Slc28a2 (Mm), Slc28a2 (Rn)

Ensembl ID

ENSG00000137860 (Hs), ENSMUSG00000027219 (Mm), ENSRNOG00000028668 (Rn)

UniProtKB AC

O43868 (Hs), O88627 (Mm), Q62773 (Rn)

Bioparadigms SLC Tables

SLC28A2 (Hs)

RESOLUTE

SLC28A2 (Hs)

Endogenous substrates

adenosine

inosine

guanosine

thymidine

Substrates

formycin B Rat [4]

cladribine [5]

fludarabine Rat [4]

vidarabine

didanosine

Stoichiometry

1 Na⁺ : 1 nucleoside (in)

CNT3 (Solute carrier family 28 member 3 / SLC28A3) C Show summary »« Hide summary

Target Id

1116

Nomenclature

Solute carrier family 28 member 3

Systematic nomenclature

SLC28A3

Common abbreviation

CNT3

Previous and unofficial names

concentrative nucleoside transporter 3 | concentrative Na(+)-nucleoside cotransporter 3 | solute carrier family 28 (sodium-coupled nucleoside transporter), member 3 | solute carrier family 28 (concentrative nucleoside transporter), member 3 | solute carrier family 28 (sodium-coupled nucleoside transporter)

Genes

SLC28A3 (Hs), Slc28a3 (Mm), Slc28a3 (Rn)

Ensembl ID

ENSG00000197506 (Hs), ENSMUSG00000021553 (Mm), ENSRNOG00000018853 (Rn)

UniProtKB AC

Q9HAS3 (Hs), Q9ERH8 (Mm), Q8VIH3 (Rn)

Bioparadigms SLC Tables

SLC28A3 (Hs)

RESOLUTE

SLC28A3 (Hs)

Endogenous substrates

adenosine

inosine

uridine

guanosine

thymidine

cytidine

Substrates

5-fluorouridine

zebularine

formycin B

gemcitabine

cladribine

floxuridine

zidovudine

zalcitabine

didanosine

Inhibitors

compound 16 [PMID: 19097778] pK_i 5.5 [3]

Stoichiometry

2 Na⁺/H⁺

Comment

CNT3 forms cyclic homotrimers [7]. Genetic variants of SLC28A3 are associated with increased risk of anthracycline-induced cardiomyopathy [6].

Comments

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References

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1. Choi MK. (2012) Variability of gemcitabine accumulation and its relationship to expression of nucleoside transporters in peripheral blood mononuclear cells. Arch Pharm Res, 35 (5): 921-7. [PMID:22644860]

2. Choi MK, Kim MH, Maeng HJ, Song IS. (2015) Contribution of CNT1 and ENT1 to ribavirin uptake in human hepatocytes. Arch Pharm Res, 38 (5): 904-13. [PMID:25011570]

3. Gupte A, Buolamwini JK. (2009) Synthesis and biological evaluation of phloridzin analogs as human concentrative nucleoside transporter 3 (hCNT3) inhibitors. Bioorg Med Chem Lett, 19 (3): 917-21. [PMID:19097778]

4. Larráyoz IM, Fernández-Nistal A, Garcés A, Gorraitz E, Lostao MP. (2006) Characterization of the rat Na+/nucleoside cotransporter 2 and transport of nucleoside-derived drugs using electrophysiological methods. Am J Physiol, Cell Physiol, 291 (6): C1395-404. [PMID:16837649]

5. Owen RP, Badagnani I, Giacomini KM. (2006) Molecular determinants of specificity for synthetic nucleoside analogs in the concentrative nucleoside transporter, CNT2. J Biol Chem, 281 (36): 26675-82. [PMID:16840788]

6. Stansberry WM, Swart M, Medeiros EB, Skaar TC, Pratt VM. (2018) Report of Confirmation of the rs7853758 and rs885004 Haplotype in SLC28A3. Genet Test Mol Biomarkers, 22 (11): 652-655. [PMID:30351207]

7. Stecula A, Schlessinger A, Giacomini KM, Sali A. (2017) Human Concentrative Nucleoside Transporter 3 (hCNT3, SLC28A3) Forms a Cyclic Homotrimer. Biochemistry, 56 (27): 3475-3483. [PMID:28661652]

NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation (select format):

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Gibb AJ, Kelly E, Mathie AA, Peach CJ, Veale EL, Armstrong JF, Faccenda E, Harding SD, Southan C, Davies JA et al. (2025) The Concise Guide to PHARMACOLOGY 2025/26: Transporters. Br J Pharmacol. 182: S404-S496.