Neutral amino acid transporter subfamily | Transporters | IUPHAR/BPS Guide to MALARIA PHARMACOLOGY

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Neutral amino acid transporter subfamily

Neutral amino acid 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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Certain members of neutral amino acid transport family are expressed upon the apical surface of epithelial cells and are important for the absorption of amino acids from the duodenum, jejunum and ileum and their reabsorption within the proximal tubule of the nephron (i.e. B⁰AT1 (SLC6A19), SLC6A18, SLC6A20). Others may function as transporters for neurotransmitters or their precursors (i.e. B⁰AT2, SLC6A17) [5]. B⁰AT1 has been proposed as a drug target to treat phenylketonuria [1].

Transporters

939

B⁰AT1 / SLC6A19 C Show summary »« Hide summary

Target Id

939

Nomenclature

B⁰AT1

Systematic nomenclature

SLC6A19

Previous and unofficial names

B⁰ neutral amino acid transporter | sodium-dependent neutral amino acid transporter B(0)AT1 | solute carrier family 6 (neurotransmitter transporter), member 19 | solute carrier family 6 member 19 | solute carrier family 6 (neutral amino acid transporter), member 19 | solute carrier family 6 (neurotransmitter transporter)

Genes

SLC6A19 (Hs), Slc6a19 (Mm), Slc6a19 (Rn)

Ensembl ID

ENSG00000174358 (Hs), ENSMUSG00000021565 (Mm), ENSRNOG00000026501 (Rn)

UniProtKB AC

Q695T7 (Hs), Q9D687 (Mm), Q2A865 (Rn)

Bioparadigms SLC Tables

SLC6A19 (Hs)

RESOLUTE

SLC6A19 (Hs)

Endogenous substrates

L-leucine, L-methionine, L-isoleucine, L-valine > L-asparagine, L-phenylalanine, L-alanine, L-serine > L-threonine, glycine, L-proline [4]

Inhibitors

cinromide pIC₅₀ 6.4 [9]

inhibitor E18 pIC₅₀ 5.5 [13]

inhibitor CB3 pIC₅₀ 5.3 [13]

inhibitor E4 pIC₅₀ 5.1 [13]

nimesulide pIC₅₀ 4.6 [10] - Rat

benzatropine pIC₅₀ 4.4 [7]

Stoichiometry

1 Na⁺: 1 amino acid [6]

Comment

Mutations in B⁰AT1 are associated with Hartnup disorder

B⁰AT2 / SLC6A15 C Show summary »« Hide summary

B⁰AT3 / SLC6A18 C Show summary »« Hide summary

Target Id	941
Nomenclature	B⁰AT3
Systematic nomenclature	SLC6A18
Previous and unofficial names	XT2 \| XTRP2 \| solute carrier family 6 (neurotransmitter transporter), member 18 \| Rosit \| b(0)AT3 \| renal osmotic stress-induced Na-Cl organic solute cotransporter \| sodium- and chloride-dependent transporter XTRP2 \| X transporter protein 2 \| solute carrier family 6 (neutral amino acid transporter), member 18 \| solute carrier family 6 (neurotransmitter transporter)
Genes	SLC6A18 (Hs), Slc6a18 (Mm), Slc6a18 (Rn)
Ensembl ID	ENSG00000164363 (Hs), ENSMUSG00000021612 (Mm), ENSRNOG00000016253 (Rn)
UniProtKB AC	Q96N87 (Hs), O88576 (Mm), Q62687 (Rn)
Bioparadigms SLC Tables	SLC6A18 (Hs)
RESOLUTE	SLC6A18 (Hs)
Endogenous substrates	L-alanine, glycine > L-methionine, L-phenylalanine, L-leucine, L-histidine, L-glutamine [12]
Stoichiometry	Na⁺- and Cl^‑ -dependent transport [11]
Comment	SLC6A18 is a functional transporter in mouse, but not in humans.

NTT5 / SLC6A16 C Show summary »« Hide summary

Target Id	942
Nomenclature	NTT5
Systematic nomenclature	SLC6A16
Previous and unofficial names	solute carrier family 6 (neurotransmitter transporter), member 16 \| solute carrier family 6
Genes	SLC6A16 (Hs), Slc6a16 (Mm), Slc6a16 (Rn)
Ensembl ID	ENSG00000063127 (Hs), ENSMUSG00000094152 (Mm), ENSRNOG00000025220 (Rn)
UniProtKB AC	Q9GZN6 (Hs)
Bioparadigms SLC Tables	SLC6A16 (Hs)
RESOLUTE	SLC6A16 (Hs)

NTT4 / SLC6A17 C Show summary »« Hide summary

Target Id	943
Nomenclature	NTT4
Systematic nomenclature	SLC6A17
Previous and unofficial names	XT1 \| XTRP1 \| solute carrier family 6 (neurotransmitter transporter), member 17 \| orphan sodium- and chloride-dependent neurotransmitter transporter NTT4 \| solute carrier family 6 (neutral amino acid transporter), member 17 \| solute carrier family 6 (neurotransmitter transporter)
Genes	SLC6A17 (Hs), Slc6a17 (Mm), Slc6a17 (Rn)
Ensembl ID	ENSG00000197106 (Hs), ENSMUSG00000027894 (Mm), ENSRNOG00000050090 (Rn)
UniProtKB AC	Q9H1V8 (Hs), Q8BJI1 (Mm), P31662 (Rn)
Bioparadigms SLC Tables	SLC6A17 (Hs)
RESOLUTE	SLC6A17 (Hs)
Endogenous substrates	L-leucine, L-methionine, L-proline > L-cysteine, L-alanine, L-glutamine, L-serine > L-histidine, glycine [14]
Stoichiometry	Na⁺-dependent, Cl^--independent transport [14]

SIT1 / SLC6A20 C Show summary »« Hide summary

Target Id

944

Nomenclature

SIT1

Systematic nomenclature

SLC6A20

Previous and unofficial names

Genes

SLC6A20 (Hs), Slc6a20a (Mm), Slc6a20a (Rn)

Ensembl ID

ENSG00000163817 (Hs), ENSMUSG00000036814 (Mm), ENSRNOG00000006010 (Rn), ENSRNOG00000068642 (Rn)

UniProtKB AC

Q9NP91 (Hs), Q8VDB9 (Mm), Q64093 (Rn)

Bioparadigms SLC Tables

SLC6A20 (Hs)

RESOLUTE

SLC6A20 (Hs)

Endogenous substrates

L-proline

Stoichiometry

2 Na⁺: 1 Cl^-: 1 imino acid [2]

References

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1. Belanger AM, Przybylska M, Gefteas E, Furgerson M, Geller S, Kloss A, Cheng SH, Zhu Y, Yew NS. (2018) Inhibiting neutral amino acid transport for the treatment of phenylketonuria. JCI Insight, 3 (14). [PMID:30046012]

2. Bröer A, Balkrishna S, Kottra G, Davis S, Oakley A, Bröer S. (2009) Sodium translocation by the iminoglycinuria associated imino transporter (SLC6A20). Mol Membr Biol, 26 (5): 333-46. [PMID:19657969]

3. Bröer A, Tietze N, Kowalczuk S, Chubb S, Munzinger M, Bak LK, Bröer S. (2006) The orphan transporter v7-3 (slc6a15) is a Na+-dependent neutral amino acid transporter (B0AT2). Biochem J, 393 (Pt 1): 421-30. [PMID:16185194]

4. Bröer S. (2006) The SLC6 orphans are forming a family of amino acid transporters. Neurochem Int, 48 (6-7): 559-67. [PMID:16540203]

5. Bröer S. (2008) Apical transporters for neutral amino acids: physiology and pathophysiology. Physiology (Bethesda), 23: 95-103. [PMID:18400692]

6. Böhmer C, Bröer A, Munzinger M, Kowalczuk S, Rasko JE, Lang F, Bröer S. (2005) Characterization of mouse amino acid transporter B0AT1 (slc6a19). Biochem J, 389 (Pt 3): 745-51. [PMID:15804236]

7. Cheng Q, Shah N, Bröer A, Fairweather S, Jiang Y, Schmoll D, Corry B, Bröer S. (2017) Identification of novel inhibitors of the amino acid transporter B⁰ AT1 (SLC6A19), a potential target to induce protein restriction and to treat type 2 diabetes. Br J Pharmacol, 174 (6): 468-482. [PMID:28176326]

8. Cuboni S, Devigny C, Hoogeland B, Strasser A, Pomplun S, Hauger B, Höfner G, Wanner KT, Eder M, Buschauer A et al.. (2014) Loratadine and analogues: discovery and preliminary structure-activity relationship of inhibitors of the amino acid transporter B(0)AT2. J Med Chem, 57 (22): 9473-9. [PMID:25318072]

9. Danthi SJ, Liang B, Smicker O, Coupland B, Gregory J, Gefteas E, Tietz D, Klodnitsky H, Randall K, Belanger A et al.. (2019) Identification and Characterization of Inhibitors of a Neutral Amino Acid Transporter, SLC6A19, Using Two Functional Cell-Based Assays. SLAS Discov, 24 (2): 111-120. [PMID:30589598]

10. Pochini L, Seidita A, Sensi C, Scalise M, Eberini I, Indiveri C. (2014) Nimesulide binding site in the B0AT1 (SLC6A19) amino acid transporter. Mechanism of inhibition revealed by proteoliposome transport assay and molecular modelling. Biochem Pharmacol, 89 (3): 422-30. [PMID:24704252]

11. Singer D, Camargo SM, Huggel K, Romeo E, Danilczyk U, Kuba K, Chesnov S, Caron MG, Penninger JM, Verrey F. (2009) Orphan transporter SLC6A18 is renal neutral amino acid transporter B0AT3. J Biol Chem, 284 (30): 19953-60. [PMID:19478081]

12. Vanslambrouck JM, Bröer A, Thavyogarajah T, Holst J, Bailey CG, Bröer S, Rasko JE. (2010) Renal imino acid and glycine transport system ontogeny and involvement in developmental iminoglycinuria. Biochem J, 428 (3): 397-407. [PMID:20377526]

13. Yadav A, Shah N, Tiwari PK, Javed K, Cheng Q, Aidhen IS, Bröer S. (2020) Novel Chemical Scaffolds to Inhibit the Neutral Amino Acid Transporter B⁰AT1 (SLC6A19), a Potential Target to Treat Metabolic Diseases. Front Pharmacol, 11: 140. [PMID:32180718]

14. Zaia KA, Reimer RJ. (2009) Synaptic Vesicle Protein NTT4/XT1 (SLC6A17) Catalyzes Na+-coupled Neutral Amino Acid Transport. J Biol Chem, 284 (13): 8439-48. [PMID:19147495]

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, 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.