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SLC15 family of peptide transporters 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).


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The Solute Carrier 15 (SLC15) family of peptide transporters, alias H+-coupled oligopeptide cotransporter family, is a group of membrane transporters known for their key role in the cellular uptake of di- and tripeptides (di/tripeptides). Of its members, SLC15A1 (PEPT1) chiefly mediates intestinal absorption of luminal di/tripeptides from overall dietary protein digestion, SLC15A2 (PEPT2) mainly allows renal tubular reuptake of di/tripeptides from ultrafiltration and brain-to-blood efflux of di/tripeptides in the choroid plexus, SLC15A3 (PHT2) and SLC15A4 (PHT1) interact with both di/tripeptides and histidine, e.g. in certain immune cells, and SLC15A5 has unknown physiological function. In addition, the SLC15 family of peptide transporters variably interacts with a very large number of peptidomimetics and peptide-like drugs. It is conceivable, based on the currently acknowledged structural and functional differences, to divide the SLC15 family of peptide transporters into two subfamilies [3].


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PEPT1 (Peptide transporter 1 / SLC15A1) C Show summary »

PEPT2 (Peptide transporter 2 / SLC15A2) C Show summary »

Target Id 985
Nomenclature Peptide transporter 2
Systematic nomenclature SLC15A2
Common abbreviation PEPT2
Previous and unofficial names high affinity peptide transporter | Kidney H+/peptide cotransporter | oligopeptide transporter, kidney isoform | solute carrier family 15 (H+/peptide transporter) member 2 | solute carrier family 15 member 2 | solute carrier family 15 (oligopeptide transporter), member 2 | solute carrier family 15 (H+/peptide transporter)
Genes SLC15A2 (Hs), Slc15a2 (Mm), Slc15a2 (Rn)
Ensembl ID ENSG00000163406 (Hs), ENSMUSG00000022899 (Mm), ENSRNOG00000002305 (Rn)
UniProtKB AC Q16348 (Hs), Q9ES07 (Mm), Q63424 (Rn)
Bioparadigms SLC Tables SLC15A2 (Hs)
Endogenous substrates
5-aminolevulinic acid [28,55,149]
di/tripeptides including peptides with high intrinsic hydrolysis resistance such as carnosine and anserine [1,36,77,95,113,149,159]
muramyl dipeptide [52,113]
D-Ala-Lys-AMCA [67,116,142]
mirogabalin [154]
β-Ala-Lys-AMCA [1,4-5,26,67,100-101,113,117,160-161]
alafosfalin [93]
γ-iE-DAP [113,115]
acetylated prolyl-glycyl-proline (Ac-PGP; the acetylated form of the collagen-derived matrikine PGP) [97]
Javamide-I(N-coumaroyltryptophan)/-II(N-caffeoyltryptophan) esters (javamide-I-O-methyl ester and javamide-II-O-methyl ester)
Lys[Z(NO2)]-Lys[Z(NO2)] pKi 8.0 [14,126]
Lys[Z(NO2)]-Val pKi 7.0 [14,126]
Lys[Z(NO2)]-Pro pKi 6.2 [14,126]
4-AMBA pKi 2.5 [14,126]
Labelled ligands
[11C]GlySar [90]
[14C]GlySar [31-34,53,55,63,65,75,79,106,122,124]
[3H]GlySar [73,78,96,104,107,116]
[18F]FEPPG [89]
(3,5)-[19F]2-Phe-ψ-Ala [8]
[3H]mirogabalin [154]
Ac-[13C,15N]PGP [97]
Stoichiometry Transport is electrogenic and involves a variable proton-to-substrate stoichiometry for uptake of neutral and mono- or polyvalently charged peptides, as well as the other substrates tested to date.
Comment Although most di/tripeptides can bind PEPT2, not all of them are substrates. The uptake depends on the structural features (charge, hydrophobicity, size, side chain flexibility, etc.) of the di/tripeptide. Like PEPT1, PEPT2 interacts with dipeptides and drugs including D-Phe-Ala [28,125], nateglinide [124], glibenclamide [106], penicillin G (benzylpenicillin) [94], polymyxins (i.e. polymyxin B and colistin) [78] and entecavir [150]. PEPT2 has been shown to interact with dipeptides of p-borono-L-phenylalanine (BPA) and tyrosine (i.e. L-Tyr-p-L-BPA (Tyr-BPA), p-L-BPA-L-tyrosine (BPA-Tyr)) [87] and with AuIII‐peptidodithiocarbamato complexes of the type [AuIIIBr2(dtc‐AA1‐AA2‐OR), in which AA1 = N‐methylglycine (Sar), L/D‐Pro; AA2 = L/D‐Ala, α‐aminoisobutyric acid (Aib); R = OtBu, triethylene glycol methyl ether, e.g. dtc‐Pro‐Aib‐OtBu) [15].

PHT2 (Peptide transporter 3 / SLC15A3) C Show summary » More detailed page go icon to follow link

PHT1 (Peptide transporter 4 / SLC15A4) C Show summary » More detailed page go icon to follow link


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Further reading

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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.