2.A.17 The Proton-dependent Oligopeptide Transporter (POT/PTR) Family

Proteins of the POT family (also called the PTR (peptide transport) family) consist of proteins from animals, plants, yeast, archaea and both Gram-negative and Gram-positive bacteria. Several of these organisms possess multiple POT family paralogues. The proteins are of about 450-600 amino acyl residues in length with the eukaryotic proteins in general being longer than the bacterial proteins. They exhibit 12 putative or established transmembrane α-helical spanners.  The plant homologues have been examined from phylogenetic standpoints (von Wittgenstein et al. 2014). 

Pairs of salt bridge interactions between transmembrane helices work in tandem to orchestrate alternating access transport within the PTR family (Newstead 2014). Key roles for residues conserved between bacterial and eukaryotic homologues suggest a conserved mechanism of peptide recognition and transport that in some cases has been subtly modified in individual species.  PepT1 and PepT2, mammalian members of this family, are responsible for the uptake of many pharmaceutically important drug molecules, including antibiotics and antiviral medications.  Thus, their promiscuity can be used for improving the oral bioavailability of poorly absorbed compounds (Newstead 2014).

While most members of the POT family catalyze peptide transport, one is a nitrate permease and one can transport histidine as well as peptides. A nitrate permease of Arabidopsis, Chl1 (TC #2.A.17.3.1), exhibits dual affinity. When phosphorylated at threonine-101, it exhibits high affinity (50 μM) for nitrate, but when not phosphorylated, it exhibits low affinity (~5 mM) (Liu and Tsay, 2003). Some of the peptide transporters can also transport antibiotics. They function by proton symport, but the substrate:H+ stoichiometry is variable: the high affinity rat PepT2 carrier catalyzes uptake of 2 and 3H+ with neutral and anionic dipeptides, respectively, while the low affinity PepT1 carrier catalyzes uptake of one H+ per neutral peptide. In eukaryotes, some of these transporters may be in organellar membranes such as the lysosomes.

Di- and tripeptide transporters of the POT/PTR/NRT1 family are localized either to the tonoplast (TP) or plasma membrane (PM). A 7 amino acid fragment of the hydrophilic N-terminal region of Arabidopsis PTR2, PTR4 and PTR6 is required for TP localization and sufficient to redirect not only PM-localized PTR1 or PTR5, but also sucrose transporter SUC2 to the tonopolast (Komarova et al., 2012). L(11) and I(12) of PTR2 are essential for TP targeting, while only one acidic amino acid at position 5, 6 or 7 is required, revealing a dileucine (LL or LI) motif with at least one upstream acidic residue. Similar dileucine motifs could be identified in other plant TP transporters. Targeting to the PM required the loop between transmembrane domains 6 and 7 of PTR1 or PTR5. Deletion of either PM or TP targeting signals resulted in retention in internal membranes, indicating that PTR trafficking to these destination membranes requires distinct signals and is in both cases not by default (Komarova et al., 2012).

The generalized transport reaction catalyzed by the proteins of the POT family is:

Substrate (out) nH (out) → substrate (in) nH+ (in)



This family belongs to the MFS Superfamily.

 

References:

Newstead S. (2015). Molecular insights into proton coupled peptide transport in the PTR family of oligopeptide transporters. Biochim Biophys Acta. 1850(3):488-99.



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Belmondo, S., V. Fiorilli, J. Pérez-Tienda, N. Ferrol, R. Marmeisse, and L. Lanfranco. (2014). A dipeptide transporter from the arbuscular mycorrhizal fungus Rhizophagus irregularis is upregulated in the intraradical phase. Front Plant Sci 5: 436.

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Ishimaru, Y., K. Washiyama, T. Oikawa, S. Hamamoto, N. Uozumi, and M. Ueda. (2017). Dimerization of GTR1 regulates their plasma membrane localization. Plant Signal Behav 0. [Epub: Ahead of Print]

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Kanno, Y., Y. Kamiya, and M. Seo. (2013). Nitrate does not compete with abscisic acid as a substrate of AtNPF4.6/NRT1.2/AIT1 in Arabidopsis. Plant Signal Behav 8: e26624.

Karim, S., D. Lundh, K.O. Holmström, A. Mandal, and M. Pirhonen. (2005). Structural and functional characterization of AtPTR3, a stress-induced peptide transporter of Arabidopsis. J Mol Model 11: 226-236.

Karim, S., K.O. Holmström, A. Mandal, P. Dahl, S. Hohmann, G. Brader, E.T. Palva, and M. Pirhonen. (2007). AtPTR3, a wound-induced peptide transporter needed for defence against virulent bacterial pathogens in Arabidopsis. Planta 225: 1431-1445.

Knütter, I., B. Hartrodt, G. Tóth, A. Keresztes, G. Kottra, C. Mrestani-Klaus, I. Born, H. Daniel, K. Neubert, and M. Brandsch. (2007). Synthesis and characterization of a new and radiolabeled high-affinity substrate for H+/peptide cotransporters. FEBS J. 274(22):5905-5914.

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Komarova, N.Y., K. Thor, A. Gubler, S. Meier, D. Dietrich, A. Weichert, M. Suter Grotemeyer, M. Tegeder, and D. Rentsch. (2008). AtPTR1 and AtPTR5 transport dipeptides in planta. Plant Physiol. 148: 856-869.

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Liu, K.H. and Y.F. Tsay. (2003). Switching between the two action modes of the dual-affinity nitrate transporter CHL1 by phosphorylation. EMBO. J. 22: 1005-1013.

Liu, X.H., J.F. Zhao, T. Wang, and M.B. Wu. (2018). Design, identification, antifungal evaluation and molecular modeling of chlorotetaine derivatives as new anti-fungal agents. Nat Prod Res 1-9. [Epub: Ahead of Print]

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Martín, Y., F.J. Navarro, and J.M. Siverio. (2008). Functional characterization of the Arabidopsis thaliana nitrate transporter CHL1 in the yeast Hansenula polymorpha. Plant Mol. Biol. 68: 215-224.

Miyamoto, K.-I., T. Shiraga, K. Morita, H. Yamamoto, H. Haga, Y. Taketani, I. Tamai, Y. Sai, A. Tsuji, and E. Takeda. (1996). Sequence, tissue distribution and developmental changes in rat intestinal oligopeptide transporter. Biochim. Biophys. Acta 1305: 34-38.

Newstead, S., D. Drew, A.D. Cameron, V.L. Postis, X. Xia, P.W. Fowler, J.C. Ingram, E.P. Carpenter, M.S. Sansom, M.J. McPherson, S.A. Baldwin, and S. Iwata. (2011). Crystal structure of a prokaryotic homologue of the mammalian oligopeptide-proton symporters, PepT1 and PepT2. EMBO. J. 30: 417-426.

Nour-Eldin, H.H., T.G. Andersen, M. Burow, S.R. Madsen, M.E. Jørgensen, C.E. Olsen, I. Dreyer, R. Hedrich, D. Geiger, and B.A. Halkier. (2012). NRT/PTR transporters are essential for translocation of glucosinolate defence compounds to seeds. Nature 488: 531-534.

Paulsen, I.T. and R.A. Skurray. (1994). The POT family of transport proteins. Trends in Biochem. Sci. 18: 404.

Pieri, M., C. Gan, P. Bailey, and D. Meredith. (2009). The transmembrane tyrosines Y56, Y91 and Y167 play important roles in determining the affinity and transport rate of the rabbit proton-coupled peptide transporter PepT1. Int J Biochem. Cell Biol. 41: 2204-2213.

Quistgaard, E.M., M. Martinez Molledo, and C. Löw. (2017). Structure determination of a major facilitator peptide transporter: Inward facing PepTSt from Streptococcus thermophilus crystallized in space group P3121. PLoS One 12: e0173126.

Romano, A., G. Kottra, A. Barca, N. Tiso, M. Maffia, F. Argenton, H. Daniel, C. Storelli, and T. Verri. (2005). High-affinity peptide transporter PEPT2 (SLC15A2) of the zebrafish Danio rerio: functional properties, genomic organization, and expression analysis. Physiol Gen. 24: 207-217.

Rubio-Aliaga, I., M. Boll, and H. Daniel. (2000). Cloning and Characterization of the Gene Encoding the Mouse Peptide Transporter PEPT2. Biochem. and Biophys. Research Communications 276: 734-741.

Saier, M.H., Jr., B.H. Eng, S. Fard, J. Garg, D.A. Haggerty, W.J. Hutchinson, D.L. Jack, E.C. Lai, H.J. Liu, D.P. Nusinew, A.M. Omar, S.S. Pao, I.T. Paulsen, J.A. Quan, M. Sliwinski, T.-T. Tseng, S. Wachi, and G.B. Young. (1999). Phylogenetic characterization of novel transport protein families revealed by genome analyses. Biochim. Biophys. Acta 1422: 1-56.

Segonzac, C., J.C. Boyer, E. Ipotesi, W. Szponarski, P. Tillard, B. Touraine, N. Sommerer, M. Rossignol, and R. Gibrat. (2007). Nitrate efflux at the root plasma membrane: identification of an Arabidopsis excretion transporter. Plant Cell. 19: 3760-3777.

Sharma, N., N.G. Aduri, A. Iqbal, B.K. Prabhala, and O. Mirza. (2016). Peptide Selectivity of the Proton-Coupled Oligopeptide Transporter from Neisseria meningitidis. J. Mol. Microbiol. Biotechnol. 26: 312-319.

Solcan N., Kwok J., Fowler PW., Cameron AD., Drew D., Iwata S. and Newstead S. (2012). Alternating access mechanism in the POT family of oligopeptide transporters. EMBO J. 31(16):3411-21.

Sreedharan, S., O. Stephansson, H.B. Schiöth, and R. Fredriksson. (2011). Long evolutionary conservation and considerable tissue specificity of several atypical solute carrier transporters. Gene 478: 11-18.

Steiner, H.-Y., F. Naider, and J.M. Becker. (1995). The PTR family: a new group of peptide transporters. Mol. Microbiol. 16: 825-834.

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Sugiura, M., M.N. Georgescu, and M. Takahashi. (2007). A nitrite transporter associated with nitrite uptake by higher plant chloroplasts. Plant Cell Physiol. 48: 1022-1035.

Sun, J. and N. Zheng. (2015). Molecular Mechanism Underlying the Plant NRT1.1 Dual-Affinity Nitrate Transporter. Front Physiol 6: 386.

Søndergaard, H.B., B. Brodin, and C.U. Nielsen. (2008). HPEPT1 is responsible for uptake and transport of Gly-Sar in the human bronchial airway epithelial cell-line Calu-3. Pflugers Arch 456(3): 611-622.

Tsay, Y.-F., J.I. Schroeder, K.A. Feldmann, and N.M. Crawford. (1993). The herbicide sensitivity gene CHL1 of Arabidopsis encodes a nitrate-inducible nitrate transporter. Cell 72: 705-713.

Verri, T., A. Barca, P. Pisani, B. Piccinni, C. Storelli, and A. Romano. (2016). Di- and tripeptide transport in vertebrates: the contribution of teleost fish models. J Comp Physiol B. [Epub: Ahead of Print]

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Vizcaíno, J.A., R.E. Cardoza, M. Hauser, R. Hermosa, M. Rey, A. Llobell, J.M. Becker, S. Gutiérrez, and E. Monte. (2006). ThPTR2, a di/tri-peptide transporter gene from Trichoderma harzianum. Fungal Genet Biol 43: 234-246.

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Zhao, Y., G. Mao, M. Liu, L. Zhang, X. Wang, and X.C. Zhang. (2014). Crystal structure of the E. coli peptide transporter YbgH. Structure 22: 1152-1160.

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Examples:

TC#NameOrganismal TypeExample
2.A.17.1.1Di- or tripeptide:H+ symporter Bacteria DtpT of Lactococcus lactis (P0C2U2)
 
2.A.17.1.2

The di/tripeptide:H+ symport permease, TppB (DtpA or YdgR) (transports di and tripeptides and peptidomimetics such as aminocephalosporins (Weitz et al., 2007).  The transporter has two alternate conformations, one of which is promoted by inhbitor binding (Bippes et al. 2013).

Bacteria

TppB of E. coli (P77304)

 
2.A.17.1.3The dipeptide/tripeptide:H+ symport permease, DtpB (YhiP) (transports glycyl-sarcosine (Gly-Sar) with low affinity (6mM) and the toxic dipeptide, alafosfalin (Harder et al., 2008)BacteriaDtpB of E. coli (P36837)
 
2.A.17.1.4

DtpD (YbgH) peptide transporter.  A projection structure at 19 Å resolution and a high resolution x-ray structure are available; Casagrande et al., 2009; Zhao et al. 2014). Glu21 is the only conserved proton-titratable amino acyl residue (among POTs) that is located in the central cavity, and it is critical for in vivo transport (Zhao et al. 2014).

Bacteria

DtpD of E. coli (P75742)

 
2.A.17.1.5

Peptide transporter, YjdL (preference for di-peptides) (Ernst et al., 2009; Gabrielsen et al., 2011; Jensen et al., 2011).  The motif, ExxERFxxYY has been shown to be involved in proton translocation, and the nearby K117 may play a dual role in protonation and substrate binding (Jensen et al. 2014).

Bacteria

YjdL of E. coli (P39276)

 
2.A.17.1.6

POT famiy di- and tri-peptide porter, DtpT. 3-d structures (PDB:24APS; 5MMT: 5D58' 5D59) are available for an inward open conformation. A hinge-like movement in the C-terminal half facilitates opening of an intracellular gate controlling access to a central peptide binding site. Salt bridges may orchestrate alternating access (Solcan et al., 2012; Quistgaard et al. 2017).

Bacteria

Peptide porter, DtpT of Streptococcus thermophilus (Q5M4H8)

 
2.A.17.1.7

Peptide uptake transporter of 496 aas, POT.  The 3-d structure has been determined to 1.9Å resolution leading to a proposed mechanism (Doki et al. 2013).  Glu310 first may bind the carboxyl group of the peptide substrate. Then deprotonation of Glu310 in the inward open state triggers the release of the bound peptide toward the intracellular space, and salt bridge formation between Glu310 and Arg43 induces the transition state to the occluded conformation.

Firmicutes

POT of Geobacillus kaustophilus

 
2.A.17.1.8

Proton-coupled oligopeptide uptake transporter of 485 aas and 14 TMSs, DtpT or Pot.  Expression of the encoded gene is upregulated upon infection. Transports di- and tripeptides but can not accumulate peptides with a positively charged residue in the C-terminal position.  An aromatic residue patch in the active site of the transporter may be responsible for it's unusual specificity (Sharma et al. 2016).

DtpT of Neisseria meningitidis

 
Examples:

TC#NameOrganismal TypeExample
2.A.17.2.1Peptide:H+ symporter Plants PTR2-A of Arabidopsis thaliana
 
2.A.17.2.2Peptide:H+ symporter (dipeptides preferred; Cai et al., 2007).Yeast PTR2 of Saccharomyces cerevisiae
 
2.A.17.2.3

Dipeptide uptake porter, Ptr2.  Transports dipeptides such as Ala-Leu, Ala-Tyr and Tyr-Ala (Belmondo et al. 2014).

Fungi

Ptr2 of Rhizophagus irregularis (Arbuscular mycorrhizal fungus) (Glomus intraradices)

 
2.A.17.2.4

Di- and tripeptide uptake transporter, Ptr2 of 577 aas and 12 TMSs. The ptr2 gene showed increased expression upon interaction with the plant-pathogenic fungus Botrytis cinerea, suggesting that it is involved in the mycoparasitic process. Its expression was triggered by nitrogen starvation (Vizcaíno et al. 2006).

Ptr2 of Trichoderma harzianum (Hypocrea lixii)

 
2.A.17.2.5

Oligopeptide transporter of 576 aas and 12 TMSs, PTR22. Transports a variety of peptides as well as derivatives of antifungal agents, such as chlorotetaine and lysyl-cholortetaine (Liu et al. 2018).

PTR22 of Candida albicans (Yeast)

 
Examples:

TC#NameOrganismal TypeExample
2.A.17.3.1

Dual affinity Nitrate/Chlorate symporter, Nrt1.1; CHL1 (Martin et al., 2008).  The low affinity form is a homo-dimer and has Thr101 in the non-phosphorylated form; the high affinty form (0.1 micromolar Km) is a monomer and has Thr101 phosphorylated (Sun and Zheng 2015).

Plants

Ntr1.1/CHL1 of Arabidopsis thaliana

 
2.A.17.3.10

solute carrier family 15, member 5.  Function unknown as of 1/17, but probably a di- and tri-peptide uptake porter (Verri et al. 2016). The tissue expression profile has been reported (Sreedharan et al. 2011).

 

Animals

SLC15A5 of Homo sapiens

 
2.A.17.3.11

Solute carrier family 15 member 4 (Peptide transporter 4) (Peptide/histidine transporter 1) (hPHT1) present in immune cells (Verri et al. 2016).

Animals

SLC15A4 of Homo sapiens

 
2.A.17.3.12Putative peptide/nitrate transporter At3g25280PlantsAt3g25280 of Arabidopsis thaliana
 
2.A.17.3.13Probable peptide transporter At1g52190PlantsAt1g52190 of Arabidopsis thaliana
 
2.A.17.3.14Nitrate transporter 1.6PlantsNRT1.6 of Arabidopsis thaliana
 
2.A.17.3.15Nitrate transporter 1.7PlantsNRT1.7 of Arabidopsis thaliana
 
2.A.17.3.16

Nitrate transporter 1.2 (Nitrate transporter NTL1).  Low-affinity proton-dependent nitrate transporter involved in constitutive nitrate uptake but not histidine or dipeptides transport. Involved in (+)-abscisic acid (ABA) transport, but not in gibberellin, indole-3-acetic acid or jasmonic acid import (Kanno et al. 2013).

Plants

NRT1.2 of Arabidopsis thaliana

 
2.A.17.3.17

Transporter for glucosinolates (aliphatic but not indole glucosinolates such as 4-methylthiobutyl glucosinolate, major defence compounds, translocated to seeds on maturation) as well as gibberellic acid and jasmonoyl-L-isoleucine, GTR1 or NPF2.10, of 636 aas and 12 TMSs (Nour-Eldin et al. 2012; Ishimaru et al. 2017). Regulated at the transcriptional level, but also postranslationally.  Dimerization of GTR1, possibly induced by dephosphorylation of a Thr residue, regulates its plasma membrane localization, leading to increased transport of glucosinolates and gibberellic acid (Ishimaru et al. 2017).

Plants

GTR1 of Arabidopsis thaliana

 
2.A.17.3.18Nitrate transporter 1.4PlantsNRT1.4 of Arabidopsis thaliana
 
2.A.17.3.19Nitrate transporter 1.5PlantsNRT1.5 of Arabidopsis thaliana
 
2.A.17.3.2Histidine or peptide:H+ symporter Plants PTR2-B (NTR1) of Arabidopsis thaliana
 
2.A.17.3.20

High-affinity, proton-dependent glucosinolate-specific transporter-2, GTP2 or NPF2.11. Involved in apoplasmic phloem-loading of glucosinolates and in bidirectional long-distance transport of aliphatic but not indole glucosinolates. May be involved in removal of glucosinolates from the xylem in roots (Nour-Eldin et al. 2012; Andersen et al. 2013).

Plants

GTR2 of Arabidopsis thaliana

 
2.A.17.3.21

Low affinity nitrate transporter, Nrt1, of 584 aas and 13 putative TMSs.  Two splice variants, Ntr1.1a and Ntr1.1b, have been identified.  Under low nitrogen condition, Nrt1.1b accumulates more nitrogen in plants and improves rice growth, but Ntr1.1a had no such effect (Fan et al. 2015).

Ntr1 of Oryza sativa (Rice)

 
2.A.17.3.22

Uncharacterized peptide transport protein of 609 aas and 12 TMSs, PTR3-A.

PTR3-

aof Aegilops tauschii (Tausch's goatgrass) (Aegilops squarrosa)

 
2.A.17.3.3Nitrate (chlorate) or histidine:H+ symporter Plants RCH2 of Brassica napus
 
2.A.17.3.4Peptide transporter, PTR3-A (induced by histidine, leucine and phenylalanine in cotyledons and lower leaves; involved in stress tolerance in seeds during germination and in defense against virulent bacterial pathogens) (Karim et al., 2007; Karim et al., 2005)PlantsPTR3-A of Arabidopsis thaliana (Q9FNL7)
 
2.A.17.3.5The nitrate excretion transporter1, NaxT1 (in the plasma membranes of plant cells)PlantsNaxT1 of Arabidopsis thaliana (Q9M1E2)
 
2.A.17.3.6Chloroplast nitrite uptake system, Nitr1-L (Sugiura et al., 2007)PlantsNitr1-L of Arabidopsis thaliana (Q9SX20)
 
2.A.17.3.7

The root dipeptide/tripeptide transporter, PTRI (Komarova et al., 2008). Transport is electrogenic and dependent on protons. Leak currents are inhibited by Phe-Ala when this peptide binds at the active site with high affinity (Hammes et al., 2010).

Plants

PTR1 of Arabidopsis thaliana (Q9M390)

 
2.A.17.3.8

The germinating pollen dipeptide/tripeptide transporter, PTR5 (Komarova et al., 2008). Transport is electrogenic and dependent on protons. Leak currents are inhibited by Phe-Ala when this peptide binds at the active site with high affinity (Hammes et al., 2010).

Plants

PTR5 of Arabidopsis thaliana (Q0WR84)

 
2.A.17.3.9

solute carrier family 15, member 3, di- and tri-peptide uptake transporter in immune cells (Verri et al. 2016).

Animals

SLC15A3 of Homo sapiens

 
Examples:

TC#NameOrganismal TypeExample
2.A.17.4.1

Peptide:H+ symporter (transports cationic, neutral and anionic dipeptides including glycylsarcosine (gly-sar) (Søndergaard et al., 2008) as well as anserine (β-alanyl-1-N-methyl-L-histidine) and carnosine (β-alanyl-L-histidine) (Geissler et al., 2010); also transports β-lactam antibiotics, the antitumor agent, bestatin, and various protease inhibitors). It is competitively inhibited by L-4,4'-biphenylalanyl-L-proline (Bip-Pro) with ~10-20µM affinity. Inhibitors/substrates include cefadroxil, Ala-4-nitroanilide and δ-aminolevulinic acid (Knutter et al., 2007). The intracellular loop linking transmembrane domains 6 and 7 of the human dipeptide transporter hPEPT1 includes two amphipathic alpha-helices, with net positive and negative charges which interact and influence conformational changes of hPEPT1 during and after glycylsarcosine transport (Xu et al., 2010).  The rabbit orthologue provides the main pathway for dietary nitrogen uptake. Five tyrosyl residues are important for function and/or substrate binding (Pieri et al. 2009).  Human PepT1 is modified by N-glycosylation, and all six asparagine residues in the large extracellular loop between transmembrane domains 9 and 10 are subject to N-glycosylation (Chan et al. 2016).

Animals

PepT1 of Rattus norvegicus

 
2.A.17.4.10Peptide transporter 3 (Oligopeptide transporter 3)WormPept-3 of Caenorhabditis elegans
 
2.A.17.4.11

Peptide transporter, Pep1, also called CptB, Opt-2 and Pep-2.  It is of 835 aas and 11 TMSs.  It transports di-, tri- and tetra-peptides including phenylalanylmethionylarginylphenylalaninamide (FMRFamide) and N-acetylaspartylglutamate, both neuropeptides found throughout the animal kingdom. In contrast to CptA (TC# 2.A.17.4.3), CptB has low-affinity for its substrates (Fei et al. 1998).

CptB of Caenorhabditis elegans

 
2.A.17.4.2Oligopeptide transporter 1 Animals Oligopeptide transporter of Drosophila melanogaster
 
2.A.17.4.3

High affinity oligopeptide transporter, CPTA. It transports di-, tri- and tetra peptides with low specificity. Neuropeptides (FMRF-amide and N-acetyl-Asp-Glu) are also transported (Fei et al. 1998).

Animals

CPTA of Caenorhabditis elegans

 
2.A.17.4.4The renal brush-border electrogenic, proton-coupled, broad specificity, high affinity, peptide transporter, PepT2 (Rubio-Aliaga et al., 2000). It is competitively inhibited by L-4,4'-Biphenylalanyl-L-Proline (Bip-Pro) with ~10-20µM affinity. Inhibitor/substrates includes cefadroxil, Ala-4-nitroanilide and delta-aminolevulinic acid (Knutter et al., 2007).AnimalsPepT2 of Mus musculus (Q9ES07)
 
2.A.17.4.5The high affinity, low capacity, peptide transporter, PepT2 (SLC15A2) [affinity for glycyl-L-glutamine=18μM] (Romano et al., 2006)AnimalsPepT2 of Danio rerio (NP_0010349)
 
2.A.17.4.6

Oligopeptide transporter, PepT1 (Slc15A1b) (Bucking and Schulte, 2012) (expressed in freshwater acclimated fish)

Animals

PepT1b of Fundulus heteroclitus (H2DJV9)

 
2.A.17.4.7

Di-/Tri-peptide porter. 3-d structure (PDB: 2XUT) known revealing a probable alternating access mechanism of transport (Newstead et al., 2011).  A second structure shows the protein in an inward open conformation with the peptidommetic, alafosfalin, bound (Guettou et al. 2013). Appears to take up glutathione (Deutschbauer et al. 2011).

Bacteria

Di-/Tri-peptide permease of Shewanella oneidensis (Q8EKT7)

 
2.A.17.4.8

Solute carrier family 15 member 2 (Kidney H+:peptide cotransporter) (Oligopeptide transporter, kidney isoform) (Peptide transporter 2, PEPT2) (Verri et al. 2016). Transports opioid peptides (Ganapathy and Miyauchi 2005).

Animals

SLC15A2 of Homo sapiens

 
2.A.17.4.9

Solute carrier family 15 member 1 (Intestinal H+:peptide cotransporter) (Oligopeptide transporter, small intestine isoform) (Peptide transporter 1, PepT1).  Takes up oligopeptides of 2 to 4 amino acids with a preference for dipeptides, a major route for the absorption of protein digestion end-products. PepT1 is modified by N-glycosylation, and all six asparagine residues in the large extracellular loop between TMSs 9 and 10 are subject to N-glycosylation.  This allows proper association with the plasma membrane and/or stabilization (Chan et al. 2016). Transports opioid peptides (Ganapathy and Miyauchi 2005), can serve as a druh importer and plays a role in inflammatory bowel diseases (Viennois et al. 2018).

Animals

PepT1 of Homo sapiens