2.A.17 The Proton-dependent Oligopeptide Transporter (POT) 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. Some members of the POT family exhibit limited sequence similarity to protein members of the major facilitator superfamily (MFS; TC #2.A.1). Thus the POT family is a family within the MFS. 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. 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:
Chen, X.-Z., T. Zhu, D.E. Smith, and M.A. Hediger. (1999). Stoichiometry and kinetics of the high-affinity H⁺-coupled peptide transporter PepT2. J. Biol. Chem. 274: 2773-2779.
Covitz, K.-M.Y., G.L. Amidon, and W. Sadée. (1998). Membrane topology of the human dipeptide transporter, hPEPT1, determined by epitope insertions. Biochemistry 37: 15214-15221.
Daniel, H. (1996). Function and molecular structure of brush border membrane peptide/H⁺ symporters. J. Membr. Biol. 154: 197-203.
Döring, F., J. Will, S. Amasheh, W. Clauss, H. Ahlbrecht, and H. Daniel. (1998). Minimal molecular determinants of substrates for recognition by the intestinal peptide transporter. J. Biol. Chem. 273: 23211-23218.
Fang, G., W.N. Konings, and B. Poolman. (2000). Kinetics and substrate specificity of membrane-reconstituted peptide transporter DtpT of Lactococcus lactis. J. Bacteriol. 182: 2530-2535.
Fei, Y.-J., T. Fujita, D.F. Lapp, V. Ganapathy, and F.H. Leibach. (1998). Two oligopeptide transporters from Caenorhabditis elegans: molecular cloning and functional expression. Biochem. J. 322: 565-572.
Frommer, W.B., S. Hummel, and D. Rentsch. (1994). Cloning of an Arabidopsis histidine transporting protein related to nitrate and peptide transporters. FEBS Lett. 347: 185-189.
Hagting, A., E.R.S. Kunji, K.J. Leenhouts, B. Poolman, and W.N. Konings. (1994). The di- and tripeptide transport protein of Lactococcus lactis. J. Biol. Chem. 269: 11391-11399.
Hagting, A., J.v.d. Velde, B. Poolman and W.N. Konings (1997). Membrane topology of the di- and tripeptide transport protein of Lactococcus lactis. Biochemistry 36: 6777-6785.
Kottra, G., A. Stamfort, and H. Daniel. (2002). PEPT1 as a paradigm for membrane carriers that mediate electrogenic bidirectional transport of anionic, cationic, and neutral substrates. J. Biol. Chem. 277: 32683-32691.
Leibach, F.H. and V. Ganapathy. (1996). Peptide transporters in the intestine and the kidney. Annu. Rev. Nutr. 16: 99-119.
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.
Paulsen, I.T. and R.A. Skurray. (1994). The POT family of transport proteins. Trends in Biochem. Sci. 18: 404.
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.
Steiner, H.-Y., F. Naider, and J.M. Becker. (1995). The PTR family: a new group of peptide transporters. Mol. Microbiol. 16: 825-834.
Steiner, H.-Y., W. Song, L. Zhang, F. Naider, J.M. Becker, and G. Stacey. (1994). An arabidopsis peptide transporter is a member of a new class of membrane transport proteins. Plant Cell 6: 1289-1299.
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.
Zhou, J.-J., F.L. Theodoulou, I. Muldin, B. Ingemarsson, and A.J. Miller. (1998). Cloning and functional characterization of a Brassica napus transporter that is able to transport nitrate and histidine. J. Biol.Chem. 273: 12017-12023.
Zhou, X., M. Thamotharan, A. Gangopadhyay, C. Serdikoff, and S.A. Adibi. (2000). Characterization of an oligopeptide transporter in renal lysosomes. Biochim. Biophys. Acta 1466: 372-378.
Examples:
TC#	Name	Organismal Type	Example
2.A.17.1.1	Di- or tripeptide:H⁺ symporter	Bacteria	DtpT of Lactococcus lactis

2.A.17.2.1	Peptide:H⁺ symporter	Plants	PTR2-A of Arabidopsis thaliana

2.A.17.2.2	Peptide:H⁺ symporter	Yeast	PTR2 of Saccharomyces cerevisiae

2.A.17.3.1	Nitrate (chlorate):H⁺ symporter	Plants	CHL1 of Arabidopsis thaliana

2.A.17.3.2	Histidine or peptide:H⁺ symporter	Plants	PTR2-B (NTR1) of Arabidopsis thaliana

2.A.17.3.3	Nitrate (chlorate) or histitine:H⁺ symporter	Plants	RCH2 of Brassica napus

2.A.17.4.1	Peptide:H⁺ symporter (transports cationic, neutral and anionic dipeptides; also transports β-lactam antibiotics, the antitumor agent, bestatin, and various protease inhibitors)	Animals	PepT1 of Rattus norvegicus

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

2.A.17.4.3	High affinity oligopeptide transporter, CPTA (transports di-, tri- and tetra peptides with low specificity. Neuropeptides (FMRF-amide and N-acetyl-Asp-Glu) are also transported)	Animals	CPTA of Caenorhabditis elegans