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Genomic structure of proton-coupled oligopeptide transporter hPEPT1 and pH-sensing regulatory splice variant

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Abstract

Proton-coupled oligopeptide transporter PEPT1 facilitates the transport of dipeptides and peptoid drugs (including antibiotics) across the cell membranes of endothelial and epithelial cells. Substrate transport by the proton symport is driven by pH gradients, while the profile of pH sensitivity is regulated by a closely related protein. hPEPT1-RF. We investigated the genomic structure of hPEPT1 and hPEPT1-RF. Analysis of the high-throughput genomic sequence (HTGS) database revealed that hPEPT1 and hPEPT1-RF are splice variants encoded by the same gene located in chromosome 13, consisting of 24 exons. hPEPT1 is encoded by 23 exons and hPEPT1-RF by 6 exons. Coding sequences of hPEPT1-RF share 3 exons completely and 2 exons partially with hPEPT1. The genomic organization of hPEPT1 shows high similarity with its mouse orthologue. Exon-intron boundaries occur mostly in the loops connecting transmembrane segments (TMSs), suggesting a modular gene structure reflecting the TMS-loop repeat units in hPEPT1. The putative promoter region of hPEPT1 contains TATA boxes and GC-rich regions and a potential insulin responsive element.

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Authors and Affiliations

  1. Department of Biopharmaceutical Sciences, University of California San Francisco, 513 Pamassus Avenue, 94143-0446, San Francisco, CA

    Arto Urttiac Ph.D. & Wolfgang Sadée

  2. Department of Pharmaceutics, University of Kuopio, POB 1627, 70211, Kuopio, Finland

    Arto Urttiac Ph.D.

  3. Sequence Analysis & Consulting Service, Computer Graphics Laboratory, Department of Pharmaceutical Chemistry, University of California San Francisco, 513 Parnassus Ave, 94143-0446, San Francisco, CA

    Susan Jean Johns

Authors
  1. Arto Urttiac Ph.D.
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  2. Wolfgang Sadée
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  3. Susan Jean Johns
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Correspondence to Arto Urttiac Ph.D..

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Published: February 6, 2000.

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Urttiac, A., Sadée, W. & Johns, S.J. Genomic structure of proton-coupled oligopeptide transporter hPEPT1 and pH-sensing regulatory splice variant. AAPS PharmSci 3, 6 (2001). https://doi.org/10.1208/ps030106

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  • DOI: https://doi.org/10.1208/ps030106

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