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SLC36A1 Membrane Protein Introduction

Introduction of SLC36A1

Proton-coupled amino acid transporter 1 (hPAT1), also known as Solute carrier family 36 member 1 (SLC36A1), is a protein that in humans is encoded by the SLC36A1 gene. SLC36A1 functions as H+-coupled amino acid symporters. SLC36A1 is expressed at the luminal surface of the small intestine and is also commonly found in lysosomes of many cell types, including neurons. It is a multipurpose vector that has different roles in different cells, including absorption in the small intestine and as a pathway for efflux after intralysosomal protein breakdown. SLC36A1 has a relatively low affinity for its substrates, including imino acids and zwitterionic amino acids, heterocyclic amino acids and amino acid-based drugs. It is experimentally and/or clinically used to treat bacterial infections, schizophrenia, epilepsy, cancer, and hyperglycemia.

Basic Information of SLC36A1
Protein Name Proton-coupled amino acid transporter 1
Gene Name SLC36A1
Aliases Proton/amino acid transporter 1, hPAT1, Solute carrier family 36 member 1, PAT1
Organism Homo sapiens (Human)
UniProt ID Q7Z2H8
Transmembrane Times 11
Length (aa) 476
Sequence MSTQRLRNEDYHDYSSTDVSPEESPSEGLNNLSSPGSYQRFGQSNSTTWFQTLIHLLKGNIGTGLLGLPLAVKNAGIVMGPISLLIIGIVAVHCMGILVKCAHHFCRRLNKSFVDYGDTVMYGLESSPCSWLRNHAHWGRRVVDFFLIVTQLGFCCVYFVFLADNFKQVIEAANGTTNNCHNNETVILTPTMDSRLYMLSFLPFLVLLVFIRNLRALSIFSLLANITMLVSLVMIYQFIVQRIPDPSHLPLVAPWKTYPLFFGTAIFSFEGIGMVLPLENKMKDPRKFPLILYLGMVIVTILYISLGCLGYLQFGANIQGSITLNLPNCWLYQSVKLLYSIGIFFTYALQFYVPAEIIIPFFVSRAPEHCELVVDLFVRTVLVCLTCILAILIPRLDLVISLVGSVSSSALALIIPPLLEVTTFYSEGMSPLTIFKDALISILGFVGFVVGTYEALYELIQPSNAPIFINSTCAFI

Function of SLC36A1 Membrane Protein

In addition to rheogenic H+/zwitterionic amino acid transport, SLC36A1 can also act as an electroneutral transport system for H+ and fatty acids including acetate, propionate, and butyrate. Low-affinity, high-capacity, transport characteristics, and relatively broad substrate specificity identify SLC36A1 as a potential pathway for transport of orally delivered hydrophilic amino acid-based drugs across the luminal surface of the human small intestinal wall, which is the initial barrier to effective drug delivery. SLC36A1 is considered to be involved in the control of growth and proliferation.

The H+-coupled amino acid transporter PAT1 (SLC36A1) can transport a number of compounds with potential therapeutic value (shown in blue). Fig.1 The H+-coupled amino acid transporter PAT1 (SLC36A1) can transport a number of compounds with potential therapeutic values (shown in blue). (Thwaites, 2011)

Application of SLC36A1 Membrane Protein in Literature

  1. Jensen A., et al. PAT1 (SLC36A1) shows nuclear localization and affects growth of smooth muscle cells from rats. Am J Physiol Endocrinol Metab. 2014, 306(1): E65-74. PubMed ID: 24222668

    The article investigates the localization and function of PAT1 in smooth muscle cells (SMCs). Knockdown of PAT1 led to induced cellular growth, suggesting a role of PAT1 in regulating cellular proliferation of SMCs.

  2. Holm R., et al. Rectal absorption of vigabatrin, a substrate of the proton coupled amino acid transporter (PAT1, Slc36a1), in rats. Pharm Res. 2010, 29(4): 1134-42. PubMed ID: 22234618

    The article reports that although vigabatrin is a PAT1 substrate and the rPAT1 protein is expressed in the rectum epithelium, the rectal absorption of vigabatrin in rats is low.

  3. Frølund S., et al. Gaboxadol has affinity for the proton-coupled amino acid transporter 1, SLC36A1 (hPAT1)-A modelling approach to determine IC(50) values of the three ionic species of gaboxadol. Eur J Pharm Sci. 2011, 42(3): 192-8. PubMed ID: 21112392

    The article indicates that Gaboxadol has an affinity for the proton-coupled amino acid transporter 1, SLC36A1, and the positive charge is essential for Gbx binding to SLC36A1.

  4. Frølund S., et al. Delta-aminolevulinic acid is a substrate for the amino acid transporter SLC36A1 (hPAT1). Br J Pharmacol. 2010, 159(6): 1339-53. PubMed ID: 20128809

    The article reveals that ALA is a substrate for SLC36A1, and the apical absorption in Caco-2 cell is only mediated by SLC36A1 and SLC15A1.

  5. Frølund S., et al. Intestinal drug transport via the proton-coupled amino acid transporter PAT1 (SLC36A1) is inhibited by Gly-X(aa) dipeptides. Mol Pharm. 2012, 9(9): 2761-9. PubMed ID: 22853447

    Authors in this group identify the selected dipeptides as inhibitors of PAT1 mediated drug uptake in various in vitro models.

SLC36A1 Preparation Options

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Reference

  1. Thwaites D T and Anderson C M. (2011). The SLC36 family of proton-coupled amino acid transporters and their potential role in drug transport. Br J Pharmacol. 164(7): 1802-16.

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