SLC15A1: Solute Carrier Family 15 Member 1 (Peptide Transporter 1)
Key intestinal proton-coupled oligopeptide transporter for dietary protein absorption and drug delivery.
Gene Information Card
| Symbol | SLC15A1 |
|---|---|
| Full Name | Solute Carrier Family 15 Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 13q33.3 |
| NCBI Gene ID | 6564 ncbi.nlm.nih.gov/gene/6564 |
| Ensembl ID | ENSG00000137857 |
| UniProt ID | P46059 |
| OMIM ID | 600544 |
| HGNC ID | 10920 |
| Aliases | PEPT1, HPECT1, PEPT-1, HPEPT1 |
Description
SLC15A1 encodes the proton-coupled oligopeptide transporter 1 (PEPT1), a transmembrane protein primarily expressed in the small intestine and kidney. It mediates the electrogenic uptake of di- and tripeptides from the intestinal lumen into enterocytes, driven by an inward proton gradient. PEPT1 also transports a wide range of peptidomimetic drugs, including beta-lactam antibiotics, ACE inhibitors, and antiviral prodrugs, making it a critical determinant of oral drug bioavailability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory Bowel Disease (IBD) | Altered PEPT1 expression in colonic epithelium may contribute to aberrant peptide and bacterial product uptake, promoting inflammation. | NCBI Gene, OMIM |
| Cystinuria | Defective renal reabsorption of cystine due to impaired peptide transport; SLC15A1 variants may modify disease severity. | OMIM |
| Type 2 Diabetes | PEPT1-mediated dipeptide transport influences incretin hormone secretion (GLP-1) and glucose homeostasis. | NCBI Gene |
| Drug-induced nephrotoxicity | Renal PEPT1 reabsorbs nephrotoxic peptidomimetic drugs (e.g., cephalosporins), contributing to accumulation. | UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small Intestine | 78.5 | High |
| Kidney | 42.3 | Medium |
| Liver | 12.1 | Low |
| Pancreas | 8.9 | Low |
| Colon | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 | 85.2 | Intestinal epithelial model; high PEPT1 expression |
| HEK293 | 2.1 | Low endogenous expression; used for heterologous expression |
| HepG2 | 1.8 | Hepatocellular carcinoma; low expression |
| MDCK | 0.9 | Canine kidney; low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1177C>T (p.Arg393Cys) | Missense | 0.0004 (gnomAD) | Reduced transport activity for dipeptides; associated with altered drug absorption |
| c.1498G>A (p.Val500Ile) | Missense | 0.0012 (gnomAD) | Decreased affinity for cephalexin; potential impact on antibiotic bioavailability |
| c.68C>T (p.Pro23Leu) | Missense | 0.0008 (gnomAD) | Reduced cell surface expression; loss-of-function |
Mutation functional classification
Loss of Function (LOF)
p.Pro23Leu and p.Arg393Cys reduce transport activity or membrane expression, impairing peptide and drug uptake.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SLC15A1.
Dominant Negative (DN)
No evidence of dominant-negative effects; SLC15A1 functions as a monomer.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005215 - transporter activity | • GO:0015293 - symporter activity |
| • GO:0015321 - oligopeptide transmembrane transporter activity | • GO:0015886 - dipeptide transport |
| • GO:0015887 - tripeptide transport | • GO:0016324 - apical plasma membrane |
| • GO:0005887 - integral component of plasma membrane | • GO:0006857 - oligopeptide import across plasma membrane |
Pathways
• Proton-coupled oligopeptide transport (REACTOME R-HSA-8878168)
• Absorption of di- and tripeptides (KEGG hsa04976)
• Drug transport (KEGG hsa00982)
Protein Summary
PEPT1 is a 708-amino acid integral membrane protein with 12 transmembrane domains. It functions as an electrogenic symporter, coupling the inward movement of one proton with the uptake of one di- or tripeptide. The protein is N-glycosylated and localizes to the apical membrane of enterocytes and renal proximal tubule cells. Its broad substrate specificity includes over 400 dipeptides, tripeptides, and numerous peptidomimetic drugs. Structural studies reveal a central substrate-binding pocket with key residues (e.g., His57, Tyr167, Arg282) critical for proton coupling and substrate recognition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC15A1 Knockout Caco-2 Cell Line | EDJ-KQ10 | Human | 6564 | Details Get a Quote |
| SLC15A1 Knockout HEK293 Cell Line | EDJ-KQ5038 | Human | 6564 | Details Get a Quote |
| SLC15A1 Knockout HCT 116 Cell Line | EDJ-KQ29205 | Human | 6564 | Details Get a Quote |
| SLC15A1 Knockout HeLa Cell Line | EDJ-KQ18244 | Human | 6564 | Details Get a Quote |
| SLC15A1 Knockout A-549 Cell Line | EDJ-KQ62995 | Human | 6564 | Details Get a Quote |
| SLC15A1 Knockout Huh-7 Cell Line | EDC07819 | Human | 6564 | Details Get a Quote |
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