Peptide transporter 4 | SLC15 family of peptide transporters | IUPHAR/BPS Guide to PHARMACOLOGY

Peptide transporter 4

Target id: 987

Nomenclature: Peptide transporter 4

Abbreviated Name: PHT1

Systematic Nomenclature: SLC15A4

Family: SLC15 family of peptide transporters

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Peptide transporter 4 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - - SLC15A4 solute carrier family 15 member 4
Mouse - - Slc15a4 solute carrier family 15, member 4
Rat - - Slc15a4 solute carrier family 15 member 4
Previous and Unofficial Names
PHT1 | solute carrier family 15 member 4 | Peptide/histidine transporter 1 | solute carrier family 15 (oligopeptide transporter), member 4 | solute carrier family 15
Database Links
Specialist databases
Bioparadigms SLC Tables SLC15A4 (Hs)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
Substrates and Reaction Kinetics
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
muramyl dipeptide Hs - - 5
His-Leu-lopinavir Hs - - 4
glycyl-sarcosine Hs - - 1-2,8
MDP-rhodamine Hs - - 5
Tri-DAP Hs - - 3,6
C12-iE-DAP Hs - - 3
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[14C]histidine Hs Binding - - 9-10
[3H]histidine Hs - - - 1,4,8-9
Immunopharmacology Comments
SLC15A4 is an oligopeptide transporter that is expressed in early endosomes, and which is involved in NOD1-dependent NF-κB signaling [3]. SLC15A3 and SLC15A4 are preferentially expressed by cells within the lymphatic system, including dendritic cells. Expression of these two genes is upregulated in response to TLR stimulation [5,7].
Cell Type Associations
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
References:  5
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS


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1. Bhardwaj RK, Herrera-Ruiz D, Eltoukhy N, Saad M, Knipp GT. (2006) The functional evaluation of human peptide/histidine transporter 1 (hPHT1) in transiently transfected COS-7 cells. Eur J Pharm Sci, 27 (5): 533-42. [PMID:16289537]

2. Hu Y, Xie Y, Keep RF, Smith DE. (2014) Divergent developmental expression and function of the proton-coupled oligopeptide transporters PepT2 and PhT1 in regional brain slices of mouse and rat. J. Neurochem., 129 (6): 955-65. [PMID:24548120]

3. Lee J, Tattoli I, Wojtal KA, Vavricka SR, Philpott DJ, Girardin SE. (2009) pH-dependent internalization of muramyl peptides from early endosomes enables Nod1 and Nod2 signaling. J. Biol. Chem., 284 (35): 23818-29. [PMID:19570976]

4. Mandal A, Pal D, Mitra AK. (2016) Circumvention of P-gp and MRP2 mediated efflux of lopinavir by a histidine based dipeptide prodrug. Int J Pharm, 512 (1): 49-60. [PMID:27543355]

5. Nakamura N, Lill JR, Phung Q, Jiang Z, Bakalarski C, de Mazière A, Klumperman J, Schlatter M, Delamarre L, Mellman I. (2014) Endosomes are specialized platforms for bacterial sensing and NOD2 signalling. Nature, 509 (7499): 240-4. [PMID:24695226]

6. Sasawatari S, Okamura T, Kasumi E, Tanaka-Furuyama K, Yanobu-Takanashi R, Shirasawa S, Kato N, Toyama-Sorimachi N. (2011) The solute carrier family 15A4 regulates TLR9 and NOD1 functions in the innate immune system and promotes colitis in mice. Gastroenterology, 140 (5): 1513-25. [PMID:21277849]

7. Song F, Yi Y, Li C, Hu Y, Wang J, Smith DE, Jiang H. (2018) Regulation and biological role of the peptide/histidine transporter SLC15A3 in Toll-like receptor-mediated inflammatory responses in macrophage. Cell Death Dis, 9 (7): 770. [PMID:29991810]

8. Tai W, Chen Z, Cheng K. (2013) Expression profile and functional activity of peptide transporters in prostate cancer cells. Mol. Pharm., 10 (2): 477-87. [PMID:22950754]

9. Wang XX, Hu Y, Keep RF, Toyama-Sorimachi N, Smith DE. (2017) A novel role for PHT1 in the disposition of l-histidine in brain: In vitro slice and in vivo pharmacokinetic studies in wildtype and Pht1 null mice. Biochem. Pharmacol., 124: 94-102. [PMID:27845049]

10. Yamashita T, Shimada S, Guo W, Sato K, Kohmura E, Hayakawa T, Takagi T, Tohyama M. (1997) Cloning and functional expression of a brain peptide/histidine transporter. J. Biol. Chem., 272 (15): 10205-11. [PMID:9092568]


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How to cite this page

David T. Thwaites, Tiziano Verri.
SLC15 family of peptide transporters: Peptide transporter 4. Last modified on 30/07/2018. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY,