Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT8QKNP)

• DTP Name: Peptide transporter 2 (SLC15A2)
• Gene Name: SLC15A2
• UniProt ID: Q16348 (S15A2_HUMAN)
• VARIDT ID: DTD0022
• Synonyms: Kidney H(+)/peptide cotransporter; Oligopeptide transporter, kidney isoform; PEPT2; SLC15A2; Solute carrier family 15 member 2
• DTP Family: Proton-Dependent Oligopeptide Transporter (POT/PTR) Family
• Tissue Specificity: Expressed in kidney. Not detected inintestine.
• Sequence:
  MNPFQKNESKETLFSPVSIEEVPPRPPSPPKKPSPTICGSNYPLSIAFIVVNEFCERFSY
  YGMKAVLILYFLYFLHWNEDTSTSIYHAFSSLCYFTPILGAAIADSWLGKFKTIIYLSLV
  YVLGHVIKSLGALPILGGQVVHTVLSLIGLSLIALGTGGIKPCVAAFGGDQFEEKHAEER
  TRYFSVFYLSINAGSLISTFITPMLRGDVQCFGEDCYALAFGVPGLLMVIALVVFAMGSK
  IYNKPPPEGNIVAQVFKCIWFAISNRFKNRSGDIPKRQHWLDWAAEKYPKQLIMDVKALT
  RVLFLYIPLPMFWALLDQQGSRWTLQAIRMNRNLGFFVLQPDQMQVLNPLLVLIFIPLFD
  FVIYRLVSKCGINFSSLRKMAVGMILACLAFAVAAAVEIKINEMAPAQPGPQEVFLQVLN
  LADDEVKVTVVGNENNSLLIESIKSFQKTPHYSKLHLKTKSQDFHFHLKYHNLSLYTEHS
  VQEKNWYSLVIREDGNSISSMMVKDTESRTTNGMTTVRFVNTLHKDVNISLSTDTSLNVG
  EDYGVSAYRTVQRGEYPAVHCRTEDKNFSLNLGLLDFGAAYLFVITNNTNQGLQAWKIED
  IPANKMSIAWQLPQYALVTAGEVMFSVTGLEFSYSQAPSSMKSVLQAAWLLTIAVGNIIV
  LVVAQFSGLVQWAEFILFSCLLLVICLIFSIMGYYYVPVKTEDMRGPADKHIPHIQGNMI
  KLETKKTKL
• Function: This tranporter mediates intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. Transports the dipeptide-like aminopeptidase inhibitor bestatin. Can also transport the aminocephalosporin antibiotic cefadroxil.
• Endogenous Substrate(s): Peptides
• TCDB ID: 2.A.17.4.8
• Gene ID: 6565
• Reactome Pathway: Proton/oligopeptide cotransporters (R-HSA-427975)

Molecular Interaction Atlas (MIA) of This DTP

23 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aminolevulinic acid hci	DMS4BLQ	Acne vulgaris	ED80	Approved	[3]
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[4]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[5]
Benazepril	DMH1M9B	Hypertension	BA00-BA04	Approved	[6]
Bestatin	DM8L9D4	Acute myeloid leukaemia	2A60	Approved	[7]
Cefaclor	DMJXDGC	Bacterial infection	1A00-1C4Z	Approved	[4]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[8]
Cefixime	DMY60I8	Acute gonococcal cervicitis		Approved	[5]
Cefradine	DMUNSWV	Acute otitis media	AB00	Approved	[5]
Ceftibuten	DMWV2AG	Acute otitis media	AB00	Approved	[5]
Cephalexin	DMD5JU8	Acute otitis media	AB00	Approved	[5]
Cyclacillin	DMHSJB4	Bacterial infection	1A00-1C4Z	Approved	[5]
Dicloxacillin	DM8EU0Z	Bacterial infection	1A00-1C4Z	Approved	[5]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[9]
Entecavir	DM7VTQO	Hepatitis B virus infection	1E51.0	Approved	[10]
Fosinopril	DM9NJ52	Chronic heart failure	BD1Z	Approved	[11]
Latamoxef	DMANL0D	Bacterial infection	1A00-1C4Z	Approved	[5]
Moexipril	DM26E4B	Hypertension	BA00-BA04	Approved	[6]
Perindopril	DMOPZDT	Hypertension	BA00-BA04	Approved	[6]
Ramipril	DM2R68E	Acute heart failure	BD10-BD13	Approved	[6]
Spirapril	DM5XLTY	Hypertension	BA00-BA04	Approved	[6]
Trandolapril	DM4L6EU	Chronic heart failure	BD1Z	Approved	[6]
Valaciclovir	DMHKS94	Genital herpes	1A94	Approved	[12]

1 Preclinical Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metampicillin	DMQW5MH	N. A.	N. A.	Preclinical	[5]

Molecular Expression Atlas (MEA) of This DTP

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	3.19E-04	2.87E-01	5.76E-01
Adrenocortical carcinoma	2D11.Z	Kidney	1.85E-01	-1.52E-01	-6.54E-01
Alopecia	ED70	Skin from scalp	7.03E-02	2.32E-01	4.55E-01
Alzheimer's disease	8A20	Entorhinal cortex	2.34E-04	1.41E-01	2.85E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	8.22E-01	-2.00E-02	-7.85E-02
Aortic stenosis	BB70	Calcified aortic valve	7.62E-01	1.08E-01	1.65E-01
Apnea	7A40	Hyperplastic tonsil	8.08E-02	4.64E-01	1.57E+00
Arthropathy	FA00-FA5Z	Peripheral blood	2.45E-01	7.34E-02	1.93E-01
Asthma	CA23	Nasal and bronchial airway	2.19E-02	1.65E-01	2.39E-01
Atopic dermatitis	EA80	Skin	4.08E-03	1.03E-01	5.91E-01
Autism	6A02	Whole blood	7.63E-02	3.09E-01	3.95E-01
Autoimmune uveitis	9A96	Peripheral monocyte	1.57E-01	2.64E-01	1.12E+00
Autosomal dominant monocytopenia	4B04	Whole blood	7.64E-02	2.72E-01	7.48E-01
Bacterial infection of gingival	1C1H	Gingival tissue	4.00E-17	6.21E-01	1.38E+00
Batten disease	5C56.1	Whole blood	8.15E-01	3.14E-01	8.73E-01
Behcet's disease	4A62	Peripheral blood	1.56E-01	-2.09E-01	-9.19E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	5.56E-01	9.65E-02	3.41E-01
Bladder cancer	2C94	Bladder tissue	4.13E-01	-1.47E-01	-5.14E-01
Breast cancer	2C60-2C6Z	Breast tissue	1.53E-16	1.10E-01	2.50E-01
Cardioembolic stroke	8B11.20	Whole blood	9.18E-01	-1.12E-01	-3.21E-01
Cervical cancer	2C77	Cervical tissue	6.37E-01	1.36E-01	1.23E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	6.49E-01	1.75E-01	2.10E-01
Chronic hepatitis C	1E51.1	Whole blood	4.48E-01	1.45E-01	8.46E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	9.93E-01	-8.04E-03	-2.16E-02
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	6.27E-11	-5.43E-01	-1.02E+00
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	7.97E-01	-2.39E-01	-3.33E-01
Colon cancer	2B90	Colon tissue	1.80E-11	-1.77E-01	-5.07E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	9.91E-02	7.18E-01	1.12E+00
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	7.85E-01	4.11E-02	1.19E-01
Endometriosis	GA10	Endometrium tissue	9.81E-04	-6.07E-01	-3.36E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	6.75E-01	1.19E-02	4.71E-02
Familial hypercholesterolemia	5C80.00	Whole blood	7.40E-09	1.65E+00	1.91E+00
Gastric cancer	2B72	Gastric tissue	7.46E-01	1.42E-01	1.40E-01
Glioblastopma	2A00.00	Nervous tissue	5.45E-05	8.66E-02	1.48E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	4.40E-01	9.02E-02	7.00E-02
Head and neck cancer	2D42	Head and neck tissue	9.00E-18	-1.54E+00	-8.22E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	7.92E-01	6.70E-03	2.42E-02
Huntington's disease	8A01.10	Whole blood	5.15E-01	1.55E-01	7.18E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	8.52E-01	-1.18E-01	-3.01E-01
Immunodeficiency	4A00-4A20	Peripheral blood	5.69E-01	-6.71E-02	-5.07E-01
Influenza	1.00E+30	Whole blood	2.36E-01	1.28E-01	7.77E-01
Interstitial cystitis	GC00.3	Bladder tissue	6.25E-01	1.63E-01	1.91E+00
Intracranial aneurysm	8B01.0	Intracranial artery	4.18E-02	1.66E-01	8.87E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	2.14E-01	7.16E-02	1.65E-01
Ischemic stroke	8B11	Peripheral blood	2.74E-01	-3.06E-02	-2.00E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	3.46E-04	1.72E-01	2.62E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	2.87E-02	-1.02E-01	-8.17E-01
Lateral sclerosis	8B60.4	Skin	3.28E-03	1.89E-01	2.66E+00
Liver cancer	2C12.0	Liver tissue	4.71E-01	-4.68E-02	-2.26E-01
Liver failure	DB99.7-DB99.8	Liver tissue	4.64E-07	1.23E+00	4.56E+00
Lung cancer	2C25	Lung tissue	1.60E-32	-7.70E-01	-1.46E+00
Lupus erythematosus	4A40	Whole blood	6.37E-01	-2.22E-02	-1.91E-02
Major depressive disorder	6A70-6A7Z	Whole blood	1.23E-01	-8.64E-02	-1.80E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	8.33E-02	-3.63E-02	-1.27E-01
Melanoma	2C30	Skin	2.53E-01	-2.31E-01	-2.89E-01
Multiple myeloma	2A83.1	Bone marrow	9.07E-02	-3.48E-01	-5.41E-01
Multiple myeloma	2A83.1	Peripheral blood	7.36E-02	4.83E-02	3.47E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	2.00E-01	-2.80E-01	-6.74E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	2.10E-03	8.77E-01	8.21E-01
Myelofibrosis	2A20.2	Whole blood	2.74E-01	-3.22E-02	-1.07E-01
Myocardial infarction	BA41-BA50	Peripheral blood	4.65E-02	-1.70E-01	-1.84E-01
Myopathy	8C70.6	Muscle tissue	4.72E-01	-1.41E-01	-5.65E-01
Neonatal sepsis	KA60	Whole blood	4.96E-03	1.77E-01	2.96E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	2.87E-03	-8.50E-01	-2.36E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	9.12E-02	-1.32E-01	-1.01E+00
Obesity related type 2 diabetes	5A11	Omental adipose tissue	6.71E-02	1.69E-02	1.79E-01
Olive pollen allergy	CA08.00	Peripheral blood	7.37E-01	-2.36E-01	-6.35E-01
Oral cancer	2B6E	Oral tissue	7.56E-02	2.29E-01	3.48E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	4.02E-01	-3.21E-01	-8.34E-01
Osteoporosis	FB83.1	Bone marrow	3.01E-01	0.00E+00	0.00E+00
Ovarian cancer	2C73	Ovarian tissue	4.34E-03	6.68E-01	9.46E-01
Pancreatic cancer	2C10	Pancreas	5.46E-01	-3.43E-02	-7.02E-02
Parkinson's disease	8A00.0	Substantia nigra tissue	1.37E-01	1.64E-01	5.91E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	1.40E-01	-2.78E-01	-3.35E-01
Pituitary cancer	2D12	Pituitary tissue	8.53E-04	-1.13E+00	-1.78E+00
Pituitary gonadotrope tumour	2D12	Pituitary tissue	3.47E-03	-1.28E+00	-1.81E+00
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	2.72E-01	-6.60E-02	-5.26E-01
Polycythemia vera	2A20.4	Whole blood	9.80E-01	6.71E-02	1.97E-01
Pompe disease	5C51.3	Biceps muscle	8.06E-01	-3.79E-02	-1.37E-01
Preterm birth	KA21.4Z	Myometrium	1.42E-01	5.37E-02	6.99E-01
Prostate cancer	2C82	Prostate	5.87E-01	-6.25E-02	-7.13E-02
Psoriasis	EA90	Skin	1.16E-04	-6.93E-02	-2.39E-01
Rectal cancer	2B92	Rectal colon tissue	3.68E-02	-4.95E-01	-1.04E+00
Renal cancer	2C90-2C91	Kidney	4.26E-03	-9.49E-01	-1.35E+00
Retinoblastoma	2D02.2	Uvea	2.34E-09	-2.05E+00	-4.97E+00
Rheumatoid arthritis	FA20	Synovial tissue	6.36E-01	-1.67E-01	-4.94E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	7.11E-01	-2.25E-02	-6.74E-02
Schizophrenia	6A20	Prefrontal cortex	8.54E-01	-5.91E-02	-1.60E-01
Schizophrenia	6A20	Superior temporal cortex	1.14E-01	1.48E-01	6.04E-01
Scleroderma	4A42.Z	Whole blood	9.65E-01	-4.66E-03	-1.58E-02
Seizure	8A60-8A6Z	Whole blood	3.40E-01	-2.86E-02	-1.08E-01
Sensitive skin	EK0Z	Skin	2.22E-01	-2.97E-01	-1.32E+00
Sepsis with septic shock	1G41	Whole blood	5.22E-11	4.97E-01	7.33E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	4.17E-01	-6.00E-02	-1.44E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	7.91E-01	3.78E-02	2.70E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	2.84E-01	9.18E-03	1.12E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	4.91E-01	-6.28E-02	-3.63E-01
Skin cancer	2C30-2C3Z	Skin	3.51E-05	7.70E-02	2.00E-01
Thrombocythemia	3B63	Whole blood	2.02E-01	5.14E-02	1.79E-01
Thrombocytopenia	3B64	Whole blood	5.23E-01	-3.41E-02	-5.63E-02
Thyroid cancer	2D10	Thyroid	1.88E-15	-5.04E-01	-1.02E+00
Tibial muscular dystrophy	8C75	Muscle tissue	2.62E-01	1.08E-01	4.76E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	4.18E-01	-3.10E-01	-1.63E+00
Type 2 diabetes	5A11	Liver tissue	2.72E-01	1.19E-01	6.73E-01
Ureter cancer	2C92	Urothelium	7.61E-01	-2.19E-02	-9.41E-02
Uterine cancer	2C78	Endometrium tissue	1.95E-01	2.04E-01	1.33E-01
Vitiligo	ED63.0	Skin	7.99E-01	-1.95E-01	-4.77E-01

Drug Affinity of This DTP Assessed by Cell Line

Approved Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Aminolevulinic acid hci	Approved	Oocytes-PEPT2	Km = 227.0 microM	[13]
Amoxicillin	Approved	Madin-Darby canine kidney (MDCK) cells-PEPT2	Km = 1040.0 microM	[4]
Cefaclor	Approved	Madin-Darby canine kidney (MDCK) cells-PEPT2	Km = 72.0 microM	[4]
Cefadroxil	Approved	In vivo model (human)	Km = 150.8 microM	[8]

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Solute carrier family 15 member 2 (SLC15A2) DTT Info
• DTP DTT Type: Literature-reported

5 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lys[Z(NO2)]-Lys[Z(NO2)]	DMH0Q9V	Discovery agent	N.A.	Investigative	[1]
Lys[Z(NO2)]-Pro	DMJX4GA	Discovery agent	N.A.	Investigative	[2]
[11C]GlySar	DM5Q08F	Discovery agent	N.A.	Investigative	[2]
[14C]GlySar	DMGLQ72	Discovery agent	N.A.	Investigative	[2]
[3H]GlySar	DMFEYLS	Discovery agent	N.A.	Investigative	[2]

References

• [1] Defining minimal structural features in substrates of the H(+)/peptide cotransporter PEPT2 using novel amino acid and dipeptide derivatives. Mol Pharmacol. 2002 Jan;61(1):214-21.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 985).
• [3] PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes. Brain Res. 2006 Nov 29;1122(1):18-23.
• [4] Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos. 2006 Apr;34(4):547-55.
• [5] Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives. J Pharmacol Exp Ther. 2006 Jul;318(1):455-60.
• [6] Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41.
• [7] Molecular mechanism of dipeptide and drug transport by the human renal H+/oligopeptide cotransporter hPEPT2. Am J Physiol Renal Physiol. 2008 Jun;294(6):F1422-32.
• [8] Species Differences in Human and Rodent PEPT2-Mediated Transport of Glycylsarcosine and Cefadroxil in Pichia Pastoris Transformants. Drug Metab Dispos. 2017 Feb;45(2):130-136.
• [9] Ethanol inhibits functional activity of the human intestinal dipeptide transporter hPepT1 expressed in Xenopus oocytes. Alcohol Clin Exp Res. 2008 May;32(5):777-84.
• [10] The oligopeptide transporter 2-mediated reabsorption of entecavir in rat kidney. Eur J Pharm Sci. 2014 Feb 14;52:41-7.
• [11] Mechanism of intestinal absorption and renal reabsorption of an orally active ace inhibitor: uptake and transport of fosinopril in cell cultures. Drug Metab Dispos. 2001 Oct;29(10):1307-15.
• [12] Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun. 1998 May 19;246(2):470-5.
• [13] Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J Clin Invest. 1998 Jun 15;101(12):2761-7.