Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DTYVM24)

• DTP Name: Multidrug resistance-associated protein 5 (ABCC5)
• Gene Name: ABCC5
• UniProt ID: O15440 (MRP5_HUMAN)
• VARIDT ID: DTD0016
• Synonyms: ABC33; ABCC5; ATP-binding cassette sub-family C member 5; EST277145; MOAT-C; MOATC; MRP5; Multi-specific organic anion transporter C; SMRP; pABC11
• DTP Family:
  ATP-Binding Cassette (ABC) Superfamily
  Drug Conjugate Transporter (DCT) Family (ABCC)
• Tissue Specificity: All isoforms are equally expressed in retina.
• Sequence:
  MKDIDIGKEYIIPSPGYRSVRERTSTSGTHRDREDSKFRRTRPLECQDALETAARAEGLS
  LDASMHSQLRILDEEHPKGKYHHGLSALKPIRTTSKHQHPVDNAGLFSCMTFSWLSSLAR
  VAHKKGELSMEDVWSLSKHESSDVNCRRLERLWQEELNEVGPDAASLRRVVWIFCRTRLI
  LSIVCLMITQLAGFSGPAFMVKHLLEYTQATESNLQYSLLLVLGLLLTEIVRSWSLALTW
  ALNYRTGVRLRGAILTMAFKKILKLKNIKEKSLGELINICSNDGQRMFEAAAVGSLLAGG
  PVVAILGMIYNVIILGPTGFLGSAVFILFYPAMMFASRLTAYFRRKCVAATDERVQKMNE
  VLTYIKFIKMYAWVKAFSQSVQKIREEERRILEKAGYFQSITVGVAPIVVVIASVVTFSV
  HMTLGFDLTAAQAFTVVTVFNSMTFALKVTPFSVKSLSEASVAVDRFKSLFLMEEVHMIK
  NKPASPHIKIEMKNATLAWDSSHSSIQNSPKLTPKMKKDKRASRGKKEKVRQLQRTEHQA
  VLAEQKGHLLLDSDERPSPEEEEGKHIHLGHLRLQRTLHSIDLEIQEGKLVGICGSVGSG
  KTSLISAILGQMTLLEGSIAISGTFAYVAQQAWILNATLRDNILFGKEYDEERYNSVLNS
  CCLRPDLAILPSSDLTEIGERGANLSGGQRQRISLARALYSDRSIYILDDPLSALDAHVG
  NHIFNSAIRKHLKSKTVLFVTHQLQYLVDCDEVIFMKEGCITERGTHEELMNLNGDYATI
  FNNLLLGETPPVEINSKKETSGSQKKSQDKGPKTGSVKKEKAVKPEEGQLVQLEEKGQGS
  VPWSVYGVYIQAAGGPLAFLVIMALFMLNVGSTAFSTWWLSYWIKQGSGNTTVTRGNETS
  VSDSMKDNPHMQYYASIYALSMAVMLILKAIRGVVFVKGTLRASSRLHDELFRRILRSPM
  KFFDTTPTGRILNRFSKDMDEVDVRLPFQAEMFIQNVILVFFCVGMIAGVFPWFLVAVGP
  LVILFSVLHIVSRVLIRELKRLDNITQSPFLSHITSSIQGLATIHAYNKGQEFLHRYQEL
  LDDNQAPFFLFTCAMRWLAVRLDLISIALITTTGLMIVLMHGQIPPAYAGLAISYAVQLT
  GLFQFTVRLASETEARFTSVERINHYIKTLSLEAPARIKNKAPSPDWPQEGEVTFENAEM
  RYRENLPLVLKKVSFTIKPKEKIGIVGRTGSGKSSLGMALFRLVELSGGCIKIDGVRISD
  IGLADLRSKLSIIPQEPVLFSGTVRSNLDPFNQYTEDQIWDALERTHMKECIAQLPLKLE
  SEVMENGDNFSVGERQLLCIARALLRHCKILILDEATAAMDTETDLLIQETIREAFADCT
  MLTIAHRLHTVLGSDRIMVLAQGQVVEFDTPSVLLSNDSSRFYAMFAAAENKVAVKG
• Function: This transporter acts as a multispecific organic anion pump which can transport nucleotide analogs.
• Endogenous Substrate(s): 5'-FUMP; 9-(2-phosphonylmethoxyethyl)adenine; Antimonial tartrate; Folic acids; Glutamate derivatives; Glutathione conjugates; Nucleoside analogues; Nucleotide analogues; Organoanions; Reduced folates; cAMP; cGMP
• TCDB ID: 3.A.1.208.15
• Gene ID: 10057
• KEGG Pathway:
  Antifolate resistance (hsa01523)
  ABC transporters (hsa02010)
• Reactome Pathway:
  ABC-family proteins mediated transport (R-HSA-382556)
  Azathioprine ADME (R-HSA-9748787)
  Paracetamol ADME (R-HSA-9753281)
  Hyaluronan biosynthesis and export (R-HSA-2142850)

Molecular Interaction Atlas (MIA) of This DTP

10 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Adenosine	DMM2NSK	Paroxysmal supraventricular tachycardia	BC81.Z	Approved	[1]
FLUORESCEIN	DMQTFAO	Ocular disease	1F00.1Z	Approved	[2]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[3]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[4]
Ganciclovir	DM1MBYQ	Cytomegalovirus infection	1D82	Approved	[5]
Gemcitabine	DMSE3I7	Anterior urethra cancer		Approved	[6]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[7]
Mercaptopurine	DMTM2IK	Acute lymphoblastic leukaemia	2A85	Approved	[8]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[4]
Pemetrexed	DMMX2E6	Central nervous system lymphoma	2B33.5	Approved	[9]

2 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Carboxydichlorofluorescein	DMTAYMR	N. A.	N. A.	Investigative	[9]
[3H]cAMP	DMZRQU7	Discovery agent	N.A.	Investigative	[10]

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	9.63E-07	-2.80E-01	-4.65E-01
Adrenocortical carcinoma	2D11.Z	Kidney	6.29E-02	4.35E-01	8.44E-01
Alopecia	ED70	Skin from scalp	1.43E-02	9.78E-02	3.45E-01
Alzheimer's disease	8A20	Entorhinal cortex	5.23E-02	4.81E-02	1.66E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	3.79E-02	4.79E-01	1.31E+00
Aortic stenosis	BB70	Calcified aortic valve	8.89E-01	-6.27E-02	-7.55E-02
Apnea	7A40	Hyperplastic tonsil	6.58E-02	-9.96E-01	-1.05E+00
Arthropathy	FA00-FA5Z	Peripheral blood	3.98E-01	5.01E-03	1.76E-02
Asthma	CA23	Nasal and bronchial airway	9.64E-02	3.12E-01	4.07E-01
Atopic dermatitis	EA80	Skin	8.66E-08	4.55E-01	1.38E+00
Autism	6A02	Whole blood	3.25E-02	2.28E-01	5.46E-01
Autoimmune uveitis	9A96	Peripheral monocyte	7.35E-02	6.23E-01	1.54E+00
Autosomal dominant monocytopenia	4B04	Whole blood	6.15E-02	-5.66E-01	-6.33E-01
Bacterial infection of gingival	1C1H	Gingival tissue	2.76E-01	1.38E-01	2.92E-01
Batten disease	5C56.1	Whole blood	2.33E-01	1.76E-02	7.64E-02
Behcet's disease	4A62	Peripheral blood	8.26E-01	8.09E-02	4.05E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	6.38E-01	9.64E-03	4.87E-02
Bladder cancer	2C94	Bladder tissue	3.39E-03	-9.88E-01	-2.26E+00
Breast cancer	2C60-2C6Z	Breast tissue	5.09E-71	9.28E-01	1.48E+00
Cardioembolic stroke	8B11.20	Whole blood	3.09E-02	4.21E-01	9.06E-01
Cervical cancer	2C77	Cervical tissue	1.63E-01	-1.12E-01	-2.14E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	8.25E-01	-3.27E-02	-7.75E-02
Chronic hepatitis C	1E51.1	Whole blood	1.92E-01	-1.87E-01	-3.51E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	4.85E-01	9.69E-02	2.10E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	3.38E-02	-1.14E-01	-2.95E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	4.29E-04	-1.48E+00	-3.07E+00
Colon cancer	2B90	Colon tissue	1.63E-13	-3.83E-01	-7.13E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	7.40E-01	8.18E-02	2.97E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	2.09E-01	1.42E-01	3.54E-01
Endometriosis	GA10	Endometrium tissue	5.48E-03	-4.58E-01	-6.04E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	5.17E-01	8.04E-02	2.26E-01
Familial hypercholesterolemia	5C80.00	Whole blood	8.56E-04	5.79E-01	1.56E+00
Gastric cancer	2B72	Gastric tissue	2.22E-01	-1.88E+00	-1.52E+00
Glioblastopma	2A00.00	Nervous tissue	1.32E-27	-4.23E-01	-6.71E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	3.71E-01	-2.10E-02	-1.96E-02
Head and neck cancer	2D42	Head and neck tissue	7.90E-04	-3.85E-01	-3.23E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	8.88E-01	2.38E-01	4.56E-01
Huntington's disease	8A01.10	Whole blood	3.42E-01	-2.14E-02	-5.40E-02
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	7.60E-03	1.07E+00	1.70E+00
Immunodeficiency	4A00-4A20	Peripheral blood	3.40E-05	-4.21E-01	-3.13E+00
Influenza	1.00E+30	Whole blood	8.96E-01	2.90E-01	5.53E-01
Interstitial cystitis	GC00.3	Bladder tissue	1.88E-03	-1.32E+00	-2.97E+00
Intracranial aneurysm	8B01.0	Intracranial artery	1.73E-02	1.90E-01	4.25E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	9.25E-03	1.23E-01	3.41E-01
Ischemic stroke	8B11	Peripheral blood	1.27E-01	-2.29E-01	-8.16E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	7.22E-01	-1.77E-02	-5.99E-02
Lateral sclerosis	8B60.4	Cervical spinal cord	1.11E-01	1.18E-02	1.95E-02
Lateral sclerosis	8B60.4	Skin	1.52E-01	3.40E-01	1.05E+00
Liver cancer	2C12.0	Liver tissue	2.64E-14	7.10E-01	1.42E+00
Liver failure	DB99.7-DB99.8	Liver tissue	9.52E-06	1.78E+00	4.77E+00
Lung cancer	2C25	Lung tissue	3.16E-78	1.01E+00	1.96E+00
Lupus erythematosus	4A40	Whole blood	5.79E-04	3.36E-01	3.05E-01
Major depressive disorder	6A70-6A7Z	Whole blood	1.36E-01	7.90E-02	2.01E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	1.00E-01	-1.01E-01	-5.72E-01
Melanoma	2C30	Skin	1.64E-01	-4.78E-01	-4.63E-01
Multiple myeloma	2A83.1	Bone marrow	7.74E-01	-4.95E-02	-1.67E-01
Multiple myeloma	2A83.1	Peripheral blood	4.32E-01	-1.78E-02	-3.92E-02
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	9.31E-01	3.03E-02	1.15E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	1.11E-01	1.81E-01	3.17E-01
Myelofibrosis	2A20.2	Whole blood	5.13E-01	-5.70E-02	-2.28E-01
Myocardial infarction	BA41-BA50	Peripheral blood	2.72E-01	-2.16E-01	-2.74E-01
Myopathy	8C70.6	Muscle tissue	4.03E-02	-5.17E-01	-9.31E-01
Neonatal sepsis	KA60	Whole blood	3.48E-01	-8.84E-02	-1.57E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	2.38E-01	4.56E-02	9.66E-02
Non-alcoholic fatty liver disease	DB92	Liver tissue	5.76E-01	-2.54E-01	-1.14E+00
Obesity related type 2 diabetes	5A11	Omental adipose tissue	9.80E-01	5.05E-02	4.95E-02
Olive pollen allergy	CA08.00	Peripheral blood	2.45E-01	-3.45E-01	-7.96E-01
Oral cancer	2B6E	Oral tissue	3.51E-01	3.94E-01	3.77E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	8.81E-01	7.62E-03	1.06E-02
Osteoporosis	FB83.1	Bone marrow	7.55E-02	-5.17E-01	-1.01E+00
Ovarian cancer	2C73	Ovarian tissue	1.17E-02	6.11E-01	7.54E-01
Pancreatic cancer	2C10	Pancreas	8.28E-03	6.40E-01	7.46E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	7.36E-02	4.23E-01	1.10E+00
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	1.80E-02	-1.81E-01	-6.37E-01
Pituitary cancer	2D12	Pituitary tissue	8.67E-03	-4.87E-01	-9.48E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	4.21E-01	3.38E-02	5.72E-02
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	1.96E-01	-2.45E-01	-8.16E-01
Polycythemia vera	2A20.4	Whole blood	3.11E-02	-1.40E-01	-5.23E-01
Pompe disease	5C51.3	Biceps muscle	1.09E-01	4.42E-01	1.03E+00
Preterm birth	KA21.4Z	Myometrium	3.70E-01	9.51E-02	4.00E-01
Prostate cancer	2C82	Prostate	3.70E-02	6.28E-02	8.93E-02
Psoriasis	EA90	Skin	2.12E-14	5.18E-01	7.64E-01
Rectal cancer	2B92	Rectal colon tissue	6.35E-01	-1.02E-01	-3.17E-01
Renal cancer	2C90-2C91	Kidney	1.66E-01	-2.98E-01	-3.85E-01
Retinoblastoma	2D02.2	Uvea	2.71E-01	-1.56E-01	-4.65E-01
Rheumatoid arthritis	FA20	Synovial tissue	4.38E-02	-3.21E-01	-6.75E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	6.75E-01	-1.54E-01	-3.90E-01
Schizophrenia	6A20	Prefrontal cortex	3.88E-01	-1.75E-01	-2.89E-01
Schizophrenia	6A20	Superior temporal cortex	2.68E-02	1.85E-01	8.03E-01
Scleroderma	4A42.Z	Whole blood	3.42E-02	1.46E-01	6.19E-01
Seizure	8A60-8A6Z	Whole blood	8.18E-01	1.45E-01	2.71E-01
Sensitive skin	EK0Z	Skin	2.87E-01	1.84E-01	1.19E+00
Sepsis with septic shock	1G41	Whole blood	8.54E-07	-3.36E-01	-5.86E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	2.89E-01	-1.43E-01	-4.44E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	3.79E-03	3.13E-01	1.52E+00
Simpson golabi behmel syndrome	LD2C	Adipose tissue	1.72E-01	-2.76E-01	-1.35E+00
Sjogren's syndrome	4A43.2	Salivary gland tissue	2.46E-01	1.03E-02	3.55E-02
Skin cancer	2C30-2C3Z	Skin	6.22E-43	1.36E+00	1.48E+00
Thrombocythemia	3B63	Whole blood	6.60E-02	-2.41E-01	-9.52E-01
Thrombocytopenia	3B64	Whole blood	3.88E-01	-4.83E-01	-8.39E-01
Thyroid cancer	2D10	Thyroid	4.32E-05	9.33E-02	2.53E-01
Tibial muscular dystrophy	8C75	Muscle tissue	3.95E-03	-5.95E-01	-1.36E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	8.95E-01	5.26E-02	1.68E-01
Type 2 diabetes	5A11	Liver tissue	9.82E-01	-1.63E-01	-5.24E-01
Ureter cancer	2C92	Urothelium	5.41E-01	-4.58E-03	-8.85E-03
Uterine cancer	2C78	Endometrium tissue	8.00E-01	-1.49E-01	-1.88E-01
Vitiligo	ED63.0	Skin	1.20E-01	3.51E-01	9.32E-01

Drug Affinity of This DTP Assessed by Cell Line

Approved Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Folic Acid	Approved	Human embryonic kidney cells (HEK293)-MRP5	Km = 1000.0 microM	[4]
Methotrexate	Approved	Human embryonic kidney cells (HEK293)-MRP5	Km = 1174.0 microM	[9]
Methotrexate	Approved	Human embryonic kidney cells (HEK293)-MRP5	Km = 1200.0 microM	[4]
Pemetrexed	Approved	Human embryonic kidney cells (HEK293)-MRP5	Km = 281.0 microM	[9]

Investigative Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
[3H]cAMP	Investigative	Chinese hamster V79 cells (V79)-MRP5	Km = 379.0 microM	[10]

References

• [1] Role of MRP4 and MRP5 in biology and chemotherapy. AAPS PharmSci. 2002;4(3):E14.
• [2] Hyaluronan export by the ABC transporter MRP5 and its modulation by intracellular cGMP. J Biol Chem. 2007 Jul 20;282(29):20999-1004.
• [3] ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells. Pancreatology. 2009;9(1-2):136-44.
• [4] The human multidrug resistance protein MRP5 transports folates and can mediate cellular resistance against antifolates. Cancer Res. 2005 May 15;65(10):4425-30.
• [5] Cellular export of drugs and signaling molecules by the ATP-binding cassette transporters MRP4 (ABCC4) and MRP5 (ABCC5). Drug Metab Rev. 2005;37(1):253-78.
• [6] Interdependence of gemcitabine treatment, transporter expression, and resistance in human pancreatic carcinoma cells. Neoplasia. 2010 Sep;12(9):740-7.
• [7] Celecoxib upregulates multidrug resistance proteins in colon cancer: lack of synergy with standard chemotherapy. Curr Cancer Drug Targets. 2008 Aug;8(5):414-20.
• [8] Overexpression of MRP4 (ABCC4) and MRP5 (ABCC5) confer resistance to the nucleoside analogs cytarabine and troxacitabine, but not gemcitabine. Springerplus. 2014 Dec 13;3:732.
• [9] Kinetic validation of the use of carboxydichlorofluorescein as a drug surrogate for MRP5-mediated transport. Eur J Pharm Sci. 2006 Apr;27(5):524-32.
• [10] The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides. J Biol Chem. 2000 Sep 29;275(39):30069-74.