Drug Transporter (DT) Information

General Information of DT
DT ID DTD0016
Gene Name ABCC5
Protein Name Multidrug resistance-associated protein 5
Gene ID
10057
UniProt ID
O15440
TCDB ID
3.A.1.208.15
3D Structure

Modelled DT Structure

Method:homology modeling

Template PDB:5UJ9_A

Identity:38.53%

Minimized Score:-2759.769 kcal/mol

Detail: Structure Info

Synonyms ABC33; ABCC5; ATP-binding cassette sub-family C member 5; EST277145; MOAT-C; MOATC; MRP5; Multi-specific organic anion transporter C; SMRP; pABC11
DT Family ATP-Binding Cassette (ABC) Superfamily
Drug Conjugate Transporter (DCT) Family (ABCC)
Tissue Specificity All isoforms are equally expressed in retina.
Function This transporter acts as a multispecific organic anion pump which can transport nucleotide analogs.
Disease(s) Colorectal cancer [ICD-11:2B91]
Cytomegalovirus infections [ICD-11:1D82]
Malignant pleural mesothelioma [ICD-11:2C26.0]
Cholangiocarcinoma [ICD-11:2C12.10]
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
Variability Data of This Drug Transporter (DT)

Regulatory Variability Data of This DT (VARIDT 4.0)

(α) Tissue Distribution Level of Multidrug resistance-associated protein 5
Tissue Distribution Level (TD)

(β) Cell Distribution Level of Multidrug resistance-associated protein 5
Cell Distribution Level (CD)

(γ) Organelle Distribution Level of Multidrug resistance-associated protein 5
Organelle Distribution Level (Subc)

Regulatory Variability Data of This DT

(α) Microbiota Influence of Multidrug resistance-associated protein 5
Microbiota Influence (MBI)

(β) Post-translational Modification of Multidrug resistance-associated protein 5
Post-translational Modification (PTM)

(γ) Transcriptional Regulation of Multidrug resistance-associated protein 5
Transcriptional Regulation (TSR)

(δ) Epigenetic Regulation of Multidrug resistance-associated protein 5
Epigenetic Regulation (EGR)

(ε) Exogenous Modulation of Multidrug resistance-associated protein 5
Exogenous Modulation (EGM)

Structural Variability Data of This DT

(β) Inter-species Structural Differences
Inter-species Structural Differences (ISD)

(γ) Outward/inward-facing Conformation
Outward/inward-facing Conformation (OIC)

(δ) Xenobiotics-regulated Structural Variability
Xenobiotics-regulated Structural Variability (XSV)

General Variability Data of This DT

(α) Genetic Polymorphisms of Multidrug resistance-associated protein 5
Genetic Polymorphisms of This DT (GPD)

(β) Disease-specific Protein Abundances of Multidrug resistance-associated protein 5
Disease-specific Protein Abundances of This DT (DPAD)

(γ) Species- and Tissue-specific DT Abundances
Species/Tissue-specific Protein Abundances of This DT (S/TPAD)
Molecular Transporting Profile of This DT

Full List of Drug(s) Transported by This DT

 Approved Drug

 Click to Show/Hide the Full List of Drug:         10 Drugs in Total
Drug Name Highest Status Detail Indication ICD 11 Ref
Adenosine
 Approved Drug Info Anxiety MB24.3 [1]
Fluorescein
 Approved Drug Info Ocular disease 9E1Z [2]
Fluorouracil
 Approved Drug Info Stomach cancer 2B72 [3]
Folic acid
 Approved Drug Info Vitamin deficiency 5B55-5B7Z [4]
Ganciclovir
 Approved Drug Info Cytomegalovirus infections 1D82 [5]
Gemcitabine
 Approved Drug Info Cholangiocarcinoma 2C12.10 [6]
Irinotecan
 Approved Drug Info Colorectal cancer 2B91 [7]
Mercaptopurine
 Approved Drug Info Acute lymphoblastic leukemia 2B33.0 [8]
Methotrexate
 Approved Drug Info Leukemia 2A60-2B33 [4]
Pemetrexed
 Approved Drug Info Malignant pleural mesothelioma 2C26.0 [9]

Endogenous Metabolites (EMs) Handled by This DT

 Endogenous Metabolites (EMs)

 Click to Show/Hide the Full List of EMs:           1 EMs in Total
EM Name PubChem CID Detail Experimental Material Ref
Octadecenylcarnitine
53481695
EM Info Identified using HEK293 cells-ABCC5 [10]

Drug-DT Affinity Assessed by Cell Line

 Approved Drug

 Click to Show/Hide the Full List of Drug:         53 Drugs in Total
Drug Name Highest Status Detail Cell Line Affinity Ref
Folic acid Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1000 microM [4]
Folic acid Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1000 microM [4]
Folic acid Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1000 microM [4]
Folic acid Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1000 microM [4]
Folic acid Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1000 microM [4]
Folic acid Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1000 microM [4]
Folic acid Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1000 microM [4]
Folic acid Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1000 microM [4]
Folic acid Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1000 microM [4]
Folic acid Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1000 microM [4]
Folic acid Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1000 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1174 microM [9]
Methotrexate Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =1200 microM [4]
Pemetrexed Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =281 microM [9]
Pemetrexed Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =281 microM [9]
Pemetrexed Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =281 microM [9]
Pemetrexed Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =281 microM [9]
Pemetrexed Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =281 microM [9]
Pemetrexed Approved Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =281 microM [9]

 Withdrawn, Discontinued or Preclinical Drug

 Click to Show/Hide the Full List of Drug:           3 Drugs in Total
Drug Name Highest Status Detail Cell Line Affinity Ref
Carboxydichlorofluorescein Investigative Drug Info Human embryonic kidney cells (HEK293)-MRP5 Km =11.6 microM [9]
Cyclic adenosine monophosphate Investigative Drug Info Chinese hamster V79 cells (V79)-MRP5 Km =379 microM [11]
Cyclic adenosine monophosphate Investigative Drug Info Chinese hamster V79 cells (V79)-MRP5 Km =379 microM [11]
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 N-lactoyl-amino acids are ubiquitous metabolites that originate from CNDP2-mediated reverse proteolysis of lactate and amino acids. Proc Natl Acad Sci U S A. 2015 May 26;112(21):6601-6.
11 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.

If you find any error in data or bug in web service, please kindly report it to Dr. Li and Dr. Fu.