RGD Reference Report - Cloning and characterization of the rat multidrug resistance-associated protein 1. - Rat Genome Database

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Cloning and characterization of the rat multidrug resistance-associated protein 1.

Authors: Yang, Z  Li, CS  Shen, DD  Ho, RJ 
Citation: Yang Z, etal., AAPS PharmSci 2002;4(3):E15.
RGD ID: 633704
Pubmed: PMID:12423064   (View Abstract at PubMed)
PMCID: PMC2751354   (View Article at PubMed Central)
DOI: DOI:10.1208/ps040315   (Journal Full-text)

Multidrug resistance-associated protein 1 (MRP1) was originally shown to confer resistance of human tumor cells to a broad range of natural product anticancer drugs. MRP1 has also been shown to mediate efflux transport of glutathione and glucuronide conjugates of drugs and endogenous substrates. An ortholog of MRP1 in the mouse has been cloned and characterized. Significant functional differences between murine and human MRP1 have been noted. Since drug disposition and pharmacology studies often are conducted in rats, there is a need to clone and characterize the rat ortholog of MRP1. We isolated a rat MRP1 (rMRP1) cDNA from rat brain astrocytes, characterized its coding sequences, and verified the transport activity of the protein expressed in MRP1 cDNA-transfected Madin-Darby canine kidney (MDCK) cells. Our results showed that rMRP1 has a coding sequence of 4599 bp, which predicts a polypeptide of 1533 amino acids with an apparent molecular weight of 190 kd by Western immunoblot analysis. rMRP1-transfected MDCK cells are capable of efflux transport of a fluorescent MRP1 marker - calcein - that is inhibitable by known MRP1 inhibitors, indomethacin, and MK571. Sequence analysis indicates that rMRP1 is more closely related to mouse MRP1 than human MRP1.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Abcc1Rattransmembrane transport  IDA  RGD 
Abcc1Ratxenobiotic detoxification by transmembrane export across the plasma membrane  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Abcc1Ratamide transmembrane transporter activity  IDA  RGD 
Abcc1Ratefflux transmembrane transporter activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcc1  (ATP binding cassette subfamily C member 1)

Objects referenced in this article
Gene Abcb1b ATP-binding cassette, sub-family B member 1B Rattus norvegicus

Additional Information