ABCC1 (ATP-binding cassette, sub-family C (CFTR/MRP), member 1)

1998-11-01   Franck Viguié 

Laboratoire de Cytogenetique - Service dHematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France

Identity

HGNC
LOCATION
16p13.11
LOCUSID
ALIAS
ABC29,ABCC,DFNA77,GS-X,MRP,MRP1
FUSION GENES

DNA/RNA

Description

spans at least 200 kb and contains 31 exons

Transcription

7kb mRNA transcript; significant level of variant transcripts due to alternative splicing.

Proteins

Description

1531 amino acids, 190 kDa; contains two ATP binding domains and three membrane-spanning helices; member of the ATP-binding cassette proteins (ABC proteins).

Expression

expressed at a basal level in a wide variety of normal tissues, including epithelial cells and all hematopoietic cell types, which suggests a function common to most cell types; increased expression in various tumor cell type.

Localisation

in normal cells, predominant localisation in the cytoplasm; in tumor cells, predominant in plasma membrane, but also found in endoplasmic reticulum, indicating a probable different function as in normal cells.

Function

plasma membrane drug-efflux pump; MRP induces a multidrug resistance phenotype (MDR phenotype); overexpression confers tumor cell resistance to a wide variety of hydrophobic drugs: doxorubicin, daunorubicin, vinblastine, vincristine, colchicine, VP16, Rhodamin 123; glutathione is required for the effective expulsion of the chemotherapeutic agents; the mode of action of MRP is very similar to the one of P-glycoprotein, the main protein responsible for the MDR phenotype; however, MRP does not confer resistance to Taxol or m-AMSA, but it is able to transport metallic oxyanions, glutathione and other glutathione conjugates; inhibitors of organic anion transport, such as probenecid, can block MRP activity.

Homology

structural and/or functional homology with other ABC transporter proteins (CFTR, Pgp, MOAT).

Implicated in

Entity name
induced resistance to chemotherapeutic agents
Disease
in a wide variety of solid and hematological tumors
Oncogenesis
MRP hyperexpression may confer therapeutic resistance in leukemia and solid tumor; however its relative importance, in comparison with other proteins able to induce the MDR phenotype (P-gp, LRP), is not yet clear; hyperexpression is probably linked to transcriptional activation of the gene and/or increased mRNA stability, and not to gene amplification; increased expression of MRP mRNA and protein is a factor of bad prognostic in neuroblastoma, retinoblastoma, and non small cell lung carcinoma. In haematological malignancies, overexpression is frequent in chronic lymphocytic leukemia and prolymphocytic leukemia, occasional in acute myeloid leukemia and rare in acute lymphoid leukemia, lymphoma, multiple myeloma and myeloproliferative disorders.

Bibliography

Pubmed IDLast YearTitleAuthors
91847951997Multidrug resistance-associated protein: a protein distinct from P-glycoprotein involved in cytotoxic drug expulsion.Barrand MA et al
79115481994Expression of the multidrug resistance-associated protein (MRP) in acute and chronic leukemias.Burger H et al
13607041992Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line.Cole SP et al
94419481997Function, evolution and structure of multidrug resistance protein (MRP).Deeley RG et al
91476061997The role of multidrug resistance-associated protein (MRP) expression in multidrug resistance.Kavallaris M et al
92721261997Multidrug resistance: molecular mechanisms and clinical relevance.Ling V et al
94089581997The prognostic significance of the expression and function of multidrug resistance transporter proteins in acute myeloid leukemia: studies of the Southwest Oncology Group Leukemia Research Program.Willman CL et al
79164581994The human multidrug resistance-associated protein MRP is a plasma membrane drug-efflux pump.Zaman GJ et al

Other Information

Locus ID:

NCBI: 4363
MIM: 158343
HGNC: 51
Ensembl: ENSG00000103222

Variants:

dbSNP: 4363
ClinVar: 4363
TCGA: ENSG00000103222
COSMIC: ABCC1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000103222ENST00000399408A0A0A0MS99
ENSG00000103222ENST00000399410P33527
ENSG00000103222ENST00000572053I3L2H9
ENSG00000103222ENST00000572882I3L4X2

Expression (GTEx)

0
10
20
30
40
50
60
70

Pathways

PathwaySourceExternal ID
ABC transportersKEGGko02010
ABC transportersKEGGhsa02010
Vitamin digestion and absorptionKEGGko04977
Vitamin digestion and absorptionKEGGhsa04977
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
Sphingolipid signaling pathwayKEGGhsa04071
Sphingolipid signaling pathwayKEGGko04071
Transmembrane transport of small moleculesREACTOMER-HSA-382551
ABC-family proteins mediated transportREACTOMER-HSA-382556
MetabolismREACTOMER-HSA-1430728
Metabolism of lipids and lipoproteinsREACTOMER-HSA-556833
Arachidonic acid metabolismREACTOMER-HSA-2142753
Synthesis of Leukotrienes (LT) and Eoxins (EX)REACTOMER-HSA-2142691
Metabolism of vitamins and cofactorsREACTOMER-HSA-196854
Metabolism of water-soluble vitamins and cofactorsREACTOMER-HSA-196849
Cobalamin (Cbl, vitamin B12) transport and metabolismREACTOMER-HSA-196741
Antifolate resistanceKEGGko01523
Antifolate resistanceKEGGhsa01523

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA130620651anthracyclines and related substancesChemicalClinicalAnnotationassociatedPD21900104, 23441093
PA165110775SN-38ChemicalClinicalAnnotation, VariantAnnotationassociatedPK27845419
PA165980594ponatinibChemicalMultilinkAnnotationnot associated22778153
PA378NR1I2GenePathwayassociated21151855
PA443421Arrhythmias, CardiacDiseaseClinicalAnnotationassociatedPKPD16330681
PA443434Arthritis, RheumatoidDiseaseClinicalAnnotationassociatedPD18256692, 26086825, 29743634
PA443450AsthmaDiseaseClinicalAnnotationassociatedPD
PA443937Drug ToxicityDiseaseClinicalAnnotationassociatedPKPD16330681, 18256692
PA444845Lymphoma, Non-HodgkinDiseaseClinicalAnnotationassociatedPKPD16330681
PA445062NeoplasmsDiseaseClinicalAnnotationassociatedPD21900104, 23441093
PA445113NeutropeniaDiseaseClinicalAnnotation, VariantAnnotationambiguousPD27845419
PA445451PsoriasisDiseaseClinicalAnnotationassociatedPD18256692, 29743634
PA446108Colorectal NeoplasmsDiseaseClinicalAnnotation, VariantAnnotationambiguousPKPD27845419
PA447230HIVDiseaseClinicalAnnotationassociatedPD23996099
PA449383docetaxelChemicalPathwayassociated21151855
PA449412doxorubicinChemicalClinicalAnnotationassociatedPKPD16330681
PA450085irinotecanChemicalClinicalAnnotation, VariantAnnotationambiguousPD27845419
PA450163lamivudineChemicalClinicalAnnotation, PathwayassociatedPD23996099
PA450264lopinavirChemicalClinicalAnnotationassociatedPD23996099
PA450428methotrexateChemicalClinicalAnnotation, PathwayassociatedPD18256692, 21317831, 26086825, 29743634
PA450546montelukastChemicalClinicalAnnotationassociatedPD
PA450761paclitaxelChemicalPathwayassociated21151855
PA451260ritonavirChemicalClinicalAnnotationassociatedPD23996099
PA451879vincristineChemicalPathwayassociated
PA451954zidovudineChemicalClinicalAnnotationassociatedPD23996099

References

Pubmed IDYearTitleCitations
170506922006Role of ABCC1 in export of sphingosine-1-phosphate from mast cells.160
198836302010Involvement of miR-326 in chemotherapy resistance of breast cancer through modulating expression of multidrug resistance-associated protein 1.103
163306812005NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity.96
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
193495402009Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics.74
125764562003RNA expression of breast cancer resistance protein, lung resistance-related protein, multidrug resistance-associated proteins 1 and 2, and multidrug resistance gene 1 in breast cancer: correlation with chemotherapeutic response.69
235805272013Latency-associated degradation of the MRP1 drug transporter during latent human cytomegalovirus infection.69
162938012006Influence of leukotriene pathway polymorphisms on response to montelukast in asthma.64
205302822010Pharmacogenetic predictors of adverse events and response to chemotherapy in metastatic colorectal cancer: results from North American Gastrointestinal Intergroup Trial N9741.58
151619122004Arsenic transport by the human multidrug resistance protein 1 (MRP1/ABCC1). Evidence that a tri-glutathione conjugate is required.55

Citation

Franck Viguié

ABCC1 (ATP-binding cassette, sub-family C (CFTR/MRP), member 1)

Atlas Genet Cytogenet Oncol Haematol. 1998-11-01

Online version: http://atlasgeneticsoncology.org/gene/106/abcc1-(atp-binding-cassette-sub-family-c-(cftr-mrp)-member-1)