ABCC1 (ATP-binding cassette, sub-family C (CFTR/MRP), member 1)
1998-11-01 Franck Viguié AffiliationLaboratoire 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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9184795 | 1997 | Multidrug resistance-associated protein: a protein distinct from P-glycoprotein involved in cytotoxic drug expulsion. | Barrand MA et al |
| 7911548 | 1994 | Expression of the multidrug resistance-associated protein (MRP) in acute and chronic leukemias. | Burger H et al |
| 1360704 | 1992 | Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. | Cole SP et al |
| 9441948 | 1997 | Function, evolution and structure of multidrug resistance protein (MRP). | Deeley RG et al |
| 9147606 | 1997 | The role of multidrug resistance-associated protein (MRP) expression in multidrug resistance. | Kavallaris M et al |
| 9272126 | 1997 | Multidrug resistance: molecular mechanisms and clinical relevance. | Ling V et al |
| 9408958 | 1997 | The 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 |
| 7916458 | 1994 | The 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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000103222 | ENST00000399408 | A0A0A0MS99 |
| ENSG00000103222 | ENST00000399410 | P33527 |
| ENSG00000103222 | ENST00000572053 | I3L2H9 |
| ENSG00000103222 | ENST00000572882 | I3L4X2 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA130620651 | anthracyclines and related substances | Chemical | ClinicalAnnotation | associated | PD | 21900104, 23441093 | |
| PA165110775 | SN-38 | Chemical | ClinicalAnnotation, VariantAnnotation | associated | PK | 27845419 | |
| PA165980594 | ponatinib | Chemical | MultilinkAnnotation | not associated | 22778153 | ||
| PA378 | NR1I2 | Gene | Pathway | associated | 21151855 | ||
| PA443421 | Arrhythmias, Cardiac | Disease | ClinicalAnnotation | associated | PK | PD | 16330681 |
| PA443434 | Arthritis, Rheumatoid | Disease | ClinicalAnnotation | associated | PD | 18256692, 26086825, 29743634 | |
| PA443450 | Asthma | Disease | ClinicalAnnotation | associated | PD | ||
| PA443937 | Drug Toxicity | Disease | ClinicalAnnotation | associated | PK | PD | 16330681, 18256692 |
| PA444845 | Lymphoma, Non-Hodgkin | Disease | ClinicalAnnotation | associated | PK | PD | 16330681 |
| PA445062 | Neoplasms | Disease | ClinicalAnnotation | associated | PD | 21900104, 23441093 | |
| PA445113 | Neutropenia | Disease | ClinicalAnnotation, VariantAnnotation | ambiguous | PD | 27845419 | |
| PA445451 | Psoriasis | Disease | ClinicalAnnotation | associated | PD | 18256692, 29743634 | |
| PA446108 | Colorectal Neoplasms | Disease | ClinicalAnnotation, VariantAnnotation | ambiguous | PK | PD | 27845419 |
| PA447230 | HIV | Disease | ClinicalAnnotation | associated | PD | 23996099 | |
| PA449383 | docetaxel | Chemical | Pathway | associated | 21151855 | ||
| PA449412 | doxorubicin | Chemical | ClinicalAnnotation | associated | PK | PD | 16330681 |
| PA450085 | irinotecan | Chemical | ClinicalAnnotation, VariantAnnotation | ambiguous | PD | 27845419 | |
| PA450163 | lamivudine | Chemical | ClinicalAnnotation, Pathway | associated | PD | 23996099 | |
| PA450264 | lopinavir | Chemical | ClinicalAnnotation | associated | PD | 23996099 | |
| PA450428 | methotrexate | Chemical | ClinicalAnnotation, Pathway | associated | PD | 18256692, 21317831, 26086825, 29743634 | |
| PA450546 | montelukast | Chemical | ClinicalAnnotation | associated | PD | ||
| PA450761 | paclitaxel | Chemical | Pathway | associated | 21151855 | ||
| PA451260 | ritonavir | Chemical | ClinicalAnnotation | associated | PD | 23996099 | |
| PA451879 | vincristine | Chemical | Pathway | associated | |||
| PA451954 | zidovudine | Chemical | ClinicalAnnotation | associated | PD | 23996099 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38057687 | 2024 | Restoring microRNA-34a overcomes acquired drug resistance and disease progression in human breast cancer cell lines via suppressing the ABCC1 gene. | 0 |
| 38484722 | 2024 | Overexpression of multidrug resistance-associated protein 1 protects against cardiotoxicity by augmenting the doxorubicin efflux from cardiomyocytes. | 0 |
| 38057687 | 2024 | Restoring microRNA-34a overcomes acquired drug resistance and disease progression in human breast cancer cell lines via suppressing the ABCC1 gene. | 0 |
| 38484722 | 2024 | Overexpression of multidrug resistance-associated protein 1 protects against cardiotoxicity by augmenting the doxorubicin efflux from cardiomyocytes. | 0 |
| 36221036 | 2023 | The ATP-binding cassette proteins ABCB1 and ABCC1 as modulators of glucocorticoid action. | 1 |
| 36253893 | 2023 | Genetic Polymorphisms in SLCO2B1 and ABCC1 Conjointly Modulate Atorvastatin Intracellular Accumulation in HEK293 Recombinant Cell Lines. | 0 |
| 36507589 | 2023 | Genetic variations in ABC transporter genes as a predictive biomarker for toxicity in North Indian lung cancer patients undergoing platinum-based doublet chemotherapy. | 0 |
| 36563915 | 2023 | Knockout of ABCC1 in NCI-H441 cells reveals CF to be a suboptimal substrate to study MRP1 activity in organotypic in vitro models. | 0 |
| 36729852 | 2023 | CircSETDB1 contributes to paclitaxel resistance of ovarian cancer cells by sponging miR-508-3p and regulating ABCC1 expression. | 5 |
| 37658050 | 2023 | Tumor-associated macrophages confer colorectal cancer 5-fluorouracil resistance by promoting MRP1 membrane translocation via an intercellular CXCL17/CXCL22-CCR4-ATF6-GRP78 axis. | 5 |
| 37838788 | 2023 | The role and impact of alternative polyadenylation and miRNA regulation on the expression of the multidrug resistance-associated protein 1 (MRP-1/ABCC1) in epithelial ovarian cancer. | 2 |
| 36221036 | 2023 | The ATP-binding cassette proteins ABCB1 and ABCC1 as modulators of glucocorticoid action. | 1 |
| 36253893 | 2023 | Genetic Polymorphisms in SLCO2B1 and ABCC1 Conjointly Modulate Atorvastatin Intracellular Accumulation in HEK293 Recombinant Cell Lines. | 0 |
| 36507589 | 2023 | Genetic variations in ABC transporter genes as a predictive biomarker for toxicity in North Indian lung cancer patients undergoing platinum-based doublet chemotherapy. | 0 |
| 36563915 | 2023 | Knockout of ABCC1 in NCI-H441 cells reveals CF to be a suboptimal substrate to study MRP1 activity in organotypic in vitro models. | 0 |
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
