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

1998-11-01 Franck Viguié Affiliation

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

Identity

HGNC

ABCC1

LOCATION

16p13.11

LOCUSID

4363

ALIAS

ABC29,ABCC,DFNA77,GS-X,MRP,MRP1

FUSION GENES

Show Gene Fusions

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)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
ABC transporters	KEGG	ko02010
ABC transporters	KEGG	hsa02010
Vitamin digestion and absorption	KEGG	ko04977
Vitamin digestion and absorption	KEGG	hsa04977
MicroRNAs in cancer	KEGG	hsa05206
MicroRNAs in cancer	KEGG	ko05206
Sphingolipid signaling pathway	KEGG	hsa04071
Sphingolipid signaling pathway	KEGG	ko04071
Transmembrane transport of small molecules	REACTOME	R-HSA-382551
ABC-family proteins mediated transport	REACTOME	R-HSA-382556
Metabolism	REACTOME	R-HSA-1430728
Metabolism of lipids and lipoproteins	REACTOME	R-HSA-556833
Arachidonic acid metabolism	REACTOME	R-HSA-2142753
Synthesis of Leukotrienes (LT) and Eoxins (EX)	REACTOME	R-HSA-2142691
Metabolism of vitamins and cofactors	REACTOME	R-HSA-196854
Metabolism of water-soluble vitamins and cofactors	REACTOME	R-HSA-196849
Cobalamin (Cbl, vitamin B12) transport and metabolism	REACTOME	R-HSA-196741
Antifolate resistance	KEGG	ko01523
Antifolate resistance	KEGG	hsa01523

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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/css/favicon/humanGenome