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

Identity

Other names	MRP (multidrug resistance-associated protein)
Hugo	ABCC1
Location	16p13.1

Note	MRP is a gene involved in multidrug resistance, discovered in a multidrug-resistant, P-glycoprotein negative, non small cell lung carcinoma cell line.

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.

Protein

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	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.

External links

	Nomenclature
Hugo	ABCC1
GDB	ABCC1
Entrez_Gene	ABCC1  4363  ATP-binding cassette, sub-family C (CFTR/MRP), member 1
	Cards
Atlas	MRPID106
GeneCards	ABCC1
Ensembl	ABCC1 [Search_View]   ENSG00000103222 [Gene_View]
Genatlas	ABCC1
GeneLynx	ABCC1
eGenome	ABCC1
euGene	4363
	Genomic and cartography
GoldenPath	ABCC1  -  16p13.1   chr16:15950935-16144431 +  16p13.1   [Description]    (hg18-Mar_2006)
Ensembl	ABCC1 - 16p13.1 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	ABCC1
	Gene and transcription
Genbank	AB209120 [ ENTREZ ]
Genbank	BC001636 [ ENTREZ ]
Genbank	BC156353 [ ENTREZ ]
Genbank	BC157105 [ ENTREZ ]
Genbank	BX648866 [ ENTREZ ]
RefSeq	NM_004996 [ SRS ]    NM_004996 [ ENTREZ ]
RefSeq	NM_019862 [ SRS ]    NM_019862 [ ENTREZ ]
RefSeq	NM_019898 [ SRS ]    NM_019898 [ ENTREZ ]
RefSeq	NM_019899 [ SRS ]    NM_019899 [ ENTREZ ]
RefSeq	NM_019900 [ SRS ]    NM_019900 [ ENTREZ ]
RefSeq	NM_019901 [ SRS ]    NM_019901 [ ENTREZ ]
RefSeq	NM_019902 [ SRS ]    NM_019902 [ ENTREZ ]
RefSeq	AC_000059 [ SRS ]    AC_000059 [ ENTREZ ]
RefSeq	NC_000016 [ SRS ]    NC_000016 [ ENTREZ ]
RefSeq	NT_010393 [ SRS ]    NT_010393 [ ENTREZ ]
RefSeq	NW_926051 [ SRS ]    NW_926051 [ ENTREZ ]
AceView	ABCC1 AceView - NCBI
Unigene	Hs.705367 [ SRS ]    Hs.705367 [ NCBI ]     HS705367 [ spliceNest ]
Fast-db	4361 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P33527 [ SRS]    P33527 [ EXPASY ]     P33527 [ INTERPRO ]
Prosite	PS50929 ABC_TM1F [ SRS ]    PS50929 ABC_TM1F [ Expasy ]
Prosite	PS00211 ABC_TRANSPORTER_1 [ SRS ]    PS00211 ABC_TRANSPORTER_1 [ Expasy ]
Prosite	PS50893 ABC_TRANSPORTER_2 [ SRS ]    PS50893 ABC_TRANSPORTER_2 [ Expasy ]
Interpro	IPR003593 AAA+_ATPase_core [ SRS ]    IPR003593 AAA+_ATPase_core [ EBI ]
Interpro	IPR011527 ABC_TM_1 [ SRS ]    IPR011527 ABC_TM_1 [ EBI ]
Interpro	IPR001140 ABC_TM_transpt [ SRS ]    IPR001140 ABC_TM_transpt [ EBI ]
Interpro	IPR003439 ABC_transp_like [ SRS ]    IPR003439 ABC_transp_like [ EBI ]
Interpro	IPR005292 Multidrug-R_assoc_MRP [ SRS ]    IPR005292 Multidrug-R_assoc_MRP [ EBI ]
CluSTr	P33527
Pfam	PF00664 ABC_membrane [ SRS ]    PF00664 ABC_membrane [ Sanger ]    pfam00664 [ NCBI-CDD ]
Pfam	PF00005 ABC_tran [ SRS ]    PF00005 ABC_tran [ Sanger ]    pfam00005 [ NCBI-CDD ]
Smart	SM00382 AAA [EMBL]
Prodom	PD000006 ABC_transporter[INRA-Toulouse]
Prodom	P33527 MRP1_HUMAN [ Domain structure ]   P33527 MRP1_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	P33527
PDB	2CBZ [ SRS ]    2CBZ [ PdbSum ],   2CBZ [ IMB ]   2CBZ [ RSDB ]
HPRD	01153
	Protein Interaction databases
DIP	P33527
IntAct	P33527
	Polymorphism : SNP, mutations, diseases
OMIM	158343    [ map ]
GENECLINICS	158343
SNP	ABCC1 [dbSNP-NCBI]
SNP	NM_004996 [SNP-NCI]
SNP	NM_019862 [SNP-NCI]
SNP	NM_019898 [SNP-NCI]
SNP	NM_019899 [SNP-NCI]
SNP	NM_019900 [SNP-NCI]
SNP	NM_019901 [SNP-NCI]
SNP	NM_019902 [SNP-NCI]
SNP	ABCC1 [GeneSNPs - Utah]  ABCC1] [HGBASE - SRS]
HAPMAP	ABCC1 [HAPMAP]
HGMD	ABCC1
	General knowledge
Family Browser	ABCC1 [UCSC Family Browser]
SOURCE	NM_004996
SOURCE	NM_019862
SOURCE	NM_019898
SOURCE	NM_019899
SOURCE	NM_019900
SOURCE	NM_019901
SOURCE	NM_019902
SMD	Hs.705367
SAGE	Hs.705367
GO	nucleotide binding [Amigo]  nucleotide binding
GO	transporter activity [Amigo]  transporter activity
GO	ATP binding [Amigo]  ATP binding
GO	ATP binding [Amigo]  ATP binding
GO	membrane fraction [Amigo]  membrane fraction
GO	integral to plasma membrane [Amigo]  integral to plasma membrane
GO	transport [Amigo]  transport
GO	transport [Amigo]  transport
GO	membrane [Amigo]  membrane
GO	integral to membrane [Amigo]  integral to membrane
GO	ATPase activity [Amigo]  ATPase activity
GO	ATPase activity [Amigo]  ATPase activity
GO	response to drug [Amigo]  response to drug
GO	ATPase activity, coupled to transmembrane movement of substances [Amigo]  ATPase activity, coupled to transmembrane movement of substances
GO	ATPase activity, coupled to transmembrane movement of substances [Amigo]  ATPase activity, coupled to transmembrane movement of substances
BIOCARTA	Multi-Drug Resistance Factors    [Genes]
PubGene	ABCC1
TreeFam	ABCC1
CTD	4363 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	ABCC1 Related clones (RZPD - Berlin)
	PubMed
PubMed	120 Pubmed reference(s) in LocusLink

Bibliography

Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line.

Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley RG

Science (New York, N.Y.). 1992 ; 258 (5088) : 1650-1654.

PMID 1360704

Expression of the multidrug resistance-associated protein (MRP) in acute and chronic leukemias.

Burger H, Nooter K, Zaman GJ, Sonneveld P, van Wingerden KE, Oostrum RG, Stoter G

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1994 ; 8 (6) : 990-997.

PMID 7911548

The human multidrug resistance-associated protein MRP is a plasma membrane drug-efflux pump.

Zaman GJ, Flens MJ, van Leusden MR, de Haas M, Mˆºlder HS, Lankelma J, Pinedo HM, Scheper RJ, Baas F, Broxterman HJ

Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (19) : 8822-8826.

PMID 7916458

Multidrug resistance-associated protein: a protein distinct from P-glycoprotein involved in cytotoxic drug expulsion.

Barrand MA, Bagrij T, Neo SY

General pharmacology. 1997 ; 28 (5) : 639-645.

PMID 9184795

Function, evolution and structure of multidrug resistance protein (MRP).

Deeley RG, Cole SP

Seminars in cancer biology. 1997 ; 8 (3) : 193-204.

PMID 9441948

Multidrug resistance: molecular mechanisms and clinical relevance.

Ling V

Cancer chemotherapy and pharmacology. 1997 ; 40 Suppl : S3-S8.

PMID 9272126

The role of multidrug resistance-associated protein (MRP) expression in multidrug resistance.

Kavallaris M

Anti-cancer drugs. 1997 ; 8 (1) : 17-25.

PMID 9147606

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

Seminars in hematology. 1997 ; 34 (4 Suppl 5) : 25-33.

PMID 9408958

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	11-1998	Franck Viguié

Citation

This paper should be referenced as such :

Viguié F . ABCC1 (ATP-binding cassette, sub-family C (CFTR/MRP), member 1). Atlas Genet Cytogenet Oncol Haematol. November 1998 . URL : http://AtlasGeneticsOncology.org/Genes/MRPID106.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:25:06 2008