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

Identity

Other namesMRP (multidrug resistance-associated protein)
HGNC (Hugo) ABCC1
Location 16p13.1
Location_base_pair Starts at 15950935 and ends at 16144431 bp from pter ( according to hg18-Mar_2006)  [Mapping]
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
HGNC (Hugo)ABCC1   51
Entrez_Gene (NCBI)ABCC1  4363  ATP-binding cassette, sub-family C (CFTR/MRP), member 1
Cards
AtlasMRPID106
GeneCards (Weizmann)ABCC1
Ensembl (Hinxton)ENSG00000103222 [Gene_View]  ABCC1 [Vega]
AceView (NCBI)ABCC1
Genatlas (Paris)ABCC1
euGene (Indiana)4363
SOURCE (Stanford)NM_004996 NM_019862 NM_019898 NM_019899 NM_019900
Genomic and cartography
GoldenPath (UCSC)ABCC1  -  16p13.1   chr16:15950935-16144431 +  16p13.1   [Description]    (hg18-Mar_2006)
EnsemblABCC1 - 16p13.1 [CytoView]
Mapping of homologs : NCBIABCC1 [Mapview]
OMIM158343   
Gene and transcription
Gene : Genbank (Entrez)AB209120 AJ003198 AK311015 BC001636 BC156353
Reference sequence (RefSeq transcript) :SRSNM_004996 NM_019862 NM_019898 NM_019899 NM_019900
Reference transcript : EntrezNM_004996 NM_019862 NM_019898 NM_019899 NM_019900
RefSeq genomic : SRSAC_000059 AC_000148 NC_000016 NT_010393 NW_001838356 NW_926051
RefSeq genomic : EntrezAC_000059 AC_000148 NC_000016 NT_010393 NW_001838356 NW_926051
Consensus coding sequences : CCDS NCBIABCC1
Cluster EST : UnigeneHs.709181 [ SRS ] Hs.709181 [ NCBI ]
Alternative Splicing : Fast-db (Paris)4361
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtP33527 (SRS) P33527 (Expasy) P33527 (Uniprot)
With graphics : InterProP33527
Splice isoforms : VarSplice FASTAP33527(VarSplice FASTA)
Domaine pattern : Prosite (SRS)ABC_TM1F (PS50929)    ABC_TRANSPORTER_1 (PS00211)    ABC_TRANSPORTER_2 (PS50893)   
Domain pattern : Prosite (Expaxy)ABC_TM1F (PS50929)    ABC_TRANSPORTER_1 (PS00211)    ABC_TRANSPORTER_2 (PS50893)   
Domains : Interpro (SRS)AAA+_ATPase_core    ABC_TM_1    ABC_TM_transpt    ABC_transporter-like    Multidrug-R_assoc_MRP   
Domains : Interpro (EBI)AAA+_ATPase_core    ABC_TM_1    ABC_TM_transpt    ABC_transporter-like    Multidrug-R_assoc_MRP   
Related proteins : CluSTrP33527
Domain families : Pfam SRSABC_membrane (PF00664)    ABC_tran (PF00005)   
Domain families : Pfam SangerABC_membrane (PF00664)    ABC_tran (PF00005)   
Domain families : Pfam NCBIpfam00664    pfam00005   
Domain families : Smart EMBLAAA (SM00382)
Domain structure : Prodom (Prabi Lyon)ABC_transporter (PD000006)   
Blocks (Seattle)P33527
Crystal structure of protein : PDB SRS2CBZ   
Crystal structure of protein : PDBSum2CBZ   
Crystal structure of protein : IMB2CBZ   
Crystal structure of protein : PDB RSDB2CBZ   
HPRD01153
Protein Interaction databases
DIP (DOE-UCLA)P33527
IntAct (EBI)P33527
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIABCC1
SNP : GeneSNP UtahABCC1
SNP : HGBaseABCC1
Genetic variants : HAPMAPABCC1
Somatic Mutations in Cancer : COSMICABCC1 
Mutations and Diseases : HGMDABCC1
Hereditary diseases : OMIM158343   
Hereditary diseases : GENETests158343   
Diseases : Genetic AssociationABCC1
General knowledge
Homologs : HomoloGeneABCC1
Homology/Alignments : Family Browser UCSCABCC1
Phylogenetic Trees/Animal Genes : TreeFamABCC1
Chemical/Protein Interactions : CTD4363
Keywords Ontology : AmiGOnucleotide binding  transporter activity  ATP binding  membrane fraction  integral to plasma membrane  transport  membrane  ATPase activity  response to drug  ATPase activity, coupled to transmembrane movement of substances  
Keywords Ontology : EGO-EBInucleotide binding  transporter activity  ATP binding  membrane fraction  integral to plasma membrane  transport  membrane  ATPase activity  response to drug  ATPase activity, coupled to transmembrane movement of substances  
Pathways : BIOCARTAMulti-Drug Resistance Factors [Genes]   
Pathways : KEGG
Other databases
Probes
Probes : ImagenesABCC1 Related clones (RZPD - Berlin)
Literature
PubMed150 Pubmed reference(s) in Entrez
PubGeneABCC1

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 articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written11-1998Franck 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

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indexed on : Sat Jun 27 16:38:26 CEST 2009

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