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ABCB1 ATP-binding cassette, sub-family B (MDR/TAP), member 1

Identity

Other namesPGY1 (P glycoprotein1/ multidrug resistance 1)
MDR1 (multidrug resistance 1)
HGNC (Hugo) ABCB1
LocusID (NCBI) 5243
Location 7q21.12
Location_base_pair Starts at 87133179 and ends at 87342639 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Description spans on a 120 kb genomic fragment; separated from MDR3 gene (which is transcribed in the same direction) by only 34 kb of intergenic DNA
Transcription 5 kb mRNA

Protein

Description the protein is called P-glycoprotein; 170 kDa transmembrane glycoprotein which includes 10-15 kDa of N-term glycosylation; the N-term half of the molecule contains 6 transmembrane domains, followed by a large cytoplasmic domain with an ATP binding site, and then a second section with 6 transmembrane domains and an ATP binding site which shows over 65% of amino acid similarity with the first half of the polypeptide
Expression normally expressed at secretory surface of a number of tissues, including biliary canaliculi, proximal tubules of the kidney, intestinal and colonic epithelium; hematopoietic stem cells express high levels of P-glycoprotein; overexpressed in many multidrug resistant cell lines and in tumor cells resistant to chemotherapy
Localisation mainly at the cell membrane, with a secondary localisation at the Golgi apparatus
Function the P-glycoprotein is an energy-dependent efflux pump involved in extrusion of many types of lypophilic coumpounds; it may acts in normal tissues as a protective mechanism against noxious xenobiotics and as a transporter of endogenous substrates; in tumour cells, the drug efflux pump results in a decrease in intracellular drug concentration
Homology closely related gene to MDR3 (also called PGY3), located at the same chromosomal site but not implicated in multidrug resistance; there are 3 murine homolog genes (mdr1, mdr2, mdr3) out of which only 2 (mdr1 and mdr3) are involved in multidrug resistance; member of a large superfamily of transmembrane transporter proteins named ATP Binding Cassette (ABC) transporters or Traffic ATPases; structural homology with other ABC transporter proteins (CFTR, MRP)

Implicated in

Entity tumor cells resistance
Disease tumor cells resistance to a wide variety of antineoplasic agents: doxorubicin, daunorubicin, vinblastine, vincristine, colchicine, actinomycine D, etoposide, tenoposide, mitoxantrone, homoharringtonine; this phenomenon is named "multidrug resistance" (MDR); P-glycoprotein is the main protein responsible for the MDR phenotype; however, other agents may be involved in MDR, independently or in association with P-glycoprotein: "multidrug resistant associated protein" (MRP), "lung resistance protein" (LRP), "anthracycline associated resistance protein" (ARX)
  
Entity leukemias
Disease In leukemia, MDR1 overexpression is observed in patients with a lower complete remission rate and with a shortening of overall survival; frequently associated with intermediate and poor prognosis karyotype; in ANLL, approximately 50% of patients are MDR positive at diagnosis (range 22-70%) and the MDR phenotype is more frequently observed in CD34+ leukemias; in ALL, the average number of MDR-positive cases is 22% at diagnosis
  
Entity tumour cell lines: in numerous continuous tumour cell lines which acquired experimentally a MDR phenotype when cultured with progressively increasing drug concentration, the acquisition of MDR was associated with hyperexpression of P-glycoprotein; for the higher levels of expression, southern blots revealed an increase in the number of copies of the MDR1 gene per cell
Cytogenetics the genomic amplification of MDR1 appears as extrachromosomic "double-minute chromosomes" (DM) or intrachromosomic "homogeneous staining regions" (HSR)
Oncogenesis amplification
  

External links

Nomenclature
HGNC (Hugo)ABCB1   40
Cards
AtlasPGY1ID105
Entrez_Gene (NCBI)ABCB1  5243  ATP-binding cassette, sub-family B (MDR/TAP), member 1
GeneCards (Weizmann)ABCB1
Ensembl (Hinxton)ENSG00000085563 [Gene_View]  chr7:87133179-87342639 [Contig_View]  ABCB1 [Vega]
ICGC DataPortalENSG00000085563
cBioPortalABCB1
AceView (NCBI)ABCB1
Genatlas (Paris)ABCB1
WikiGenes5243
SOURCE (Princeton)NM_000927
Genomic and cartography
GoldenPath (UCSC)ABCB1  -  7q21.12   chr7:87133179-87342639 -  7q21.12   [Description]    (hg19-Feb_2009)
EnsemblABCB1 - 7q21.12 [CytoView]
Mapping of homologs : NCBIABCB1 [Mapview]
OMIM120080   171050   612244   
Gene and transcription
Genbank (Entrez)AA776371 AB208970 AF016535 AF345625 AK290159
RefSeq transcript (Entrez)NM_000927
RefSeq genomic (Entrez)AC_000068 AC_000139 NC_000007 NC_018918 NG_011513 NT_007933 NT_079595 NW_001839064 NW_004929332
Consensus coding sequences : CCDS (NCBI)ABCB1
Cluster EST : UnigeneHs.737655 [ NCBI ]
CGAP (NCI)Hs.737655
Alternative Splicing : Fast-db (Paris)GSHG0028333
Alternative Splicing GalleryENSG00000085563
Gene ExpressionABCB1 [ NCBI-GEO ]     ABCB1 [ SEEK ]   ABCB1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP08183 (Uniprot)
NextProtP08183  [Medical]
With graphics : InterProP08183
Splice isoforms : SwissVarP08183 (Swissvar)
Catalytic activity : Enzyme3.6.3.44 [ Enzyme-Expasy ]   3.6.3.443.6.3.44 [ IntEnz-EBI ]   3.6.3.44 [ BRENDA ]   3.6.3.44 [ KEGG ]   
Domaine pattern : Prosite (Expaxy)ABC_TM1F (PS50929)    ABC_TRANSPORTER_1 (PS00211)    ABC_TRANSPORTER_2 (PS50893)   
Domains : Interpro (EBI)AAA+_ATPase [organisation]   ABC1_TM_dom [organisation]   ABC_transporter-like [organisation]   ABC_transporter_CS [organisation]   ABC_transptr_TM_dom [organisation]   P-loop_NTPase [organisation]  
Related proteins : CluSTrP08183
Domain families : Pfam (Sanger)ABC_membrane (PF00664)    ABC_tran (PF00005)   
Domain families : Pfam (NCBI)pfam00664    pfam00005   
Domain families : Smart (EMBL)AAA (SM00382)  
DMDM Disease mutations5243
Blocks (Seattle)P08183
Human Protein AtlasENSG00000085563 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP08183
HPRD01370
IPIIPI00027481   IPI01009677   IPI01009153   IPI00925262   IPI00792032   
Protein Interaction databases
DIP (DOE-UCLA)P08183
IntAct (EBI)P08183
FunCoupENSG00000085563
BioGRIDABCB1
InParanoidP08183
Interologous Interaction database P08183
IntegromeDBABCB1
STRING (EMBL)ABCB1
Ontologies - Pathways
Ontology : AmiGOG2/M transition of mitotic cell cycle  Golgi membrane  transporter activity  protein binding  ATP binding  plasma membrane  transport  drug transmembrane transport  xenobiotic-transporting ATPase activity  cell surface  membrane  integral to membrane  apical plasma membrane  response to drug  ATPase activity, coupled to transmembrane movement of substances  small molecule metabolic process  intercellular canaliculus  transmembrane transport  transmembrane transport  stem cell proliferation  
Ontology : EGO-EBIG2/M transition of mitotic cell cycle  Golgi membrane  transporter activity  protein binding  ATP binding  plasma membrane  transport  drug transmembrane transport  xenobiotic-transporting ATPase activity  cell surface  membrane  integral to membrane  apical plasma membrane  response to drug  ATPase activity, coupled to transmembrane movement of substances  small molecule metabolic process  intercellular canaliculus  transmembrane transport  transmembrane transport  stem cell proliferation  
Pathways : BIOCARTAMulti-Drug Resistance Factors [Genes]    Nuclear Receptors in Lipid Metabolism and Toxicity [Genes]    Hypoxia and p53 in the Cardiovascular system [Genes]   
Pathways : KEGGABC transporters    Bile secretion    MicroRNAs in cancer   
Protein Interaction DatabaseABCB1
Wikipedia pathwaysABCB1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)ABCB1
snp3D : Map Gene to Disease5243
SNP (GeneSNP Utah)ABCB1
SNP : HGBaseABCB1
Genetic variants : HAPMAPABCB1
Exome VariantABCB1
1000_GenomesABCB1 
ICGC programENSG00000085563 
Somatic Mutations in Cancer : COSMICABCB1 
CONAN: Copy Number AnalysisABCB1 
Mutations and Diseases : HGMDABCB1
Genomic VariantsABCB1  ABCB1 [DGVbeta]
dbVarABCB1
ClinVarABCB1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM120080    171050    612244   
MedgenABCB1
GENETestsABCB1
Disease Genetic AssociationABCB1
Huge Navigator ABCB1 [HugePedia]  ABCB1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneABCB1
Homology/Alignments : Family Browser (UCSC)ABCB1
Phylogenetic Trees/Animal Genes : TreeFamABCB1
Chemical/Protein Interactions : CTD5243
Chemical/Pharm GKB GenePA267
Clinical trialABCB1
Cancer Resource (Charite)ENSG00000085563
Other databases
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineABCB1
iHOPABCB1

Bibliography

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PMID 2648129
 
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Baer MR, Bloomfield CD
Journal of the National Cancer Institute. 1991 ; 83 (10) : 663-665.
PMID 2023265
 
Double minute chromosomes carrying the human multidrug resistance 1 and 2 genes are generated from the dimerization of submicroscopic circular DNAs in colchicine-selected KB carcinoma cells.
Schoenlein PV, Shen DW, Barrett JT, Pastan I, Gottesman MM
Molecular biology of the cell. 1992 ; 3 (5) : 507-520.
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Cell biological mechanisms of multidrug resistance in tumors.
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PMID 7909602
 
A YAC-based contig of 1.5 Mb spanning the human multidrug resistance gene region and delineating the amplification unit in three human multidrug-resistant cell lines.
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PMID 8876632
 
P-glycoprotein and multidrug resistance.
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Current opinion in genetics & development. 1996 ; 6 (5) : 610-617.
PMID 8939727
 
The MDR phenotype in hematologic malignancies: prognostic relevance and future perspectives.
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Annals of hematology. 1996 ; 72 (3) : 105-117.
PMID 8766251
 
Sequential emergence of MRP- and MDR1-gene over-expression as well as MDR1-gene translocation in homoharringtonine-selected K562 human leukemia cell lines.
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International journal of cancer. Journal international du cancer. 1996 ; 65 (3) : 365-371.
PMID 8575859
 
Multidrug resistance gene expression in acute myeloid leukemia: major prognosis significance for in vivo drug resistance to induction treatment.
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Annals of hematology. 1997 ; 74 (2) : 65-71.
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Functional expression of MDR-1 in acute myeloid leukemia: correlation with the clinical-biological, immunophenotypical, and prognostic disease characteristics.
Martˆ‚nez A, San Miguel JF, Valverde B, Bˆ°rez A, Moro MJ, Garcˆ‚a-Marcos MA, Pˆ©rez-Simˆ„n JA, Vidriales B, Orfao A
Annals of hematology. 1997 ; 75 (3) : 81-86.
PMID 9368475
 
MDR 1 expression is an independent prognostic factor for response and survival in de novo acute myeloid leukaemia.
van den Heuvel-Eibrink MM, van der Holt B, te Boekhorst PA, Pieters R, Schoester M, Lˆwenberg B, Sonneveld P
British journal of haematology. 1997 ; 99 (1) : 76-83.
PMID 9359506
 
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
 
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Contributor(s)

Written03-1998Franck Viguié

Citation

This paper should be referenced as such :
Viguié, F
ABCB1 (ATP-binding cassette, sub-family B (MDR/TAP), member 1)
Atlas Genet Cytogenet Oncol Haematol. 1998;2(2):45-46.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/PGY1ID105.html

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indexed on : Fri Jul 11 16:55:47 CEST 2014

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