Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

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

Written1998-03Franck Viguié
Laboratoire de Cytogenetique - Service d'Hematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France

(Note : for Links provided by Atlas : click)

Identity

Other namesPGY1 (P glycoprotein1/ multidrug resistance 1)
MDR1 (multidrug resistance 1)
HGNC (Hugo) ABCB1
LocusID (NCBI) 5243
Atlas_Id 105
Location 7q21.12  [Link to chromosome band 7q21]
Location_base_pair Starts at 87133179 and ends at 87342639 bp from pter ( according to hg19-Feb_2009)  [Mapping ABCB1.png]
Fusion genes
(updated 2016)
GRM3 (7q21.11) / ABCB1 (7q21.12)

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

Note
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 AML, 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
  

Bibliography

Multidrug resistance in acute myeloid leukemia.
Baer MR, Bloomfield CD
Journal of the National Cancer Institute. 1991 ; 83 (10) : 663-665.
PMID 2023265
 
P-glycoprotein multidrug resistance and cancer.
Bosch I, Croop J
Biochimica et biophysica acta. 1996 ; 1288 (2) : F37-F54.
PMID 8876632
 
P-glycoprotein and multidrug resistance.
Gottesman MM, Pastan I, Ambudkar SV
Current opinion in genetics & development. 1996 ; 6 (5) : 610-617.
PMID 8939727
 
The MDR phenotype in hematologic malignancies: prognostic relevance and future perspectives.
Hegewisch-Becker S, Hossfeld DK
Annals of hematology. 1996 ; 72 (3) : 105-117.
PMID 8766251
 
Multidrug resistance gene expression in acute myeloid leukemia: major prognosis significance for in vivo drug resistance to induction treatment.
Hunault M, Zhou D, Delmer A, Ramond S, Viguié F, Cadiou M, Perrot JY, Levy V, Rio B, Cymbalista F, Zittoun R, Marie JP
Annals of hematology. 1997 ; 74 (2) : 65-71.
PMID 9063375
 
Functional expression of MDR-1 in acute myeloid leukemia: correlation with the clinical-biological, immunophenotypical, and prognostic disease characteristics.
Martínez A, San Miguel JF, Valverde B, Bárez A, Moro MJ, García-Marcos MA, Pérez-Simó JA, Vidriales B, Orfao A
Annals of hematology. 1997 ; 75 (3) : 81-86.
PMID 9368475
 
Autonomously replicating episomes contain mdr1 genes in a multidrug-resistant human cell line.
Ruiz JC, Choi KH, von Hoff DD, Roninson IB, Wahl GM
Molecular and cellular biology. 1989 ; 9 (1) : 109-115.
PMID 2648129
 
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.
PMID 1611154
 
Cell biological mechanisms of multidrug resistance in tumors.
Simon SM, Schindler M
Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (9) : 3497-3504.
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.
Torigoe K, Sato S, Kusaba H, Kohno K, Kuwano M, Okumura K, Green ED, Tsui LC, Scherer SW, Schlessinger D, Wada M
Genome research. 1995 ; 5 (3) : 233-244.
PMID 8593611
 
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
 
Sequential emergence of MRP- and MDR1-gene over-expression as well as MDR1-gene translocation in homoharringtonine-selected K562 human leukemia cell lines.
Zhou DC, Ramond S, Viguie F, Faussat AM, Zittoun R, Marie JP
International journal of cancer. Journal international du cancer. 1996 ; 65 (3) : 365-371.
PMID 8575859
 
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, Löwenberg B, Sonneveld P
British journal of haematology. 1997 ; 99 (1) : 76-83.
PMID 9359506
 

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 journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PGY1ID105.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  idic(7)(q11.2)

External links

Nomenclature
HGNC (Hugo)ABCB1   40
Cards
AtlasPGY1ID105
Entrez_Gene (NCBI)ABCB1  5243  ATP binding cassette subfamily B member 1
AliasesABC20; CD243; CLCS; GP170; 
MDR1; P-GP; PGY1
GeneCards (Weizmann)ABCB1
Ensembl hg19 (Hinxton)ENSG00000085563 [Gene_View]  chr7:87133179-87342639 [Contig_View]  ABCB1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000085563 [Gene_View]  chr7:87133179-87342639 [Contig_View]  ABCB1 [Vega]
ICGC DataPortalENSG00000085563
TCGA cBioPortalABCB1
AceView (NCBI)ABCB1
Genatlas (Paris)ABCB1
WikiGenes5243
SOURCE (Princeton)ABCB1
Genomic and cartography
GoldenPath hg19 (UCSC)ABCB1  -     chr7:87133179-87342639 -  7q21.12   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)ABCB1  -     7q21.12   [Description]    (hg38-Dec_2013)
EnsemblABCB1 - 7q21.12 [CytoView hg19]  ABCB1 - 7q21.12 [CytoView hg38]
Mapping of homologs : NCBIABCB1 [Mapview hg19]  ABCB1 [Mapview hg38]
OMIM120080   171050   612244   
Gene and transcription
Genbank (Entrez)AA776371 AB208970 AF016535 AF345623 AF345624
RefSeq transcript (Entrez)NM_000927
RefSeq genomic (Entrez)NC_000007 NC_018918 NG_011513 NT_007933 NW_004929332
Consensus coding sequences : CCDS (NCBI)ABCB1
Cluster EST : UnigeneHs.737655 [ NCBI ]
CGAP (NCI)Hs.737655
Alternative Splicing GalleryENSG00000085563
Gene ExpressionABCB1 [ NCBI-GEO ]   ABCB1 [ EBI - ARRAY_EXPRESS ]   ABCB1 [ SEEK ]   ABCB1 [ MEM ]
Gene Expression Viewer (FireBrowse)ABCB1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5243
GTEX Portal (Tissue expression)ABCB1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP08183 (Uniprot)
NextProtP08183  [Sequence]  [Exons]  [Medical]  [Publications]
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 ]   
PhosPhoSitePlusP08183
Domaine pattern : Prosite (Expaxy)ABC_TM1F (PS50929)    ABC_TRANSPORTER_1 (PS00211)    ABC_TRANSPORTER_2 (PS50893)   
Domains : Interpro (EBI)AAA+_ATPase    ABC1_TM_dom    ABC_transporter-like    ABC_transporter_CS    P-loop_NTPase   
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)ABCB1
SuperfamilyP08183
Human Protein AtlasENSG00000085563
Peptide AtlasP08183
HPRD01370
IPIIPI00027481   IPI01009677   IPI01009153   IPI00925262   IPI00792032   
Protein Interaction databases
DIP (DOE-UCLA)P08183
IntAct (EBI)P08183
FunCoupENSG00000085563
BioGRIDABCB1
STRING (EMBL)ABCB1
ZODIACABCB1
Ontologies - Pathways
QuickGOP08183
Ontology : AmiGOG2/M transition of mitotic cell cycle  antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent  antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent  antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent  positive regulation of antigen processing and presentation of peptide antigen via MHC class I  transporter activity  protein binding  ATP binding  plasma membrane  transport  drug transmembrane transport  drug transmembrane transport  metabolic process  xenobiotic-transporting ATPase activity  cell surface  membrane  integral component of membrane  response to drug  ATPase activity, coupled to transmembrane movement of substances  xenobiotic transport  xenobiotic transport  transmembrane transport  extracellular exosome  stem cell proliferation  
Ontology : EGO-EBIG2/M transition of mitotic cell cycle  antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent  antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent  antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent  positive regulation of antigen processing and presentation of peptide antigen via MHC class I  transporter activity  protein binding  ATP binding  plasma membrane  transport  drug transmembrane transport  drug transmembrane transport  metabolic process  xenobiotic-transporting ATPase activity  cell surface  membrane  integral component of membrane  response to drug  ATPase activity, coupled to transmembrane movement of substances  xenobiotic transport  xenobiotic transport  transmembrane transport  extracellular exosome  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   
REACTOMEP08183 [protein]
REACTOME PathwaysR-HSA-382556 ABC-family proteins mediated transport [pathway]
REACTOME PathwaysR-HSA-2161517 Abacavir transmembrane transport [pathway]
NDEx NetworkABCB1
Atlas of Cancer Signalling NetworkABCB1
Wikipedia pathwaysABCB1
Orthology - Evolution
OrthoDB5243
GeneTree (enSembl)ENSG00000085563
Phylogenetic Trees/Animal Genes : TreeFamABCB1
Homologs : HomoloGeneABCB1
Homology/Alignments : Family Browser (UCSC)ABCB1
Gene fusions - Rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerABCB1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ABCB1
dbVarABCB1
ClinVarABCB1
1000_GenomesABCB1 
Exome Variant ServerABCB1
ExAC (Exome Aggregation Consortium)ABCB1 (select the gene name)
Genetic variants : HAPMAP5243
Genomic Variants (DGV)ABCB1 [DGVbeta]
Mutations
ICGC Data PortalABCB1 
TCGA Data PortalABCB1 
Broad Tumor PortalABCB1
OASIS PortalABCB1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICABCB1 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Pharmacogenomics of Infectious Diseases (PGx_IfD )
BioMutasearch ABCB1
DgiDB (Drug Gene Interaction Database)ABCB1
DoCM (Curated mutations)ABCB1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ABCB1 (select a term)
intoGenABCB1
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)7:87133179-87342639  ENSG00000085563
CONAN: Copy Number AnalysisABCB1 
Mutations and Diseases : HGMDABCB1
OMIM120080    171050    612244   
MedgenABCB1
Genetic Testing Registry ABCB1
NextProtP08183 [Medical]
TSGene5243
GENETestsABCB1
Huge Navigator ABCB1 [HugePedia]
snp3D : Map Gene to Disease5243
BioCentury BCIQABCB1
ClinGenABCB1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5243
Chemical/Pharm GKB GenePA267
Clinical trialABCB1
Miscellaneous
canSAR (ICR)ABCB1 (select the gene name)
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineABCB1
EVEXABCB1
GoPubMedABCB1
iHOPABCB1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Sep 19 19:25:47 CEST 2016

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.