Reviewed,
UniProtKB/Swiss-Prot P08183 (MDR1_HUMAN)
Last modified
June 16, 2009.
Version 120.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
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Names and origin
| Protein names | Recommended name: Multidrug resistance protein 1 EC=3.6.3.44 Alternative name(s): ATP-binding cassette sub-family B member 1 P-glycoprotein 1 CD_antigen=CD243 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1280 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells. |
| Catalytic activity | ATP + H2O + xenobiotic(In) = ADP + phosphate + xenobiotic(Out). |
| Subcellular location | |
| Tissue specificity | Expressed in liver, kidney, small intestine and brain. |
| Polymorphism | Genetic variation in ABCB1 may play a role in patients who do not respond to drug treatment. |
| Involvement in disease | Genetic variations in ABCB1 are associated with susceptibility to inflammatory bowel disease type 13 (IBD13) [MIM:612244]. Inflammatory bowel disease is characterized by a chronic relapsing intestinal inflammation. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may involve any part of the gastrointestinal tract, but most frequently the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. Crohn disease and ulcerative colitis are commonly classified as autoimmune diseases. |
| Sequence similarities | Belongs to the ABC transporter family. Multidrug resistance exporter (TC 3.A.1.201) subfamily. [View classification] Contains 2 ABC transmembrane type-1 domains. Contains 2 ABC transporter domains. |
| Sequence caution | The sequence AAB69423.1 differs from that shown. Reason: Erroneous gene model prediction. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Transport |
| Cellular component | Membrane |
| Coding sequence diversity | Polymorphism |
| Domain | Repeat Transmembrane |
| Ligand | ATP-binding Nucleotide-binding |
| Molecular function | Hydrolase |
| PTM | Glycoprotein Phosphoprotein |
| Gene Ontology (GO) | |
| Biological process | response to drug Traceable author statement. Source: ProtInc transportTraceable author statement. Source: ProtInc |
| Cellular component | cell surface Inferred from direct assay. Source: UniProtKB integral to membraneTraceable author statement. Source: ProtInc membrane fractionTraceable author statement. Source: ProtInc |
| Molecular function | ATP binding Traceable author statement. Source: ProtInc protein bindingInferred from physical interaction. Source: IntAct xenobiotic-transporting ATPase activityInferred from electronic annotation. Source: EC |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1280 | 1280 | Multidrug resistance protein 1 | PRO_0000093332 | |||||
Regions | |||||||||
| Topological domain | 1 – 51 | 51 | Cytoplasmic Potential | ||||||
| Transmembrane | 52 – 72 | 21 | Potential | ||||||
| Transmembrane | 120 – 140 | 21 | Potential | ||||||
| Transmembrane | 189 – 209 | 21 | Potential | ||||||
| Transmembrane | 216 – 236 | 21 | Potential | ||||||
| Transmembrane | 297 – 317 | 21 | Potential | ||||||
| Transmembrane | 326 – 346 | 21 | Potential | ||||||
| Topological domain | 347 – 710 | 364 | Cytoplasmic Potential | ||||||
| Transmembrane | 711 – 731 | 21 | Potential | ||||||
| Transmembrane | 757 – 777 | 21 | Potential | ||||||
| Transmembrane | 833 – 853 | 21 | Potential | ||||||
| Transmembrane | 854 – 874 | 21 | Potential | ||||||
| Transmembrane | 937 – 957 | 21 | Potential | ||||||
| Transmembrane | 974 – 994 | 21 | Potential | ||||||
| Topological domain | 995 – 1280 | 286 | Cytoplasmic Potential | ||||||
| Domain | 51 – 357 | 307 | ABC transmembrane type-1 1 | ||||||
| Domain | 392 – 628 | 237 | ABC transporter 1 | ||||||
| Domain | 711 – 1000 | 290 | ABC transmembrane type-1 2 | ||||||
| Domain | 1035 – 1273 | 239 | ABC transporter 2 | ||||||
| Nucleotide binding | 427 – 434 | 8 | ATP 1 By similarity | ||||||
| Nucleotide binding | 1070 – 1077 | 8 | ATP 2 By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 660 | 1 | Phosphoserine By similarity | ||||||
| Glycosylation | 91 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 94 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 99 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Natural variant | 17 | 1 | F → L: dbSNP rs28381804. | VAR_022276 | |||||
| Natural variant | 21 | 1 | N → D: dbSNP rs9282564. | VAR_014704 | |||||
| Natural variant | 44 | 1 | N → S: dbSNP rs1202183. | VAR_055423 | |||||
| Natural variant | 80 | 1 | A → E: dbSNP rs9282565. | VAR_055424 | |||||
| Natural variant | 103 | 1 | F → L Rare polymorphism. Ref.12 | VAR_015001 | |||||
| Natural variant | 108 | 1 | E → K Ref.14 | VAR_018351 | |||||
| Natural variant | 185 | 1 | G → V in a colchicine-selected multidrug-resistant cell line; confers increased resistance to colchicine. dbSNP rs1128501. Ref.1 Ref.3 Ref.9 | VAR_015002 | |||||
| Natural variant | 261 | 1 | I → V: dbSNP rs36008564. | VAR_055425 | |||||
| Natural variant | 400 | 1 | S → N: dbSNP rs2229109. | VAR_015003 | |||||
| Natural variant | 566 | 1 | E → K: dbSNP rs28381902. | VAR_022277 | |||||
| Natural variant | 593 | 1 | R → C: dbSNP rs28381914. | VAR_022278 | |||||
| Natural variant | 599 | 1 | A → T: dbSNP rs2235036. | VAR_055426 | |||||
| Natural variant | 669 | 1 | R → C: dbSNP rs35023033. | VAR_055427 | |||||
| Natural variant | 801 | 1 | V → M: dbSNP rs2235039. | VAR_055428 | |||||
| Natural variant | 829 | 1 | I → V: dbSNP rs2032581. | VAR_055429 | |||||
| Natural variant | 836 | 1 | I → V: dbSNP rs28381967. | VAR_022279 | |||||
| Natural variant | 887 | 1 | K → N in a colorectal cancer sample; somatic mutation. Ref.19 | VAR_035737 | |||||
| Natural variant | 893 | 1 | S → A Common allele; associated with susceptibility to IBD13; has decreased enzyme activity. dbSNP rs2032582. | VAR_013361 | |||||
| Natural variant | 893 | 1 | S → T Rare allele. dbSNP rs2032582. | VAR_013362 | |||||
| Natural variant | 986 | 1 | M → V | VAR_018352 | |||||
| Natural variant | 999 | 1 | A → T Ref.10 | VAR_015004 | |||||
| Natural variant | 1051 | 1 | P → A: dbSNP rs28401798. | VAR_022280 | |||||
| Natural variant | 1107 | 1 | Q → P: dbSNP rs55852620. | VAR_015005 | |||||
| Natural variant | 1141 | 1 | S → T: dbSNP rs2229107. | VAR_022281 | |||||
| Natural variant | 1251 | 1 | V → I Ref.4 Ref.15 | VAR_018353 | |||||
Experimental info | |||||||||
| Sequence conflict | 23 | 1 | S → R in CAA41558. Ref.7 | ||||||
| Sequence conflict | 336 | 1 | Missing in AAB69423. Ref.3 | ||||||
| Sequence conflict | 412 | 1 | G → A Ref.3 | ||||||
| Sequence conflict | 438 | 1 | Q → S Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells." Chen C.-J., Chin J.E., Ueda K., Clark D.P., Pastan I., Gottesman M.M., Roninson I.B. Cell 47:381-389(1986) [PubMed: 2876781] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS VAL-185 AND ALA-893. |
| [2] | "Genomic organization of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins." Chen C.-J., Clark D.P., Ueda K., Pastan I., Gottesman M.M., Roninson I.B. J. Biol. Chem. 265:506-514(1990) [PubMed: 1967175] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-893. |
| [3] | "Multidrug-resistant human sarcoma cells with a mutant P-glycoprotein, altered phenotype, and resistance to cyclosporins." Chen G., Duran G.E., Steger K.A., Lacayo N.J., Jaffrezou J.P., Dumontet C., Sikic B.I. J. Biol. Chem. 272:5974-5982(1997) [PubMed: 9038218] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS VAL-185 AND ALA-893. |
| [4] | NIEHS SNPs program Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-17; ASP-21; ASN-400; LYS-566; CYS-593; VAL-836; ALA-893; ALA-1051; THR-1141 AND ILE-1251. |
| [5] | "The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. Wilson R.K.Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | "mdr1/P-glycoprotein gene segments analyzed from various human leukemic cell lines exhibiting different multidrug resistance profiles." Gekeler V., Weger S., Probst H. Biochem. Biophys. Res. Commun. 169:796-802(1990) [PubMed: 1972623] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 178-215 AND 800-856. |
| [7] | "P-glycoprotein gene (MDR1) cDNA from human adrenal: normal P-glycoprotein carries Gly185 with an altered pattern of multidrug resistance." Kioka N., Tsubota J., Kakehi Y., Komano T., Gottesman M.M., Pastan I., Ueda K. Biochem. Biophys. Res. Commun. 162:224-231(1989) [PubMed: 2568832] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-23. |
| [8] | "ABC drug transporters: hereditary polymorphisms and pharmacological impact in MDR1, MRP1 and MRP2." Kerb R., Hoffmeyer S., Brinkmann U. Pharmacogenomics 2:51-64(2001) [PubMed: 11258197] [Abstract] Cited for: REVIEW. |
| [9] | "An altered pattern of cross-resistance in multidrug-resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene." Choi K.H., Chen C.-J., Kriegler M., Roninson I.B. Cell 53:519-529(1988) [PubMed: 2897240] [Abstract] Cited for: VARIANT VAL-185. |
| [10] | "Genetic polymorphism in MDR-1: a tool for examining allelic expression in normal cells, unselected and drug-selected cell lines, and human tumors." Mickley L.A., Lee J.-S., Weng Z., Zhan Z., Alvarez M., Wilson W., Bates S.E., Fojo T. Blood 91:1749-1756(1998) [PubMed: 9473242] [Abstract] Cited for: VARIANTS ALA-893 AND THR-999. |
| [11] | "A new polymorphism (N21D) in the exon 2 of the human MDR1 gene encoding the P-glycoprotein." Decleves X., Chevillard S., Charpentier C., Vielh P., Laplanche J.-L. Hum. Mutat. 15:486-486(2000) [PubMed: 10790226] [Abstract] Cited for: VARIANT ASP-21. |
| [12] | "Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo." Hoffmeyer S., Burk O., von Richter O., Arnold H.P., Brockmoeller J., Johne A., Cascorbi I., Gerloff T., Roots I., Eichelbaum M., Brinkmann U. Proc. Natl. Acad. Sci. U.S.A. 97:3473-3478(2000) [PubMed: 10716719] [Abstract] Cited for: VARIANTS ASP-21; LEU-103 AND ASN-400. |
| [13] | "Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects." Cascorbi I., Gerloff T., Johne A., Meisel C., Hoffmeyer S., Schwab M., Schaeffeler E., Eichelbaum M., Brinkmann U., Roots I. Clin. Pharmacol. Ther. 69:169-174(2001) [PubMed: 11240981] [Abstract] Cited for: VARIANTS ASP-21; ASN-400; ALA-893; THR-893 AND PRO-1107. |
| [14] | "Polymorphism of MDR1 gene in healthy Japanese subjects: a novel SNP with an amino acid substitution (Glu108Lys)." Honda T., Dan Y., Koyabu N., Ieiri I., Otsubo K., Higuchi S., Ohtani H., Sawada J. Drug Metab. Pharmacokinet. 17:479-481(2002) [PubMed: 15618700] [Abstract] Cited for: VARIANT LYS-108. |
| [15] | "Twelve novel single nucleotide polymorphisms in ABCB1/MDR1 among Japanese patients with ventricular tachycardia who were administered amiodarone." Itoda M., Saito Y., Komamura K., Ueno K., Kamakura S., Ozawa S., Sawada J. Drug Metab. Pharmacokinet. 17:566-571(2002) [PubMed: 15618713] [Abstract] Cited for: VARIANT ILE-1251. |
| [16] | "Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population." Saito S., Iida A., Sekine A., Miura Y., Ogawa C., Kawauchi S., Higuchi S., Nakamura Y. J. Hum. Genet. 47:38-50(2002) [PubMed: 11829140] [Abstract] Cited for: VARIANTS ALA-893 AND THR-893. |
| [17] | "MDR1 Ala893 polymorphism is associated with inflammatory bowel disease." Brant S.R., Panhuysen C.I.M., Nicolae D., Reddy D.M., Bonen D.K., Karaliukas R., Zhang L., Swanson E., Datta L.W., Moran T., Ravenhill G., Duerr R.H., Achkar J.-P., Karban A.S., Cho J.H. Am. J. Hum. Genet. 73:1282-1292(2003) [PubMed: 14610718] [Abstract] Cited for: VARIANTS ALA-893 AND THR-893, ASSOCIATION WITH SUSCEPTIBILITY TO IBD13. |
| [18] | Erratum Brant S.R., Panhuysen C.I.M., Nicolae D., Reddy D.M., Bonen D.K., Karaliukas R., Zhang L., Swanson E., Datta L.W., Moran T., Ravenhill G., Duerr R.H., Achkar J.-P., Karban A.S., Cho J.H. Am. J. Hum. Genet. 74:1080-1080(2004) |
| [19] | "The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. Velculescu V.E.Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-887. |
| + | Additional computationally mapped references. |
Web resources
| Atlas of Genetics and Cytogenetics in Oncology and Haematology |
| NIEHS-SNPs |
| SHMPD The Singapore human mutation and polymorphism database |
| Wikipedia P-glycoprotein entry |
Cross-references
Sequence databases | |
|---|---|
| M14758 mRNA. Translation: AAA59575.1. M29447 M29446 Genomic DNA. Translation: AAA59576.1. AF016535 mRNA. Translation: AAB69423.1. AY910577 Genomic DNA. Translation: AAW82430.1. AC002457 Genomic DNA. Translation: AAM49149.1. Sequence problems. AC005068 Genomic DNA. No translation available. M37724 Genomic DNA. Translation: AAA88047.1. M37725 Genomic DNA. Translation: AAA88048.1. X58723 Genomic DNA. Translation: CAA41558.1. | |
| IPI | IPI00027481. |
| PIR | DVHU1. A34914. |
| RefSeq | NP_000918.2. |
| UniGene | Hs.489033 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1MT0 based on UniProtKB P08716. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P08183. 2 interactions. |
Protein family/group databases | |
| TCDB | 3.A.1.201.1. ATP-binding cassette (ABC) superfamily. |
PTM databases | |
| PhosphoSite | P08183. |
Proteomic databases | |
| PRIDE | P08183. |
Genome annotation databases | |
| Ensembl | ENSG00000085563. Homo sapiens. [Contig view] |
| GeneID | 5243. |
| KEGG | hsa:5243. |
Organism-specific databases | |
| GeneCards | GC07M086970. |
| H-InvDB | HIX0033521. HIX0033618. |
| HGNC | HGNC:40. ABCB1. |
| HPA | CAB001716. |
| MIM | 120080. phenotype. 171050. gene. 612244. phenotype. |
| PharmGKB | PA267. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | P08183. |
| HOVERGEN | P08183. |
Enzyme and pathway databases | |
| BRENDA | 3.6.3.44. 247. |
| Pathway_Interaction_DB | hif1_tfpathway. HIF-1-alpha transcription factor network. |
Gene expression databases | |
| ArrayExpress | P08183. |
| Bgee | P08183. |
| CleanEx | HS_ABCB1. |
| GermOnline | ENSG00000085563. Homo sapiens. |
Family and domain databases | |
| ProDom | PD000006. ABC_transporter. 2 hits. [Graphical view] [Entries sharing at least one domain] |
| PROSITE | PS50929. ABC_TM1F. 2 hits. PS00211. ABC_TRANSPORTER_1. 2 hits. PS50893. ABC_TRANSPORTER_2. 2 hits. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| DrugBank | DB00171. Adenosine triphosphate. DB00802. Alfentanil. DB01169. Arsenic trioxide. DB01072. Atazanavir. DB01136. Carvedilol. DB01394. Colchicine. DB00091. Cyclosporine. DB00694. Daunorubicin. DB00975. Dipyridamole. DB01196. Estramustine. DB00875. Flupenthixol. DB00619. Imatinib. DB01167. Itraconazole. DB00622. Nicardipine. DB01182. Propafenone. DB01103. Quinacrine. DB00908. Quinidine. DB00243. Ranolazine. DB01045. Rifampin. DB00778. Roxithromycin. DB01232. Saquinavir. DB00675. Tamoxifen. DB00570. Vinblastine. |
| NextBio | 20254. |
| SOURCE | Search... |
Entry information
| Entry name | MDR1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P08183 Secondary accession number(s): Q12755, Q14812 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human cell differentiation molecules CD nomenclature of surface proteins of human leucocytes and list of entries |
| Human chromosome 7 Human chromosome 7: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |
| Recent format changes Overview of recent format changes |

Clusters with


