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Literature summary for 7.6.2.2 extracted from
- Structural determinants of substrate specificity differences between human multidrug resistance protein (MRP) 1 (ABCC1) and MRP3 (ABCC3) (2008), Drug Metab. Dispos., 36, 2571-2581.
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| wild-type MRP1 and mutant hybrid MRP1/MRP3 are expressed in Sf21 insect cells as two half-molecules, comprising amino acids 1 to 932 and 932 to 1531, respectively, using the baculovirus expression vector, expression of wild-type and mutant MRP1 in HEK-293 cell membranes | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| A481G/V482A/M483V/M485V | the MRP1 mutant shows altered transport activities compared to the wild-type MRP1 | Homo sapiens |
| A493K/H494Q/S497L/N500S | the MRP1 mutant shows altered transport activities compared to the wild-type MRP1 | Homo sapiens |
| A493K/H494Q/S497L/N500S/N506S | the MRP1 mutant shows altered transport activities compared to the wild-type MRP1 | Homo sapiens |
| A493K/H494Q/S497L/N506S/T487M/K488R/T489A/Y490F | the MRP1 mutant shows altered transport activities compared to the wild-type MRP1 | Homo sapiens |
| I441L | the mutant shows reduced activity with vincristine, VP-16, and doxorubicin compared to the wild-type enzyme | Homo sapiens |
| M443L | the mutant shows reduced activity with vincristine, VP-16, and doxorubicin compared to the wild-type enzyme | Homo sapiens |
| M443L/Y440F/1441L | the MRP1 mutant shows altered transport activities compared to the wild-type MRP1 | Homo sapiens |
| additional information | construction of a series of MRP1/MRP3 hybrids. Substitution of the region encompassing transmembrane helices 8 and 9 and portions of cytoplasmic loops 4 and 5 of MRP1 with the equivalent region of MRP3 eliminates LTC4 transport | Homo sapiens |
| V479L/A481G/V482A/M483V/M485V | the MRP1 mutant shows altered transport activities compared to the wild-type MRP1 | Homo sapiens |
| V479L/A481G/V482A/M483V/N500S | the MRP1 mutant shows altered transport activities compared to the wild-type MRP1 | Homo sapiens |
| Y440F | MRP1 mutant, substitution of Tyr440 with Phe, as found in MRP3, reduces leukotriene C4 and GSH-stimulated estrone-3-sulfate transport without affecting transport of other substrates. The mutation increased the Km for LTC4 5fold and substantially reduces photolabeling of MRP1 by both LTC4 and the GSH derivative, azidophenacyl-GSH | Homo sapiens |
| Y440F | the mutant shows reduced activity with vincristine, VP-16, and doxorubicin compared to the wild-type enzyme | Homo sapiens |
| Y440F/1441L | the mutant shows reduced activity with vincristine, VP-16, and doxorubicin compared to the wild-type enzyme | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| membrane | - |
Homo sapiens | 16020 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | - |
Homo sapiens |  |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + H2O + 17beta-estradiol 17-(beta-D-glucuronide)/in | Homo sapiens | transported by MRP1 and MRP3 | ADP + phosphate + 17beta-estradiol 17-(beta-D-glucuronide)/out | - |
? | |
| ATP + H2O + estrone-3-sulfate/in | Homo sapiens | - |
ADP + phosphate + estrone-3-sulfate/out | - |
? | |
| ATP + H2O + leukotriene C4/in | Homo sapiens | - |
ADP + phosphate + leukotriene C4/out | - |
? | |
| ATP + H2O + xenobiotic/in | Homo sapiens | MRP1 transports a wide range of natural product drugs and structurally diverse conjugated and unconjugated organic anions. Its closest relative is MRP3. MRP1 transports GSH and GSH conjugates and displays GSH-stimulated transport of a number of unconjugated and conjugated compounds. In contrast, MRP3 does not transport GSH and is a poor transporter of GSH conjugates | ADP + phosphate + xenobiotic/out | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| additional information | - |
relative drug resistance factor of wild-type MRP1and MRP3, and mutants, overview. Transport activities of wild-type MRP1 and of the mutant hybride MRP1/MRP3 prepared from Sf21 cells, overview | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + H2O + 17beta-estradiol 17-(beta-D-glucuronide)/in | transported by MRP1 and MRP3 | Homo sapiens | ADP + phosphate + 17beta-estradiol 17-(beta-D-glucuronide)/out | - |
? | |
| ATP + H2O + doxorubicin/in | - |
Homo sapiens | ADP + phosphate + doxorubicin/out | - |
? | |
| ATP + H2O + estrone-3-sulfate/in | - |
Homo sapiens | ADP + phosphate + estrone-3-sulfate/out | - |
? | |
| ATP + H2O + leukotriene C4/in | - |
Homo sapiens | ADP + phosphate + leukotriene C4/out | - |
? | |
| ATP + H2O + methotrexate/in | - |
Homo sapiens | ADP + phosphate + methotrexate/out | - |
? | |
| ATP + H2O + vincristine/in | - |
Homo sapiens | ADP + phosphate + vincristine/out | - |
? | |
| ATP + H2O + VP-16/in | - |
Homo sapiens | ADP + phosphate + VP-16/out | - |
? | |
| ATP + H2O + xenobiotic/in | MRP1 transports a wide range of natural product drugs and structurally diverse conjugated and unconjugated organic anions. Its closest relative is MRP3. MRP1 transports GSH and GSH conjugates and displays GSH-stimulated transport of a number of unconjugated and conjugated compounds. In contrast, MRP3 does not transport GSH and is a poor transporter of GSH conjugates | Homo sapiens | ADP + phosphate + xenobiotic/out | - |
? | |
| ATP + H2O + xenobiotic/in | ATP-dependent transport into inside-out membrane vesicles by recombinant enzymes, overview | Homo sapiens | ADP + phosphate + xenobiotic/out | - |
? | |
| additional information | Tyr440, naturally occuring in wild-type MRP3 and recombinantly in MRP1 mutants, makes a major contribution to recognition of GSH and the GSH moiety of conjugates such as LTC4 | Homo sapiens | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| ABCC1 | - |
Homo sapiens |
| ABCC3 | - |
Homo sapiens |
| More | multidrug resistance proteins are members of the C branch of the ATP-binding cassette transporter superfamily | Homo sapiens |
| MRP1 | - |
Homo sapiens |
| MRP3 | - |
Homo sapiens |
| multidrug resistance protein 1 | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 23 | 37 | assay at 23°C or at 37°C dependent on the substrate | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | dependent on | Homo sapiens | |
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