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Literature summary extracted from

  • Wittgen, H.G.; van den Heuvel, J.J.; Krieger, E.; Schaftenaar, G.; Russel, F.G.; Koenderink, J.B.
    Phenylalanine 368 of multidrug resistance-associated protein 4 (MRP4/ABCC4) plays a crucial role in substrate-specific transport activity (2012), Biochem. Pharmacol., 84, 366-373.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
7.6.2.2 expression in HEK-293 cell, using baculoviral system Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
7.6.2.2 homology modeling with estradiol 17-beta-D-glucuronide, cyclic guanosine monophosphate, methotrextae and folic acid as substrates Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
7.6.2.2 F368A almost complete disruption of transport activity for all substrates tested Homo sapiens
7.6.2.2 F368W F368W-mediated estradiol 17-beta-D-glucuronide transport is increased to 250% of wild type MRP4, whereas cyclic guanosine monophosphate transport is decreased to 24% , and methotrextae and folic acid transport is reduced to 5580% of wild type transport activity Homo sapiens
7.6.2.2 F368Y F368Y-mediated cyclic guanosine monophosphate transport is increased to 160%, while transport of the other substrates is decreased by 2050% compared to wild type Homo sapiens
7.6.2.2 additional information residues F368 and W995 do not play an important role in the initial binding of substrates Homo sapiens
7.6.2.2 R998K almost complete disruption of transport activity for all substrates tested Homo sapiens
7.6.2.2 R998L almost complete disruption of transport activity for all substrates tested Homo sapiens
7.6.2.2 R998S almost complete disruption of transport activity for all substrates tested Homo sapiens
7.6.2.2 R998Y almost complete disruption of transport activity for all substrates tested Homo sapiens
7.6.2.2 W995A almost complete disruption of transport activity for all substrates tested Homo sapiens
7.6.2.2 W995F significantly decreased transport of all substrates Homo sapiens
7.6.2.2 W995Y significantly decreased transport of all substrates Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
7.6.2.2 0.013
-
 estradiol 17-beta-D-glucuronide/in mutant W995Y, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.017
-
 estradiol 17-beta-D-glucuronide/in wild-type, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.017
-
 estradiol 17-beta-D-glucuronide/in mutant F368W, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.031
-
 estradiol 17-beta-D-glucuronide/in mutant F368Y, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.054
-
 estradiol 17-beta-D-glucuronide/in mutant W995F, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.13
-
 folic acid/in mutant W995Y, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.15
-
 folic acid/in mutant W995F, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.16
-
 folic acid/in mutant F368W, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.17
-
 estradiol 17-beta-D-glucuronide/in wild-type, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.24
-
 methotrexate/in mutant F368W, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.25
-
 methotrexate/in wild-type, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.26
-
 folic acid/in mutant F368Y, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.3
-
 methotrexate/in mutant F368Y, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.35
-
 methotrexate/in mutant W995F, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.36
-
 cyclic guanosine monophosphate/in mutant W995F, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.39
-
 methotrexate/in mutant W995Y, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.48
-
 cyclic guanosine monophosphate/in mutant F368Y, pH 7.5, 37°C Homo sapiens
7.6.2.2 0.63
-
 cyclic guanosine monophosphate/in wild-type, pH 7.5, 37°C Homo sapiens
7.6.2.2 1.8
-
 cyclic guanosine monophosphate/in mutant W995Y, pH 7.5, 37°C Homo sapiens
7.6.2.2 2
-
 cyclic guanosine monophosphate/in mutant F368W, pH 7.5, 37°C Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
7.6.2.2 Homo sapiens
-
-
-

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
7.6.2.2 270
-
 wild-type, substrate methotrexate, pH 7.5, 37°C Homo sapiens
7.6.2.2 580
-
 wild-type, substrate estradiol 17-beta-D-glucuronide, pH 7.5, 37°C Homo sapiens
7.6.2.2 650
-
 wild-type, substrate folic acid, pH 7.5, 37°C Homo sapiens
7.6.2.2 3500
-
 wild-type, substrate cyclic guanosine monophosphate, pH 7.5, 37°C Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
7.6.2.2 ATP + H2O + cyclic guanosine monophosphate/in
-
 Homo sapiens ADP + phosphate + cyclic guanosine monophosphate/out
-
 ?
7.6.2.2 ATP + H2O + estradiol 17-beta-D-glucuronide/in
-
 Homo sapiens ADP + phosphate + estradiol 17-beta-D-glucuronide/out
-
 ?
7.6.2.2 ATP + H2O + folic acid/in
-
 Homo sapiens ADP + phosphate + folic acid/out
-
 ?
7.6.2.2 ATP + H2O + methotrexate/in
-
 Homo sapiens ADP + phosphate + methotrexate/out
-
 ?

Synonyms

EC Number Synonyms Comment Organism
7.6.2.2 ABCC4
-
 Homo sapiens
7.6.2.2 MRP4
-
 Homo sapiens