{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"O15439","secondaryAccessions":["A9Z1Z7","B7Z3Q7","Q8IVZ4","Q8IZN6","Q8NEW8","Q9Y6J2"],"uniProtkbId":"MRP4_HUMAN","entryAudit":{"firstPublicDate":"1998-07-15","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2008-09-23","entryVersion":226,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"ATP-binding cassette sub-family C member 4"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11856762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12523936"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12835412"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12883481"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15364914"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15454390"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16282361"}],"value":"7.6.2.-"},{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11856762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12105214"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15454390"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17344354"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18300232"}],"value":"7.6.2.2"},{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17959747"}],"value":"7.6.2.3"}]},"alternativeNames":[{"fullName":{"value":"MRP/cMOAT-related ABC transporter"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"9661885"}],"value":"Multi-specific organic anion transporter B"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"9661885"}],"value":"MOAT-B"}]},{"fullName":{"value":"Multidrug resistance-associated protein 4"}}]},"genes":[{"geneName":{"value":"ABCC4"},"synonyms":[{"value":"MOATB"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"29175180"}],"value":"MRP4"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11106685"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11856762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12036927"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12105214"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12523936"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12835412"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12883481"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15364914"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15454390"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16282361"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17344354"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17959747"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18300232"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26721430"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29175180"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38886124"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39993711"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40138312"}],"value":"ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells (PubMed:11856762, PubMed:12523936, PubMed:15364914, PubMed:38886124, PubMed:40138312). Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430, PubMed:38886124, PubMed:40138312). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). May contribute to hepatic, intestinal and renal excretion of steroid conjugates. Selectively transports steroid glucuronates and sulfates. Mediates the efflux of estrogens glucuronated at C-16 and C-17 positions, but has no transporter activity toward estrogens glucuronated at C-3. Has high affinity for dehydroepiandrosterone-3-sulfate and can also transport testosterone-17-sulfate, but has no transporter activity toward androsterone and etiocholanolone sulfate conjugates. Does not transport estrone 3-sulfate (PubMed:29175180, PubMed:39993711). Displays low affinity and high transport velocity for folates (PubMed:12036927). Transports a wide range of drugs and their metabolites. including anticancer, antiviral and antibiotic molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). May confer resistance to anticancer agents. Can mediate the efflux of methotrexate but is inactive toward polyglutaminated methotrexate, which is the predominant intracellular form (PubMed:11106685, PubMed:12036927)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"an S-substituted glutathione(in) + ATP + H2O = an S-substituted glutathione(out) + ADP + phosphate + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:19121"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:90779"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"7.6.2.3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17959747"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:19122"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"17959747"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"ATP + H2O + xenobioticSide 1 = ADP + phosphate + xenobioticSide 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H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:60128"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:82961"},{"database":"ChEBI","id":"CHEBI:456216"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11856762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26721430"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:60129"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"11856762"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"26721430"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"16alpha,17beta-estriol 16-O-(beta-D-glucuronate)(in) + ATP + H2O = 16alpha,17beta-estriol 16-O-(beta-D-glucuronate)(out) + ADP + phosphate + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:86863"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:136650"},{"database":"ChEBI","id":"CHEBI:456216"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29175180"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:86864"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"29175180"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"dehydroepiandrosterone 3-sulfate(in) + ATP + H2O = dehydroepiandrosterone 3-sulfate(out) + ADP + phosphate + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:61364"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:57905"},{"database":"ChEBI","id":"CHEBI:456216"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12523936"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39993711"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:61365"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"12523936"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"39993711"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"testosterone 17-sulfate(in) + ATP + H2O = testosterone 17-sulfate(out) + ADP + phosphate + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:86827"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:190489"},{"database":"ChEBI","id":"CHEBI:456216"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39993711"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:86828"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"39993711"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"leukotriene C4(in) + ATP + H2O = leukotriene C4(out) + ADP + phosphate + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:38963"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:57973"},{"database":"ChEBI","id":"CHEBI:456216"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17959747"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:38964"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"17959747"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"leukotriene B4(in) + ATP + H2O = leukotriene B4(out) + ADP + phosphate + 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H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:16461"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:17775"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:456216"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15454390"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:16462"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"15454390"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"3',5'-cyclic GMP(in) + ATP + H2O = 3',5'-cyclic GMP(out) + ADP + phosphate + 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Urate inhibits methotrexate transport but stimulates cGMP transport (PubMed:15454390). 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