MRP4_MOUSE
ID MRP4_MOUSE Reviewed; 1325 AA.
AC E9Q236; A0A1C9IC75; B7ZWC5; Q3TZN9;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=ATP-binding cassette sub-family C member 4;
DE EC=7.6.2.- {ECO:0000250|UniProtKB:O15439};
DE EC=7.6.2.2 {ECO:0000305|PubMed:15314169, ECO:0000305|PubMed:17210706};
DE EC=7.6.2.3 {ECO:0000250|UniProtKB:O15439};
DE AltName: Full=Multidrug resistance-associated protein 4;
GN Name=Abcc4 {ECO:0000312|MGI:MGI:2443111};
GN Synonyms=Mrp4 {ECO:0000303|PubMed:15314169};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND DEVELOPMENTAL STAGE (ISOFORM
RP 3).
RX PubMed=27613143; DOI=10.1016/j.gene.2016.08.058;
RA Rehman S.U., Ishqi H.M., Husain M.A., Sarwar T., Tabish M.;
RT "A novel exon generates ubiquitously expressed alternatively spliced new
RT transcript of mouse Abcc4 gene.";
RL Gene 594:131-137(2016).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=12883481; DOI=10.1053/jhep.2003.50331;
RA Rius M., Nies A.T., Hummel-Eisenbeiss J., Jedlitschky G., Keppler D.;
RT "Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4)
RT localized to the basolateral hepatocyte membrane.";
RL Hepatology 38:374-384(2003).
RN [9]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=15314169; DOI=10.1128/mcb.24.17.7612-7621.2004;
RA Leggas M., Adachi M., Scheffer G.L., Sun D., Wielinga P., Du G.,
RA Mercer K.E., Zhuang Y., Panetta J.C., Johnston B., Scheper R.J.,
RA Stewart C.F., Schuetz J.D.;
RT "Mrp4 confers resistance to topotecan and protects the brain from
RT chemotherapy.";
RL Mol. Cell. Biol. 24:7612-7621(2004).
RN [10]
RP DISRUPTION PHENOTYPE, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17210706; DOI=10.1158/0008-5472.can-06-2680;
RA Belinsky M.G., Guo P., Lee K., Zhou F., Kotova E., Grinberg A.,
RA Westphal H., Shchaveleva I., Klein-Szanto A., Gallo J.M., Kruh G.D.;
RT "Multidrug resistance protein 4 protects bone marrow, thymus, spleen, and
RT intestine from nucleotide analogue-induced damage.";
RL Cancer Res. 67:262-268(2007).
CC -!- FUNCTION: ATP-dependent transporter of the ATP-binding cassette (ABC)
CC family that actively extrudes physiological compounds and xenobiotics
CC from cells. Transports a range of endogenous molecules that have a key
CC role in cellular communication and signaling, including cyclic
CC nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile
CC acids, steroid conjugates, urate, and prostaglandins. Mediates also the
CC ATP-dependent efflux of glutathione conjugates such as leukotriene C4
CC (LTC4) and leukotriene B4 (LTB4). The presence of GSH is necessary for
CC the ATP-dependent transport of LTB4, whereas GSH is not required for
CC the transport of LTC4. Mediates the cotransport of bile acids with
CC reduced glutathione (GSH). Transports a wide range of drugs and their
CC metabolites, including anticancer, antiviral and antibiotics molecules
CC (Probable). Confers resistance to anticancer agents (Probable).
CC {ECO:0000305|PubMed:15314169, ECO:0000305|PubMed:17210706}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC xenobioticSide 2.; EC=7.6.2.2; Evidence={ECO:0000305|PubMed:15314169,
CC ECO:0000305|PubMed:17210706};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an S-substituted glutathione(in) + ATP + H2O = ADP + an S-
CC substituted glutathione(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:19121, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:90779,
CC ChEBI:CHEBI:456216; EC=7.6.2.3;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19122;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol 17-O-(beta-D-glucuronate)(in) + ATP + H2O =
CC 17beta-estradiol 17-O-(beta-D-glucuronate)(out) + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:60128, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:82961, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60129;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + dehydroepiandrosterone 3-sulfate(in) + H2O = ADP +
CC dehydroepiandrosterone 3-sulfate(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:61364, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57905,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61365;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + leukotriene C4(in) = ADP + H(+) + leukotriene
CC C4(out) + phosphate; Xref=Rhea:RHEA:38963, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57973, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38964;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + leukotriene B4(in) = ADP + H(+) + leukotriene
CC B4(out) + phosphate; Xref=Rhea:RHEA:66424, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57461, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + urate(in) = ADP + H(+) + phosphate + urate(out);
CC Xref=Rhea:RHEA:16461, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17775, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16462;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic GMP(in) + ATP + H2O = 3',5'-cyclic GMP(out) + ADP
CC + H(+) + phosphate; Xref=Rhea:RHEA:66188, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57746, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66189;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic AMP(in) + ATP + H2O = 3',5'-cyclic AMP(out) + ADP
CC + H(+) + phosphate; Xref=Rhea:RHEA:66184, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58165, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66185;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + prostaglandin E2(in) = ADP + H(+) + phosphate +
CC prostaglandin E2(out); Xref=Rhea:RHEA:66388, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456216, ChEBI:CHEBI:606564;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66389;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + prostaglandin E1(in) = ADP + H(+) + phosphate +
CC prostaglandin E1(out); Xref=Rhea:RHEA:66392, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57397, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66393;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glutathione(in) + glycodeoxycholate(in) + H2O = ADP +
CC glutathione(out) + glycodeoxycholate(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:66380, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:82982, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66381;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + cholate(in) + glutathione(in) + H2O = ADP + cholate(out)
CC + glutathione(out) + H(+) + phosphate; Xref=Rhea:RHEA:66396,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29747,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66397;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glutathione(in) + glycocholate(in) + H2O = ADP +
CC glutathione(out) + glycocholate(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:66400, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29746, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66401;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glutathione(in) + H2O + taurocholate(in) = ADP +
CC glutathione(out) + H(+) + phosphate + taurocholate(out);
CC Xref=Rhea:RHEA:66404, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:36257, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66405;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glutathione(in) + glycochenodeoxycholate(in) + H2O = ADP
CC + glutathione(out) + glycochenodeoxycholate(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:66408, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:36252, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66409;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glutathione(in) + H2O + taurochenodeoxycholate(in) = ADP
CC + glutathione(out) + H(+) + phosphate + taurochenodeoxycholate(out);
CC Xref=Rhea:RHEA:66412, ChEBI:CHEBI:9407, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66413;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glutathione(in) + glycoursodeoxycholate(in) + H2O = ADP
CC + glutathione(out) + glycoursodeoxycholate(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:66416, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:132030, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66417;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glutathione(in) + H2O + tauroursodeoxycholate(in) = ADP
CC + glutathione(out) + H(+) + phosphate + tauroursodeoxycholate(out);
CC Xref=Rhea:RHEA:66420, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:132028, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66421;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O15439};
CC -!- SUBUNIT: Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain);
CC this interaction accelerates MRP4 internalization.
CC {ECO:0000250|UniProtKB:O15439}.
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000269|PubMed:12883481, ECO:0000269|PubMed:15314169}; Multi-pass
CC membrane protein {ECO:0000255}. Apical cell membrane
CC {ECO:0000269|PubMed:15314169}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Its localization to the basolateral or apical
CC membranes is tissue-dependent. {ECO:0000269|PubMed:15314169}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=E9Q236-1; Sequence=Displayed;
CC Name=2;
CC IsoId=E9Q236-2; Sequence=VSP_060952;
CC Name=3; Synonyms=ABCC4-N {ECO:0000303|PubMed:27613143};
CC IsoId=E9Q236-3; Sequence=VSP_060951, VSP_060952;
CC -!- DEVELOPMENTAL STAGE: [Isoform 3]: Ubiquitously expressed across all
CC developmental stages. {ECO:0000269|PubMed:27613143}.
CC -!- PTM: N-glycosylated; leading to substrate-selective effects on its
CC transport activity. {ECO:0000250|UniProtKB:O15439}.
CC -!- DISRUPTION PHENOTYPE: Homozygous null mice are viable and fertile and
CC exhibit any overt phenotype under normal conditions. However deficient
CC mice show impaired anion transport in the blood-brain and blood-
CC cerebrospinal fluid barriers and kidney. Deficient mice show an
CC accumulation of the anticancer agent topotecan in brain and
CC cerebrospinal fluid (CSF) (PubMed:15314169). In addition, penetration
CC of PMEA, an antiviral agent, into the brain is increased in deficient
CC mice (PubMed:17210706). {ECO:0000269|PubMed:15314169,
CC ECO:0000269|PubMed:17210706}.
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DR EMBL; AK157723; BAE34169.1; -; mRNA.
DR EMBL; KX013261; AOP00017.1; -; mRNA.
DR EMBL; AC154419; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC167668; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CT025694; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC171974; AAI71974.1; -; mRNA.
DR CCDS; CCDS27335.1; -. [E9Q236-1]
DR CCDS; CCDS49565.1; -. [E9Q236-2]
DR RefSeq; NP_001028508.2; NM_001033336.3. [E9Q236-1]
DR RefSeq; NP_001157147.1; NM_001163675.1.
DR AlphaFoldDB; E9Q236; -.
DR SMR; E9Q236; -.
DR STRING; 10090.ENSMUSP00000042186; -.
DR iPTMnet; Q3TZN9; -.
DR PhosphoSitePlus; E9Q236; -.
DR SwissPalm; E9Q236; -.
DR jPOST; E9Q236; -.
DR MaxQB; E9Q236; -.
DR PaxDb; E9Q236; -.
DR PRIDE; E9Q236; -.
DR ProteomicsDB; 316165; -.
DR Antibodypedia; 3448; 459 antibodies from 37 providers.
DR Ensembl; ENSMUST00000036554; ENSMUSP00000042186; ENSMUSG00000032849. [E9Q236-1]
DR Ensembl; ENSMUST00000166646; ENSMUSP00000129677; ENSMUSG00000032849. [E9Q236-2]
DR GeneID; 239273; -.
DR KEGG; mmu:239273; -.
DR UCSC; uc007uyv.2; mouse. [E9Q236-1]
DR CTD; 10257; -.
DR MGI; MGI:2443111; Abcc4.
DR VEuPathDB; HostDB:ENSMUSG00000032849; -.
DR eggNOG; KOG0054; Eukaryota.
DR GeneTree; ENSGT00940000153931; -.
DR InParanoid; E9Q236; -.
DR OMA; TFEWEES; -.
DR OrthoDB; 138195at2759; -.
DR PhylomeDB; E9Q236; -.
DR TreeFam; TF105202; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR Reactome; R-MMU-382556; ABC-family proteins mediated transport.
DR Reactome; R-MMU-9748787; Azathioprine ADME.
DR Reactome; R-MMU-9753281; Paracetamol ADME.
DR BioGRID-ORCS; 239273; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Abcc4; mouse.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; E9Q236; protein.
DR Bgee; ENSMUSG00000032849; Expressed in urinary bladder urothelium and 209 other tissues.
DR ExpressionAtlas; E9Q236; baseline and differential.
DR Genevisible; E9Q236; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0031088; C:platelet dense granule membrane; ISO:MGI.
DR GO; GO:0015432; F:ABC-type bile acid transporter activity; ISS:UniProtKB.
DR GO; GO:0015431; F:ABC-type glutathione S-conjugate transporter activity; ISS:UniProtKB.
DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IEA:UniProtKB-EC.
DR GO; GO:0015665; F:alcohol transmembrane transporter activity; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015562; F:efflux transmembrane transporter activity; ISO:MGI.
DR GO; GO:0034634; F:glutathione transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0001409; F:guanine nucleotide transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015132; F:prostaglandin transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015216; F:purine nucleotide transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015143; F:urate transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015721; P:bile acid and bile salt transport; ISS:UniProtKB.
DR GO; GO:0070730; P:cAMP transport; ISS:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; ISO:MGI.
DR GO; GO:0140115; P:export across plasma membrane; ISO:MGI.
DR GO; GO:1901571; P:fatty acid derivative transport; ISO:MGI.
DR GO; GO:0071716; P:leukotriene transport; ISS:UniProtKB.
DR GO; GO:0015850; P:organic hydroxy compound transport; ISO:MGI.
DR GO; GO:0032310; P:prostaglandin secretion; ISO:MGI.
DR GO; GO:0015732; P:prostaglandin transport; ISS:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0015747; P:urate transport; ISS:UniProtKB.
DR GO; GO:0006855; P:xenobiotic transmembrane transport; TAS:MGI.
DR Gene3D; 1.20.1560.10; -; 2.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR030240; ABCC4.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR24223:SF357; PTHR24223:SF357; 1.
DR Pfam; PF00664; ABC_membrane; 2.
DR Pfam; PF00005; ABC_tran; 2.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF90123; SSF90123; 2.
DR PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 2.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell membrane; Lipid transport;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1325
FT /note="ATP-binding cassette sub-family C member 4"
FT /id="PRO_0000452319"
FT TRANSMEM 93..113
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 136..156
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 205..225
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 227..247
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 322..342
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 351..371
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 710..730
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 761..781
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 849..869
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 954..974
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 977..997
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT DOMAIN 93..377
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 410..633
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 714..1005
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1041..1274
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 657..690
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1322..1325
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:O15439"
FT BINDING 445..452
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1075..1082
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 646
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O15439"
FT MOD_RES 648
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O15439"
FT MOD_RES 664
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15439"
FT MOD_RES 668
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15439"
FT VAR_SEQ 2..25
FT /note="LPVHTEVKPNPLQDANLCSRVFFW -> EMLPSEVVKPREER (in
FT isoform 3)"
FT /id="VSP_060951"
FT VAR_SEQ 103..177
FT /note="Missing (in isoform 2 and isoform 3)"
FT /id="VSP_060952"
FT CONFLICT 682
FT /note="T -> M (in Ref. 4; AAI71974)"
FT /evidence="ECO:0000305"
FT CONFLICT 704
FT /note="Y -> C (in Ref. 1; BAE34169)"
FT /evidence="ECO:0000305"
FT CONFLICT 769
FT /note="A -> T (in Ref. 4; AAI71974)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1325 AA; 148888 MW; 3F1469648CBE9699 CRC64;
MLPVHTEVKP NPLQDANLCS RVFFWWLNPL FKTGHKRRLE EDDMFSVLPE DRSKHLGEEL
QRYWDKELLR AKKDSRKPSL TKAIIKCYWK SYLILGIFTL IEEGTRVVQP LFLGKIIEYF
EKYDPDDSVA LHTAYGYAAV LSMCTLILAI LHHLYFYHVQ CAGMRLRVAM CHMIYRKALR
LSNSAMGKTT TGQIVNLLSN DVNKFDQVTI FLHFLWAGPL QAIAVTVLLW VEIGISCLAG
LAVLVILLPL QSCIGKLFSS LRSKTAAFTD ARIRTMNEVI TGMRIIKMYA WEKSFADLIA
NLRKKEISKI LGSSYLRGMN MASFFIANKV ILFVTFTSYV LLGNEITASH VFVAMTLYGA
VRLTVTLFFP SAIERGSEAI VSIRRIKNFL LLDELPQRKA HVPSDGKAIV HVQDFTAFWD
KALDSPTLQG LSFIARPGEL LAVVGPVGAG KSSLLSAVLG ELPPASGLVS VHGRIAYVSQ
QPWVFSGTVR SNILFGKKYE KERYEKVIKA CALKKDLQLL EDGDLTVIGD RGATLSGGQK
ARVNLARAVY QDADIYLLDD PLSAVDAEVG KHLFQLCICQ ALHEKITILV THQLQYLKAA
SHILILKDGE MVQKGTYTEF LKSGVDFGSL LKKENEEAEP STAPGTPTLR KRTFSEASIW
SQQSSRPSLK DGAPEGQDAE NTQAVQPEES RSEGRIGFKA YKNYFSAGAS WFFIIFLVLL
NMVGQVFYVL QDWWLSHWAN KQGALNNTRN ANGNITETLD LSWYLGIYAG LTAVTVLFGI
ARSLLVFYIL VNASQTLHNR MFESILKAPV LFFDRNPIGR ILNRFSKDIG HMDDLLPLTF
LDFIQTLLLV VSVIAVAAAV IPWILIPLVP LSVVFLVLRR YFLETSRDVK RLESTTRSPV
FSHLSSSLQG LWTIRAYKAE ERCQELFDAH QDLHSEAWFL FLTTSRWFAV RLDAICAIFV
IVVAFGSLVL AKTLNAGQVG LALSYALTLM GMFQWSVRQS AEVENMMISV ERVIEYTDLE
KEAPWECKKR PPPGWPHEGV IVFDNVNFTY SLDGPLVLKH LTALIKSREK VGIVGRTGAG
KSSLISALFR LSEPEGKIWI DKILTTEIGL HDLRKKMSII PQEPVLFTGT MRKNLDPFNE
HTDEELWRAL EEVQLKEAIE DLPGKMDTEL AESGSNFSVG QRQLVCLARA ILKNNRILII
DEATANVDPR TDELIQQKIR EKFAQCTVLT IAHRLNTIID SDKIMVLDSG RLKEYDEPYV
LLQNPESLFY KMVQQLGKGE AAALTETAKQ VYFRRNYPDI TFTSPAVMNT SNGQPSALTI
FETAL
