MRP2_HUMAN
ID MRP2_HUMAN Reviewed; 1545 AA.
AC Q92887; B2RMT8; Q14022; Q5T2B1; Q92500; Q92798; Q99663; Q9UMS2;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=ATP-binding cassette sub-family C member 2;
DE EC=7.6.2.- {ECO:0000269|PubMed:10421658, ECO:0000269|PubMed:16332456};
DE EC=7.6.2.2 {ECO:0000269|PubMed:10220572, ECO:0000269|PubMed:11500505, ECO:0000269|PubMed:12441801};
DE EC=7.6.2.3 {ECO:0000269|PubMed:10220572, ECO:0000269|PubMed:11500505};
DE AltName: Full=Canalicular multidrug resistance protein;
DE AltName: Full=Canalicular multispecific organic anion transporter 1 {ECO:0000305};
DE AltName: Full=Multidrug resistance-associated protein 2;
GN Name=ABCC2 {ECO:0000312|HGNC:HGNC:53};
GN Synonyms=CMOAT, CMOAT1, CMRP {ECO:0000303|PubMed:8662992}, MRP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PHE-39.
RX PubMed=8797578;
RA Taniguchi K., Wada M., Kohno K., Nakamura T., Kawabe T., Kawakami M.,
RA Kagotani K., Okumura K., Akiyama S., Kuwano M.;
RT "A human canalicular multispecific organic anion transporter (cMOAT) gene
RT is overexpressed in cisplatin-resistant human cancer cell lines with
RT decreased drug accumulation.";
RL Cancer Res. 56:4124-4129(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS PHE-39; GLU-1188 AND TYR-1515.
RA Kool M., de Haas M., Ponne N.J., Paulusma C.C., Oude-Elferink R.P.J.,
RA Baas F., Borst P.;
RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PHE-39.
RX PubMed=8662992; DOI=10.1074/jbc.271.25.15091;
RA Buechler M., Koenig J., Brom M., Kartenbeck J., Spring H., Horie T.,
RA Keppler D.;
RT "cDNA cloning of the hepatocyte canalicular isoform of the multidrug
RT resistance protein, cMrp, reveals a novel conjugate export pump deficient
RT in hyperbilirubinemic mutant rats.";
RL J. Biol. Chem. 271:15091-15098(1996).
RN [4]
RP SEQUENCE REVISION.
RA Keppler D.;
RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PHE-39 AND DJS
RP 1392-ARG-MET-1393 DEL.
RX PubMed=10464142; DOI=10.1016/s0016-5085(99)70459-2;
RA Tsujii H., Koenig J., Rost D., Stoeckel B., Leuschner U., Keppler D.;
RT "Exon-intron organization of the human multidrug-resistance protein 2
RT (MRP2) gene mutated in Dubin-Johnson syndrome.";
RL Gastroenterology 117:653-660(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PHE-39.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PHE-39.
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 [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10421658; DOI=10.1002/hep.510300220;
RA Kamisako T., Leier I., Cui Y., Koenig J., Buchholz U.,
RA Hummel-Eisenbeiss J., Keppler D.;
RT "Transport of monoglucuronosyl and bisglucuronosyl bilirubin by recombinant
RT human and rat multidrug resistance protein 2.";
RL Hepatology 30:485-490(1999).
RN [10]
RP CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=10220572;
RA Cui Y., Koenig J., Buchholz J.K., Spring H., Leier I., Keppler D.;
RT "Drug resistance and ATP-dependent conjugate transport mediated by the
RT apical multidrug resistance protein, MRP2, permanently expressed in human
RT and canine cells.";
RL Mol. Pharmacol. 55:929-937(1999).
RN [11]
RP MUTAGENESIS OF TRP-1254, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11500505; DOI=10.1074/jbc.m105160200;
RA Ito K., Oleschuk C.J., Westlake C., Vasa M.Z., Deeley R.G., Cole S.P.C.;
RT "Mutation of Trp1254 in the multispecific organic anion transporter,
RT multidrug resistance protein 2 (MRP2) (ABCC2), alters substrate specificity
RT and results in loss of methotrexate transport activity.";
RL J. Biol. Chem. 276:38108-38114(2001).
RN [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12441801; DOI=10.1097/00002030-200211220-00009;
RA Huisman M.T., Smit J.W., Crommentuyn K.M., Zelcer N., Wiltshire H.R.,
RA Beijnen J.H., Schinkel A.H.;
RT "Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors,
RT and transport can be enhanced by other drugs.";
RL AIDS 16:2295-2301(2002).
RN [13]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16332456; DOI=10.1016/j.bbalip.2005.10.006;
RA Hayashi H., Takada T., Suzuki H., Onuki R., Hofmann A.F., Sugiyama Y.;
RT "Transport by vesicles of glycine- and taurine-conjugated bile salts and
RT taurolithocholate 3-sulfate: a comparison of human BSEP with rat Bsep.";
RL Biochim. Biophys. Acta 1738:54-62(2005).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-283 AND SER-878, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-926; SER-930 AND SER-938, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-878 AND SER-1438, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP VARIANT DJS TRP-768.
RX PubMed=9425227; DOI=10.1093/hmg/7.2.203;
RA Wada M., Toh S., Taniguchi K., Nakamura T., Uchiumi T., Kohno K.,
RA Yoshida I., Kimura A., Sakisaka S., Adachi Y., Kuwano M.;
RT "Mutations in the canalicular multispecific organic anion transporter
RT (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia
RT II/Dubin-Johnson syndrome.";
RL Hum. Mol. Genet. 7:203-207(1998).
RN [21]
RP VARIANTS DJS TRP-768 AND ARG-1382.
RX PubMed=10053008; DOI=10.1086/302292;
RA Toh S., Wada M., Uchiumi T., Inokuchi A., Makino Y., Horie Y., Adachi Y.,
RA Sakisaka S., Kuwano M.;
RT "Genomic structure of the canalicular multispecific organic anion-
RT transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette
RT region in Dubin-Johnson syndrome.";
RL Am. J. Hum. Genet. 64:739-746(1999).
RN [22]
RP CHARACTERIZATION OF VARIANT DJS 1392-ARG-MET-1393 DEL, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11093739; DOI=10.1053/jhep.2000.19791;
RA Keitel V., Kartenbeck J., Nies A.T., Spring H., Brom M., Keppler D.;
RT "Impaired protein maturation of the conjugate export pump multidrug
RT resistance protein 2 as a consequence of a deletion mutation in Dubin-
RT Johnson syndrome.";
RL Hepatology 32:1317-1328(2000).
RN [23]
RP VARIANTS DJS HIS-1150 AND PHE-1173, AND VARIANTS ASN-281 AND ILE-417.
RX PubMed=11477083; DOI=10.1074/jbc.m105047200;
RA Mor-Cohen R., Zivelin A., Rosenberg N., Shani M., Muallem S., Seligsohn U.;
RT "Identification and functional analysis of two novel mutations in the
RT multidrug resistance protein 2 gene in Israeli patients with Dubin-Johnson
RT syndrome.";
RL J. Biol. Chem. 276:36923-36930(2001).
RN [24]
RP VARIANT DJS TRP-768, AND VARIANTS ILE-417; PHE-789 AND THR-1450.
RX PubMed=11266082; DOI=10.1097/00008571-200103000-00008;
RA Ito S., Ieiri I., Tanabe M., Suzuki A., Higuchi S., Otsubo K.;
RT "Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in
RT healthy Japanese subjects.";
RL Pharmacogenetics 11:175-184(2001).
RN [25]
RP VARIANTS PHE-39; GLY-333; HIS-353; ILE-486; THR-670; SER-921; THR-1036;
RP HIS-1174; LEU-1181; GLU-1188; LEU-1291 AND TYR-1515, CHARACTERIZATION OF
RP VARIANTS DJS PHE-1173, AND CHARACTERIZATION OF VARIANTS GLY-333; HIS-353;
RP ILE-486; SER-921; THR-1036; HIS-1174; LEU-1181; LYS-1244 AND LEU-1291.
RX PubMed=22290738; DOI=10.1002/humu.22041;
RA Arlanov R., Porter A., Strand D., Brough R., Karpova D., Kerb R.,
RA Wojnowski L., Schwab M., Lang T.;
RT "Functional characterization of protein variants of the human multidrug
RT transporter ABCC2 by a novel targeted expression system in fibrosarcoma
RT cells.";
RL Hum. Mutat. 33:750-762(2012).
RN [26]
RP VARIANT DJS TRP-768, AND VARIANT ILE-417.
RX PubMed=25336012; DOI=10.1111/ped.12404;
RA Okada H., Kusaka T., Fuke N., Kunikata J., Kondo S., Iwase T., Nan W.,
RA Hirota T., Ieiri I., Itoh S.;
RT "Neonatal Dubin-Johnson syndrome: novel compound heterozygous mutation in
RT the ABCC2 gene.";
RL Pediatr. Int. 56:E62-E62(2014).
CC -!- FUNCTION: ATP-dependent transporter of the ATP-binding cassette (ABC)
CC family that binds and hydrolyzes ATP to enable active transport of
CC various substrates including many drugs, toxicants and endogenous
CC compound across cell membranes. Transports a wide variety of conjugated
CC organic anions such as sulfate-, glucuronide- and glutathione (GSH)-
CC conjugates of endo- and xenobiotics substrates (PubMed:10220572,
CC PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates
CC hepatobiliary excretion of mono- and bis-glucuronidated bilirubin
CC molecules and therefore play an important role in bilirubin
CC detoxification (PubMed:10421658). Mediates also hepatobiliary excretion
CC of others glucuronide conjugates such as 17beta-estradiol 17-
CC glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports
CC sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456).
CC Transport various anticancer drugs, such as anthracycline, vinca
CC alkaloid and methotrexate and HIV-drugs such as protease inhibitors
CC (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance
CC to several anti-cancer drugs including cisplatin, doxorubicin,
CC epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572,
CC PubMed:11500505). {ECO:0000269|PubMed:10220572,
CC ECO:0000269|PubMed:10421658, ECO:0000269|PubMed:11500505,
CC ECO:0000269|PubMed:12441801, ECO:0000269|PubMed:16332456}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC xenobioticSide 2.; EC=7.6.2.2; Evidence={ECO:0000269|PubMed:10220572,
CC ECO:0000269|PubMed:11500505, ECO:0000269|PubMed:12441801};
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:0000269|PubMed:10220572, ECO:0000269|PubMed:11500505};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19122;
CC Evidence={ECO:0000305|PubMed:10220572, ECO:0000305|PubMed:11500505};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + taurolithocholate 3-sulfate(in) = ADP + H(+) +
CC phosphate + taurolithocholate 3-sulfate(out); Xref=Rhea:RHEA:50084,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58301, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:16332456};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50085;
CC Evidence={ECO:0000269|PubMed:16332456};
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:0000269|PubMed:10220572, ECO:0000269|PubMed:11500505};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38964;
CC Evidence={ECO:0000305|PubMed:11500505};
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:0000269|PubMed:10220572, ECO:0000269|PubMed:11500505};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60129;
CC Evidence={ECO:0000305|PubMed:11500505};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + bilirubin-glucuronoside(in) + H2O = ADP + bilirubin-
CC glucuronoside(out) + H(+) + phosphate; Xref=Rhea:RHEA:66180,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57767, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:10421658};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66181;
CC Evidence={ECO:0000305|PubMed:10421658};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + bilirubin-bisglucuronoside(in) + H2O = ADP + bilirubin-
CC bisglucuronoside(out) + H(+) + phosphate; Xref=Rhea:RHEA:66192,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58471, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000305|PubMed:10421658};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.2 uM for 17beta-estradiol 17-O-(beta-D-glucuronate)
CC {ECO:0000269|PubMed:10220572};
CC KM=1 uM for leukotriene C4 {ECO:0000269|PubMed:10220572};
CC KM=0.7 uM for bilirubin-glucuronoside {ECO:0000269|PubMed:10421658};
CC KM=0.9 uM for bilirubin-bisglucuronoside
CC {ECO:0000269|PubMed:10421658};
CC KM=8.2 uM for taurolithocholate sulfate
CC {ECO:0000269|PubMed:16332456};
CC Vmax=321 pmol/min/mg enzyme for bilirubin-glucuronoside transport
CC {ECO:0000269|PubMed:10421658};
CC Vmax=255 pmol/min/mg enzyme bilirubin-bisglucuronoside transport
CC {ECO:0000269|PubMed:10421658};
CC Vmax=1530 pmol/min/mg enzyme for taurolithocholate sulfate transport
CC {ECO:0000269|PubMed:16332456};
CC -!- INTERACTION:
CC Q92887; P19838: NFKB1; NbExp=3; IntAct=EBI-3916193, EBI-300010;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:10220572, ECO:0000269|PubMed:11093739}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed by polarized cells in liver, kidney and
CC intestine. The highest expression is found in liver.
CC -!- DISEASE: Dubin-Johnson syndrome (DJS) [MIM:237500]: Autosomal recessive
CC disorder characterized by conjugated hyperbilirubinemia, an increase in
CC the urinary excretion of coproporphyrin isomer I, deposition of
CC melanin-like pigment in hepatocytes, and prolonged retention of
CC sulfobromophthalein, but otherwise normal liver function.
CC {ECO:0000269|PubMed:10053008, ECO:0000269|PubMed:10464142,
CC ECO:0000269|PubMed:11093739, ECO:0000269|PubMed:11266082,
CC ECO:0000269|PubMed:11477083, ECO:0000269|PubMed:22290738,
CC ECO:0000269|PubMed:25336012, ECO:0000269|PubMed:9425227}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC family.
CC Conjugate transporter (TC 3.A.1.208) subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins;
CC URL="http://abcm2.hegelab.org/search";
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DR EMBL; U63970; AAB39892.1; -; mRNA.
DR EMBL; U49248; AAB09422.1; -; mRNA.
DR EMBL; X96395; CAA65259.2; -; mRNA.
DR EMBL; AJ132244; CAB45309.1; -; Genomic_DNA.
DR EMBL; AJ132287; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ245625; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132288; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132289; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132290; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132291; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132292; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132293; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132294; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132295; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132296; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132297; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132298; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132299; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132300; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132301; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132302; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132303; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ245626; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132304; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132305; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132306; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132307; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132308; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ245627; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132309; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132310; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132311; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132312; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132313; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AJ132314; CAB45309.1; JOINED; Genomic_DNA.
DR EMBL; AL392107; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL133353; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49853.1; -; Genomic_DNA.
DR EMBL; BC136419; AAI36420.1; -; mRNA.
DR CCDS; CCDS7484.1; -.
DR PIR; S71841; S71841.
DR RefSeq; NP_000383.1; NM_000392.4.
DR AlphaFoldDB; Q92887; -.
DR SMR; Q92887; -.
DR BioGRID; 107647; 98.
DR IntAct; Q92887; 8.
DR MINT; Q92887; -.
DR STRING; 9606.ENSP00000359478; -.
DR BindingDB; Q92887; -.
DR ChEMBL; CHEMBL5748; -.
DR DrugBank; DB04789; 5-methyltetrahydrofolic acid.
DR DrugBank; DB00345; Aminohippuric acid.
DR DrugBank; DB01169; Arsenic trioxide.
DR DrugBank; DB01076; Atorvastatin.
DR DrugBank; DB00171; ATP.
DR DrugBank; DB09060; Avibactam.
DR DrugBank; DB00207; Azithromycin.
DR DrugBank; DB15719; Belantamab mafodotin.
DR DrugBank; DB12151; Brincidofovir.
DR DrugBank; DB08907; Canagliflozin.
DR DrugBank; DB00564; Carbamazepine.
DR DrugBank; DB00958; Carboplatin.
DR DrugBank; DB00439; Cerivastatin.
DR DrugBank; DB02659; Cholic Acid.
DR DrugBank; DB00515; Cisplatin.
DR DrugBank; DB00286; Conjugated estrogens.
DR DrugBank; DB00091; Cyclosporine.
DR DrugBank; DB01234; Dexamethasone.
DR DrugBank; DB14649; Dexamethasone acetate.
DR DrugBank; DB01248; Docetaxel.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB09272; Eluxadoline.
DR DrugBank; DB00876; Eprosartan.
DR DrugBank; DB00199; Erythromycin.
DR DrugBank; DB00977; Ethinylestradiol.
DR DrugBank; DB00773; Etoposide.
DR DrugBank; DB00973; Ezetimibe.
DR DrugBank; DB00950; Fexofenadine.
DR DrugBank; DB01095; Fluvastatin.
DR DrugBank; DB00695; Furosemide.
DR DrugBank; DB02703; Fusidic acid.
DR DrugBank; DB08884; Gadoxetic acid.
DR DrugBank; DB00798; Gentamicin.
DR DrugBank; DB00143; Glutathione.
DR DrugBank; DB01016; Glyburide.
DR DrugBank; DB00365; Grepafloxacin.
DR DrugBank; DB01892; Hyperforin.
DR DrugBank; DB00224; Indinavir.
DR DrugBank; DB09374; Indocyanine green acid form.
DR DrugBank; DB00328; Indomethacin.
DR DrugBank; DB00762; Irinotecan.
DR DrugBank; DB00602; Ivermectin.
DR DrugBank; DB00709; Lamivudine.
DR DrugBank; DB12070; Letermovir.
DR DrugBank; DB00978; Lomefloxacin.
DR DrugBank; DB06448; Lonafarnib.
DR DrugBank; DB00227; Lovastatin.
DR DrugBank; DB14642; Lypressin.
DR DrugBank; DB00563; Methotrexate.
DR DrugBank; DB00688; Mycophenolate mofetil.
DR DrugBank; DB01115; Nifedipine.
DR DrugBank; DB00698; Nitrofurantoin.
DR DrugBank; DB00957; Norgestimate.
DR DrugBank; DB00104; Octreotide.
DR DrugBank; DB01165; Ofloxacin.
DR DrugBank; DB00275; Olmesartan.
DR DrugBank; DB00526; Oxaliplatin.
DR DrugBank; DB01229; Paclitaxel.
DR DrugBank; DB01174; Phenobarbital.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB08860; Pitavastatin.
DR DrugBank; DB06813; Pralatrexate.
DR DrugBank; DB01411; Pranlukast.
DR DrugBank; DB00175; Pravastatin.
DR DrugBank; DB01032; Probenecid.
DR DrugBank; DB04216; Quercetin.
DR DrugBank; DB00908; Quinidine.
DR DrugBank; DB00481; Raloxifene.
DR DrugBank; DB00206; Reserpine.
DR DrugBank; DB01045; Rifampicin.
DR DrugBank; DB00503; Ritonavir.
DR DrugBank; DB01098; Rosuvastatin.
DR DrugBank; DB01232; Saquinavir.
DR DrugBank; DB06290; Simeprevir.
DR DrugBank; DB00641; Simvastatin.
DR DrugBank; DB00398; Sorafenib.
DR DrugBank; DB01208; Sparfloxacin.
DR DrugBank; DB00421; Spironolactone.
DR DrugBank; DB00795; Sulfasalazine.
DR DrugBank; DB01138; Sulfinpyrazone.
DR DrugBank; DB01268; Sunitinib.
DR DrugBank; DB11770; Talinolol.
DR DrugBank; DB00675; Tamoxifen.
DR DrugBank; DB04348; Taurocholic acid.
DR DrugBank; DB00966; Telmisartan.
DR DrugBank; DB00300; Tenofovir disoproxil.
DR DrugBank; DB00116; Tetrahydrofolic acid.
DR DrugBank; DB04100; Tricarbonyl(1,10-phenanthroline)rhenium(1+).
DR DrugBank; DB01586; Ursodeoxycholic acid.
DR DrugBank; DB00177; Valsartan.
DR DrugBank; DB00067; Vasopressin.
DR DrugBank; DB00570; Vinblastine.
DR DrugBank; DB00541; Vincristine.
DR DrugCentral; Q92887; -.
DR GuidetoPHARMACOLOGY; 780; -.
DR SwissLipids; SLP:000001599; -.
DR TCDB; 3.A.1.208.2; the atp-binding cassette (abc) superfamily.
DR GlyGen; Q92887; 3 sites.
DR iPTMnet; Q92887; -.
DR PhosphoSitePlus; Q92887; -.
DR BioMuta; ABCC2; -.
DR DMDM; 308153583; -.
DR EPD; Q92887; -.
DR jPOST; Q92887; -.
DR MassIVE; Q92887; -.
DR MaxQB; Q92887; -.
DR PaxDb; Q92887; -.
DR PeptideAtlas; Q92887; -.
DR PRIDE; Q92887; -.
DR ProteomicsDB; 75571; -.
DR Antibodypedia; 17520; 375 antibodies from 39 providers.
DR DNASU; 1244; -.
DR Ensembl; ENST00000647814.1; ENSP00000497274.1; ENSG00000023839.12.
DR GeneID; 1244; -.
DR KEGG; hsa:1244; -.
DR MANE-Select; ENST00000647814.1; ENSP00000497274.1; NM_000392.5; NP_000383.2.
DR UCSC; uc001kqf.3; human.
DR CTD; 1244; -.
DR DisGeNET; 1244; -.
DR GeneCards; ABCC2; -.
DR HGNC; HGNC:53; ABCC2.
DR HPA; ENSG00000023839; Tissue enhanced (intestine, liver).
DR MalaCards; ABCC2; -.
DR MIM; 237500; phenotype.
DR MIM; 601107; gene.
DR neXtProt; NX_Q92887; -.
DR OpenTargets; ENSG00000023839; -.
DR Orphanet; 234; Dubin-Johnson syndrome.
DR PharmGKB; PA116; -.
DR VEuPathDB; HostDB:ENSG00000023839; -.
DR eggNOG; KOG0054; Eukaryota.
DR GeneTree; ENSGT00940000161741; -.
DR HOGENOM; CLU_000604_27_3_1; -.
DR InParanoid; Q92887; -.
DR OMA; ICMATPV; -.
DR OrthoDB; 227725at2759; -.
DR PhylomeDB; Q92887; -.
DR TreeFam; TF105199; -.
DR BRENDA; 7.6.2.2; 2681.
DR BRENDA; 7.6.2.3; 2681.
DR PathwayCommons; Q92887; -.
DR Reactome; R-HSA-189483; Heme degradation.
DR Reactome; R-HSA-382556; ABC-family proteins mediated transport.
DR Reactome; R-HSA-5679001; Defective ABCC2 causes DJS.
DR Reactome; R-HSA-9749641; Aspirin ADME.
DR Reactome; R-HSA-9753281; Paracetamol ADME.
DR Reactome; R-HSA-9754706; Atorvastatin ADME.
DR SABIO-RK; Q92887; -.
DR SignaLink; Q92887; -.
DR SIGNOR; Q92887; -.
DR BioGRID-ORCS; 1244; 11 hits in 1076 CRISPR screens.
DR ChiTaRS; ABCC2; human.
DR GeneWiki; Multidrug_resistance-associated_protein_2; -.
DR GenomeRNAi; 1244; -.
DR Pharos; Q92887; Tchem.
DR PRO; PR:Q92887; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q92887; protein.
DR Bgee; ENSG00000023839; Expressed in right lobe of liver and 97 other tissues.
DR ExpressionAtlas; Q92887; baseline and differential.
DR Genevisible; Q92887; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0046581; C:intercellular canaliculus; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015431; F:ABC-type glutathione S-conjugate transporter activity; IMP:UniProtKB.
DR GO; GO:0140359; F:ABC-type transporter activity; TAS:Reactome.
DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IMP:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043225; F:ATPase-coupled inorganic anion transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015127; F:bilirubin transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0008514; F:organic anion transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015721; P:bile acid and bile salt transport; IMP:UniProtKB.
DR GO; GO:0015723; P:bilirubin transport; IMP:UniProtKB.
DR GO; GO:0042167; P:heme catabolic process; TAS:Reactome.
DR GO; GO:0071716; P:leukotriene transport; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:ARUK-UCL.
DR GO; GO:0070633; P:transepithelial transport; ISS:ARUK-UCL.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR GO; GO:0046618; P:xenobiotic export from cell; IMP:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR GO; GO:0006855; P:xenobiotic transmembrane transport; IMP:UniProtKB.
DR GO; GO:1990962; P:xenobiotic transport across blood-brain barrier; ISS:ARUK-UCL.
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; IPR030247; ABCC2.
DR InterPro; IPR005292; Multidrug-R_assoc.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR24223:SF176; PTHR24223:SF176; 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 TIGRFAMs; TIGR00957; MRP_assoc_pro; 1.
DR PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Disease variant; Glycoprotein; Lipid transport;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1545
FT /note="ATP-binding cassette sub-family C member 2"
FT /id="PRO_0000093356"
FT TOPO_DOM 1..27
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 28..48
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 49..68
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 69..89
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 90..93
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 94..114
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 115..126
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 127..147
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 148..165
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 166..186
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 187..313
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 314..334
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 335..360
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 361..381
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 382..437
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 438..458
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 459..461
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 462..482
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 483..544
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 545..565
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 566..587
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 588..608
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 609..971
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 972..992
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 993..1033
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1034..1054
FT /note="Helical; Name=13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1055..1097
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 1098..1118
FT /note="Helical; Name=14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1119
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1120..1140
FT /note="Helical; Name=15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1141..1211
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 1212..1232
FT /note="Helical; Name=16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1233..1234
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1235..1255
FT /note="Helical; Name=17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1256..1545
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 322..605
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 637..861
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 979..1264
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1300..1534
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 253..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 262..284
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 671..678
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1334..1341
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63120"
FT MOD_RES 283
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 878
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 926
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 930
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 938
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1438
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 7
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 12
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1011
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 39
FT /note="Y -> F (in dbSNP:rs927344)"
FT /evidence="ECO:0000269|PubMed:10464142,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:22290738,
FT ECO:0000269|PubMed:8662992, ECO:0000269|PubMed:8797578,
FT ECO:0000269|Ref.2, ECO:0000269|Ref.7"
FT /id="VAR_047152"
FT VARIANT 246
FT /note="M -> L (in dbSNP:rs17222744)"
FT /id="VAR_029113"
FT VARIANT 281
FT /note="S -> N (in dbSNP:rs56131651)"
FT /evidence="ECO:0000269|PubMed:11477083"
FT /id="VAR_013324"
FT VARIANT 333
FT /note="D -> G (decreased expression; altered subcellular
FT localization; altered transporter activity;
FT dbSNP:rs17222674)"
FT /evidence="ECO:0000269|PubMed:22290738"
FT /id="VAR_020226"
FT VARIANT 353
FT /note="R -> H (altered transporter activity;
FT dbSNP:rs7080681)"
FT /evidence="ECO:0000269|PubMed:22290738"
FT /id="VAR_020227"
FT VARIANT 417
FT /note="V -> I (in dbSNP:rs2273697)"
FT /evidence="ECO:0000269|PubMed:11266082,
FT ECO:0000269|PubMed:11477083, ECO:0000269|PubMed:25336012"
FT /id="VAR_013325"
FT VARIANT 486
FT /note="T -> I (altered transporter activity;
FT dbSNP:rs17222589)"
FT /evidence="ECO:0000269|PubMed:22290738"
FT /id="VAR_070607"
FT VARIANT 495
FT /note="K -> E (in dbSNP:rs17222561)"
FT /id="VAR_029115"
FT VARIANT 562
FT /note="F -> L (in dbSNP:rs17216233)"
FT /id="VAR_029116"
FT VARIANT 670
FT /note="I -> T (in dbSNP:rs17222632)"
FT /evidence="ECO:0000269|PubMed:22290738"
FT /id="VAR_020228"
FT VARIANT 768
FT /note="R -> W (in DJS; dbSNP:rs56199535)"
FT /evidence="ECO:0000269|PubMed:10053008,
FT ECO:0000269|PubMed:11266082, ECO:0000269|PubMed:25336012,
FT ECO:0000269|PubMed:9425227"
FT /id="VAR_000099"
FT VARIANT 789
FT /note="S -> F (in dbSNP:rs56220353)"
FT /evidence="ECO:0000269|PubMed:11266082"
FT /id="VAR_013326"
FT VARIANT 849
FT /note="L -> R (in dbSNP:rs17222617)"
FT /id="VAR_020229"
FT VARIANT 921
FT /note="G -> S (altered transporter activity;
FT dbSNP:rs41318029)"
FT /evidence="ECO:0000269|PubMed:22290738"
FT /id="VAR_070608"
FT VARIANT 982
FT /note="I -> V (in dbSNP:rs17222554)"
FT /id="VAR_029117"
FT VARIANT 1036
FT /note="I -> T (no effect on transporter activity;
FT dbSNP:rs45441199)"
FT /evidence="ECO:0000269|PubMed:22290738"
FT /id="VAR_020230"
FT VARIANT 1063
FT /note="N -> S (in dbSNP:rs17222540)"
FT /id="VAR_029118"
FT VARIANT 1150
FT /note="R -> H (in DJS; protein is properly localized at the
FT plasma membrane, but transporter activity is impaired;
FT dbSNP:rs72558200)"
FT /evidence="ECO:0000269|PubMed:11477083"
FT /id="VAR_013327"
FT VARIANT 1173
FT /note="I -> F (in DJS; decreased expression and mislocation
FT to the endoplasmic reticulum; dbSNP:rs72558201)"
FT /evidence="ECO:0000269|PubMed:11477083,
FT ECO:0000269|PubMed:22290738"
FT /id="VAR_013328"
FT VARIANT 1174
FT /note="R -> H (decreased expression; altered subcellular
FT localization; decreased transporter activity;
FT dbSNP:rs139188247)"
FT /evidence="ECO:0000269|PubMed:22290738"
FT /id="VAR_070609"
FT VARIANT 1181
FT /note="R -> L (decreased expression; dbSNP:rs8187692)"
FT /evidence="ECO:0000269|PubMed:22290738"
FT /id="VAR_020231"
FT VARIANT 1188
FT /note="V -> E (in dbSNP:rs17222723)"
FT /evidence="ECO:0000269|PubMed:22290738, ECO:0000269|Ref.2"
FT /id="VAR_020232"
FT VARIANT 1244
FT /note="N -> K (decreased transporter activity;
FT dbSNP:rs757141905)"
FT /evidence="ECO:0000269|PubMed:22290738"
FT /id="VAR_070610"
FT VARIANT 1273
FT /note="T -> A (in dbSNP:rs8187699)"
FT /id="VAR_024360"
FT VARIANT 1291
FT /note="P -> L (altered transporter activity;
FT dbSNP:rs17216317)"
FT /evidence="ECO:0000269|PubMed:22290738"
FT /id="VAR_020233"
FT VARIANT 1382
FT /note="Q -> R (in DJS; dbSNP:rs72558202)"
FT /evidence="ECO:0000269|PubMed:10053008"
FT /id="VAR_010756"
FT VARIANT 1392..1393
FT /note="Missing (in DJS; impaired transport from the
FT endoplasmic reticulum to the apical plasma membrane
FT associated with impaired maturation)"
FT /evidence="ECO:0000269|PubMed:10464142,
FT ECO:0000269|PubMed:11093739"
FT /id="VAR_013329"
FT VARIANT 1450
FT /note="A -> T (in dbSNP:rs56296335)"
FT /evidence="ECO:0000269|PubMed:11266082"
FT /id="VAR_013330"
FT VARIANT 1515
FT /note="C -> Y (in dbSNP:rs8187710)"
FT /evidence="ECO:0000269|PubMed:22290738, ECO:0000269|Ref.2"
FT /id="VAR_020234"
FT MUTAGEN 1254
FT /note="W->A,C: Fails to transport methotrexate, leukotriene
FT C4 and estradiol glucuronide."
FT /evidence="ECO:0000269|PubMed:11500505"
FT MUTAGEN 1254
FT /note="W->F: Fails to transport methotrexate and
FT leukotriene C4. Does not affect estradiol glucuronide
FT transport."
FT /evidence="ECO:0000269|PubMed:11500505"
FT MUTAGEN 1254
FT /note="W->Y: Fails to transport methotrexate; reduces
FT leukotriene C4 transport. Does not affect estradiol
FT glucuronide transport."
FT /evidence="ECO:0000269|PubMed:11500505"
FT CONFLICT 1430
FT /note="V -> G (in Ref. 5; CAB45309)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1545 AA; 174207 MW; C5F8984FFCDF9799 CRC64;
MLEKFCNSTF WNSSFLDSPE ADLPLCFEQT VLVWIPLGYL WLLAPWQLLH VYKSRTKRSS
TTKLYLAKQV FVGFLLILAA IELALVLTED SGQATVPAVR YTNPSLYLGT WLLVLLIQYS
RQWCVQKNSW FLSLFWILSI LCGTFQFQTL IRTLLQGDNS NLAYSCLFFI SYGFQILILI
FSAFSENNES SNNPSSIASF LSSITYSWYD SIILKGYKRP LTLEDVWEVD EEMKTKTLVS
KFETHMKREL QKARRALQRR QEKSSQQNSG ARLPGLNKNQ SQSQDALVLE DVEKKKKKSG
TKKDVPKSWL MKALFKTFYM VLLKSFLLKL VNDIFTFVSP QLLKLLISFA SDRDTYLWIG
YLCAILLFTA ALIQSFCLQC YFQLCFKLGV KVRTAIMASV YKKALTLSNL ARKEYTVGET
VNLMSVDAQK LMDVTNFMHM LWSSVLQIVL SIFFLWRELG PSVLAGVGVM VLVIPINAIL
STKSKTIQVK NMKNKDKRLK IMNEILSGIK ILKYFAWEPS FRDQVQNLRK KELKNLLAFS
QLQCVVIFVF QLTPVLVSVV TFSVYVLVDS NNILDAQKAF TSITLFNILR FPLSMLPMMI
SSMLQASVST ERLEKYLGGD DLDTSAIRHD CNFDKAMQFS EASFTWEHDS EATVRDVNLD
IMAGQLVAVI GPVGSGKSSL ISAMLGEMEN VHGHITIKGT TAYVPQQSWI QNGTIKDNIL
FGTEFNEKRY QQVLEACALL PDLEMLPGGD LAEIGEKGIN LSGGQKQRIS LARATYQNLD
IYLLDDPLSA VDAHVGKHIF NKVLGPNGLL KGKTRLLVTH SMHFLPQVDE IVVLGNGTIV
EKGSYSALLA KKGEFAKNLK TFLRHTGPEE EATVHDGSEE EDDDYGLISS VEEIPEDAAS
ITMRRENSFR RTLSRSSRSN GRHLKSLRNS LKTRNVNSLK EDEELVKGQK LIKKEFIETG
KVKFSIYLEY LQAIGLFSIF FIILAFVMNS VAFIGSNLWL SAWTSDSKIF NSTDYPASQR
DMRVGVYGAL GLAQGIFVFI AHFWSAFGFV HASNILHKQL LNNILRAPMR FFDTTPTGRI
VNRFAGDIST VDDTLPQSLR SWITCFLGII STLVMICMAT PVFTIIVIPL GIIYVSVQMF
YVSTSRQLRR LDSVTRSPIY SHFSETVSGL PVIRAFEHQQ RFLKHNEVRI DTNQKCVFSW
ITSNRWLAIR LELVGNLTVF FSALMMVIYR DTLSGDTVGF VLSNALNITQ TLNWLVRMTS
EIETNIVAVE RITEYTKVEN EAPWVTDKRP PPDWPSKGKI QFNNYQVRYR PELDLVLRGI
TCDIGSMEKI GVVGRTGAGK SSLTNCLFRI LEAAGGQIII DGVDIASIGL HDLREKLTII
PQDPILFSGS LRMNLDPFNN YSDEEIWKAL ELAHLKSFVA SLQLGLSHEV TEAGGNLSIG
QRQLLCLGRA LLRKSKILVL DEATAAVDLE TDNLIQTTIQ NEFAHCTVIT IAHRLHTIMD
SDKVMVLDNG KIIECGSPEE LLQIPGPFYF MAKEAGIENV NSTKF
