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 24-JAN-2024, entry version 218. 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], VARIANT PHE-39, AND VARIANT 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 SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=28408210; DOI=10.1016/j.xphs.2017.04.001; RA Keiser M., Kaltheuner L., Wildberg C., Mueller J., Grube M., Partecke L.I., RA Heidecke C.D., Oswald S.; RT "The Organic Anion-Transporting Peptide 2B1 Is Localized in the Basolateral RT Membrane of the Human Jejunum and Caco-2 Monolayers."; RL J. Pharm. Sci. 106:2657-2663(2017). RN [21] 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 [22] 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 [23] 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 [24] 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 [25] 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 [26] 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 [27] 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 Transports 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, CC ECO:0000269|PubMed:28408210}; Multi-pass membrane protein CC {ECO:0000255}. Note=Localized to the apical membrane of enterocytes. CC {ECO:0000269|PubMed:28408210}. CC -!- TISSUE SPECIFICITY: Expressed by polarized cells in liver, kidney and CC intestine. The highest expression is found in liver. Expressed in small CC intestine (PubMed:28408210). {ECO:0000269|PubMed:28408210}. 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EMDB; EMD-29637; -. DR SMR; Q92887; -. DR BioGRID; 107647; 100. DR IntAct; Q92887; 8. DR MINT; Q92887; -. DR STRING; 9606.ENSP00000497274; -. 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; DB16407; Azvudine. 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; DB00619; Imatinib. 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; DB12713; Sotagliflozin. 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 GlyCosmos; Q92887; 3 sites, No reported glycans. 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; 9606-ENSP00000359478; -. DR PeptideAtlas; Q92887; -. DR ProteomicsDB; 75571; -. DR Pumba; Q92887; -. DR Antibodypedia; 17520; 440 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 AGR; HGNC:53; -. 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; RRRYILW; -. DR OrthoDB; 3384185at2759; -. 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; 14 hits in 1162 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 99 other cell types or tissues. DR ExpressionAtlas; Q92887; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0046581; C:intercellular canaliculus; IEA:Ensembl. 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:0016887; F:ATP hydrolysis activity; IEA:InterPro. 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 CDD; cd18595; ABC_6TM_MRP1_2_3_6_D1_like; 1. DR CDD; cd18603; ABC_6TM_MRP1_2_3_6_D2_like; 1. DR CDD; cd03250; ABCC_MRP_domain1; 1. DR CDD; cd03244; ABCC_MRP_domain2; 1. DR Gene3D; 1.20.1560.10; ABC transporter type 1, transmembrane domain; 2. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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; IPR005292; MRP. DR InterPro; IPR027417; P-loop_NTPase. DR NCBIfam; TIGR00957; MRP_assoc_pro; 1. DR PANTHER; PTHR24223; ATP-BINDING CASSETTE SUB-FAMILY C; 1. DR PANTHER; PTHR24223:SF176; ATP-BINDING CASSETTE SUB-FAMILY C MEMBER 2; 1. DR Pfam; PF00664; ABC_membrane; 2. DR Pfam; PF00005; ABC_tran; 2. DR SMART; SM00382; AAA; 2. DR SUPFAM; SSF90123; ABC transporter transmembrane region; 2. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2. DR PROSITE; PS50929; ABC_TM1F; 2. DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1. DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2. DR Genevisible; Q92887; HS. 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 //