| IED ID | IndEnz0002006206 |
| Enzyme Type ID | protease006206 |
| Protein Name |
ATP-binding cassette sub-family C member 2 EC 7.6.2.- EC 7.6.2.2 EC 7.6.2.3 Canalicular multidrug resistance protein Canalicular multispecific organic anion transporter 1 Multidrug resistance-associated protein 2 |
| Gene Name | ABCC2 CMOAT CMOAT1 CMRP MRP2 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MLEKFCNSTFWNSSFLDSPEADLPLCFEQTVLVWIPLGYLWLLAPWQLLHVYKSRTKRSSTTKLYLAKQVFVGFLLILAAIELALVLTEDSGQATVPAVRYTNPSLYLGTWLLVLLIQYSRQWCVQKNSWFLSLFWILSILCGTFQFQTLIRTLLQGDNSNLAYSCLFFISYGFQILILIFSAFSENNESSNNPSSIASFLSSITYSWYDSIILKGYKRPLTLEDVWEVDEEMKTKTLVSKFETHMKRELQKARRALQRRQEKSSQQNSGARLPGLNKNQSQSQDALVLEDVEKKKKKSGTKKDVPKSWLMKALFKTFYMVLLKSFLLKLVNDIFTFVSPQLLKLLISFASDRDTYLWIGYLCAILLFTAALIQSFCLQCYFQLCFKLGVKVRTAIMASVYKKALTLSNLARKEYTVGETVNLMSVDAQKLMDVTNFMHMLWSSVLQIVLSIFFLWRELGPSVLAGVGVMVLVIPINAILSTKSKTIQVKNMKNKDKRLKIMNEILSGIKILKYFAWEPSFRDQVQNLRKKELKNLLAFSQLQCVVIFVFQLTPVLVSVVTFSVYVLVDSNNILDAQKAFTSITLFNILRFPLSMLPMMISSMLQASVSTERLEKYLGGDDLDTSAIRHDCNFDKAMQFSEASFTWEHDSEATVRDVNLDIMAGQLVAVIGPVGSGKSSLISAMLGEMENVHGHITIKGTTAYVPQQSWIQNGTIKDNILFGTEFNEKRYQQVLEACALLPDLEMLPGGDLAEIGEKGINLSGGQKQRISLARATYQNLDIYLLDDPLSAVDAHVGKHIFNKVLGPNGLLKGKTRLLVTHSMHFLPQVDEIVVLGNGTIVEKGSYSALLAKKGEFAKNLKTFLRHTGPEEEATVHDGSEEEDDDYGLISSVEEIPEDAASITMRRENSFRRTLSRSSRSNGRHLKSLRNSLKTRNVNSLKEDEELVKGQKLIKKEFIETGKVKFSIYLEYLQAIGLFSIFFIILAFVMNSVAFIGSNLWLSAWTSDSKIFNSTDYPASQRDMRVGVYGALGLAQGIFVFIAHFWSAFGFVHASNILHKQLLNNILRAPMRFFDTTPTGRIVNRFAGDISTVDDTLPQSLRSWITCFLGIISTLVMICMATPVFTIIVIPLGIIYVSVQMFYVSTSRQLRRLDSVTRSPIYSHFSETVSGLPVIRAFEHQQRFLKHNEVRIDTNQKCVFSWITSNRWLAIRLELVGNLTVFFSALMMVIYRDTLSGDTVGFVLSNALNITQTLNWLVRMTSEIETNIVAVERITEYTKVENEAPWVTDKRPPPDWPSKGKIQFNNYQVRYRPELDLVLRGITCDIGSMEKIGVVGRTGAGKSSLTNCLFRILEAAGGQIIIDGVDIASIGLHDLREKLTIIPQDPILFSGSLRMNLDPFNNYSDEEIWKALELAHLKSFVASLQLGLSHEVTEAGGNLSIGQRQLLCLGRALLRKSKILVLDEATAAVDLETDNLIQTTIQNEFAHCTVITIAHRLHTIMDSDKVMVLDNGKIIECGSPEELLQIPGPFYFMAKEAGIENVNSTKF |
| Enzyme Length | 1545 |
| Uniprot Accession Number | Q92887 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + H(2)O + xenobiotic(Side 1) = ADP + phosphate + xenobiotic(Side 2).; EC=7.6.2.2; Evidence={ECO:0000269|PubMed:10220572, ECO:0000269|PubMed:11500505, ECO:0000269|PubMed:12441801}; CATALYTIC ACTIVITY: Reaction=an S-substituted glutathione(in) + ATP + H2O = ADP + an S-substituted glutathione(out) + H(+) + phosphate; Xref=Rhea:RHEA:19121, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:90779, ChEBI:CHEBI:456216; EC=7.6.2.3; Evidence={ECO:0000269|PubMed:10220572, ECO:0000269|PubMed:11500505};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19122; Evidence={ECO:0000305|PubMed:10220572, ECO:0000305|PubMed:11500505}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + taurolithocholate 3-sulfate(in) = ADP + H(+) + phosphate + taurolithocholate 3-sulfate(out); Xref=Rhea:RHEA:50084, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58301, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:16332456};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50085; Evidence={ECO:0000269|PubMed:16332456}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + leukotriene C4(in) = ADP + H(+) + leukotriene C4(out) + phosphate; Xref=Rhea:RHEA:38963, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57973, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:10220572, ECO:0000269|PubMed:11500505};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38964; Evidence={ECO:0000305|PubMed:11500505}; CATALYTIC ACTIVITY: Reaction=17beta-estradiol 17-O-(beta-D-glucuronate)(in) + ATP + H2O = 17beta-estradiol 17-O-(beta-D-glucuronate)(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:60128, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:82961, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:10220572, ECO:0000269|PubMed:11500505};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60129; Evidence={ECO:0000305|PubMed:11500505}; CATALYTIC ACTIVITY: Reaction=ATP + bilirubin-glucuronoside(in) + H2O = ADP + bilirubin-glucuronoside(out) + H(+) + phosphate; Xref=Rhea:RHEA:66180, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57767, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:10421658};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66181; Evidence={ECO:0000305|PubMed:10421658}; CATALYTIC ACTIVITY: Reaction=ATP + bilirubin-bisglucuronoside(in) + H2O = ADP + bilirubin-bisglucuronoside(out) + H(+) + phosphate; Xref=Rhea:RHEA:66192, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58471, ChEBI:CHEBI:456216; Evidence={ECO:0000305|PubMed:10421658}; |
| DNA Binding | |
| EC Number | 7.6.2.-; 7.6.2.2; 7.6.2.3 |
| Enzyme Function | FUNCTION: ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transport various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505). {ECO:0000269|PubMed:10220572, ECO:0000269|PubMed:10421658, ECO:0000269|PubMed:11500505, ECO:0000269|PubMed:12441801, ECO:0000269|PubMed:16332456}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 671..678; /note=ATP 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00434; NP_BIND 1334..1341; /note=ATP 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00434 |
| Features | Chain (1); Compositional bias (1); Domain (4); Glycosylation (3); Modified residue (7); Mutagenesis (3); Natural variant (29); Nucleotide binding (2); Region (1); Sequence conflict (1); Topological domain (18); Transmembrane (17) |
| Keywords | ATP-binding;Cell membrane;Disease variant;Glycoprotein;Lipid transport;Membrane;Nucleotide-binding;Phosphoprotein;Reference proteome;Repeat;Translocase;Transmembrane;Transmembrane helix;Transport |
| Interact With | P19838 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000269|PubMed:10220572, ECO:0000269|PubMed:11093739}; Multi-pass membrane protein {ECO:0000255}. |
| Modified Residue | MOD_RES 281; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q63120"; MOD_RES 283; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 878; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:24275569"; MOD_RES 926; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 930; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 938; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 1438; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569" |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11581266; 11901087; 11937269; 11952788; 12388192; 12395335; 12576456; 12615054; 12628490; 12702717; 12704183; 12890151; 12942343; 12960109; 14568249; 15057744; 15211708; 15226675; 15519273; 15801936; 15848949; 15870973; 15922475; 16041239; 16330681; 16385451; 16426233; 16505951; 16542205; 16628674; 16771603; 16788565; 16791115; 16816140; 16821592; 16946557; 17047488; 17060857; 17083032; 17112803; 17145840; 17156953; 17185998; 17241877; 17287630; 17403188; 17478601; 17485564; 17494643; 17502832; 17534875; 17578901; 17606722; 17725603; 17825285; 17890284; 17906856; 17924828; 17925548; 17997497; 18038766; 18176959; 18180270; 18192894; 18221820; 18294295; 18334920; 18381564; 18381794; 18416940; 18439156; 18445995; 18498916; 18509327; 18518855; 18597651; 18690847; 18695635; 18697280; 18799096; 18838068; 18926681; 18946804; 18974617; 18981587; 19010343; 19017997; 19020751; 19038257; 19074644; 19098406; 19167193; 19170196; 19214140; 19343046; 19349540; 19400747; 19415824; 19421150; 19442037; 19451719; 19480556; 19494809; 19513507; 19541926; 19568750; 19625176; 19636001; 19692168; 19696793; 19730281; 19771428; 19776292; 19842932; 19857663; 19865079; 19885582; 19885591; 19937833; 19944137; 19956635; 19956884; 20061166; 20082599; 20102361; 20124171; 20147615; 20173083; 20190787; 20193114; 20200426; 20204280; 20216337; 20351751; 20368715; 20404332; 20439344; 20453000; 20530282; 20565459; 20658178; 20679960; 20702406; 20720558; 20738239; 20922799; 20943283; 20973683; 21039333; 21044052; 21059598; 21072184; 21134393; 21160029; 21170509; 21206495; 21449672; 21451505; 21541183; 21691255; 21799461; 21864659; 21899702; 21918980; 21945491; 21986666; 21988832; 22027652; 22062654; 22112610; 22178260; 22186618; 22201120; 22256867; 22275271; 22307138; 22318656; 22406294; 22407408; 22428913; 22454528; 22469515; 22473764; 22534871; 22630058; 22664480; 22673116; 22676135; 22695893; 22744337; 22899102; 22922069; 23052037; 23069858; 23131697; 23135210; 23188068; 23190519; 23222202; 23232902; 23237922; 23278697; 23381786; 23506516; 23556446; 23562342; 23633119; 23697249; 23700788; 23717663; 23841074; 23896815; 24325761; 24404132; 24552501; 24567120; 24624913; 24711118; 24732756; 24743544; 24788661; 25060527; 25155934; 25162314; 25163515; 25388687; 25425682; 25744397; 25788542; 25793771; 25801567; 25823783; 25847339; 25890497; 26067485; 26109419; 26212029; 26292095; 26295158; 26350512; 26403473; 26502886; 27109321; 27180762; 27394416; 27527855; 27590272; 27816260; 27886333; 27943270; 28196047; 28405913; 28442702; 28532626; 28532671; 28753789; 29052767; 29178257; 29453415; 29464551; 29660381; 29873816; 30024814; 30345879; 30360603; 30458661; 30629142; 30767719; 30783141; 30896644; 30959153; 31132291; 31195293; 31244920; 31544333; 31615114; 31677118; 31691080; 31870219; 31874997; 32183854; 32727778; 32815556; 33208122; 33323685; 34273652; 34309735; 34638773; 34684087; |
| Motif | |
| Gene Encoded By | |
| Mass | 174,207 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=7.2 uM for 17beta-estradiol 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:10220572}; KM=1 uM for leukotriene C4 {ECO:0000269|PubMed:10220572}; KM=0.7 uM for bilirubin-glucuronoside {ECO:0000269|PubMed:10421658}; KM=0.9 uM for bilirubin-bisglucuronoside {ECO:0000269|PubMed:10421658}; KM=8.2 uM for taurolithocholate sulfate {ECO:0000269|PubMed:16332456}; Vmax=321 pmol/min/mg enzyme for bilirubin-glucuronoside transport {ECO:0000269|PubMed:10421658}; Vmax=255 pmol/min/mg enzyme bilirubin-bisglucuronoside transport {ECO:0000269|PubMed:10421658}; Vmax=1530 pmol/min/mg enzyme for taurolithocholate sulfate transport {ECO:0000269|PubMed:16332456}; |
| Metal Binding | |
| Rhea ID | RHEA:19121; RHEA:19122; RHEA:50084; RHEA:50085; RHEA:38963; RHEA:38964; RHEA:60128; RHEA:60129; RHEA:66180; RHEA:66181; RHEA:66192 |
| Cross Reference Brenda | 7.6.2.2;7.6.2.3; |