MRP2_RABIT
ID MRP2_RABIT Reviewed; 1564 AA.
AC Q28689;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=ATP-binding cassette sub-family C member 2;
DE EC=7.6.2.- {ECO:0000269|PubMed:9614209};
DE EC=7.6.2.2 {ECO:0000250|UniProtKB:Q92887};
DE EC=7.6.2.3 {ECO:0000269|PubMed:9614209};
DE AltName: Full=Canalicular multidrug resistance protein;
DE AltName: Full=Canalicular multispecific organic anion transporter 1 {ECO:0000250|UniProtKB:Q92887};
DE AltName: Full=Epithelial basolateral chloride conductance regulator {ECO:0000303|PubMed:8643587};
DE AltName: Full=Multidrug resistance-associated protein 2;
GN Name=ABCC2 {ECO:0000250|UniProtKB:Q92887};
GN Synonyms=EBCR {ECO:0000303|PubMed:8643587},
GN MRP2 {ECO:0000303|PubMed:9614209};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC TISSUE=Ileum;
RX PubMed=8643587; DOI=10.1073/pnas.93.11.5401;
RA van Kuijck M.A., van Aubel R.A.M.H., Busch A.E., Lang F., Russel F.G.M.,
RA Bindels R.J.M., van Os C.H., Deen P.M.T.;
RT "Molecular cloning and expression of a cyclic AMP-activated chloride
RT conductance regulator: a novel ATP-binding cassette transporter.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:5401-5406(1996).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9614209;
RA van Aubel R.A.M.H., van Kuijck M.A., Koenderink J.B., Deen P.M.T.,
RA van Os C.H., Russel F.G.M.;
RT "Adenosine triphosphate-dependent transport of anionic conjugates by the
RT rabbit multidrug resistance-associated protein Mrp2 expressed in insect
RT cells.";
RL Mol. Pharmacol. 53:1062-1067(1998).
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 (PubMed:9614209). Transports a wide
CC variety of conjugated organic anions such as sulfate-, glucuronide- and
CC glutathione (GSH)-conjugates of endo- and xenobiotics substrates.
CC Mediates hepatobiliary excretion of mono- and bis-glucuronidated
CC bilirubin molecules and therefore play an important role in bilirubin
CC detoxification (By similarity). Mediates also hepatobiliary excretion
CC of others glucuronide conjugates such as 17beta-estradiol 17-
CC glucosiduronic acid and leukotriene C4 (PubMed:9614209). Transports
CC sulfated bile salt such as taurolithocholate sulfate. Transport various
CC anticancer drugs, such as anthracycline, vinca alkaloid and
CC methotrexate and HIV-drugs such as protease inhibitors (By similarity).
CC {ECO:0000250|UniProtKB:Q92887, ECO:0000269|PubMed:9614209}.
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:9614209};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19122;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC xenobioticSide 2.; EC=7.6.2.2;
CC Evidence={ECO:0000250|UniProtKB:Q92887};
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:0000250|UniProtKB:Q92887};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50085;
CC Evidence={ECO:0000250|UniProtKB:Q92887};
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:9614209};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38964;
CC Evidence={ECO:0000269|PubMed:9614209};
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:9614209};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60129;
CC Evidence={ECO:0000250|UniProtKB:Q92887};
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:0000250|UniProtKB:Q92887};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66181;
CC Evidence={ECO:0000250|UniProtKB:Q92887};
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:0000250|UniProtKB:Q92887};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=623 uM for 17beta-estradiol 17-O-(beta-D-glucuronate)
CC {ECO:0000269|PubMed:9614209};
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:Q92887}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in liver, kidney and small intestine.
CC {ECO:0000269|PubMed:8643587}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC family.
CC Conjugate transporter (TC 3.A.1.208) subfamily. {ECO:0000305}.
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DR EMBL; Z49144; CAA89004.1; -; Genomic_DNA.
DR AlphaFoldDB; Q28689; -.
DR SMR; Q28689; -.
DR STRING; 9986.ENSOCUP00000007069; -.
DR PRIDE; Q28689; -.
DR eggNOG; KOG0054; Eukaryota.
DR InParanoid; Q28689; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0015431; F:ABC-type glutathione S-conjugate transporter activity; IMP:UniProtKB.
DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0008514; F:organic anion transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0015721; P:bile acid and bile salt transport; ISS:UniProtKB.
DR GO; GO:0071716; P:leukotriene transport; IMP:UniProtKB.
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; Glycoprotein; Lipid transport; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1564
FT /note="ATP-binding cassette sub-family C member 2"
FT /id="PRO_0000093358"
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..311
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 312..332
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 333..358
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 359..379
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 380..435
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 436..456
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 457..459
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 460..480
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 481..542
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 543..563
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 564..585
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 586..606
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 607..969
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 970..990
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 991..1031
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1032..1052
FT /note="Helical; Name=13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1053..1095
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 1096..1116
FT /note="Helical; Name=14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1117
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1118..1138
FT /note="Helical; Name=15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1139..1209
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 1210..1230
FT /note="Helical; Name=16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1231..1232
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1233..1253
FT /note="Helical; Name=17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1254..1543
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 320..603
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 635..859
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 977..1262
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1298..1532
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 258..283
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 909..939
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 267..283
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 669..676
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1332..1339
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 279
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63120"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92887"
FT MOD_RES 876
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92887"
FT MOD_RES 925
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92887"
FT MOD_RES 929
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92887"
FT MOD_RES 1436
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92887"
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 1009
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1564 AA; 175544 MW; D8FBF5AC8FE45873 CRC64;
MLDKFCNSTF WNSSLLDSPE ADLPLCFEQT VLVWIPLIFL WLLAPWQLFH VYRSRTKRSP
ITKFYLAKQV LVGCLLILAV IELILVLTEN SGQATIPAVR YTNPILYLVT WLLVLLIQHS
RQSCVQKNSW FLSLFWILSI LCGTFQFQTL IRTLLRDSNS NLAYSCLFFI SYGFQILILI
LSAFSEKDNS SKNPSVTASF LSKISFSWYD SVVLKGYKRP LTLEDVWDID EEFKAKTIVS
RFEVHMAKEL KKARKAFQKR QQKKSQKNSR LQGLNKNQSQ SQDVLVLEET KKKNKKSGTT
KDFPKSWLVK TIFKTFYMVL LKSFLLKLVY DLLTFLNPQL LKLLITFVSD PNSYAWLGYI
FAILLFAVAL IQSICLQTYF HMCFNLGMCV GTTVMATVYK KALTISNLAK RQYTIGETVN
LMSVDAQKLM DVTNFIHLVW SSVLQIVLSI YFLWVELGPS VLAGVGVMVL LIPVNGILAT
KNRNIQFKNM KYKDKRLRIM NEILSGMKIL KYFAWEPSFK DQVHNLRKKE LKNLRTFAYM
QSVVMFLLYL TPVLVSVTTF SVYVLVDSNN ILDAEKAFTS ITLFNILRFP MSMLPNVISA
MLQASVSVDR LEKYLSGDDL DTSAIQRDPN FDKAVQFSEA SFTWDRNLEP TIRNVNLDIM
PGQLVAVVGT VGSGKSSLMS AMLGEMENVH GHITIKGTTA YVPQQSWIQN GTIKDNILFG
AEFDERRYQR VLEACALLPD LEILPGGDLA EIGEKGINLS GGQKQRISLA RASYQNSDIY
ILDDPLSAVD AHVGKHIFNK VLGPNGLLNG KTRLLVTHSL HFLPQVDEIV VVENGTILEK
GSYSSLLAKK GVFAKNLKMF VKHTDSEGEV TVNDGSEEDD DDDSGLISSI EEFPEDSISL
TLKRENSLHR TLSRSSRSSG RRLKSLKNSL KAQNGKTPKE EEVVKGQKLI KKEFMETGKV
KFSIYLKYLQ AIGWCSIVGI IFAYVLNSVA FIGSNLWLSA WTSDSNTYNG TNYPASQRDL
RIGIFGVLGL AQGLTVLVAS FWSASGCAHA SNILHKQLLN NILRAPMSFF NTTPIGRIVN
RFAGDISTVD DTLPQSLRSW MMCFLAIIST LIMICMATPV FAVIIIPLAI IYVAVQVFYV
ATSRQLRRLD SVTRSPIYSH FTETVSGLPV IRAFEHQQRF LKQNEIGIDT NQKCVSSWIT
SNRWLAFRLE LVGNLVVFSS ALMMVIYRDT LSGDVVGFVL SNALNITQTL NWLVRMTSET
ETNIVAVERI TEYIKVENEA PWVTDKRPPA GWPHKGEIQF SNYQVRYRPE LDLVLKGINC
DIKSMEKIGV VGRTGAGKSS LTNCLFRILE AAGGHITIDG IDIASIGLHD LRGKLTIIPQ
DPVLFSGSLR MNLDPFNNYS DEEIWRALEL AHLKSFVAGL QHGLSREVSE AEDNLSIGQR
QLLCLGRALL RKSKILVLDE ATAAVDLETD HLIQTTIRNE FSHCTVITIA HRLHTIMDSD
KIMVLDNGNI VEYGSPEELL ESAGPFSLMA KESGIENVNN TAFWAAAARD AGAGRLSPGF
ASVT
