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Canalicular multispecific organic anion transporter 1 (ATP-binding cassette sub-family C member 2) (Canalicular multidrug resistance protein) (Multidrug resistance-associated protein 2)

 MRP2_RAT                Reviewed;        1541 AA.
Q63120; Q63145;
15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
01-NOV-1996, sequence version 1.
12-SEP-2018, entry version 140.
RecName: Full=Canalicular multispecific organic anion transporter 1;
AltName: Full=ATP-binding cassette sub-family C member 2;
AltName: Full=Canalicular multidrug resistance protein;
AltName: Full=Multidrug resistance-associated protein 2;
Name=Abcc2; Synonyms=Cmoat, Cmrp, Mrp2;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=Wistar; TISSUE=Liver;
PubMed=8599091; DOI=10.1126/science.271.5252.1126;
Paulusma C.C., Bosma P.J., Zaman G.J.R., Bakker C.T.M., Otter M.,
Scheffer G.L., Scheper R.J., Borst P., Oude Elferink R.P.J.;
"Congenital jaundice in rats with a mutation in a multidrug
resistance-associated protein gene.";
Science 271:1126-1128(1996).
[2]
NUCLEOTIDE SEQUENCE [MRNA], AND INVOLVEMENT IN EHBR.
STRAIN=Wistar; TISSUE=Liver;
PubMed=8662992; DOI=10.1074/jbc.271.25.15091;
Buechler M., Koenig J., Brom M., Kartenbeck J., Spring H., Horie T.,
Keppler D.;
"cDNA cloning of the hepatocyte canalicular isoform of the multidrug
resistance protein, cMrp, reveals a novel conjugate export pump
deficient in hyperbilirubinemic mutant rats.";
J. Biol. Chem. 271:15091-15098(1996).
[3]
NUCLEOTIDE SEQUENCE [MRNA], AND INVOLVEMENT IN EHBR.
STRAIN=Sprague-Dawley; TISSUE=Liver;
Ito K., Suzuki H., Hirohashi T., Kume K., Shimizu T., Sugiyama Y.;
"Expression of the putative ATP-binding cassette region, homologous to
that in multidrug resistance associated protein (MRP), is hereditarily
defective in Eisai hyperbilirubinemic rats (EHBR).";
Int. Hepatol. Commun. 292:292-299(1996).
[4]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-279; SER-281 AND
SER-874, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].
PubMed=22673903; DOI=10.1038/ncomms1871;
Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A.,
Lundby C., Olsen J.V.;
"Quantitative maps of protein phosphorylation sites across 14
different rat organs and tissues.";
Nat. Commun. 3:876-876(2012).
-!- FUNCTION: Mediates hepatobiliary excretion of numerous organic
anions.
-!- SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000250}; Multi-
pass membrane protein {ECO:0000255|PROSITE-ProRule:PRU00441}.
-!- TISSUE SPECIFICITY: Mainly expressed in the liver.
-!- DISEASE: Note=Defects in Abcc2 are a cause of hereditary
conjugated hyperbilirubinemia (EHBR). {ECO:0000269|PubMed:8599091,
ECO:0000269|Ref.3}.
-!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC
family. Conjugate transporter (TC 3.A.1.208) subfamily.
{ECO:0000305}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
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EMBL; L49379; AAC42087.1; -; mRNA.
EMBL; X96393; CAA65257.1; -; mRNA.
EMBL; D86086; BAA13016.1; -; mRNA.
PIR; S71839; S71839.
RefSeq; NP_036965.1; NM_012833.2.
UniGene; Rn.10265; -.
ProteinModelPortal; Q63120; -.
SMR; Q63120; -.
BioGrid; 247342; 1.
IntAct; Q63120; 1.
MINT; Q63120; -.
STRING; 10116.ENSRNOP00000064799; -.
BindingDB; Q63120; -.
ChEMBL; CHEMBL2073676; -.
CarbonylDB; Q63120; -.
iPTMnet; Q63120; -.
PhosphoSitePlus; Q63120; -.
PaxDb; Q63120; -.
PRIDE; Q63120; -.
Ensembl; ENSRNOT00000070861; ENSRNOP00000064799; ENSRNOG00000046727.
GeneID; 25303; -.
KEGG; rno:25303; -.
CTD; 1244; -.
RGD; 2366; Abcc2.
eggNOG; KOG0054; Eukaryota.
eggNOG; COG1132; LUCA.
GeneTree; ENSGT00880000137856; -.
HOVERGEN; HBG108314; -.
InParanoid; Q63120; -.
KO; K05666; -.
OMA; DLPLCFE; -.
OrthoDB; EOG091G00IN; -.
PhylomeDB; Q63120; -.
Reactome; R-RNO-382556; ABC-family proteins mediated transport.
SABIO-RK; Q63120; -.
PRO; PR:Q63120; -.
Proteomes; UP000002494; Chromosome 1.
Bgee; ENSRNOG00000046727; Expressed in 8 organ(s), highest expression level in liver.
Genevisible; Q63120; RN.
GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
GO; GO:0031526; C:brush border membrane; IDA:RGD.
GO; GO:0009986; C:cell surface; IEA:Ensembl.
GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
GO; GO:0046581; C:intercellular canaliculus; IEA:Ensembl.
GO; GO:0016020; C:membrane; IDA:RGD.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0042626; F:ATPase activity, coupled to transmembrane movement of substances; IBA:GO_Central.
GO; GO:0008514; F:organic anion transmembrane transporter activity; TAS:RGD.
GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
GO; GO:0016999; P:antibiotic metabolic process; IMP:RGD.
GO; GO:1901086; P:benzylpenicillin metabolic process; IMP:RGD.
GO; GO:0015722; P:canalicular bile acid transport; IMP:RGD.
GO; GO:0030644; P:cellular chloride ion homeostasis; IDA:RGD.
GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
GO; GO:0071354; P:cellular response to interleukin-6; IEP:RGD.
GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
GO; GO:0006855; P:drug transmembrane transport; IMP:RGD.
GO; GO:0007565; P:female pregnancy; IEP:RGD.
GO; GO:0015694; P:mercury ion transport; IMP:RGD.
GO; GO:0015711; P:organic anion transport; TAS:RGD.
GO; GO:0015732; P:prostaglandin transport; IMP:RGD.
GO; GO:0097327; P:response to antineoplastic agent; IEP:RGD.
GO; GO:0046685; P:response to arsenic-containing substance; IEP:RGD.
GO; GO:0042493; P:response to drug; IDA:RGD.
GO; GO:0043627; P:response to estrogen; IDA:RGD.
GO; GO:0033762; P:response to glucagon; IEP:RGD.
GO; GO:0009408; P:response to heat; IEP:RGD.
GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
GO; GO:0031427; P:response to methotrexate; IEP:RGD.
GO; GO:0006979; P:response to oxidative stress; IEP:RGD.
GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
GO; GO:0070327; P:thyroid hormone transport; IMP:RGD.
Gene3D; 1.20.1560.10; -; 2.
InterPro; IPR003593; AAA+_ATPase.
InterPro; IPR011527; ABC1_TM_dom.
InterPro; IPR036640; ABC1_TM_sf.
InterPro; IPR003439; ABC_transporter-like.
InterPro; IPR017871; ABC_transporter_CS.
InterPro; IPR030247; ABCC2.
InterPro; IPR005292; Multidrug-R_assoc.
InterPro; IPR027417; P-loop_NTPase.
PANTHER; PTHR24223:SF176; PTHR24223:SF176; 1.
Pfam; PF00664; ABC_membrane; 2.
Pfam; PF00005; ABC_tran; 2.
SMART; SM00382; AAA; 2.
SUPFAM; SSF52540; SSF52540; 2.
SUPFAM; SSF90123; SSF90123; 2.
TIGRFAMs; TIGR00957; MRP_assoc_pro; 1.
PROSITE; PS50929; ABC_TM1F; 2.
PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
1: Evidence at protein level;
ATP-binding; Cell membrane; Complete proteome; Glycoprotein; Membrane;
Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
Transmembrane; Transmembrane helix; Transport.
CHAIN 1 1541 Canalicular multispecific organic anion
transporter 1.
/FTId=PRO_0000093359.
TOPO_DOM 1 26 Extracellular. {ECO:0000250}.
TRANSMEM 27 47 Helical; Name=1. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 48 67 Cytoplasmic. {ECO:0000250}.
TRANSMEM 68 88 Helical; Name=2. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 89 92 Extracellular. {ECO:0000250}.
TRANSMEM 93 113 Helical; Name=3. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 114 125 Cytoplasmic. {ECO:0000250}.
TRANSMEM 126 146 Helical; Name=4. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 147 164 Extracellular. {ECO:0000250}.
TRANSMEM 165 185 Helical; Name=5. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 186 309 Cytoplasmic. {ECO:0000250}.
TRANSMEM 310 330 Helical; Name=6. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 331 356 Extracellular. {ECO:0000250}.
TRANSMEM 357 377 Helical; Name=7. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 378 433 Cytoplasmic. {ECO:0000250}.
TRANSMEM 434 454 Helical; Name=8. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 455 457 Extracellular. {ECO:0000250}.
TRANSMEM 458 478 Helical; Name=9. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 479 540 Cytoplasmic. {ECO:0000250}.
TRANSMEM 541 561 Helical; Name=10. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 562 583 Extracellular. {ECO:0000250}.
TRANSMEM 584 604 Helical; Name=11. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 605 967 Cytoplasmic. {ECO:0000250}.
TRANSMEM 968 988 Helical; Name=12. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 989 1029 Extracellular. {ECO:0000250}.
TRANSMEM 1030 1050 Helical; Name=13. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 1051 1093 Cytoplasmic. {ECO:0000250}.
TRANSMEM 1094 1114 Helical; Name=14. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 1115 1115 Extracellular. {ECO:0000250}.
TRANSMEM 1116 1136 Helical; Name=15. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 1137 1207 Cytoplasmic. {ECO:0000250}.
TRANSMEM 1208 1228 Helical; Name=16. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 1229 1230 Extracellular. {ECO:0000250}.
TRANSMEM 1231 1251 Helical; Name=17. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TOPO_DOM 1252 1541 Cytoplasmic. {ECO:0000250}.
DOMAIN 318 601 ABC transmembrane type-1 1.
{ECO:0000255|PROSITE-ProRule:PRU00441}.
DOMAIN 633 857 ABC transporter 1. {ECO:0000255|PROSITE-
ProRule:PRU00434}.
DOMAIN 975 1260 ABC transmembrane type-1 2.
{ECO:0000255|PROSITE-ProRule:PRU00441}.
DOMAIN 1296 1530 ABC transporter 2. {ECO:0000255|PROSITE-
ProRule:PRU00434}.
NP_BIND 667 674 ATP 1. {ECO:0000255|PROSITE-
ProRule:PRU00434}.
NP_BIND 1330 1337 ATP 2. {ECO:0000255|PROSITE-
ProRule:PRU00434}.
MOD_RES 279 279 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
MOD_RES 281 281 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
MOD_RES 874 874 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
MOD_RES 922 922 Phosphoserine.
{ECO:0000250|UniProtKB:Q92887}.
MOD_RES 926 926 Phosphoserine.
{ECO:0000250|UniProtKB:Q92887}.
MOD_RES 1434 1434 Phosphoserine.
{ECO:0000250|UniProtKB:Q92887}.
CARBOHYD 6 6 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 1007 1007 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 1010 1010 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 1011 1011 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CONFLICT 420 420 M -> V (in Ref. 3; BAA13016).
{ECO:0000305}.
SEQUENCE 1541 AA; 173384 MW; D5FB55571BFDDB39 CRC64;
MDKFCNSTFW DLSLLESPEA DLPLCFEQTV LVWIPLGFLW LLAPWQLYSV YRSRTKRSSI
TKFYLAKQVF VVFLLILAAI DLSLALTEDT GQATVPPVRY TNPILYLCTW LLVLAVQHSR
QWCVRKNSWF LSLFWILSVL CGVFQFQTLI RALLKDSKSN MAYSYLFFVS YGFQIVLLIL
TAFSGPSDST QTPSVTASFL SSITFSWYDR TVLKGYKHPL TLEDVWDIDE GFKTRSVTSK
FEAAMTKDLQ KARQAFQRRL QKSQRKPEAT LHGLNKKQSQ SQDVLVLEEA KKKSEKTTKD
YPKSWLIKSL FKTFHVVILK SFILKLIHDL LVFLNPQLLK LLIGFVKSSN SYVWFGYICA
ILMFAVTLIQ SFCLQSYFQH CFVLGMCVRT TVMSSIYKKA LTLSNLARKQ YTIGETVNLM
SVDSQKLMDA TNYMQLVWSS VIQITLSIFF LWRELGPSIL AGVGVMVLLI PVNGVLATKI
RNIQVQNMKN KDKRLKIMNE ILSGIKILKY FAWEPSFQEQ VQGIRKKELK NLLRFGQLQS
LLIFILQITP ILVSVVTFSV YVLVDSANVL NAEKAFTSIT LFNILRFPLS MLPMVTSSIL
QASVSVDRLE RYLGGDDLDT SAIRRVSNFD KAVKFSEASF TWDPDLEATI QDVNLDIKPG
QLVAVVGTVG SGKSSLVSAM LGEMENVHGH ITIQGSTAYV PQQSWIQNGT IKDNILFGSE
YNEKKYQQVL KACALLPDLE ILPGGDMAEI GEKGINLSGG QKQRVSLARA AYQDADIYIL
DDPLSAVDAH VGKHIFNKVV GPNGLLAGKT RIFVTHGIHF LPQVDEIVVL GKGTILEKGS
YRDLLDKKGV FARNWKTFMK HSGPEGEATV NNDSEAEDDD DGLIPTMEEI PEDAASLAMR
RENSLRRTLS RSSRSSSRRG KSLKNSLKIK NVNVLKEKEK EVEGQKLIKK EFVETGKVKF
SIYLKYLQAV GWWSILFIIL FYGLNNVAFI GSNLWLSAWT SDSDNLNGTN NSSSHRDMRI
GVFGALGLAQ GICLLISTLW SIYACRNASK ALHGQLLTNI LRAPMRFFDT TPTGRIVNRF
SGDISTVDDL LPQTLRSWMM CFFGIAGTLV MICMATPVFA IIIIPLSILY ISVQVFYVAT
SRQLRRLDSV TKSPIYSHFS ETVTGLPIIR AFEHQQRFLA WNEKQIDINQ KCVFSWITSN
RWLAIRLELV GNLVVFCSAL LLVIYRKTLT GDVVGFVLSN ALNITQTLNW LVRMTSEAET
NIVAVERISE YINVENEAPW VTDKRPPADW PRHGEIQFNN YQVRYRPELD LVLKGITCNI
KSGEKVGVVG RTGAGKSSLT NCLFRILESA GGQIIIDGID VASIGLHDLR ERLTIIPQDP
ILFSGSLRMN LDPFNKYSDE EVWRALELAH LRSFVSGLQL GLLSEVTEGG DNLSIGQRQL
LCLGRAVLRK SKILVLDEAT AAVDLETDSL IQTTIRKEFS QCTVITIAHR LHTIMDSDKI
MVLDNGKIVE YGSPEELLSN RGSFYLMAKE AGIENVNHTE L


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