Full text data of ABCC5
ABCC5
(MRP5)
[Confidence: high (present in two of the MS resources)]
Multidrug resistance-associated protein 5 (ATP-binding cassette sub-family C member 5; Multi-specific organic anion transporter C; MOAT-C; SMRP; pABC11)
Multidrug resistance-associated protein 5 (ATP-binding cassette sub-family C member 5; Multi-specific organic anion transporter C; MOAT-C; SMRP; pABC11)
UniProt
O15440
ID MRP5_HUMAN Reviewed; 1437 AA.
AC O15440; B9EIQ2; O14517; Q29ZA9; Q29ZB1; Q86W30; Q9UN85; Q9UNP5;
read moreAC Q9UQC3;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=Multidrug resistance-associated protein 5;
DE AltName: Full=ATP-binding cassette sub-family C member 5;
DE AltName: Full=Multi-specific organic anion transporter C;
DE Short=MOAT-C;
DE AltName: Full=SMRP;
DE AltName: Full=pABC11;
GN Name=ABCC5; Synonyms=MRP5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9827529; DOI=10.1093/jnci/90.22.1735;
RA Belinsky M.G., Bain L.J., Balsara B.B., Testa J.R., Kruh G.D.;
RT "Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT
RT subfamily of transporter proteins.";
RL J. Natl. Cancer Inst. 90:1735-1741(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10438534; DOI=10.1074/jbc.274.33.23541;
RA McAleer M.A., Breen M.A., White N.L., Matthews N.;
RT "pABC11 (also known as MOAT-C and MRP5), a member of the ABC family of
RT proteins, has anion transporter activity but does not confer multidrug
RT resistance when overexpressed in human embryonic kidney 293 cells.";
RL J. Biol. Chem. 274:23541-23548(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10721709; DOI=10.1016/S0378-1119(99)00529-6;
RA Suzuki T., Sasaki H., Kuh H.J., Agui M., Tatsumi Y., Tanabe S.,
RA Terada M., Saijo N., Nishio K.;
RT "Detailed structural analysis on both human MRP5 and mouse mrp5
RT transcripts.";
RL Gene 242:167-173(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC TISSUE=Brain, and Ovarian carcinoma;
RX PubMed=10840050; DOI=10.1073/pnas.120159197;
RA Wijnholds J., Mol C.A.A.M., van Deemter L., de Haas M., Scheffer G.L.,
RA Baas F., Beijnen J.H., Scheper R.J., Hatse S., De Clercq E.,
RA Balzarini J., Borst P.;
RT "Multidrug-resistance protein 5 is a multispecific organic anion
RT transporter able to transport nucleotide analogs.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7476-7481(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), TISSUE SPECIFICITY,
RP AND ALTERNATIVE SPLICING.
RC TISSUE=Retina;
RX PubMed=17521428; DOI=10.1186/1471-2199-8-42;
RA Stojic J., Stohr H., Weber B.H.;
RT "Three novel ABCC5 splice variants in human retina and their role as
RT regulators of ABCC5 gene expression.";
RL BMC Mol. Biol. 8:42-42(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Pancreas;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 492-1437 (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=9325169; DOI=10.1006/bbrc.1997.7346;
RA Suzuki T., Nishio K., Sasaki H., Kurokawa H., Saito-Ohara F.,
RA Ikeuch T., Tanabe S., Terada M., Saijo N.;
RT "cDNA cloning of a short type of multidrug resistance protein
RT homologue, SMRP, from a human lung cancer cell line.";
RL Biochem. Biophys. Res. Commun. 238:790-794(1997).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1216-1437 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9270026;
RA Kool M., de Haas M., Scheffer G.L., Scheper R.J., van Eijk M.J.,
RA Juijn J.A., Baas F., Borst P.;
RT "Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5,
RT homologues of the multidrug resistance-associated protein gene (MRP1),
RT in human cancer cell lines.";
RL Cancer Res. 57:3537-3547(1997).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-509 AND THR-513, AND
RP MASS SPECTROMETRY.
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-509, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
CC -!- FUNCTION: Acts as a multispecific organic anion pump which can
CC transport nucleotide analogs.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O15440-1; Sequence=Displayed;
CC Name=2; Synonyms=SV1;
CC IsoId=O15440-2; Sequence=VSP_043397, VSP_043402;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=3; Synonyms=SV2;
CC IsoId=O15440-3; Sequence=VSP_043398, VSP_043401, VSP_043402;
CC Note=Predominant isoform in retinal pigment epithelium, bladder,
CC and stomach;
CC Name=4; Synonyms=SV3;
CC IsoId=O15440-4; Sequence=VSP_043399, VSP_043400, VSP_043402;
CC -!- TISSUE SPECIFICITY: All isoforms are equally expressed in retina.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC
CC family. Conjugate transporter (TC 3.A.1.208) subfamily.
CC -!- SIMILARITY: Contains 2 ABC transmembrane type-1 domains.
CC -!- SIMILARITY: Contains 2 ABC transporter domains.
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC
CC proteins;
CC URL="http://abcmutations.hegelab.org/proteinDetails?uniprot_id=O15440";
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DR EMBL; AF104942; AAD04169.1; -; mRNA.
DR EMBL; AF146074; AAD37716.1; -; mRNA.
DR EMBL; AB019002; BAA76608.1; -; mRNA.
DR EMBL; U83661; AAB71758.2; -; mRNA.
DR EMBL; AY754874; AAW82948.1; -; mRNA.
DR EMBL; AY754875; AAW82949.1; -; mRNA.
DR EMBL; AY754876; AAW82950.1; -; mRNA.
DR EMBL; AC068644; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78308.1; -; Genomic_DNA.
DR EMBL; BC050744; AAH50744.1; -; mRNA.
DR EMBL; BC140771; AAI40772.1; -; mRNA.
DR EMBL; BC142719; AAI42720.1; -; mRNA.
DR EMBL; AB005659; BAA22887.1; -; mRNA.
DR PIR; JC5667; JC5667.
DR RefSeq; NP_001018881.1; NM_001023587.1.
DR RefSeq; NP_005679.2; NM_005688.2.
DR RefSeq; XP_005247115.1; XM_005247058.1.
DR RefSeq; XP_005247116.1; XM_005247059.1.
DR RefSeq; XP_005247117.1; XM_005247060.1.
DR UniGene; Hs.368563; -.
DR UniGene; Hs.743953; -.
DR ProteinModelPortal; O15440; -.
DR SMR; O15440; 532-843, 910-1428.
DR IntAct; O15440; 5.
DR STRING; 9606.ENSP00000333926; -.
DR ChEMBL; CHEMBL2046258; -.
DR TCDB; 3.A.1.208.15; the atp-binding cassette (abc) superfamily.
DR PhosphoSite; O15440; -.
DR PaxDb; O15440; -.
DR PRIDE; O15440; -.
DR Ensembl; ENST00000334444; ENSP00000333926; ENSG00000114770.
DR Ensembl; ENST00000382494; ENSP00000371934; ENSG00000114770.
DR Ensembl; ENST00000392579; ENSP00000376358; ENSG00000114770.
DR Ensembl; ENST00000443376; ENSP00000416840; ENSG00000114770.
DR GeneID; 10057; -.
DR KEGG; hsa:10057; -.
DR UCSC; uc003fmg.3; human.
DR CTD; 10057; -.
DR GeneCards; GC03M183637; -.
DR HGNC; HGNC:56; ABCC5.
DR HPA; HPA052295; -.
DR MIM; 605251; gene.
DR neXtProt; NX_O15440; -.
DR PharmGKB; PA395; -.
DR eggNOG; COG1132; -.
DR HOGENOM; HOG000116132; -.
DR HOVERGEN; HBG108314; -.
DR InParanoid; O15440; -.
DR KO; K05668; -.
DR OMA; LFSVLHI; -.
DR OrthoDB; EOG7MWGW0; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR ChiTaRS; ABCC5; human.
DR GeneWiki; ABCC5; -.
DR GenomeRNAi; 10057; -.
DR NextBio; 37997; -.
DR PRO; PR:O15440; -.
DR ArrayExpress; O15440; -.
DR Bgee; O15440; -.
DR CleanEx; HS_ABCC5; -.
DR Genevestigator; O15440; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; TAS:ProtInc.
DR GO; GO:0042626; F:ATPase activity, coupled to transmembrane movement of substances; IEA:InterPro.
DR GO; GO:0008514; F:organic anion transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0006200; P:ATP catabolic process; IEA:GOC.
DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:Reactome.
DR GO; GO:0030213; P:hyaluronan biosynthetic process; TAS:Reactome.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR003439; ABC_transporter-like.
DR InterPro; IPR017871; ABC_transporter_CS.
DR InterPro; IPR001140; ABC_transptr_TM_dom.
DR InterPro; IPR027417; P-loop_NTPase.
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 PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 2.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Complete proteome; Glycoprotein;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1 1437 Multidrug resistance-associated protein
FT 5.
FT /FTId=PRO_0000093363.
FT TRANSMEM 179 199 Helical; (Potential).
FT TRANSMEM 219 239 Helical; (Potential).
FT TRANSMEM 296 316 Helical; (Potential).
FT TRANSMEM 317 337 Helical; (Potential).
FT TRANSMEM 400 420 Helical; (Potential).
FT TRANSMEM 434 454 Helical; (Potential).
FT TRANSMEM 608 628 Helical; (Potential).
FT TRANSMEM 848 868 Helical; (Potential).
FT TRANSMEM 917 937 Helical; (Potential).
FT TRANSMEM 997 1017 Helical; (Potential).
FT TRANSMEM 1018 1038 Helical; (Potential).
FT TRANSMEM 1104 1124 Helical; (Potential).
FT TRANSMEM 1127 1147 Helical; (Potential).
FT DOMAIN 179 459 ABC transmembrane type-1 1.
FT DOMAIN 562 783 ABC transporter 1.
FT DOMAIN 859 1155 ABC transmembrane type-1 2.
FT DOMAIN 1193 1427 ABC transporter 2.
FT NP_BIND 595 602 ATP 1 (Potential).
FT NP_BIND 1227 1234 ATP 2 (Potential).
FT MOD_RES 509 509 Phosphoserine.
FT MOD_RES 513 513 Phosphothreonine.
FT CARBOHYD 494 494 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 636 636 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 684 684 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 890 890 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 897 897 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1044 1044 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1329 1329 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1417 1417 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 198 225 AFMVKHLLEYTQATESNLQYSLLLVLGL -> PSFGDCSIS
FT AEVCGNRLHCTAILLSCFT (in isoform 2).
FT /FTId=VSP_043397.
FT VAR_SEQ 198 212 AFMVKHLLEYTQATE -> LAWCCQDLDLGGVSL (in
FT isoform 3).
FT /FTId=VSP_043398.
FT VAR_SEQ 198 208 AFMVKHLLEYT -> NFQDGCILRSE (in isoform
FT 4).
FT /FTId=VSP_043399.
FT VAR_SEQ 209 225 Missing (in isoform 4).
FT /FTId=VSP_043400.
FT VAR_SEQ 213 225 Missing (in isoform 3).
FT /FTId=VSP_043401.
FT VAR_SEQ 226 1437 Missing (in isoform 2, isoform 3 and
FT isoform 4).
FT /FTId=VSP_043402.
FT CONFLICT 176 176 R -> P (in Ref. 3; BAA76608).
FT CONFLICT 400 400 S -> G (in Ref. 1; AAD04169).
FT CONFLICT 581 581 I -> V (in Ref. 2; AAD37716).
FT CONFLICT 1383 1383 T -> N (in Ref. 3; BAA76608 and 7;
FT BAA22887).
SQ SEQUENCE 1437 AA; 160660 MW; 00558076B3BB4C00 CRC64;
MKDIDIGKEY IIPSPGYRSV RERTSTSGTH RDREDSKFRR TRPLECQDAL ETAARAEGLS
LDASMHSQLR ILDEEHPKGK YHHGLSALKP IRTTSKHQHP VDNAGLFSCM TFSWLSSLAR
VAHKKGELSM EDVWSLSKHE SSDVNCRRLE RLWQEELNEV GPDAASLRRV VWIFCRTRLI
LSIVCLMITQ LAGFSGPAFM VKHLLEYTQA TESNLQYSLL LVLGLLLTEI VRSWSLALTW
ALNYRTGVRL RGAILTMAFK KILKLKNIKE KSLGELINIC SNDGQRMFEA AAVGSLLAGG
PVVAILGMIY NVIILGPTGF LGSAVFILFY PAMMFASRLT AYFRRKCVAA TDERVQKMNE
VLTYIKFIKM YAWVKAFSQS VQKIREEERR ILEKAGYFQS ITVGVAPIVV VIASVVTFSV
HMTLGFDLTA AQAFTVVTVF NSMTFALKVT PFSVKSLSEA SVAVDRFKSL FLMEEVHMIK
NKPASPHIKI EMKNATLAWD SSHSSIQNSP KLTPKMKKDK RASRGKKEKV RQLQRTEHQA
VLAEQKGHLL LDSDERPSPE EEEGKHIHLG HLRLQRTLHS IDLEIQEGKL VGICGSVGSG
KTSLISAILG QMTLLEGSIA ISGTFAYVAQ QAWILNATLR DNILFGKEYD EERYNSVLNS
CCLRPDLAIL PSSDLTEIGE RGANLSGGQR QRISLARALY SDRSIYILDD PLSALDAHVG
NHIFNSAIRK HLKSKTVLFV THQLQYLVDC DEVIFMKEGC ITERGTHEEL MNLNGDYATI
FNNLLLGETP PVEINSKKET SGSQKKSQDK GPKTGSVKKE KAVKPEEGQL VQLEEKGQGS
VPWSVYGVYI QAAGGPLAFL VIMALFMLNV GSTAFSTWWL SYWIKQGSGN TTVTRGNETS
VSDSMKDNPH MQYYASIYAL SMAVMLILKA IRGVVFVKGT LRASSRLHDE LFRRILRSPM
KFFDTTPTGR ILNRFSKDMD EVDVRLPFQA EMFIQNVILV FFCVGMIAGV FPWFLVAVGP
LVILFSVLHI VSRVLIRELK RLDNITQSPF LSHITSSIQG LATIHAYNKG QEFLHRYQEL
LDDNQAPFFL FTCAMRWLAV RLDLISIALI TTTGLMIVLM HGQIPPAYAG LAISYAVQLT
GLFQFTVRLA SETEARFTSV ERINHYIKTL SLEAPARIKN KAPSPDWPQE GEVTFENAEM
RYRENLPLVL KKVSFTIKPK EKIGIVGRTG SGKSSLGMAL FRLVELSGGC IKIDGVRISD
IGLADLRSKL SIIPQEPVLF SGTVRSNLDP FNQYTEDQIW DALERTHMKE CIAQLPLKLE
SEVMENGDNF SVGERQLLCI ARALLRHCKI LILDEATAAM DTETDLLIQE TIREAFADCT
MLTIAHRLHT VLGSDRIMVL AQGQVVEFDT PSVLLSNDSS RFYAMFAAAE NKVAVKG
//
ID MRP5_HUMAN Reviewed; 1437 AA.
AC O15440; B9EIQ2; O14517; Q29ZA9; Q29ZB1; Q86W30; Q9UN85; Q9UNP5;
read moreAC Q9UQC3;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=Multidrug resistance-associated protein 5;
DE AltName: Full=ATP-binding cassette sub-family C member 5;
DE AltName: Full=Multi-specific organic anion transporter C;
DE Short=MOAT-C;
DE AltName: Full=SMRP;
DE AltName: Full=pABC11;
GN Name=ABCC5; Synonyms=MRP5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9827529; DOI=10.1093/jnci/90.22.1735;
RA Belinsky M.G., Bain L.J., Balsara B.B., Testa J.R., Kruh G.D.;
RT "Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT
RT subfamily of transporter proteins.";
RL J. Natl. Cancer Inst. 90:1735-1741(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10438534; DOI=10.1074/jbc.274.33.23541;
RA McAleer M.A., Breen M.A., White N.L., Matthews N.;
RT "pABC11 (also known as MOAT-C and MRP5), a member of the ABC family of
RT proteins, has anion transporter activity but does not confer multidrug
RT resistance when overexpressed in human embryonic kidney 293 cells.";
RL J. Biol. Chem. 274:23541-23548(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10721709; DOI=10.1016/S0378-1119(99)00529-6;
RA Suzuki T., Sasaki H., Kuh H.J., Agui M., Tatsumi Y., Tanabe S.,
RA Terada M., Saijo N., Nishio K.;
RT "Detailed structural analysis on both human MRP5 and mouse mrp5
RT transcripts.";
RL Gene 242:167-173(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC TISSUE=Brain, and Ovarian carcinoma;
RX PubMed=10840050; DOI=10.1073/pnas.120159197;
RA Wijnholds J., Mol C.A.A.M., van Deemter L., de Haas M., Scheffer G.L.,
RA Baas F., Beijnen J.H., Scheper R.J., Hatse S., De Clercq E.,
RA Balzarini J., Borst P.;
RT "Multidrug-resistance protein 5 is a multispecific organic anion
RT transporter able to transport nucleotide analogs.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7476-7481(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), TISSUE SPECIFICITY,
RP AND ALTERNATIVE SPLICING.
RC TISSUE=Retina;
RX PubMed=17521428; DOI=10.1186/1471-2199-8-42;
RA Stojic J., Stohr H., Weber B.H.;
RT "Three novel ABCC5 splice variants in human retina and their role as
RT regulators of ABCC5 gene expression.";
RL BMC Mol. Biol. 8:42-42(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Pancreas;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 492-1437 (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=9325169; DOI=10.1006/bbrc.1997.7346;
RA Suzuki T., Nishio K., Sasaki H., Kurokawa H., Saito-Ohara F.,
RA Ikeuch T., Tanabe S., Terada M., Saijo N.;
RT "cDNA cloning of a short type of multidrug resistance protein
RT homologue, SMRP, from a human lung cancer cell line.";
RL Biochem. Biophys. Res. Commun. 238:790-794(1997).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1216-1437 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9270026;
RA Kool M., de Haas M., Scheffer G.L., Scheper R.J., van Eijk M.J.,
RA Juijn J.A., Baas F., Borst P.;
RT "Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5,
RT homologues of the multidrug resistance-associated protein gene (MRP1),
RT in human cancer cell lines.";
RL Cancer Res. 57:3537-3547(1997).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-509 AND THR-513, AND
RP MASS SPECTROMETRY.
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-509, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
CC -!- FUNCTION: Acts as a multispecific organic anion pump which can
CC transport nucleotide analogs.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O15440-1; Sequence=Displayed;
CC Name=2; Synonyms=SV1;
CC IsoId=O15440-2; Sequence=VSP_043397, VSP_043402;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=3; Synonyms=SV2;
CC IsoId=O15440-3; Sequence=VSP_043398, VSP_043401, VSP_043402;
CC Note=Predominant isoform in retinal pigment epithelium, bladder,
CC and stomach;
CC Name=4; Synonyms=SV3;
CC IsoId=O15440-4; Sequence=VSP_043399, VSP_043400, VSP_043402;
CC -!- TISSUE SPECIFICITY: All isoforms are equally expressed in retina.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC
CC family. Conjugate transporter (TC 3.A.1.208) subfamily.
CC -!- SIMILARITY: Contains 2 ABC transmembrane type-1 domains.
CC -!- SIMILARITY: Contains 2 ABC transporter domains.
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC
CC proteins;
CC URL="http://abcmutations.hegelab.org/proteinDetails?uniprot_id=O15440";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; AF104942; AAD04169.1; -; mRNA.
DR EMBL; AF146074; AAD37716.1; -; mRNA.
DR EMBL; AB019002; BAA76608.1; -; mRNA.
DR EMBL; U83661; AAB71758.2; -; mRNA.
DR EMBL; AY754874; AAW82948.1; -; mRNA.
DR EMBL; AY754875; AAW82949.1; -; mRNA.
DR EMBL; AY754876; AAW82950.1; -; mRNA.
DR EMBL; AC068644; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78308.1; -; Genomic_DNA.
DR EMBL; BC050744; AAH50744.1; -; mRNA.
DR EMBL; BC140771; AAI40772.1; -; mRNA.
DR EMBL; BC142719; AAI42720.1; -; mRNA.
DR EMBL; AB005659; BAA22887.1; -; mRNA.
DR PIR; JC5667; JC5667.
DR RefSeq; NP_001018881.1; NM_001023587.1.
DR RefSeq; NP_005679.2; NM_005688.2.
DR RefSeq; XP_005247115.1; XM_005247058.1.
DR RefSeq; XP_005247116.1; XM_005247059.1.
DR RefSeq; XP_005247117.1; XM_005247060.1.
DR UniGene; Hs.368563; -.
DR UniGene; Hs.743953; -.
DR ProteinModelPortal; O15440; -.
DR SMR; O15440; 532-843, 910-1428.
DR IntAct; O15440; 5.
DR STRING; 9606.ENSP00000333926; -.
DR ChEMBL; CHEMBL2046258; -.
DR TCDB; 3.A.1.208.15; the atp-binding cassette (abc) superfamily.
DR PhosphoSite; O15440; -.
DR PaxDb; O15440; -.
DR PRIDE; O15440; -.
DR Ensembl; ENST00000334444; ENSP00000333926; ENSG00000114770.
DR Ensembl; ENST00000382494; ENSP00000371934; ENSG00000114770.
DR Ensembl; ENST00000392579; ENSP00000376358; ENSG00000114770.
DR Ensembl; ENST00000443376; ENSP00000416840; ENSG00000114770.
DR GeneID; 10057; -.
DR KEGG; hsa:10057; -.
DR UCSC; uc003fmg.3; human.
DR CTD; 10057; -.
DR GeneCards; GC03M183637; -.
DR HGNC; HGNC:56; ABCC5.
DR HPA; HPA052295; -.
DR MIM; 605251; gene.
DR neXtProt; NX_O15440; -.
DR PharmGKB; PA395; -.
DR eggNOG; COG1132; -.
DR HOGENOM; HOG000116132; -.
DR HOVERGEN; HBG108314; -.
DR InParanoid; O15440; -.
DR KO; K05668; -.
DR OMA; LFSVLHI; -.
DR OrthoDB; EOG7MWGW0; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR ChiTaRS; ABCC5; human.
DR GeneWiki; ABCC5; -.
DR GenomeRNAi; 10057; -.
DR NextBio; 37997; -.
DR PRO; PR:O15440; -.
DR ArrayExpress; O15440; -.
DR Bgee; O15440; -.
DR CleanEx; HS_ABCC5; -.
DR Genevestigator; O15440; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; TAS:ProtInc.
DR GO; GO:0042626; F:ATPase activity, coupled to transmembrane movement of substances; IEA:InterPro.
DR GO; GO:0008514; F:organic anion transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0006200; P:ATP catabolic process; IEA:GOC.
DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:Reactome.
DR GO; GO:0030213; P:hyaluronan biosynthetic process; TAS:Reactome.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR003439; ABC_transporter-like.
DR InterPro; IPR017871; ABC_transporter_CS.
DR InterPro; IPR001140; ABC_transptr_TM_dom.
DR InterPro; IPR027417; P-loop_NTPase.
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 PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 2.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Complete proteome; Glycoprotein;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1 1437 Multidrug resistance-associated protein
FT 5.
FT /FTId=PRO_0000093363.
FT TRANSMEM 179 199 Helical; (Potential).
FT TRANSMEM 219 239 Helical; (Potential).
FT TRANSMEM 296 316 Helical; (Potential).
FT TRANSMEM 317 337 Helical; (Potential).
FT TRANSMEM 400 420 Helical; (Potential).
FT TRANSMEM 434 454 Helical; (Potential).
FT TRANSMEM 608 628 Helical; (Potential).
FT TRANSMEM 848 868 Helical; (Potential).
FT TRANSMEM 917 937 Helical; (Potential).
FT TRANSMEM 997 1017 Helical; (Potential).
FT TRANSMEM 1018 1038 Helical; (Potential).
FT TRANSMEM 1104 1124 Helical; (Potential).
FT TRANSMEM 1127 1147 Helical; (Potential).
FT DOMAIN 179 459 ABC transmembrane type-1 1.
FT DOMAIN 562 783 ABC transporter 1.
FT DOMAIN 859 1155 ABC transmembrane type-1 2.
FT DOMAIN 1193 1427 ABC transporter 2.
FT NP_BIND 595 602 ATP 1 (Potential).
FT NP_BIND 1227 1234 ATP 2 (Potential).
FT MOD_RES 509 509 Phosphoserine.
FT MOD_RES 513 513 Phosphothreonine.
FT CARBOHYD 494 494 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 636 636 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 684 684 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 890 890 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 897 897 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1044 1044 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1329 1329 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1417 1417 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 198 225 AFMVKHLLEYTQATESNLQYSLLLVLGL -> PSFGDCSIS
FT AEVCGNRLHCTAILLSCFT (in isoform 2).
FT /FTId=VSP_043397.
FT VAR_SEQ 198 212 AFMVKHLLEYTQATE -> LAWCCQDLDLGGVSL (in
FT isoform 3).
FT /FTId=VSP_043398.
FT VAR_SEQ 198 208 AFMVKHLLEYT -> NFQDGCILRSE (in isoform
FT 4).
FT /FTId=VSP_043399.
FT VAR_SEQ 209 225 Missing (in isoform 4).
FT /FTId=VSP_043400.
FT VAR_SEQ 213 225 Missing (in isoform 3).
FT /FTId=VSP_043401.
FT VAR_SEQ 226 1437 Missing (in isoform 2, isoform 3 and
FT isoform 4).
FT /FTId=VSP_043402.
FT CONFLICT 176 176 R -> P (in Ref. 3; BAA76608).
FT CONFLICT 400 400 S -> G (in Ref. 1; AAD04169).
FT CONFLICT 581 581 I -> V (in Ref. 2; AAD37716).
FT CONFLICT 1383 1383 T -> N (in Ref. 3; BAA76608 and 7;
FT BAA22887).
SQ SEQUENCE 1437 AA; 160660 MW; 00558076B3BB4C00 CRC64;
MKDIDIGKEY IIPSPGYRSV RERTSTSGTH RDREDSKFRR TRPLECQDAL ETAARAEGLS
LDASMHSQLR ILDEEHPKGK YHHGLSALKP IRTTSKHQHP VDNAGLFSCM TFSWLSSLAR
VAHKKGELSM EDVWSLSKHE SSDVNCRRLE RLWQEELNEV GPDAASLRRV VWIFCRTRLI
LSIVCLMITQ LAGFSGPAFM VKHLLEYTQA TESNLQYSLL LVLGLLLTEI VRSWSLALTW
ALNYRTGVRL RGAILTMAFK KILKLKNIKE KSLGELINIC SNDGQRMFEA AAVGSLLAGG
PVVAILGMIY NVIILGPTGF LGSAVFILFY PAMMFASRLT AYFRRKCVAA TDERVQKMNE
VLTYIKFIKM YAWVKAFSQS VQKIREEERR ILEKAGYFQS ITVGVAPIVV VIASVVTFSV
HMTLGFDLTA AQAFTVVTVF NSMTFALKVT PFSVKSLSEA SVAVDRFKSL FLMEEVHMIK
NKPASPHIKI EMKNATLAWD SSHSSIQNSP KLTPKMKKDK RASRGKKEKV RQLQRTEHQA
VLAEQKGHLL LDSDERPSPE EEEGKHIHLG HLRLQRTLHS IDLEIQEGKL VGICGSVGSG
KTSLISAILG QMTLLEGSIA ISGTFAYVAQ QAWILNATLR DNILFGKEYD EERYNSVLNS
CCLRPDLAIL PSSDLTEIGE RGANLSGGQR QRISLARALY SDRSIYILDD PLSALDAHVG
NHIFNSAIRK HLKSKTVLFV THQLQYLVDC DEVIFMKEGC ITERGTHEEL MNLNGDYATI
FNNLLLGETP PVEINSKKET SGSQKKSQDK GPKTGSVKKE KAVKPEEGQL VQLEEKGQGS
VPWSVYGVYI QAAGGPLAFL VIMALFMLNV GSTAFSTWWL SYWIKQGSGN TTVTRGNETS
VSDSMKDNPH MQYYASIYAL SMAVMLILKA IRGVVFVKGT LRASSRLHDE LFRRILRSPM
KFFDTTPTGR ILNRFSKDMD EVDVRLPFQA EMFIQNVILV FFCVGMIAGV FPWFLVAVGP
LVILFSVLHI VSRVLIRELK RLDNITQSPF LSHITSSIQG LATIHAYNKG QEFLHRYQEL
LDDNQAPFFL FTCAMRWLAV RLDLISIALI TTTGLMIVLM HGQIPPAYAG LAISYAVQLT
GLFQFTVRLA SETEARFTSV ERINHYIKTL SLEAPARIKN KAPSPDWPQE GEVTFENAEM
RYRENLPLVL KKVSFTIKPK EKIGIVGRTG SGKSSLGMAL FRLVELSGGC IKIDGVRISD
IGLADLRSKL SIIPQEPVLF SGTVRSNLDP FNQYTEDQIW DALERTHMKE CIAQLPLKLE
SEVMENGDNF SVGERQLLCI ARALLRHCKI LILDEATAAM DTETDLLIQE TIREAFADCT
MLTIAHRLHT VLGSDRIMVL AQGQVVEFDT PSVLLSNDSS RFYAMFAAAE NKVAVKG
//
MIM
605251
*RECORD*
*FIELD* NO
605251
*FIELD* TI
*605251 ATP-BINDING CASSETTE, SUBFAMILY C, MEMBER 5; ABCC5
;;MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 5; MRP5;;
read moreMOATC
*FIELD* TX
Multidrug resistance (MDR) proteins (MRPs) mediate the extrusion of
drugs from normal cells and tumors. MDR/ATP-binding cassette (ABC)
membrane proteins are involved in energy-dependent transport of a wide
variety of substrates.
Allikmets et al. (1996) and Kool et al. (1997) used EST database
searching to identify partial cDNAs encoding ABCC5 (see ABCC4, 605250).
Using RT-PCR with degenerate primers, Suzuki et al. (1997) isolated a
cDNA encoding short MRP, an apparent splice variant of ABCC5 (Suzuki et
al., 2000). By EST database searching, followed by 5-prime RACE,
Belinsky et al. (1998) obtained a cDNA encoding full-length ABCC5, which
they termed MOATC (multispecific organic anion transporter C). Sequence
analysis predicted that the 1,437-amino acid protein, like other ABC
transporters, contains Walker A, B and C motifs, nucleotide-binding
folds, and 12 transmembrane spanning helices in 2 hydrophobic domains.
Kool et al. (1997), Suzuki et al. (1997), and Belinsky et al. (1998)
performed Northern blot analysis which revealed ubiquitous expression of
a 6.6-kb ABCC5 transcript with highest levels in skeletal muscle
followed by brain, kidney, testis, and heart.
McAleer et al. (1999) found differential expression of at least 3
different ABCC5 transcripts of approximately 10, 6.0 and 5.5 kb.
Immunofluorescence analysis revealed predominant plasma membrane
expression with some intracellular punctate staining. Overexpression of
ABCC5 did not increase resistance to various classes of anticancer
drugs.
Wijnholds et al. (2000) reported the functional characterization of
human MRP5. They found resistance against the thiopurine anticancer
drugs 6-mercaptopurine (6-MP) and thioguanine, and the anti-HIV drug
9-(2-phosphonylmethoxyethyl)adenine (PMEA). This resistance was due to
an increased extrusion of PMEA and 6-thioinosine monophosphate from the
cells that overproduce MRP5. The authors speculated that MRP5 may play a
role in some cases of unexplained resistance to thiopurines in acute
lymphoblastic leukemia and/or to antiretroviral nucleoside analogs in
HIV-affected patients.
Oguri et al. (2000) noted that the effectiveness of platinum drugs in
lung cancer is limited by the development of drug resistance to them.
Quantitative RT-PCR analysis showed that expression of ABCC5, like that
of ABCC1 (158343) and gamma-glutamylcysteine synthetase (see 606857), is
increased in normal and tumor lung tissue from patients with previous
platinum exposure. However, in vitro exposure of lung cancer cells to
the platinum drug cisplatin, or of mononuclear cells to carboplatin,
does not cause increased expression of ABCC5.
By radiation hybrid analysis, Kool et al. (1997) mapped the ABCC5 gene
to chromosome 3. Using FISH, Suzuki et al. (1997) and Belinsky et al.
(1998) refined the localization to 3q27.
*FIELD* RF
1. Allikmets, R.; Gerrard, B.; Hutchinson, A.; Dean, M.: Characterization
of the human ABC superfamily: isolation and mapping of 21 new genes
using the expressed sequence tags database. Hum. Molec. Genet. 5:
1649-1655, 1996.
2. Belinsky, M. G.; Bain, L. J.; Balsara, B. B.; Testa, J. R.; Kruh,
G. D.: Characterization of MOAT-C and MOAT-D, new members of the
MRP/cMOAT subfamily of transporter proteins. J. Nat. Cancer Inst. 90:
1735-1741, 1998.
3. Kool, M.; de Haas, M.; Scheffer, G. L.; Scheper, R. J.; van Eijk,
M. J.; Juijn, J. A.; Baas, F.; Borst, P.: Analysis of expression
of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug
resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer
Res. 57: 3537-3547, 1997.
4. McAleer, M. A.; Breen, M. A.; White, N. L.; Matthews, N.: pABC11
(also known as MOAT-C and MRP5), a member of the ABC family of proteins,
has anion transporter activity but does not confer multidrug resistance
when overexpressed in human embryonic kidney 293 cells. J. Biol.
Chem. 274: 23541-23548, 1999.
5. Oguri, T.; Isobe, T.; Suzuki, T.; Nishio, K.; Fujiwara, Y.; Katoh,
O.; Yamakido, M.: Increased expression of the MRP5 gene is associated
with exposure to platinum drugs in lung cancer. Int. J. Cancer 86:
95-100, 2000.
6. Suzuki, T.; Nishio, K.; Sasaki, H.; Kurokawa, H.; Saito-Ohara,
F.; Ikeuchi, T.; Tanabe, S.; Terada, M.; Saijo, N.: cDNA cloning
of a short type of multidrug resistance protein homologue, SMRP, from
a human lung cancer cell line. Biochem. Biophys. Res. Commun. 238:
790-794, 1997.
7. Suzuki, T.; Sasaki, H.; Kuh, H.-J.; Agui, M.; Tatsumi, Y.; Tanabe,
S.; Terada, M.; Saijo, N.; Nishio, K.: Detailed structural analysis
on both human MRP5 and mouse mrp5 transcripts. Gene 242: 167-173,
2000.
8. Wijnholds, J.; Mol, C. A. A. M.; van Deemter, L.; de Haas, M.;
Scheffer, G. L.; Baas, F.; Beijnen, J. H.; Scheper, R. J.; Hatse,
S.; De Clercq, E.; Balzarini, J.; Borst, P.: Multidrug-resistance
protein 5 is a multispecific organic anion transporter able to transport
nucleotide analogs. Proc. Nat. Acad. Sci. 97: 7476-7481, 2000.
*FIELD* CN
Victor A. McKusick - updated: 9/12/2000
*FIELD* CD
Paul J. Converse: 8/31/2000
*FIELD* ED
carol: 04/17/2002
carol: 9/12/2000
*RECORD*
*FIELD* NO
605251
*FIELD* TI
*605251 ATP-BINDING CASSETTE, SUBFAMILY C, MEMBER 5; ABCC5
;;MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 5; MRP5;;
read moreMOATC
*FIELD* TX
Multidrug resistance (MDR) proteins (MRPs) mediate the extrusion of
drugs from normal cells and tumors. MDR/ATP-binding cassette (ABC)
membrane proteins are involved in energy-dependent transport of a wide
variety of substrates.
Allikmets et al. (1996) and Kool et al. (1997) used EST database
searching to identify partial cDNAs encoding ABCC5 (see ABCC4, 605250).
Using RT-PCR with degenerate primers, Suzuki et al. (1997) isolated a
cDNA encoding short MRP, an apparent splice variant of ABCC5 (Suzuki et
al., 2000). By EST database searching, followed by 5-prime RACE,
Belinsky et al. (1998) obtained a cDNA encoding full-length ABCC5, which
they termed MOATC (multispecific organic anion transporter C). Sequence
analysis predicted that the 1,437-amino acid protein, like other ABC
transporters, contains Walker A, B and C motifs, nucleotide-binding
folds, and 12 transmembrane spanning helices in 2 hydrophobic domains.
Kool et al. (1997), Suzuki et al. (1997), and Belinsky et al. (1998)
performed Northern blot analysis which revealed ubiquitous expression of
a 6.6-kb ABCC5 transcript with highest levels in skeletal muscle
followed by brain, kidney, testis, and heart.
McAleer et al. (1999) found differential expression of at least 3
different ABCC5 transcripts of approximately 10, 6.0 and 5.5 kb.
Immunofluorescence analysis revealed predominant plasma membrane
expression with some intracellular punctate staining. Overexpression of
ABCC5 did not increase resistance to various classes of anticancer
drugs.
Wijnholds et al. (2000) reported the functional characterization of
human MRP5. They found resistance against the thiopurine anticancer
drugs 6-mercaptopurine (6-MP) and thioguanine, and the anti-HIV drug
9-(2-phosphonylmethoxyethyl)adenine (PMEA). This resistance was due to
an increased extrusion of PMEA and 6-thioinosine monophosphate from the
cells that overproduce MRP5. The authors speculated that MRP5 may play a
role in some cases of unexplained resistance to thiopurines in acute
lymphoblastic leukemia and/or to antiretroviral nucleoside analogs in
HIV-affected patients.
Oguri et al. (2000) noted that the effectiveness of platinum drugs in
lung cancer is limited by the development of drug resistance to them.
Quantitative RT-PCR analysis showed that expression of ABCC5, like that
of ABCC1 (158343) and gamma-glutamylcysteine synthetase (see 606857), is
increased in normal and tumor lung tissue from patients with previous
platinum exposure. However, in vitro exposure of lung cancer cells to
the platinum drug cisplatin, or of mononuclear cells to carboplatin,
does not cause increased expression of ABCC5.
By radiation hybrid analysis, Kool et al. (1997) mapped the ABCC5 gene
to chromosome 3. Using FISH, Suzuki et al. (1997) and Belinsky et al.
(1998) refined the localization to 3q27.
*FIELD* RF
1. Allikmets, R.; Gerrard, B.; Hutchinson, A.; Dean, M.: Characterization
of the human ABC superfamily: isolation and mapping of 21 new genes
using the expressed sequence tags database. Hum. Molec. Genet. 5:
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*FIELD* CN
Victor A. McKusick - updated: 9/12/2000
*FIELD* CD
Paul J. Converse: 8/31/2000
*FIELD* ED
carol: 04/17/2002
carol: 9/12/2000