TCDB is operated by the Saier Lab Bioinformatics Group
« See all members of the family


3.A.1.208.9
Canicular multispecific organic anion MDR transporter, MRP3 (also called ABCC3) (most similar in sequence to MRP2). MRP3 exports epipodophyllotoxins, etoposide and teniposide, estradiol 17-β-D-glucuronide, leukotriene C4, dinitrophenyl S-glutathione, epoposide glucuronide, methotrexate, bilirubin-glucuronides, bile acids, GSH-X (LTC4, DNP-SG) and sulfate-X (taurolithocholate-3-sulfate).  Substrate translocation and stimulated ATP hydrolysis show positive cooperativity (Hill coefficient = 2) and are half-coupled (Seelheim et al. 2012).  ABCC3 is overexpressed in various types of cancer including carcinogenic stem cells, and plays a role in liver cancer progression (Carrasco-Torres et al. 2015). Psoraleae Fructus ethanol extracts induced hepatotoxicity by damaging mitochondria, reducing fatty acid beta-oxidation levels, and inhibiting fatty acids ingested by bile in part due to overexpression of ABCC3 (Guo et al. 2023).  Steroid hormones are substrates of the ABCC3 transporter, binding in a compatible amphiphilic substrate-binding pocket (Wang et al. 2023).  Activities of lysosomal ABCC3, ABCC5 and ABCC10 are responsible for lysosomal sequestration of doxorubicin and paclitaxel-oregongreen488 in paclitaxel-resistant cancer cell lines (Gronkowska et al. 2023).  

Accession Number:O15438
Protein Name:MRP3 aka ABCC3 aka CMOAT2 aka MLP2
Length:1527
Molecular Weight:169343.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:17
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate methotrexate, leukotriene C4, steroid hormone, teniposide, bile acid, 4'-demethylepipodophyllotoxin, etoposide

Cross database links:

RefSeq: NP_001137542.1    NP_003777.2   
Entrez Gene ID: 8714   
Pfam: PF00664    PF00005   
OMIM: 604323  gene

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005624 C:membrane fraction
GO:0005524 F:ATP binding
GO:0042626 F:ATPase activity, coupled to transmembrane m...
GO:0008514 F:organic anion transmembrane transporter act...
GO:0055085 P:transmembrane transport

References (9)

[1] “Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport.”  Uchiumi T.et.al.   9813153
[2] “cDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3).”  Kiuchi Y.et.al.   9738950
[3] “Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins.”  Belinsky M.G.et.al.   9827529
[4] “Human MRP3 transporter: identification of the 5'-flanking region, genomic organization and alternative splice variants.”  Fromm M.F.et.al.   9889399
[5] “Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane.”  Koenig J.et.al.   10094960
[6] “DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.”  Zody M.C.et.al.   16625196
[7] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[8] “Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines.”  Kool M.et.al.   9270026
[9] “An unappreciated role for RNA surveillance.”  Hillman R.T.et.al.   14759258

External Searches:

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence
1:	MDALCGSGEL GSKFWDSNLS VHTENPDLTP CFQNSLLAWV PCIYLWVALP CYLLYLRHHC 
61:	RGYIILSHLS KLKMVLGVLL WCVSWADLFY SFHGLVHGRA PAPVFFVTPL VVGVTMLLAT 
121:	LLIQYERLQG VQSSGVLIIF WFLCVVCAIV PFRSKILLAK AEGEISDPFR FTTFYIHFAL 
181:	VLSALILACF REKPPFFSAK NVDPNPYPET SAGFLSRLFF WWFTKMAIYG YRHPLEEKDL 
241:	WSLKEEDRSQ MVVQQLLEAW RKQEKQTARH KASAAPGKNA SGEDEVLLGA RPRPRKPSFL 
301:	KALLATFGSS FLISACFKLI QDLLSFINPQ LLSILIRFIS NPMAPSWWGF LVAGLMFLCS 
361:	MMQSLILQHY YHYIFVTGVK FRTGIMGVIY RKALVITNSV KRASTVGEIV NLMSVDAQRF 
421:	MDLAPFLNLL WSAPLQIILA IYFLWQNLGP SVLAGVAFMV LLIPLNGAVA VKMRAFQVKQ 
481:	MKLKDSRIKL MSEILNGIKV LKLYAWEPSF LKQVEGIRQG ELQLLRTAAY LHTTTTFTWM 
541:	CSPFLVTLIT LWVYVYVDPN NVLDAEKAFV SVSLFNILRL PLNMLPQLIS NLTQASVSLK 
601:	RIQQFLSQEE LDPQSVERKT ISPGYAITIH SGTFTWAQDL PPTLHSLDIQ VPKGALVAVV 
661:	GPVGCGKSSL VSALLGEMEK LEGKVHMKGS VAYVPQQAWI QNCTLQENVL FGKALNPKRY 
721:	QQTLEACALL ADLEMLPGGD QTEIGEKGIN LSGGQRQRVS LARAVYSDAD IFLLDDPLSA 
781:	VDSHVAKHIF DHVIGPEGVL AGKTRVLVTH GISFLPQTDF IIVLADGQVS EMGPYPALLQ 
841:	RNGSFANFLC NYAPDEDQGH LEDSWTALEG AEDKEALLIE DTLSNHTDLT DNDPVTYVVQ 
901:	KQFMRQLSAL SSDGEGQGRP VPRRHLGPSE KVQVTEAKAD GALTQEEKAA IGTVELSVFW 
961:	DYAKAVGLCT TLAICLLYVG QSAAAIGANV WLSAWTNDAM ADSRQNNTSL RLGVYAALGI 
1021:	LQGFLVMLAA MAMAAGGIQA ARVLHQALLH NKIRSPQSFF DTTPSGRILN CFSKDIYVVD 
1081:	EVLAPVILML LNSFFNAIST LVVIMASTPL FTVVILPLAV LYTLVQRFYA ATSRQLKRLE 
1141:	SVSRSPIYSH FSETVTGASV IRAYNRSRDF EIISDTKVDA NQRSCYPYII SNRWLSIGVE 
1201:	FVGNCVVLFA ALFAVIGRSS LNPGLVGLSV SYSLQVTFAL NWMIRMMSDL ESNIVAVERV 
1261:	KEYSKTETEA PWVVEGSRPP EGWPPRGEVE FRNYSVRYRP GLDLVLRDLS LHVHGGEKVG 
1321:	IVGRTGAGKS SMTLCLFRIL EAAKGEIRID GLNVADIGLH DLRSQLTIIP QDPILFSGTL 
1381:	RMNLDPFGSY SEEDIWWALE LSHLHTFVSS QPAGLDFQCS EGGENLSVGQ RQLVCLARAL 
1441:	LRKSRILVLD EATAAIDLET DNLIQATIRT QFDTCTVLTI AHRLNTIMDY TRVLVLDKGV 
1501:	VAEFDSPANL IAARGIFYGM ARDAGLA