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3.A.1.208.15
The general organic anion exporter, MRP5 (MOATC or ABCC5). It exports cyclic AMP, cyclic GMP, cyclic UMP, cyclicCMP, 5'-FUMP, glutathione and glutathione conjugates, and antimonial tartrate) (Schneider and Seifert 2017). It also transports reduced folates as well as mono-, di- and tri-glutamate derivatives of folic acid and methotrexate (Assaraf et al., 2006). When overexpressed, it can lower the intracellular concentration of nucleoside/nucleotide analogs, such as the antiviral compounds PMEA (9-(2-phosphonylmethoxyethyl)adenine) or ganciclovir, and of anticancer nucleobase analogues, such as 6-mercaptopurine, after their conversion into the respective nucleotides (Ritter et al., 2005). ABCC5 is a biomarker for hepatocellular carcinoma (Qiu et al. 2021). It also exports  anticancer and antivirus drugs, driving multidrug resistance. CryoEM depictions have appeared  revealing an autoinhibitory N-terminal peptide that must dissociate to permit subsequent substrate recruitment (Huang et al. 2024).  The authors design an inhibitory peptide that blocks substrate entry into the transport pathway. They also identify a regulatory motif, comprising a positively charged cluster and hydrophobic patches, within the first nucleotide-binding domain that modulates hMRP5 localization by engaging with membranes (Huang et al. 2024).

Accession Number:O15440
Protein Name:Multidrug resistance-associated protein 5 aka ABCC5 aka MRP5
Length:1437
Molecular Weight:160660.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:14
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate folic acid, methotrexate, 3',5'-cyclic GMP, 3',5'-cyclic AMP, adefovir, ganciclovir, glutathione conjugate, nucleoside analogue, dinucleotide analogue, mercaptopurine, antiviral agent

Cross database links:

RefSeq: NP_005679.2   
Entrez Gene ID: 10057   
Pfam: PF00664    PF00005   
OMIM: 605251  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 (8)

[1] “Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins.”  Belinsky M.G.et.al.   9827529
[2] “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.”  McAleer M.A.et.al.   10438534
[3] “Detailed structural analysis on both human MRP5 and mouse mrp5 transcripts.”  Suzuki T.et.al.   10721709
[4] “Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs.”  Wijnholds J.et.al.   10840050
[5] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[6] “cDNA cloning of a short type of multidrug resistance protein homologue, SMRP, from a human lung cancer cell line.”  Suzuki T.et.al.   9325169
[7] “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
[8] “A quantitative atlas of mitotic phosphorylation.”  Dephoure N.et.al.   18669648

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MKDIDIGKEY IIPSPGYRSV RERTSTSGTH RDREDSKFRR TRPLECQDAL ETAARAEGLS 
61:	LDASMHSQLR ILDEEHPKGK YHHGLSALKP IRTTSKHQHP VDNAGLFSCM TFSWLSSLAR 
121:	VAHKKGELSM EDVWSLSKHE SSDVNCRRLE RLWQEELNEV GPDAASLRRV VWIFCRTRLI 
181:	LSIVCLMITQ LAGFSGPAFM VKHLLEYTQA TESNLQYSLL LVLGLLLTEI VRSWSLALTW 
241:	ALNYRTGVRL RGAILTMAFK KILKLKNIKE KSLGELINIC SNDGQRMFEA AAVGSLLAGG 
301:	PVVAILGMIY NVIILGPTGF LGSAVFILFY PAMMFASRLT AYFRRKCVAA TDERVQKMNE 
361:	VLTYIKFIKM YAWVKAFSQS VQKIREEERR ILEKAGYFQS ITVGVAPIVV VIASVVTFSV 
421:	HMTLGFDLTA AQAFTVVTVF NSMTFALKVT PFSVKSLSEA SVAVDRFKSL FLMEEVHMIK 
481:	NKPASPHIKI EMKNATLAWD SSHSSIQNSP KLTPKMKKDK RASRGKKEKV RQLQRTEHQA 
541:	VLAEQKGHLL LDSDERPSPE EEEGKHIHLG HLRLQRTLHS IDLEIQEGKL VGICGSVGSG 
601:	KTSLISAILG QMTLLEGSIA ISGTFAYVAQ QAWILNATLR DNILFGKEYD EERYNSVLNS 
661:	CCLRPDLAIL PSSDLTEIGE RGANLSGGQR QRISLARALY SDRSIYILDD PLSALDAHVG 
721:	NHIFNSAIRK HLKSKTVLFV THQLQYLVDC DEVIFMKEGC ITERGTHEEL MNLNGDYATI 
781:	FNNLLLGETP PVEINSKKET SGSQKKSQDK GPKTGSVKKE KAVKPEEGQL VQLEEKGQGS 
841:	VPWSVYGVYI QAAGGPLAFL VIMALFMLNV GSTAFSTWWL SYWIKQGSGN TTVTRGNETS 
901:	VSDSMKDNPH MQYYASIYAL SMAVMLILKA IRGVVFVKGT LRASSRLHDE LFRRILRSPM 
961:	KFFDTTPTGR ILNRFSKDMD EVDVRLPFQA EMFIQNVILV FFCVGMIAGV FPWFLVAVGP 
1021:	LVILFSVLHI VSRVLIRELK RLDNITQSPF LSHITSSIQG LATIHAYNKG QEFLHRYQEL 
1081:	LDDNQAPFFL FTCAMRWLAV RLDLISIALI TTTGLMIVLM HGQIPPAYAG LAISYAVQLT 
1141:	GLFQFTVRLA SETEARFTSV ERINHYIKTL SLEAPARIKN KAPSPDWPQE GEVTFENAEM 
1201:	RYRENLPLVL KKVSFTIKPK EKIGIVGRTG SGKSSLGMAL FRLVELSGGC IKIDGVRISD 
1261:	IGLADLRSKL SIIPQEPVLF SGTVRSNLDP FNQYTEDQIW DALERTHMKE CIAQLPLKLE 
1321:	SEVMENGDNF SVGERQLLCI ARALLRHCKI LILDEATAAM DTETDLLIQE TIREAFADCT 
1381:	MLTIAHRLHT VLGSDRIMVL AQGQVVEFDT PSVLLSNDSS RFYAMFAAAE NKVAVKG