ABCC subfamily | Transporters | IUPHAR/BPS Guide to IMMUNOPHARMACOLOGY

ABCC subfamily C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Subfamily ABCC contains thirteen members and nine of these transporters are referred to as the Multidrug Resistance Proteins (MRPs). The MRP proteins are found throughout nature and they mediate many important functions. They are known to be involved in ion transport, toxin secretion, and signal transduction [1,5].

Transporters

Targets of relevance to immunopharmacology are highlighted in blue

MRP1 (ABCC1) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

779

Systematic nomenclature

ABCC1

Common abbreviation

MRP1

Previous and unofficial names

Genes

ABCC1 (Hs), Abcc1 (Mm), Abcc1 (Rn)

Ensembl ID

ENSG00000103222 (Hs), ENSMUSG00000023088 (Mm), ENSRNOG00000022305 (Rn)

UniProtKB AC

P33527 (Hs), O35379 (Mm), Q8CG09 (Rn)

Inhibitors

WP814 pK_i 7.2 [8]

Comment

Exhibits a broad substrate specificity [2], including LTC₄ (K_m 97 nM [6]) and estradiol-17β-glucuronide [12].

MRP2, cMOAT (ABCC2) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

780

Systematic nomenclature

ABCC2

Common abbreviation

MRP2, cMOAT

Previous and unofficial names

Genes

ABCC2 (Hs), Abcc2 (Mm), Abcc2 (Rn)

Ensembl ID

ENSG00000023839 (Hs), ENSMUSG00000025194 (Mm), ENSRNOG00000046727 (Rn)

UniProtKB AC

Q92887 (Hs), Q8VI47 (Mm), Q63120 (Rn)

Inhibitors

PAK-104P pK_i 5.4 [4]

Comment

Loss-of-function mutations are associated with Dubin-Johnson syndrome, in which plasma levels of conjugated bilirubin are elevated (OMIM: 237500).

MRP3 (ABCC3) C Show summary »« Hide summary

Target Id	781
Systematic nomenclature	ABCC3
Common abbreviation	MRP3
Previous and unofficial names	MOAT-D \| Multidrug resistance-associated protein 3 \| multi-specific organic anion transporter-D \| cMOAT2 \| MLP2 \| MRP3 \| ATP-binding cassette, sub-family C (CFTR/MRP), member 3 \| MRP-like protein 2 \| multidrug resistance protein 3 \| organic anion transporter \| canalicular multispecific organic anion transporter 2 \| ATP-binding cassette, subfamily C (CFTR/MRP), member 3 \| ATP-binding cassette
Genes	ABCC3 (Hs), Abcc3 (Mm), Abcc3 (Rn)
Ensembl ID	ENSG00000108846 (Hs), ENSMUSG00000020865 (Mm), ENSRNOG00000002948 (Rn)
UniProtKB AC	O15438 (Hs), B2RX12 (Mm), O88563 (Rn)
Comment	Transports conjugates of glutathione, sulfate or glucuronide [3]

MRP4 (ABCC4) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

782

Systematic nomenclature

ABCC4

Common abbreviation

MRP4

Previous and unofficial names

Genes

ABCC4 (Hs), Abcc4 (Mm), Abcc4 (Rn)

Ensembl ID

ENSG00000125257 (Hs), ENSMUSG00000032849 (Mm), ENSRNOG00000010064 (Rn)

UniProtKB AC

O15439 (Hs)

Inhibitors

estradiol disulfate pIC₅₀ 6.7 [14]

Comment

Although reported to facilitate cellular cyclic nucleotide export, this role has been questioned [3]; reported to export prostaglandins in a manner sensitive to NSAIDS [10]. A common binding site accommodates substrates including PGE₁, PGE₂ and dehydroepiandrosterone sulphate (DHEAS) [7].

MRP5 (ABCC5) C Show summary »« Hide summary

Target Id

783

Systematic nomenclature

ABCC5

Common abbreviation

MRP5

Previous and unofficial names

Genes

ABCC5 (Hs), Abcc5 (Mm), Abcc5 (Rn)

Ensembl ID

ENSG00000114770 (Hs), ENSMUSG00000022822 (Mm), ENSRNOG00000029178 (Rn)

UniProtKB AC

O15440 (Hs), Q9R1X5 (Mm), Q9QYM0 (Rn)

Inhibitors

compound 2 [PMID: 22380603] pK_i 7.2 [11]

sildenafil pK_i 5.9 [11]

Comment

Although reported to facilitate cellular cyclic nucleotide export, this role has been questioned [3]

MRP6 (ABCC6) C Show summary »« Hide summary

Target Id	784
Systematic nomenclature	ABCC6
Common abbreviation	MRP6
Previous and unofficial names	anthracycline resistance-associated protein \| MOAT-E \| Multidrug resistance-associated protein 6 \| multi-specific organic anion transporter-E \| ARA \| MLP1 \| MRP6 \| URG7 \| ATP-binding cassette, sub-family C (CFTR/MRP), member 6 \| liver multidrug resistance-associated protein 6 \| MRP-like protein 1 \| DCC \| Dyscalc1 \| ATP-binding cassette, subfamily C (CFTR/MRP), member 6 \| ATP-binding cassette
Genes	ABCC6 (Hs), Abcc6 (Mm), Abcc6 (Rn)
Ensembl ID	ENSG00000091262 (Hs), ENSMUSG00000030834 (Mm), ENSRNOG00000028781 (Rn)
UniProtKB AC	O95255 (Hs), Q9R1S7 (Mm), O88269 (Rn)
Comment	Loss-of-function mutations in ABCC6 are associated with pseudoxanthoma elasticum (OMIM: 264800).

SUR1 (ATP-binding cassette, sub-family C (CFTR/MRP), member 8 / ABCC8) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

2594

Nomenclature

ATP-binding cassette, sub-family C (CFTR/MRP), member 8

Systematic nomenclature

ABCC8

Common abbreviation

SUR1

Previous and unofficial names

ABC36 | ATP-binding cassette | ATP-binding cassette, subfamily C (CFTR/MRP), member 8 | HHF1 | HI | MRP8 | PHHI | SUR1 | TNDM2

Genes

ABCC8 (Hs), Abcc8 (Mm), Abcc8 (Rn)

Ensembl ID

ENSG00000006071 (Hs), ENSMUSG00000040136 (Mm), ENSRNOG00000021130 (Rn)

UniProtKB AC

Q09428 (Hs), Q09429 (Rn)

Selective inhibitors

repaglinide pIC₅₀ 7.0 [13]

Comment

The sulfonylurea drugs (acetohexamide, tolbutamide and glibenclamide) act through 'sulfonylurea receptors'; tritiated glibenclamide can be used to identify a 140 kDa protein called SUR1 (now known as ABCC8) [9].

SUR2 (ABCC9) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id	2746
Nomenclature	ABCC9
Common abbreviation	SUR2
Previous and unofficial names	CDMD10 \| sulfonylurea receptor 2 \| SUR2 \| ATP-binding cassette, sub-family C (CFTR/MRP), member 9 \| ATP-binding cassette, subfamily C (CFTR/MRP), member 9 \| ATP-binding cassette
Genes	ABCC9 (Hs), Abcc9 (Mm), Abcc9 (Rn)
Ensembl ID	ENSG00000069431 (Hs), ENSMUSG00000030249 (Mm), ENSRNOG00000036960 (Rn)
UniProtKB AC	O60706 (Hs), P70170 (Mm), Q63563 (Rn)
Comment	Associated with familial atrial fibrillation, Cantu syndrome and familial isolated dilated cardiomyopathy.

MRP7 (ABCC10) Show summary »« Hide summary

Target Id	785
Systematic nomenclature	ABCC10
Common abbreviation	MRP7
Previous and unofficial names	Multidrug resistance-associated protein 7 \| MRP7 \| ATP-binding cassette, sub-family C (CFTR/MRP), member 10 \| SIMRP7 \| ATP-binding cassette, subfamily C (CFTR/MRP), member 10 \| ATP-binding cassette
Genes	ABCC10 (Hs), Abcc10 (Mm), Abcc10 (Rn)
Ensembl ID	ENSG00000124574 (Hs), ENSMUSG00000032842 (Mm), ENSRNOG00000018863 (Rn)
UniProtKB AC	Q5T3U5 (Hs), Q8R4P9 (Mm)

MRP8 (ABCC11) C Show summary »« Hide summary

Target Id	786
Systematic nomenclature	ABCC11
Common abbreviation	MRP8
Previous and unofficial names	Multidrug resistance-associated protein 8 \| MRP8 \| ATP-binding cassette, sub-family C (CFTR/MRP), member 11
Genes	ABCC11 (Hs)
Ensembl ID	ENSG00000121270 (Hs)
UniProtKB AC	Q96J66 (Hs)
Comment	Single nucleotide polymorphisms distinguish wet vs. dry earwax (OMIM: 117800); an association between earwax allele and breast cancer risk is reported in Japanese but not European populations.

MRP9 (ABCC12) Show summary »« Hide summary

Target Id	787
Systematic nomenclature	ABCC12
Common abbreviation	MRP9
Previous and unofficial names	Multidrug resistance-associated protein 9 \| MRP9 \| ATP-binding cassette protein C12 \| ATP-binding cassette, sub-family C (CFTR/MRP), member 12 \| ATP-binding cassette, subfamily C (CFTR/MRP), member 12 \| ATP-binding cassette
Genes	ABCC12 (Hs), Abcc12 (Mm), Abcc12 (Rn)
Ensembl ID	ENSG00000140798 (Hs), ENSMUSG00000036872 (Mm), ENSRNOG00000015666 (Rn)
UniProtKB AC	Q96J65 (Hs), Q80WJ6 (Mm), Q6Y306 (Rn)

Comments

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References

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1. Alexander SPH, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL et al.. (2019) THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters. Br J Pharmacol, 176 Suppl 1: S397-S493. [PMID:31710713]

2. Bakos E, Homolya L. (2007) Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1). Pflugers Arch, 453 (5): 621-41. [PMID:17187268]

3. Borst P, de Wolf C, van de Wetering K. (2007) Multidrug resistance-associated proteins 3, 4, and 5. Pflugers Arch, 453 (5): 661-73. [PMID:16586096]

4. Chen ZS, Kawabe T, Ono M, Aoki S, Sumizawa T, Furukawa T, Uchiumi T, Wada M, Kuwano M, Akiyama SI. (1999) Effect of multidrug resistance-reversing agents on transporting activity of human canalicular multispecific organic anion transporter. Mol Pharmacol, 56 (6): 1219-28. [PMID:10570049]

5. Dean M, Hamon Y, Chimini G. (2001) The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res, 42 (7): 1007-17. [PMID:11441126]

6. Leier I, Jedlitschky G, Buchholz U, Cole SP, Deeley RG, Keppler D. (1994) The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates. J Biol Chem, 269 (45): 27807-10. [PMID:7961706]

7. Pourmal S, Green E, Bajaj R, Chemmama IE, Knudsen GM, Gupta M, Sali A, Cheng Y, Craik CS, Kroetz DL et al.. (2024) Structural basis of prostaglandin efflux by MRP4. Nat Struct Mol Biol, 31 (4): 621-632. [PMID:38216659]

8. Priebe W, Krawczyk M, Kuo MT, Yamane Y, Savaraj N, Ishikawa T. (1998) Doxorubicin- and daunorubicin-glutathione conjugates, but not unconjugated drugs, competitively inhibit leukotriene C4 transport mediated by MRP/GS-X pump. Biochem Biophys Res Commun, 247 (3): 859-63. [PMID:9647783]

9. Rehmann H. (2012) Epac2: a sulfonylurea receptor?. Biochem Soc Trans, 40 (1): 6-10. [PMID:22260657]

10. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P. (2003) The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci USA, 100 (16): 9244-9. [PMID:12835412]

11. Sager G, Ørvoll EØ, Lysaa RA, Kufareva I, Abagyan R, Ravna AW. (2012) Novel cGMP efflux inhibitors identified by virtual ligand screening (VLS) and confirmed by experimental studies. J Med Chem, 55 (7): 3049-57. [PMID:22380603]

12. Suzuki H, Sugiyama Y. (1998) Excretion of GSSG and glutathione conjugates mediated by MRP1 and cMOAT/MRP2. Semin Liver Dis, 18 (4): 359-76. [PMID:9875554]

13. Wängler B, Beck C, Shiue CY, Schneider S, Schwanstecher C, Schwanstecher M, Feilen PJ, Alavi A, Rösch F, Schirrmacher R. (2004) Synthesis and in vitro evaluation of (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic acid ([11C]methoxy-repaglinide): a potential beta-cell imaging agent. Bioorg Med Chem Lett, 14 (20): 5205-9. [PMID:15380228]

14. Zelcer N, Reid G, Wielinga P, Kuil A, van der Heijden I, Schuetz JD, Borst P. (2003) Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem J, 371 (Pt 2): 361-7. [PMID:12523936]

NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation (select format):

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Transporters. Br J Pharmacol. 180 Suppl 2:S374-469.