ABCC4

ATP-binding cassette, sub-family C (CFTR/MRP), member 4
Identifiers
Symbols	ABCC4 ; MOAT-B; MOATB; MRP4
External IDs	OMIM: 605250 MGI: 2443111 HomoloGene: 74563 IUPHAR: 782 ChEMBL: 1743128 GeneCards: ABCC4 Gene
EC number	3.6.3.49
Gene ontology Molecular function • ATP binding • 15-hydroxyprostaglandin dehydrogenase (NAD+) activity • ATPase activity, coupled to transmembrane movement of substances Cellular component • plasma membrane • membrane • integral component of membrane • basolateral plasma membrane • platelet dense granule membrane Biological process • platelet degranulation • blood coagulation • biological_process • platelet activation • transmembrane transport • oxidation-reduction process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10257	239273
Ensembl	ENSG00000125257	ENSMUSG00000032849
UniProt	O15439	E9Q236
RefSeq (mRNA)	NM_001105515	NM_001033336
RefSeq (protein)	NP_001098985	NP_001028508
Location (UCSC)	Chr 13: 95.02 – 95.3 Mb	Chr 14: 118.48 – 118.71 Mb
PubMed search

ATP-binding cassette sub-family C member 4 (ABCC4), also known as the multidrug resistance-associated protein 4 (MRP4) or multi-specific organic anion transporter B (MOAT-B), is a protein that in humans is encoded by the ABCC4 gene.^[1][2]

ABCC4 acts as a regulator of intracellular cyclic nucleotide levels and as a mediator of cAMP-dependent signal transduction to the nucleus.^[3] MRP4/ABCC4 also transports prostaglandins, for example PGE2, out of the cell where they can bind receptors.^[4]

MRP4/ABCC4 expression is dysregulated in several cancers ^[5][6][7] and is also upregulated in peritoneal endometriosis.^[8]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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|{{{bSize}}}px|alt=Fluorouracil (5-FU) Activity edit]]

Fluorouracil (5-FU) Activity edit

1. The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

See also

• ATP-binding cassette transporter

References

1. "Entrez Gene: ATP-binding cassette".
2. Lee K, Belinsky MG, Bell DW, Testa JR, Kruh GD (July 1998). "Isolation of MOAT-B, a widely expressed multidrug resistance-associated protein/canalicular multispecific organic anion transporter-related transporter". Cancer Res. 58 (13): 2741–7. PMID 9661885.
3. Sassi Y, Lipskaia L, Vandecasteele G, Nikolaev VO, Hatem SN, Cohen Aubart F, Russel FG, Mougenot N, Vrignaud C, Lechat P, Lompré AM, Hulot JS (August 2008). "Multidrug resistance-associated protein 4 regulates cAMP-dependent signaling pathways and controls human and rat SMC proliferation". J. Clin. Invest. 118 (8): 2747–57. doi:10.1172/JCI35067. PMC 2467383. PMID 18636120.
4. Reid G, Wielinga P, Zelcer N,van der Heijden I, Kuil A, de Haas M, et al. The human multidrug resistanceprotein MRP4 functions as a prostaglandin efflux transporter and is inhibitedby nonsteroidal antiinflammatory drugs" Proc Natl Acad Sci U S A2003;100(16) 9244-9.
5. Ho LL, Kench JG, Handelsman DJ,Scheffer GL, Stricker PD, Grygiel JG, et al. Androgen regulation of multidrugresistance-associated protein 4 (MRP4/ABCC4) in prostate cancer" Prostate2008;68(13) 1421-9.
6. Copsel S, Garcia C, Diez F,Vermeulem M, Baldi A, Bianciotti LG, et al. Multidrug resistance protein 4(MRP4/ABCC4) regulates cAMP cellular levels and controls human leukemia cellproliferation and differentiation" J Biol Chem 2011;286(9) 6979-88.
7. Holla VR, Backlund MG, Yang P,Newman RA, DuBois RN. Regulation of prostaglandin transporters in colorectalneoplasia. Cancer Prev Res (Phila). 2008;1(2) 93-9.
8. Gori I, Rodriguez Y, Pellegrini C, Achtari C, Hornung D, Chardonnens E, Wunder D, Fiche M, CannyGO. Augmented epithelial multidrug resistance-associated protein 4 expression in peritoneal endometriosis: regulation by lipoxin A(4)" Fertil Steril 2013 Jun;99(7) 1965-73.e2. doi:10.1016/j.fertnstert.2013.01.146

Further reading

• Guey LT, GarcÃa-Closas M, Murta-Nascimento C; et al. (2010). "Genetic susceptibility to distinct bladder cancer subphenotypes.". Eur. Urol. 57 (2): 283–92. doi:10.1016/j.eururo.2009.08.001. PMC 3220186. PMID 19692168.
• Rose JE, Behm FM, Drgon T; et al. (2010). "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.". Mol. Med. 16 (7–8): 247–53. doi:10.2119/molmed.2009.00159. PMC 2896464. PMID 20379614.
• Rodríguez-Návoa S, Labarga P, Soriano V; et al. (2009). "Predictors of kidney tubular dysfunction in HIV-infected patients treated with tenofovir: a pharmacogenetic study". Clin. Infect. Dis. 48 (11): e108–16. doi:10.1086/598507. PMID 19400747.
• Holmes MV, Shah T, Vickery C; et al. (2009). Luo, Yuan, ed. "Fulfilling the promise of personalized medicine? Systematic review and field synopsis of pharmacogenetic studies". PLoS ONE 4 (12): e7960. doi:10.1371/journal.pone.0007960. PMC 2778625. PMID 19956635.
• Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE; et al. (2010). "Human skeletal muscle drug transporters determine local exposure and toxicity of statins". Circ. Res. 106 (2): 297–306. doi:10.1161/CIRCRESAHA.109.203596. PMID 19940267.
• Jedlitschky G, Cattaneo M, Lubenow LE; et al. (2010). "Role of MRP4 (ABCC4) in platelet adenine nucleotide-storage: evidence from patients with delta-storage pool deficiencies". Am. J. Pathol. 176 (3): 1097–103. doi:10.2353/ajpath.2010.090425. PMC 2832132. PMID 20133816.
• Saito A, Kawamoto M, Kamatani N (2009). "Association study between single-nucleotide polymorphisms in 199 drug-related genes and commonly measured quantitative traits of 752 healthy Japanese subjects". J. Hum. Genet. 54 (6): 317–23. doi:10.1038/jhg.2009.31. PMID 19343046.
• Hosgood HD, Menashe I, He X; et al. (2009). "PTEN identified as important risk factor of chronic obstructive pulmonary disease". Respir Med 103 (12): 1866–70. doi:10.1016/j.rmed.2009.06.016. PMC 2783799. PMID 19625176.
• Ban H, Andoh A, Imaeda H; et al. (2010). "The multidrug-resistance protein 4 polymorphism is a new factor accounting for thiopurine sensitivity in Japanese patients with inflammatory bowel disease". Journal of gastroenterology 45 (10): HASH(0x1e0d7f0). doi:10.1007/s00535-010-0248-y. PMID 20393862.
• Kucka M, Kretschmannova K, Murano T; et al. (2010). "Dependence of multidrug resistance protein-mediated cyclic nucleotide efflux on the background sodium conductance". Mol. Pharmacol. 77 (2): 270–9. doi:10.1124/mol.109.059386. PMC 2812068. PMID 19903828.
• Aleksunes LM, Yeager RL, Klaassen CD (2009). "Application of multivariate statistical procedures to identify transcription factors that correlate with MRP2, 3, and 4 mRNA in adult human livers". Xenobiotica 39 (7): 514–22. doi:10.1080/00498250902952514. PMC 2698955. PMID 19480556.
• Ming X, Thakker DR (2010). "Role of basolateral efflux transporter MRP4 in the intestinal absorption of the antiviral drug adefovir dipivoxil". Biochem. Pharmacol. 79 (3): 455–62. doi:10.1016/j.bcp.2009.08.029. PMID 19735648.
• Brüggemann M, Trautmann H, Hoelzer D; et al. (2009). "Multidrug resistance-associated protein 4 (MRP4) gene polymorphisms and treatment response in adult acute lymphoblastic leukemia". Blood 114 (26): 5400–1; author reply 5401–2. doi:10.1182/blood-2009-09-243741. PMID 20018925.
• Clemente MI, Alvarez S, SerramÃa MJ; et al. (2009). "Non-steroidal anti-inflammatory drugs increase the antiretroviral activity of nucleoside reverse transcriptase inhibitors in HIV type-1-infected T-lymphocytes: role of multidrug resistance protein 4". Antivir. Ther. (Lond.) 14 (8): 1101–11. doi:10.3851/IMP1468. PMID 20032540.
• Radilova H, Libra A, Holasova S; et al. (2009). "COX-1 is coupled with mPGES-1 and ABCC4 in human cervix cancer cells". Mol. Cell. Biochem. 330 (1–2): 131–40. doi:10.1007/s11010-009-0126-1. PMID 19399588.
• Low SK, Kiyotani K, Mushiroda T; et al. (2009). "Association study of genetic polymorphism in ABCC4 with cyclophosphamide-induced adverse drug reactions in breast cancer patients". J. Hum. Genet. 54 (10): 564–71. doi:10.1038/jhg.2009.79. PMID 19696793.
• Ansari M, Sauty G, Labuda M; et al. (2009). "Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia". Blood 114 (7): 1383–6. doi:10.1182/blood-2008-11-191098. PMID 19515727.
• Yuasa I, Umetsu K, Matsusue A; et al. (2010). "A Japanese-specific allele in the GALNT11 gene". Leg Med (Tokyo) 12 (4): 208–11. doi:10.1016/j.legalmed.2010.04.001. PMID 20547088.
• Moyer AM, Sun Z, Batzler AJ; et al. (2010). "Glutathione pathway genetic polymorphisms and lung cancer survival after platinum-based chemotherapy". Cancer Epidemiol. Biomarkers Prev. 19 (3): 811–21. doi:10.1158/1055-9965.EPI-09-0871. PMC 2837367. PMID 20200426.
• Xu S, Weerachayaphorn J, Cai SY; et al. (2010). "Aryl hydrocarbon receptor and NF-E2-related factor 2 are key regulators of human MRP4 expression". Am. J. Physiol. Gastrointest. Liver Physiol. 299 (1): G126–35. doi:10.1152/ajpgi.00522.2010. PMC 2904108. PMID 20395535.

External links

• ABCC4 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)