ABCC4

ABCC4
Identifiers
Aliases	ABCC4 , MOAT-B, MOATB, MRP4, ATP binding cassette subfamily C member 4
External IDs	OMIM: 605250; MGI: 2443111; HomoloGene: 74563; GeneCards: ABCC4; OMA:ABCC4 - orthologs
Gene location (Human) Chr. Chromosome 13 (human) [1] Band 13q32.1 Start 95,019,835 bp [1] End 95,301,475 bp [1]
Gene location (Mouse) Chr. Chromosome 14 (mouse) [2] Band 14|14 E4 Start 118,720,104 bp [2] End 118,943,631 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in palpebral conjunctiva secondary oocyte buccal mucosa cell corpus epididymis kidney tubule mucosa of urinary bladder Epithelium of choroid plexus epithelium of nasopharynx mucosa of sigmoid colon stromal cell of endometrium Top expressed in transitional epithelium of urinary bladder conjunctival fornix Epithelium of choroid plexus olfactory epithelium lacrimal gland iris ciliary body retinal pigment epithelium cornea lumbar spinal ganglion More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding ATPase activity ATP binding 15-hydroxyprostaglandin dehydrogenase (NAD+) activity ATPase-coupled inorganic anion transmembrane transporter activity P-type ion transporter activity ATPase-coupled transmembrane transporter activity protein binding Cellular component integral component of membrane platelet dense granule membrane membrane plasma membrane basolateral plasma membrane integral component of plasma membrane Biological process prostaglandin secretion platelet degranulation response to organic cyclic compound response to organic substance positive regulation of smooth muscle cell proliferation response to organonitrogen compound transmembrane transport cilium assembly transport ion transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10257 239273 Ensembl ENSG00000125257 ENSMUSG00000032849 UniProt O15439 E9Q236 RefSeq (mRNA) NM_001105515 NM_001301829 NM_001301830 NM_005845 NM_001033336 NM_001163675 NM_001163676 RefSeq (protein) NP_001098985 NP_001288758 NP_001288759 NP_005836 NP_001028508 NP_001157147 NP_001157148 Location (UCSC) Chr 13: 95.02 – 95.3 Mb Chr 14: 118.72 – 118.94 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. ^{[5] [6]}

ABCC4 acts as a regulator of intracellular cyclic nucleotide levels and as a mediator of cAMP-dependent signal transduction to the nucleus. ^[7] MRP4/ABCC4 also transports prostaglandins, for example PGE2, out of the cell where they can bind receptors. ^[8]

MRP4/ABCC4 expression is dysregulated in several cancers ^{[9] [10] [11]} and is also upregulated in peritoneal endometriosis. ^[12]

Interactive pathway map

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

[[File:

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

|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. GRCh38: Ensembl release 89: ENSG00000125257 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000032849 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: ATP-binding cassette".
6. 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 Research. 58 (13): 2741–7. PMID   9661885.
7. 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". The Journal of Clinical Investigation. 118 (8): 2747–57. doi:10.1172/JCI35067. PMC   2467383 . PMID   18636120.
8. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, et al. (2003). "The human multidrug resistanceprotein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs". Proc Natl Acad Sci U S A. 100 (16): 9244–9. Bibcode:2003PNAS..100.9244R. doi: 10.1073/pnas.1033060100 . PMC   170903 . PMID   12835412.
9. Ho LL, Kench JG, Handelsman DJ, Scheffer GL, Stricker PD, Grygiel JG, et al. (2008). "Androgen regulation of multidrugresistance-associated protein 4 (MRP4/ABCC4) in prostate cancer". Prostate. 68 (13): 1421–9. doi:10.1002/pros.20809. PMID   18615486. S2CID   42717909.
10. Copsel S, Garcia C, Diez F, Vermeulem M, Baldi A, Bianciotti LG, et al. (2011). "Multidrug resistance protein 4(MRP4/ABCC4) regulates cAMP cellular levels and controls human leukemia cellproliferation and differentiation". J Biol Chem. 286 (9): 6979–88. doi: 10.1074/jbc.m110.166868 . PMC   3044954 . PMID   21205825.
11. 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.
12. Gori I, Rodriguez Y, Pellegrini C, Achtari C, Hornung D, Chardonnens E, Wunder D, Fiche M, Canny GO (2013). "Augmented epithelial multidrug resistance-associated protein 4 expression in peritoneal endometriosis: regulation by lipoxin A(4)". Fertil Steril. 99 (7): 1965–1973.e2. doi: 10.1016/j.fertnstert.2013.01.146 . PMID   23472950.

Further reading

• Guey LT, García-Closas M, Murta-Nascimento C, Lloreta J, Palencia L, Kogevinas M, Rothman N, Vellalta G, Calle ML, Marenne G, Tardón A, Carrato A, García-Closas R, Serra C, Silverman DT, Chanock S, Real FX, Malats N (February 2010). "Genetic susceptibility to distinct bladder cancer subphenotypes". European Urology. 57 (2): 283–92. doi:10.1016/j.eururo.2009.08.001. PMC   3220186 . PMID   19692168.
• Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR (2010). "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Molecular Medicine. 16 (7–8): 247–53. doi:10.2119/molmed.2009.00159. PMC   2896464 . PMID   20379614.
• Rodríguez-Nóvoa S, Labarga P, Soriano V, Egan D, Albalater M, Morello J, Cuenca L, González-Pardo G, Khoo S, Back D, Owen A (June 2009). "Predictors of kidney tubular dysfunction in HIV-infected patients treated with tenofovir: a pharmacogenetic study". Clinical Infectious Diseases. 48 (11): e108-16. doi: 10.1086/598507 . PMID   19400747.
• Holmes MV, Shah T, Vickery C, Smeeth L, Hingorani AD, Casas JP (2009). Luo Y (ed.). "Fulfilling the promise of personalized medicine? Systematic review and field synopsis of pharmacogenetic studies". PLOS ONE. 4 (12): e7960. Bibcode:2009PLoSO...4.7960H. doi: 10.1371/journal.pone.0007960 . PMC   2778625 . PMID   19956635.
• Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona RG (February 2010). "Human skeletal muscle drug transporters determine local exposure and toxicity of statins" . Circulation Research. 106 (2): 297–306. doi: 10.1161/CIRCRESAHA.109.203596 . PMID   19940267.
• Jedlitschky G, Cattaneo M, Lubenow LE, Rosskopf D, Lecchi A, Artoni A, Motta G, Niessen J, Kroemer HK, Greinacher A (March 2010). "Role of MRP4 (ABCC4) in platelet adenine nucleotide-storage: evidence from patients with delta-storage pool deficiencies". The American Journal of Pathology. 176 (3): 1097–103. doi:10.2353/ajpath.2010.090425. PMC   2832132 . PMID   20133816.
• Saito A, Kawamoto M, Kamatani N (June 2009). "Association study between single-nucleotide polymorphisms in 199 drug-related genes and commonly measured quantitative traits of 752 healthy Japanese subjects". Journal of Human Genetics. 54 (6): 317–23. doi: 10.1038/jhg.2009.31 . PMID   19343046.
• Hosgood HD, Menashe I, He X, Chanock S, Lan Q (December 2009). "PTEN identified as important risk factor of chronic obstructive pulmonary disease". Respiratory Medicine. 103 (12): 1866–70. doi:10.1016/j.rmed.2009.06.016. PMC   2783799 . PMID   19625176.
• Ban H, Andoh A, Imaeda H, Kobori A, Bamba S, Tsujikawa T, Sasaki M, Saito Y, Fujiyama Y (October 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): 1014–21. doi:10.1007/s00535-010-0248-y. PMID   20393862. S2CID   586429.
• Kucka M, Kretschmannova K, Murano T, Wu CP, Zemkova H, Ambudkar SV, Stojilkovic SS (February 2010). "Dependence of multidrug resistance protein-mediated cyclic nucleotide efflux on the background sodium conductance". Molecular Pharmacology. 77 (2): 270–9. doi:10.1124/mol.109.059386. PMC   2812068 . PMID   19903828.
• Aleksunes LM, Yeager RL, Klaassen CD (July 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 (February 2010). "Role of basolateral efflux transporter MRP4 in the intestinal absorption of the antiviral drug adefovir dipivoxil". Biochemical Pharmacology. 79 (3): 455–62. doi:10.1016/j.bcp.2009.08.029. PMID   19735648.
• Brüggemann M, Trautmann H, Hoelzer D, Kneba M, Gökbuget N, Raff T (December 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, Serramía MJ, Turriziani O, Genebat M, Leal M, Fresno M, Muñoz-Fernández MA (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". Antiviral Therapy. 14 (8): 1101–11. doi: 10.3851/IMP1468 . PMID   20032540. S2CID   30947345.
• Radilova H, Libra A, Holasova S, Safarova M, Viskova A, Kunc F, Buncek M (October 2009). "COX-1 is coupled with mPGES-1 and ABCC4 in human cervix cancer cells". Molecular and Cellular Biochemistry. 330 (1–2): 131–40. doi:10.1007/s11010-009-0126-1. PMID   19399588. S2CID   25586752.
• Low SK, Kiyotani K, Mushiroda T, Daigo Y, Nakamura Y, Zembutsu H (October 2009). "Association study of genetic polymorphism in ABCC4 with cyclophosphamide-induced adverse drug reactions in breast cancer patients". Journal of Human Genetics. 54 (10): 564–71. doi: 10.1038/jhg.2009.79 . PMID   19696793.
• Ansari M, Sauty G, Labuda M, Gagné V, Laverdière C, Moghrabi A, Sinnett D, Krajinovic M (August 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, Nishimukai H, Harihara S, Fukumori Y, Saitou N, Jin F, Chattopadhyay PK, Henke L, Henke J (July 2010). "A Japanese-specific allele in the GALNT11 gene". Legal Medicine. 12 (4): 208–11. doi:10.1016/j.legalmed.2010.04.001. PMID   20547088.
• Moyer AM, Sun Z, Batzler AJ, Li L, Schaid DJ, Yang P, Weinshilboum RM (March 2010). "Glutathione pathway genetic polymorphisms and lung cancer survival after platinum-based chemotherapy". Cancer Epidemiology, Biomarkers & Prevention. 19 (3): 811–21. doi:10.1158/1055-9965.EPI-09-0871. PMC   2837367 . PMID   20200426.
• Xu S, Weerachayaphorn J, Cai SY, Soroka CJ, Boyer JL (July 2010). "Aryl hydrocarbon receptor and NF-E2-related factor 2 are key regulators of human MRP4 expression". American Journal of Physiology. Gastrointestinal and Liver Physiology. 299 (1): G126-35. doi:10.1152/ajpgi.00522.2010. PMC   2904108 . PMID   20395535.

External links

• ABCC4+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human ABCC4 genome location and ABCC4 gene details page in the UCSC Genome Browser .