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Multidrug resistance-associated protein 5 is a protein that in humans is encoded by the ABCC5gene.[5][6][7]
Function
The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions in the cellular export of its substrate, cyclic nucleotides. This export contributes to the degradation of phosphodiesterases and possibly an elimination pathway for cyclic nucleotides. Studies show that this protein provides resistance to thiopurine anticancer drugs, 6-mercatopurine and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine. This protein may be involved in resistance to thiopurines in acute lymphoblastic leukemia and antiretroviral nucleoside analogs in HIV-infected patients. Alternative splicing of this gene has been detected; however, the complete sequence and translation initiation site is unclear.[7]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Allikmets R, Gerrard B, Hutchinson A, Dean M (Oct 1996). "Characterization of the human ABC superfamily: isolation and mapping of 21 new genes using the expressed sequence tags database". Human Molecular Genetics. 5 (10): 1649–55. doi:10.1093/hmg/5.10.1649. PMID8894702.
^Belinsky MG, Bain LJ, Balsara BB, Testa JR, Kruh GD (Nov 1998). "Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins". Journal of the National Cancer Institute. 90 (22): 1735–41. doi:10.1093/jnci/90.22.1735. PMID9827529.
Kool M, de Haas M, Scheffer GL, Scheper RJ, van Eijk MJ, Juijn JA, Baas F, Borst P (Aug 1997). "Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines". Cancer Research. 57 (16): 3537–47. PMID9270026.
Suzuki T, Nishio K, Sasaki H, Kurokawa H, Saito-Ohara F, Ikeuchi T, Tanabe S, Terada M, Saijo N (Sep 1997). "cDNA cloning of a short type of multidrug resistance protein homologue, SMRP, from a human lung cancer cell line". Biochemical and Biophysical Research Communications. 238 (3): 790–4. doi:10.1006/bbrc.1997.7346. PMID9325169.
Cole SP (May 1999). "Re: Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins". Journal of the National Cancer Institute. 91 (10): 888–9. doi:10.1093/jnci/91.10.888. PMID10340910.
McAleer MA, Breen MA, White NL, Matthews N (Aug 1999). "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". The Journal of Biological Chemistry. 274 (33): 23541–8. doi:10.1074/jbc.274.33.23541. PMID10438534.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Suzuki T, Sasaki H, Kuh HJ, Agui M, Tatsumi Y, Tanabe S, Terada M, Saijo N, Nishio K (Jan 2000). "Detailed structural analysis on both human MRP5 and mouse mrp5 transcripts". Gene. 242 (1–2): 167–73. doi:10.1016/S0378-1119(99)00529-6. PMID10721709.
Oguri T, Isobe T, Suzuki T, Nishio K, Fujiwara Y, Katoh O, Yamakido M (Apr 2000). "Increased expression of the MRP5 gene is associated with exposure to platinum drugs in lung cancer". International Journal of Cancer. Journal International Du Cancer. 86 (1): 95–100. doi:10.1002/(SICI)1097-0215(20000401)86:1<95::AID-IJC15>3.0.CO;2-G. PMID10728601.
Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ (Mar 2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3491–6. doi:10.1073/pnas.97.7.3491. PMC16267. PMID10737800.
Jedlitschky G, Burchell B, Keppler D (Sep 2000). "The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides". The Journal of Biological Chemistry. 275 (39): 30069–74. doi:10.1074/jbc.M005463200. PMID10893247.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Alcorn J, Lu X, Moscow JA, McNamara PJ (Nov 2002). "Transporter gene expression in lactating and nonlactating human mammary epithelial cells using real-time reverse transcription-polymerase chain reaction". The Journal of Pharmacology and Experimental Therapeutics. 303 (2): 487–96. doi:10.1124/jpet.102.038315. PMID12388627.
Wielinga PR, van der Heijden I, Reid G, Beijnen JH, Wijnholds J, Borst P (May 2003). "Characterization of the MRP4- and MRP5-mediated transport of cyclic nucleotides from intact cells". The Journal of Biological Chemistry. 278 (20): 17664–71. doi:10.1074/jbc.M212723200. PMID12637526.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Pascolo L, Fernetti C, Pirulli D, Crovella S, Amoroso A, Tiribelli C (Mar 2003). "Effects of maturation on RNA transcription and protein expression of four MRP genes in human placenta and in BeWo cells". Biochemical and Biophysical Research Communications. 303 (1): 259–65. doi:10.1016/S0006-291X(03)00327-9. PMID12646196.
Reid G, Wielinga P, Zelcer N, De Haas M, Van Deemter L, Wijnholds J, Balzarini J, Borst P (May 2003). "Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5". Molecular Pharmacology. 63 (5): 1094–103. doi:10.1124/mol.63.5.1094. PMID12695538.
Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW (Jun 2004). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nature Biotechnology. 22 (6): 707–16. doi:10.1038/nbt971. PMID15146197.
Jedlitschky G, Tirschmann K, Lubenow LE, Nieuwenhuis HK, Akkerman JW, Greinacher A, Kroemer HK (Dec 2004). "The nucleotide transporter MRP4 (ABCC4) is highly expressed in human platelets and present in dense granules, indicating a role in mediator storage". Blood. 104 (12): 3603–10. doi:10.1182/blood-2003-12-4330. PMID15297306.
