Multidrug resistance-associated protein 5 is a protein that in humans is encoded by the ABCC5gene.
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.
^Allikmets R, Gerrard B, Hutchinson A, Dean M (Feb 1997). "Characterization of the human ABC superfamily: isolation and mapping of 21 new genes using the expressed sequence tags database". Hum Mol Genet5 (10): 1649–55. doi:10.1093/hmg/5.10.1649. PMID8894702.
^Belinsky MG, Bain LJ, Balsara BB, Testa JR, Kruh GD (Dec 1998). "Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins". J Natl Cancer Inst90 (22): 1735–41. doi:10.1093/jnci/90.22.1735. PMID9827529.
Kool M, de Haas M, Scheffer GL et al. (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 Res.57 (16): 3537–47. PMID9270026.
Suzuki T, Nishio K, Sasaki H et al. (1997). "cDNA cloning of a short type of multidrug resistance protein homologue, SMRP, from a human lung cancer cell line". Biochem. Biophys. Res. Commun.238 (3): 790–4. doi:10.1006/bbrc.1997.7346. PMID9325169.
Cole SP (1999). "Re: Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins". J. Natl. Cancer Inst.91 (10): 888–9. doi:10.1093/jnci/91.10.888. PMID10340910.
McAleer MA, Breen MA, White NL, Matthews N (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". J. Biol. Chem.274 (33): 23541–8. doi:10.1074/jbc.274.33.23541. PMID10438534.
Jedlitschky G, Burchell B, Keppler D (2000). "The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides". J. Biol. Chem.275 (39): 30069–74. doi:10.1074/jbc.M005463200. PMID10893247.
Alcorn J, Lu X, Moscow JA, McNamara PJ (2002). "Transporter gene expression in lactating and nonlactating human mammary epithelial cells using real-time reverse transcription-polymerase chain reaction". J. Pharmacol. Exp. Ther.303 (2): 487–96. doi:10.1124/jpet.102.038315. PMID12388627.
Wielinga PR, van der Heijden I, Reid G et al. (2003). "Characterization of the MRP4- and MRP5-mediated transport of cyclic nucleotides from intact cells". J. Biol. Chem.278 (20): 17664–71. doi:10.1074/jbc.M212723200. PMID12637526.
Pascolo L, Fernetti C, Pirulli D et al. (2003). "Effects of maturation on RNA transcription and protein expression of four MRP genes in human placenta and in BeWo cells". Biochem. Biophys. Res. Commun.303 (1): 259–65. doi:10.1016/S0006-291X(03)00327-9. PMID12646196.
Reid G, Wielinga P, Zelcer N et al. (2003). "Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5". Mol. Pharmacol.63 (5): 1094–103. doi:10.1124/mol.63.5.1094. PMID12695538.
Brandenberger R, Wei H, Zhang S et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol.22 (6): 707–16. doi:10.1038/nbt971. PMID15146197.
Jedlitschky G, Tirschmann K, Lubenow LE et al. (2004). "The nucleotide transporter MRP4 (ABCC4) is highly expressed in human platelets and present in dense granules, indicating a role in mediator storage". Blood104 (12): 3603–10. doi:10.1182/blood-2003-12-4330. PMID15297306.