ABCC5 explained

Multidrug resistance-associated protein 5 is a protein that in humans is encoded by the ABCC5 gene.^{[1] [2] [3]}

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-mercaptopurine 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.

See also

• ATP-binding cassette transporter

Further reading

• Kool M, de Haas M, Scheffer GL, Scheper RJ, van Eijk MJ, Juijn JA, Baas F, Borst P . 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 . Aug 1997 . 9270026 .
• Suzuki T, Nishio K, Sasaki H, Kurokawa H, Saito-Ohara F, Ikeuchi T, Tanabe S, Terada M, Saijo N . 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 . Sep 1997 . 9325169 . 10.1006/bbrc.1997.7346 .
• Cole SP . 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 . May 1999 . 10340910 . 10.1093/jnci/91.10.888 . free .
• McAleer MA, Breen MA, White NL, Matthews N . 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 . Aug 1999 . 10438534 . 10.1074/jbc.274.33.23541 . free .
• Suzuki T, Sasaki H, Kuh HJ, Agui M, Tatsumi Y, Tanabe S, Terada M, Saijo N, Nishio K . Detailed structural analysis on both human MRP5 and mouse mrp5 transcripts . Gene . 242 . 1–2 . 167–73 . Jan 2000 . 10721709 . 10.1016/S0378-1119(99)00529-6 .
• Oguri T, Isobe T, Suzuki T, Nishio K, Fujiwara Y, Katoh O, Yamakido M . Increased expression of the MRP5 gene is associated with exposure to platinum drugs in lung cancer . International Journal of Cancer . 86 . 1 . 95–100 . Apr 2000 . 10728601 . 10.1002/(SICI)1097-0215(20000401)86:1<95::AID-IJC15>3.0.CO;2-G . free .
• 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 . 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 . Mar 2000 . 10737800 . 16267 . 10.1073/pnas.97.7.3491 . 2000PNAS...97.3491D . free .
• Wijnholds J, Mol CA, van Deemter L, de Haas M, Scheffer GL, Baas F, Beijnen JH, Scheper RJ, Hatse S, De Clercq E, Balzarini J, Borst P . Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs . Proceedings of the National Academy of Sciences of the United States of America . 97 . 13 . 7476–81 . Jun 2000 . 10840050 . 16570 . 10.1073/pnas.120159197 . 2000PNAS...97.7476W . free .
• Jedlitschky G, Burchell B, Keppler D . The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides . The Journal of Biological Chemistry . 275 . 39 . 30069–74 . Sep 2000 . 10893247 . 10.1074/jbc.M005463200 . free .
• Alcorn J, Lu X, Moscow JA, McNamara PJ . 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 . Nov 2002 . 12388627 . 10.1124/jpet.102.038315 . 16195525 .
• Wielinga PR, van der Heijden I, Reid G, Beijnen JH, Wijnholds J, Borst P . Characterization of the MRP4- and MRP5-mediated transport of cyclic nucleotides from intact cells . The Journal of Biological Chemistry . 278 . 20 . 17664–71 . May 2003 . 12637526 . 10.1074/jbc.M212723200 . free .
• Pascolo L, Fernetti C, Pirulli D, Crovella S, Amoroso A, Tiribelli C. Claudio Tiribelli . 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 . Mar 2003 . 12646196 . 10.1016/S0006-291X(03)00327-9 .
• Reid G, Wielinga P, Zelcer N, De Haas M, Van Deemter L, Wijnholds J, Balzarini J, Borst P . 7444400 . Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5 . Molecular Pharmacology . 63 . 5 . 1094–103 . May 2003 . 12695538 . 10.1124/mol.63.5.1094 .
• Dazert P, Meissner K, Vogelgesang S, Heydrich B, Eckel L, Böhm M, Warzok R, Kerb R, Brinkmann U, Schaeffeler E, Schwab M, Cascorbi I, Jedlitschky G, Kroemer HK . Expression and localization of the multidrug resistance protein 5 (MRP5/ABCC5), a cellular export pump for cyclic nucleotides, in human heart . The American Journal of Pathology . 163 . 4 . 1567–77 . Oct 2003 . 14507663 . 1868287 . 10.1016/S0002-9440(10)63513-4 .
• 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 . Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation . Nature Biotechnology . 22 . 6 . 707–16 . Jun 2004 . 15146197 . 10.1038/nbt971 . 27764390 .
• Jedlitschky G, Tirschmann K, Lubenow LE, Nieuwenhuis HK, Akkerman JW, Greinacher A, Kroemer HK . 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 . Dec 2004 . 15297306 . 10.1182/blood-2003-12-4330 . free .
• Meyer Zu Schwabedissen HE, Grube M, Heydrich B, Linnemann K, Fusch C, Kroemer HK, Jedlitschky G . Expression, localization, and function of MRP5 (ABCC5), a transporter for cyclic nucleotides, in human placenta and cultured human trophoblasts: effects of gestational age and cellular differentiation . The American Journal of Pathology . 166 . 1 . 39–48 . Jan 2005 . 15631998 . 1602292 . 10.1016/S0002-9440(10)62230-4 .

Notes and References

1. Allikmets R, Gerrard B, Hutchinson A, Dean M . 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 . Oct 1996 . 8894702 . 10.1093/hmg/5.10.1649 . free .
2. Belinsky MG, Bain LJ, Balsara BB, Testa JR, Kruh GD . 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 . Nov 1998 . 9827529 . 10.1093/jnci/90.22.1735 . free .
3. Web site: Entrez Gene: ABCC5 ATP-binding cassette, sub-family C (CFTR/MRP), member 5.