ATP-binding cassette sub-family C member 5

Definition:

ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of endogenous metabolites such as cAMP and cGMP, folic acid and N-lactoyl-amino acids (in vitro). Acts also as a general glutamate conjugate and analog transporter that can limit the brain levels of endogenous metabolites, drugs, and toxins. Confers resistance to the antiviral agent PMEA. Able to transport several anticancer drugs including methotrexate, and nucleotide analogs in vitro, however it does with low affinity, thus the exact role of ABCC5 in mediating resistance still needs to be elucidated. Acts as a heme transporter required for the translocation of cytosolic heme to the secretory pathway. May play a role in energy metabolism by regulating the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine cells (By similarity).

References:

[1]. Cornelia J F de Wolf, et al. cGMP transport by vesicles from human and mouse erythrocytes. FEBS J. 2007 Jan;274(2):439-50. [Content Brief]

[2]. Tamara Korolnek, et al. Control of metazoan heme homeostasis by a conserved multidrug resistance protein. Cell Metab. 2014 Jun 3;19(6):1008-19. [Content Brief]

[3]. G Jedlitschky, et al. The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides. J Biol Chem. 2000 Sep 29;275(39):30069-74. [Content Brief]

[4]. Peter R Wielinga, et al. Characterization of the MRP4- and MRP5-mediated transport of cyclic nucleotides from intact cells. J Biol Chem. 2003 May 16;278(20):17664-71. [Content Brief]

[5]. Glen Reid, et al. Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol Pharmacol. 2003 May;63(5):1094-103. [Content Brief]

[6]. Peter Wielinga, et al. The human multidrug resistance protein MRP5 transports folates and can mediate cellular resistance against antifolates. Cancer Res. 2005 May 15;65(10):4425-30. [Content Brief]

[7]. J Wijnholds, et al. Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7476-81. [Content Brief]

[8]. Robert S Jansen, et al. ATP-binding Cassette Subfamily C Member 5 (ABCC5) Functions as an Efflux Transporter of Glutamate Conjugates and Analogs. J Biol Chem. 2015 Dec 18;290(51):30429-40. [Content Brief]

[9]. P R Wielinga, et al. Thiopurine metabolism and identification of the thiopurine metabolites transported by MRP4 and MRP5 overexpressed in human embryonic kidney cells. Mol Pharmacol. 2002 Dec;62(6):1321-31. [Content Brief]

[10]. Robert S Jansen, et al. N-lactoyl-amino acids are ubiquitous metabolites that originate from CNDP2-mediated reverse proteolysis of lactate and amino acids. Proc Natl Acad Sci U S A. 2015 May 26;112(21):6601-6. [Content Brief]

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