ABCC5 Membrane Protein Introduction

Introduction of ABCC5

ABCC5, also known as MRP5, PABC11, ABC33, MOATC, EST277145, canalicular multi-specific organic anion transporter C, or ATP-binding cassette, subfamily C (CFTR/MRP), member 5, is a 160.7 kDa transmembrane transporter composed by 1437 amino acids length. In humans, it is encoded by the ABCC5 gene which is located on chromosome 3q27.1. ABCC5 belongs to the C branch of the ATP-binding cassette transporter superfamily, utilizing the energy provided by the hydrolysis of ATP to transport substrates across the cell plasma membrane. This protein is widely expressed in all tissues, with particularly high levels in brains and muscles. In most cells, ABCC5 routes to the basolateral plasma membrane, whereas in brain capillary endothelial cells forming the blood-brain barrier, it seems to reside in the apical membrane.

Function of ABCC5 Membrane Protein

ABCC5 is one of ABC transporters which are structurally associated membrane protein characterizing intracellular motifs that show ATPase activity. The protein is also a member of multidrug resistance-associated protein (MRP) subfamily and it is clinically relevant for its capacity to confer multidrug resistance through actively effluxing anticancer drugs. The protein ABCC5 plays roles in the cellular export of its substrate, cyclic nucleotides. This export benefits the degradation of phosphodiesterase and possibly an elimination process for cyclic nucleotides. Studies manifested that ABCC5 provides resistance to thiopurine anticancer drugs that are 6-mercaptopurine, thioguanine, together with anti-HIV drug 9-(2-phosphonylmethoxyethyl) adenine. Additionally, ABCC5 has been considered as an efflux transporter of cyclic guanosine monophosphate (cGMP). Increased intracellular expressions of cGMP in cancer cells have been implicated in certain clinical research that is likely to induce apoptosis, and thus various cancer cells seem to overcome this deleterious effect by elevated efflux of cGMP via ABCC5.

Fig.1 (A) Topology of ABCC5. (B) Superimposition of the ABCC5 model (blue) and the template x-ray crystal structure of the p-glycoprotein (red). (Singh, 2016)

Application of ABCC5 Membrane Protein in Literature

1. Bai F., et al. Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer. Int J Nanomedicine. 2018, 13: 1327-1339. PubMed ID: 29563790
   
   

   Nanomedicine was gradually becoming a potential technique to overcome cancer multidrug resistant (MDR). The results in this paper found that pemetrexed-loaded d-alpha tocopheryl polyethylene glycol 1000 succinate liposomes were developed as an approach to overcome MDR to pemetrexed in breast cancers.

2. Pandey V., et al. Molecular modeling and in silico characterization of GmABCC5: a phytate transporter and potential target for low-phytate crops. 3 Biotech. 2018, 8(1): 54. PubMed ID: 29354365
   
   

   The study provided valuable insights into the structural and functional characteristics of GmABCC5, which was probably further used for the improvement of nutritionally enriched low-phytate soybean with developed mineral bioavailability.

3. Hou Y., et al. The FOXM1-ABCC5 axis contributes to paclitaxel resistance in nasopharyngeal carcinoma cells. Cell Death Dis. 2017, 8(3): e2659. PubMed ID: 28277541
   
   

   It was the first study to confirm the role of FOXM1 in drug efflux and paclitaxel resistance by regulating the gene transcription of one of the ABC transporters, ABCC5. ABCC5 or small molecular inhibitors of FOXM1 have a potential to overcome paclitaxel chemoresistance in nasopharyngeal carcinoma (NPC) patients.

4. Lal S., et al. Pharmacogenetics of ABCB5, ABCC5 and RLIP76 and doxorubicin pharmacokinetics in Asian breast cancer patients. Pharmacogenomics J. 2017, 17(4): 337-343. PubMed ID: 26975227
   
   

   This review explored the impact of ABCC5, ABCB5, and RLIP76 polymorphisms on doxorubicin pharmacokinetics in Asian patients with breast cancers (N=62). Direct sequencing was operated to screen for formerly identified ABCC5 polymorphisms and polymorphisms in the exons and exon-intron boundaries of ABCB5, RLIP76 genes.

5. Tang F.Y., et al. Genetic association of the PARL-ABCC5-HTR3D-HTR3C locus with primary angle-closure glaucoma in Chinese. Invest Ophthalmol Vis Sci. 2017, 58(10): 4384-4389. PubMed ID: 28813580
   
   

   These findings of the report enriched the allelic spectrum of ABCC5 in primary angle closure glaucoma (PACG). They identified no tagging SNP in charge of the association of whole regions. And the further deep sequencing analysis of this region should be warranted to unclose whether there was still disease correlated variant in this region.

ABCC5 Preparation Options

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Reference

1. Singh N. (2016). Molecular Modelling of Human Multidrug Resistance Protein 5 (ABCC5). Journal of Biophysical Chemistry. 7, 61-73.

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