SLCO1A2 Membrane Protein Introduction

Introduction of SLCO1A2

SLCO1A2, the official full name is solute carrier organic anion transporter family member 1A2. It is also known as solute carrier family 21 member 3. It is encoded by the SLCO1A2 gene in humans and belongs to the SLC21A family of solute carriers. This gene is conserved in chimpanzee, monkey, cow, rat, dog, mouse and chicken. It has been reported that 113 organisms have orthologs with this gene. SLCO1A2 is widely expressed in brain, lung and 2 other tissues, and is involved in cellular uptake of organic ions in the liver.

Function of SLCO1A2 Membrane Protein

SLCO1A2 is also known as solute carrier family 21 member 3 which belongs to SLC21A family of solute carriers. SLCO1A2 is shown to be a sodium-independent transporter and can mediate cellular uptake of organic ions in the liver. The substrates of this transporter include bromosulphophthalein, bile acids, and some steroidal compounds. Multiple transcript variants can be generated because of different splicing of SLCO1A2 gene. SLCO1A2 can be selectively inhibited by the grapefruit juice component naringin. SLCO1A2 is involved in the cellular uptake of methotrexate and plays a critical role in the elimination of MTX. In addition, a microRNA binding site polymorphism in SLCO1A2 is associated with delayed methotrexate elimination in Chinese children with acute lymphoblastic leukemia. In addition, SLCO1A2 was identified as novel loci in progressive supranuclear palsy, and this will provide mechanistic insights for therapeutic strategies. SLCO1A2 polymorphisms are associated with chloroquine/primaquine responses. SLCO1A2 regulates cellular uptake of ochratoxin A, and this can aggravate OTA toxicity.

Fig.1 Representation of transport and exchange of methotrexate in the brain. (Mikkelsen, 2011)

Application of SLCO1A2 Membrane Protein in Literature

1. Sanchez-Contreras M.Y., et al. Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci. Mol Neurodegener. 2018, 13(1): 37. PubMed ID: 29986742
   
   

   This article indicates that SLCO1A2 is identified as novel loci in progressive supranuclear palsy, and this will provide mechanistic insights for therapeutic strategies.

2. Xiang Z., et al. Identification of an NF-κB Inhibition Site on the Proximal Promoter Region of Human Organic Anion Transporting Polypeptide 1A2 Coding Gene SLCO1A2. Drug Metab Dispos. 2018, 46(5): 643-651. PubMed ID: 29549185
   
   

   This article identifies the NF-kB inhibition binding site on the promoter region of SLCO1A2.

3. Wang S.M., et al. Association between a microRNA binding site polymorphism in SLCO1A2 and the risk of delayed methotrexate elimination in Chinese children with acute lymphoblastic leukemia. Leuk Res. 2018, 65: 61-66. PubMed ID: 29306656
   
   

   This article indicates that microRNA binding site polymorphism in SLCO1A2 is associated with the risk of delayed methotrexate elimination for acute lymphoblastic leukemia, and concludes that polymorphism (rs4149009 G > A) might affect MTX pharmacokinetics through interfering with the function of miRNAs.

4. Sortica V.A., et al. SLCO1A2, SLCO1B1 and SLCO2B1 polymorphisms influence chloroquine and primaquine treatment in Plasmodium vivax malaria. Pharmacogenomics. 2017, 18(15): 1393-1400. PubMed ID: 28975866
   
   

   This article shows that SLCO1A2 polymorphisms are associated with chloroquine/primaquine responses.

5. Qi X., et al. Ochratoxin A transport by the human breast cancer resistance protein (BCRP), multidrug resistance protein 2 (MRP2), and organic anion-transporting polypeptides 1A2, 1B1 and 2B1. Toxicol Appl Pharmacol. 2017, 329: 18-25. PubMed ID: 28532671
   
   

   This article shows that SLCO1A2 regulates cellular uptake of Ochratoxin A, and this can aggravate OTA toxicity.

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Reference

1. Mikkelsen T S, et al. (2011). PharmGKB summary: methotrexate pathway. Pharmacogenet Genomics. 21(10): 679-86.

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