SLC48A1 Membrane Protein Introduction

Introduction of SLC48A1

SLC48A1 is encoded by the SLC48A1 gene which is located on 12q13.11. The molecular mass of SLC48A1 is about 16 KDa. And it belongs to the HRG family. In mammals, SLC48A1 only has a single homolog. By contrast, it has four paralogs in C. elegans, CeHRG-1, CeHRG-4, CeHRG-5, and CeHRG-6. It is predicted that SLC48A1 has a conserved tyrosine and four transmembrane domains (TMDs) and acidic-dileucine-based sorting signal in the cytoplasmic carboxy-terminus according to the topology modeling and motif analysis. Accordingly, SLC48A1 has conserved functions across metazoan.

Function of SLC48A1 Membrane Protein

SLC48A1 is a membrane protein of endosome or a lysosomerelated organelle. It is mainly expressed in the brain, kidney, heart, and skeletal muscle, and it can also be detected in the liver, lung, placenta and small intestine moderately. The main functions of SLC48A1 are heme binding and heme transporter activity, which can regulate intracellular heme availability by the endosomal or lysosomal compartment, because the acid environment in the two organelles would permit heme to remain soluble. Besides, the movement and regulation of heme mediated by SLC48A1 are conserved in metazoans. So SLC48A1 is crucial for heme homeostasis and normal development in worms and vertebrates. It has been suggested that there is the reaction between SLC48A1 and the C subunit of the V-ATPase, and it can regulate V-ATPase activity, which is quietly important for heme binding, endosomal acidification, and receptor trafficking in mammalian cells. It has been revealed that SLC48A1 expression at the plasma membrane enhances V-ATPase activity, drives glycolytic flux and facilitates cancer cell growth, migration and invasion Beyond that, SLC4A1 regulates trafficking of the glucose transporter-1 with a concomitant change in glucose uptake and lactate production.

Fig.1 Putative topology of hHRG-1SLC48A1 (Yuan, 2011).

Application of SLC48A1 Membrane Protein in Literature

1. Fogarty F.M., et al. HRG-1 enhances cancer cell invasive potential and couples glucose metabolism to cytosolic/extracellular pH gradient regulation by the vacuolar-H+ ATPase. Oncogene. 2014, 33(38):4653. PubMed ID: 24141772
   
   

   This article reports the V-ATPase and HRG-1/SLC48A1 are co-expressed at the plasma membrane in highly invasive and migratory cancer cell lines, and then SLC48A1 will enhance V-ATPase activity and regulate glycolytic flux and cancer cell growth, migration and invasion.

2. Yuan X., et al. Topologically conserved residues direct heme transport in HRG-1-related proteins. Journal of Biological Chemistry. 2011, 287(7):4914-4924. PubMed ID: 22174408
   
   

   Authors in this article study some topologically conserved residues of HRG-1/SLC48A1. These residues are positioned on the exoplasmic, cytoplasmic, and transmembrane regions of HRG-1/SLC48A1, and they will direct the heme transport mediated by SLC48A1.

3. Rajagopal A., et al. Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins. Nature. 2008, 453(7198):1127-1131. PubMed ID: 18418376
   
   

   This article reveals that HRG-1/SLC48A1 is crucial for heme homeostasis and normal development in worms and vertebrates. It suggests conserved pathways for cellular heme trafficking in animals. The haem homeostasis is regulated by SLC48A1.

4. O'Callaghan K.M., et al. Heme-binding protein HRG-1 is induced by insulin-like growth factor I and associates with the vacuolar H+-ATPase to control endosomal pH and receptor trafficking. Journal of Biological Chemistry. 2010, 285(1):381-91. PubMed ID: 19875448
   
   

   This article reveals that HRG-1/SLC48A1 can regulate V-ATPase activity, HRG-1/SLC48A1 may be related the tumor growth and cancer progression because V-ATPase plays an essential role in endosomal acidification, heme binding, and receptor trafficking in mammalian cells.

5. Jiang G, et al. Expression and function of hypertension related gene hrg--1 during redifferentiation of vascular smooth muscle cells. Chinese Journal of Biochemistry & Molecular Biology. 2004, 20(2):195-199. PubMed ID: 400112
   
   

   This article reveals that HRG-1/SLC48A1 gene expression changes significantly during VSMC redifferentiation. HRG-1/SLC48A1 is related to SM alpha-actin in cytoplasm, its expression is related to VSMC differentiation, and HRG-1/SLC48A1 takes part in the construction of cytoskeleton and regulate contraction and migration of VSMCs.

SLC48A1 Preparation Options

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Reference

1. Yuan X., et al. (2011). Topologically conserved residues direct heme transport in hrg-1-related proteins. Journal of Biological Chemistry, 287(7), 4914-4924.

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