Equilibrative nucleoside transporter 1 (SLC29A1)
The protein contains 456 amino acids for an estimated molecular weight of 50219 Da.
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) and is sodium-independent. It has a higher affinity for adenosine. Inhibited by dipyridamole and dilazep (anticancer chemotherapeutics drugs). (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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Biological Process
Adenosine transport
Cellular response to glucose stimulus
Cellular response to hypoxia
Excitatory postsynaptic potential
Lactation
Neurotransmitter reuptake
Neurotransmitter transport
Neurotransmitter uptake
Nucleobase-containing compound metabolic process
Nucleoside transmembrane transport
Nucleoside transport
Purine nucleoside transmembrane transport
Pyrimidine-containing compound transmembrane transport
Sleep
Transmembrane transport
Transport across blood-brain barrier
Uridine transport
The reference OMIM entry for this protein is 602193
Solute carrier family 29 (nucleoside transporter), member 1; slc29a1
Equilibrative nucleoside transporter 1; ent1
DESCRIPTION
The uptake of nucleosides by transporters, such as SLC29A1, is essential for nucleotide synthesis by salvage pathways in cells that lack de novo biosynthetic pathways. Nucleoside transport also plays a key role in the regulation of many physiologic processes through its effect on adenosine concentration at the cell surface. There are 2 major families of nucleoside transporters, the concentrative and the equilibrative. Concentrative nucleoside transporters appear to be restricted in their distribution within cells and tissues and also in their selectivity of nucleoside permeants. In contrast, equilibrative nucleoside transporters appear to be widely distributed and have a broad substrate specificity. SLC29A1 is an equilibrative nucleoside transporter (Griffiths et al., 1997).CLONING
Griffiths et al. (1997) cloned the cDNA for the prototypic equilibrative transporter SLC29A1, which they called ENT1, from human placenta. The deduced 456-amino acid glycoprotein has 11 predicted transmembrane domains. Choi et al. (2000) cloned and sequenced the mouse Ent1 gene. Northern blot analysis detected expression of Ent1 in all tissues except skeletal muscle, with highest levels in liver, heart, testis, spleen, lung, kidney, and brain.GENE FUNCTION
Griffiths et al. (1997) found that both ENT1 and ENT2 (SLC29A2; 602110) showed saturable sodium-independent equilibrative transport of adenosine and uridine following expression in Xenopus oocytes. ENT1 was more efficient than ENT2 in transport of both substrates, and ENT1, but not ENT2, was sensitive to inhibition by nitrobenzylmercaptopurine riboside (NBMPR). Ward et al. (2000) found that human ENT1 showed higher affinity than ENT2 for transport of thymidine, adenosine, cytidine, and guanosine following expression in porcine kidney cells. However, ENT2 showed 4-fold higher affinity than ENT1 for inosine. The nucleobase hypoxanthine inhibited uridine uptake by ENT2, but had minimal effect on ENT1. Yao et al. (2001) expressed rat and human ENT1 and ENT2 in Xenopus oocytes and characterized their ability to transport three 3-prime-deoxy-nucleoside analogs used in human immunodeficiency virus (HIV) therapy: 2-prime,3-prime-dideoxycytidine (ddC), 3-prime-azido-3-prime-deoxythymidine (AZT), and 2-prime,3-prime-dideoxyinosine (ddI). Rat and human ENT2 transported ddC, AZT, and ddI, whereas rat and human ENT1 transported ddC and ddI only. Relative to uridine, ENT2 mediated substantially larger fluxes of ddC and ddI compared with ENT1. Fusion of the N-terminal half of rat Ent2 with rat Ent1 allowed Ent1 to transport AZT and enhanced its uptake of ddC and ddI, indicating that the N-terminal region of ENT proteins is the major site of 3-prime-deoxy-nucleoside interaction. SenGupta et al. (2002) found that mutation of gly179 in transmembrane domain 5 of human ENT1 to leu, cys, or val abolished transport of nucleoside analogs in a yeast nucleoside transporter assay. These mutations had no effect on targeting of the transporter to the plasma membrane. More conservative mutations, such as gly179 to ala or ser, preserved both targeting and transport activity of ENT1 in yeast, although the gly179-to-ala mutation was associated with reduced uridine transport compared with wildtype ENT1 and a small but significantly reduced sensitivity to NBMPR. Point mutations at gly184 resulted in poor targeting of ENT1 to the plasma membrane and, consequently, little or no transport activity ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602193 was added.