Q8IDM6 · ENT1_PLAF7
- ProteinNucleoside transporter 1
- GeneNT1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids422 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Sodium-independent nucleoside and nucleobase transporter with a broad substrate specificity (PubMed:10744765, PubMed:10861212, PubMed:16751273, PubMed:18639591, PubMed:36977719, PubMed:25602169, PubMed:38113238, PubMed:31876139).
Plays a key role in the utilization of host purine sources by P.falciparum during intraerythrocytic development enabling parasite growth in the presence of physiological concentrations of adenosine, inosine, guanine, guanosine, xanthine and hypoxanthine (PubMed:16751273, PubMed:18639591).
Essential for parasite transition from ring to trophozoite or from trophozoite to schizont stage but not for erythrocyte invasion by merozoites (PubMed:16751273).
Plays a key role in the utilization of host purine sources by P.falciparum during intraerythrocytic development enabling parasite growth in the presence of physiological concentrations of adenosine, inosine, guanine, guanosine, xanthine and hypoxanthine (PubMed:16751273, PubMed:18639591).
Essential for parasite transition from ring to trophozoite or from trophozoite to schizont stage but not for erythrocyte invasion by merozoites (PubMed:16751273).
Miscellaneous
With an efficiency similar to that for uridine, can mediate the cellular uptake of nucleoside analogs used in cancer chemotherapy: fludarabine (9-beta-D-arabinosyl-2-fluoroadenine), cladribine (2-chloro-2'-deoxyadenosine) and gemcitabine (2',2'-difluoro-2'-deoxycytidine) (PubMed:10861212).
Unlike the mammalian transporters, can efficiently transport the anti-viral nucleoside analogs: AZT (3'-azido-3'-deoxythymidine), ddC (2',3'-dideoxycytidine) and ddI (2',3'-dideoxyinosine) (PubMed:10861212).
In contrast to the human transporter SLC29A1, has low sensitivity to the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) (PubMed:10744765).
Can transport 5-fluorouridine (PubMed:38113238).
Unlike the mammalian transporters, can efficiently transport the anti-viral nucleoside analogs: AZT (3'-azido-3'-deoxythymidine), ddC (2',3'-dideoxycytidine) and ddI (2',3'-dideoxyinosine) (PubMed:10861212).
In contrast to the human transporter SLC29A1, has low sensitivity to the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) (PubMed:10744765).
Can transport 5-fluorouridine (PubMed:38113238).
Catalytic activity
- inosine(in) = inosine(out)This reaction proceeds in the backward direction.
- adenosine(in) = adenosine(out)This reaction proceeds in the backward direction.
- hypoxanthine(out) = hypoxanthine(in)
- guanosine(in) = guanosine(out)This reaction proceeds in the backward direction.
- guanine(out) = guanine(in)
- thymidine(in) = thymidine(out)This reaction proceeds in the backward direction.
- uridine(out) = uridine(in)
- uracil(in) = uracil(out)This reaction proceeds in the backward direction.
- thymine(out) = thymine(in)
- adenine(out) = adenine(in)
- cytosine(out) = cytosine(in)
- xanthine(out) = xanthine(in)
Activity regulation
GSK4 (5-methyl-N-[2-(2-oxo-1-azepanyl)ethyl]-2-phenyl-1,3-oxazole-4-carbox-amide) disrupts the transport activity at 500 nM (PubMed:36977719).
Inhibited partially by 10 uM dipyridamole (PubMed:10744765).
Inhibited partially by N,N'-1,3-benzothiazole-2,6-diyldi(2-furamide), 2-bromo-N-(4-[1,3]oxazolo[4,5-b]pyridin-2-ylphenyl)benzamide, 4-methyl-7-[(3,4,5-trimethoxybenzyl)oxy]-2H-chromen-2-one, 2-(1-methyl-1H-indol-3-yl)-2-oxo-N-[4-(pyrrolidin-1-ylcarbonyl)phenyl]acet amide and 2-[2-(2-methylphenyl)vinyl]-4(3H)-quinazolinone (PubMed:25602169).
Inhibited partially by 10 uM dipyridamole (PubMed:10744765).
Inhibited partially by N,N'-1,3-benzothiazole-2,6-diyldi(2-furamide), 2-bromo-N-(4-[1,3]oxazolo[4,5-b]pyridin-2-ylphenyl)benzamide, 4-methyl-7-[(3,4,5-trimethoxybenzyl)oxy]-2H-chromen-2-one, 2-(1-methyl-1H-indol-3-yl)-2-oxo-N-[4-(pyrrolidin-1-ylcarbonyl)phenyl]acet amide and 2-[2-(2-methylphenyl)vinyl]-4(3H)-quinazolinone (PubMed:25602169).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
13.2 μM | adenosine | |||||
320 μM | adenosine | |||||
320 μM | adenine | |||||
410 μM | hypoxanthine | |||||
3500 μM | uridine | |||||
253 μM | inosine |
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | plasma membrane | |
Molecular Function | nucleoside transmembrane transporter activity | |
Biological Process | adenosine transport | |
Biological Process | purine nucleobase transport |
Keywords
- Biological process
Names & Taxonomy
Protein names
- Recommended nameNucleoside transporter 1
- Short namesPfNT1
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Sar > Alveolata > Apicomplexa > Aconoidasida > Haemosporida > Plasmodiidae > Plasmodium > Plasmodium (Laverania)
Accessions
- Primary accessionQ8IDM6
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-31 | Cytoplasmic | ||||
Sequence: MSTGKESSKAYADIESRGDYKDDGKKGSTLS | ||||||
Transmembrane | 32-58 | Helical | ||||
Sequence: SKQHFMLSLTFILIGLSSLNVWNTALG | ||||||
Topological domain | 59-61 | Extracellular | ||||
Sequence: LNI | ||||||
Transmembrane | 62-78 | Helical | ||||
Sequence: NFKYNTFQITGLVCSSI | ||||||
Topological domain | 79-87 | Cytoplasmic | ||||
Sequence: VALFVEIPK | ||||||
Transmembrane | 88-110 | Helical | ||||
Sequence: IMLPFLLGGLSILCAGFQISHSF | ||||||
Topological domain | 111-112 | Extracellular | ||||
Sequence: FT | ||||||
Transmembrane | 113-143 | Helical | ||||
Sequence: DTQFDTYCLVAFIVIGVVAGLAQTIAFNIGS | ||||||
Topological domain | 144-149 | Cytoplasmic | ||||
Sequence: TMEDNM | ||||||
Transmembrane | 150-173 | Helical | ||||
Sequence: GGYMSAGIGISGVFIFVINLLLDQ | ||||||
Topological domain | 174-184 | Extracellular | ||||
Sequence: FVSPEKHYGVN | ||||||
Transmembrane | 185-209 | Helical | ||||
Sequence: KAKLLYLYIICELCLILAIVFCVCN | ||||||
Topological domain | 210-229 | Cytoplasmic | ||||
Sequence: LDLTNKNNKKDEENKENNAT | ||||||
Transmembrane | 230-269 | Helical | ||||
Sequence: LSYMELFKDSYKAILTMFLVNWLTLQLFPGVGHKKWQESH | ||||||
Topological domain | 270-272 | Extracellular | ||||
Sequence: NIS | ||||||
Transmembrane | 273-295 | Helical | ||||
Sequence: DYNVTIIVGMFQVFDFLSRYPPN | ||||||
Topological domain | 296-308 | Cytoplasmic | ||||
Sequence: LTHIKIFKNFTFS | ||||||
Transmembrane | 309-331 | Helical | ||||
Sequence: LNKLLVANSLRLLFIPWFILNAC | ||||||
Topological domain | 332-339 | Extracellular | ||||
Sequence: VDHPFFKN | ||||||
Transmembrane | 340-367 | Helical | ||||
Sequence: IVQQCVCMAMLAFTNGWFNTVPFLVFVK | ||||||
Topological domain | 368-374 | Cytoplasmic | ||||
Sequence: ELKKAKK | ||||||
Transmembrane | 375-397 | Helical | ||||
Sequence: KKEIEIISTFLVIAMFVGLFCGI | ||||||
Topological domain | 398-422 | Extracellular | ||||
Sequence: WTTYIYNLFNIVLPKPDLPPIDVTQ |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Parasites are not viable if adenosine, inosine, guanine, guanosine, xanthine or hypoxanthine are present at concentrations below 50 uM and require higher concentrations of hypoxanthine, adenosine or inosine to progress beyond the ring stage of development (PubMed:16751273, PubMed:18639591).
Reduced uptake of hypoxanthine and adenosine (PubMed:25602169).
Reduced parasite growth with xanthine as the sole purine source (PubMed:25602169).
Reduced uptake of hypoxanthine and adenosine (PubMed:25602169).
Reduced parasite growth with xanthine as the sole purine source (PubMed:25602169).
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | 36 | no significant effects on affinity for hypoxanthine, inosine, adenine or adenosine. No significant effects on affinity for hypoxanthine, inosine, adenine or adenosine; when associated with I-129 | ||||
Sequence: F → S | ||||||
Mutagenesis | 48 | No significant growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. | ||||
Sequence: S → C | ||||||
Mutagenesis | 49 | Abolishes inosine binding. | ||||
Sequence: S → A | ||||||
Mutagenesis | 49 | No significant growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. | ||||
Sequence: S → C | ||||||
Mutagenesis | 50 | Reduces the binding affinity of GSK4 inhibitor. | ||||
Sequence: L → A | ||||||
Mutagenesis | 50 | Results in growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. Abolishes adenosine and uridine transport. | ||||
Sequence: L → C | ||||||
Mutagenesis | 51 | No significant growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. | ||||
Sequence: N → C | ||||||
Mutagenesis | 52 | No significant growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. | ||||
Sequence: V → C | ||||||
Mutagenesis | 53 | Reduces inosine binding and abolishes transport activity. Abolishes the GSK4 inhibitor binding. | ||||
Sequence: W → A | ||||||
Mutagenesis | 53 | Results in severe growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. | ||||
Sequence: W → C | ||||||
Mutagenesis | 73 | Reduces the binding affinity of GSK4 inhibitor. | ||||
Sequence: L → A | ||||||
Natural variant | 92 | no significant effects on affinity for hypoxanthine, inosine, adenine or adenosine | ||||
Sequence: F → I | ||||||
Natural variant | 129 | no significant effects on affinity for hypoxanthine, inosine, adenine or adenosine; when associated with S-36 or F-133 | ||||
Sequence: V → I | ||||||
Natural variant | 133 | no significant effects on affinity for hypoxanthine, inosine, adenine or adenosine; when associated with I-129 | ||||
Sequence: L → F | ||||||
Mutagenesis | 134 | No significant growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. | ||||
Sequence: A → C | ||||||
Mutagenesis | 135 | Abolishes inosine binding and transport activity. Reduces the binding affinity of GSK4 inhibitor. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 135 | Results in severe growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. Abolishes adenosine and uridine transport. | ||||
Sequence: Q → C | ||||||
Mutagenesis | 136 | No significant growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. | ||||
Sequence: T → C | ||||||
Mutagenesis | 137 | No significant growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. | ||||
Sequence: I → C | ||||||
Mutagenesis | 139 | Reduces the binding affinity of GSK4 inhibitor. | ||||
Sequence: F → A | ||||||
Natural variant | 197 | modestly increases affinity for adenine; no significant effects on affinity for hypoxanthine, inosine or adenosine | ||||
Sequence: L → F | ||||||
Natural variant | 284 | modestly decreases affinity for hypoxanthine and adenine; no significant effects on affinity for inosine or adenosine | ||||
Sequence: Q → E | ||||||
Mutagenesis | 286 | Results in severe growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. | ||||
Sequence: F → C | ||||||
Mutagenesis | 287 | Abolishes inosine binding and transport activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 287 | Results in severe growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. Abolishes adenosine and uridine transport. | ||||
Sequence: D → C | ||||||
Mutagenesis | 288 | No significant growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. | ||||
Sequence: F → C | ||||||
Mutagenesis | 289 | No significant growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. | ||||
Sequence: L → C | ||||||
Mutagenesis | 290 | Results in severe growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. | ||||
Sequence: S → C | ||||||
Mutagenesis | 291 | Abolishes transport activity while maintaining inosine binding. | ||||
Sequence: R → A | ||||||
Mutagenesis | 291 | Results in severe growth defects in adenosine-dependent proliferation assay when transporter expressed in purine auxotrophic yeast strain. Abolishes adenosine and uridine transport. | ||||
Sequence: R → C | ||||||
Natural variant | 317 | no significant effects on affinity for hypoxanthine, inosine, adenine or adenosine | ||||
Sequence: S → T | ||||||
Natural variant | 345 | no significant effects on affinity for hypoxanthine, inosine, adenine or adenosine | ||||
Sequence: V → I | ||||||
Natural variant | 351 | modestly decreases affinity for hypoxanthine and adenine; no significant effects on affinity for inosine or adenosine | ||||
Sequence: A → S | ||||||
Natural variant | 385 | no significant effects on affinity for hypoxanthine, inosine, adenine or adenosine | ||||
Sequence: L → I | ||||||
Mutagenesis | 390 | Reduces the binding affinity of GSK4 inhibitor. | ||||
Sequence: F → A | ||||||
Natural variant | 394 | modestly decreases affinity for hypoxanthine and adenine; no significant effects on affinity for inosine or adenosine | ||||
Sequence: F → L | ||||||
Natural variant | 418 | no significant effects on affinity for hypoxanthine, inosine, adenine or adenosine | ||||
Sequence: I → M |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 12 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000458985 | 1-422 | UniProt | Nucleoside transporter 1 | |||
Sequence: MSTGKESSKAYADIESRGDYKDDGKKGSTLSSKQHFMLSLTFILIGLSSLNVWNTALGLNINFKYNTFQITGLVCSSIVALFVEIPKIMLPFLLGGLSILCAGFQISHSFFTDTQFDTYCLVAFIVIGVVAGLAQTIAFNIGSTMEDNMGGYMSAGIGISGVFIFVINLLLDQFVSPEKHYGVNKAKLLYLYIICELCLILAIVFCVCNLDLTNKNNKKDEENKENNATLSYMELFKDSYKAILTMFLVNWLTLQLFPGVGHKKWQESHNISDYNVTIIVGMFQVFDFLSRYPPNLTHIKIFKNFTFSLNKLLVANSLRLLFIPWFILNACVDHPFFKNIVQQCVCMAMLAFTNGWFNTVPFLVFVKELKKAKKKKEIEIISTFLVIAMFVGLFCGIWTTYIYNLFNIVLPKPDLPPIDVTQ | |||||||
Modified residue (large scale data) | 2 | PTMeXchange | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 3 | PTMeXchange | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 8 | PTMeXchange | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 16 | PTMeXchange | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 28 | PTMeXchange | Phosphoserine | ||||
Sequence: S |
Proteomic databases
PTM databases
Expression
Developmental stage
Expressed throughout intraerythrocytic life cycle, the level increases significantly from the ring to the early trophozoite stage and remains relatively constant through the late schizont stage (at protein level) (PubMed:11682491).
The amount of protein does not coincide with the transcript levels, which are maximal in early trophozoites and subsequently down-regulated in late stage trophozoites and schizonts (PubMed:10744765).
The amount of protein does not coincide with the transcript levels, which are maximal in early trophozoites and subsequently down-regulated in late stage trophozoites and schizonts (PubMed:10744765).
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Sequence similarities
Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length422
- Mass (Da)47,631
- Last updated2003-03-01 v1
- ChecksumD9B7F277D7C68BC8
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AL844509 EMBL· GenBank· DDBJ | CAD52595.1 EMBL· GenBank· DDBJ | Genomic DNA |