RGD Reference Report - A conserved Na(+) binding site of the sodium-coupled neutral amino acid transporter 2 (SNAT2). - Rat Genome Database

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A conserved Na(+) binding site of the sodium-coupled neutral amino acid transporter 2 (SNAT2).

Authors: Zhang, Zhou  Albers, Thomas  Fiumera, Heather L  Gameiro, Armanda  Grewer, Christof 
Citation: Zhang Z, etal., J Biol Chem. 2009 Sep 11;284(37):25314-23. doi: 10.1074/jbc.M109.038422. Epub 2009 Jul 9.
RGD ID: 152995570
Pubmed: PMID:19589777   (View Abstract at PubMed)
PMCID: PMC2757233   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M109.038422   (Journal Full-text)

The SLC38 family of solute transporters mediates the coupled transport of amino acids and Na(+) into or out of cells. The structural basis for this coupled transport process is not known. Here, a profile-based sequence analysis approach was used, predicting a distant relationship with the SLC5/6 transporter families. Homology models using the LeuT(Aa) and Mhp1 transporters of known structure as templates were established, predicting the location of a conserved Na(+) binding site in the center of membrane helices 1 and 8. This homology model was tested experimentally in the SLC38 member SNAT2 by analyzing the effect of a mutation to Thr-384, which is predicted to be part of this Na(+) binding site. The results show that the T384A mutation not only inhibits the anion leak current, which requires Na(+) binding to SNAT2, but also dramatically lowers the Na(+) affinity of the transporter. This result is consistent with a previous analysis of the N82A mutant transporter, which has a similar effect on anion leak current and Na(+) binding and which is also expected to form part of the Na(+) binding site. In contrast, random mutations to other sites in the transporter had little or no effect on Na(+) affinity. Our results are consistent with a cation binding site formed by transmembrane helices 1 and 8 that is conserved among the SLC38 transporters as well as among many other bacterial and plant transporter families of unknown structure, which are homologous to SLC38.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc38a2Ratalanine transport involved_inIDA PMID:19589777UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc38a2Ratplasma membrane located_inIDA PMID:19589777UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc38a2Ratalanine:sodium symporter activity enablesIDA PMID:19589777UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Slc38a2  (solute carrier family 38, member 2)


Additional Information