Disease relevance of GTR1

• Recombinant Gtr1p and Gtr2p were purified as a complex from Escherichia coli [1].

High impact information on GTR1

• The complex contains two small GTPases (Gtr1p and Gtr2p) and three other proteins (Ybr077c, Ykr007w and Ltv1p) that are located in the late endosomal membrane [2].
• The latter phenotypes were shown to be due to a defect in Pi uptake, and the Gtr1 protein was found to be functionally associated with the Pho84 Pi transporter [3].
• In Saccharomyces cerevisiae, this gene is distal to the TUB3 locus on the left arm of chromosome XIII and is named GTR1 [3].
• Disruption of the GTR1 gene resulted in slow growth at 30 degrees C and no growth at 15 degrees C; other phenotypes resembled those of pho84 mutants and included constitutive synthesis of repressible acid phosphatase, reduced Pi transport activity, and resistance to arsenate [3].
• GTR1 encodes a protein consisting of 310 amino acid residues containing, in its N-terminal region, the characteristic tripartite consensus elements for binding GTP conserved in GTP-binding proteins, except for histidine in place of a widely conserved aspargine residue in element III [3].

Biological context of GTR1

• We found that gtr1-11 caused a single amino acid substitution in Gtr1p, forming S20L, which is a putative GDP-bound mutant protein, while Gtr1p has been reported to bind to GTP alone [4].
• A multiple sequence alignment indicated that RagA and RagB cannot be assigned to any of the known subfamilies of Ras-related GTPases but exhibit a 52% identity with a yeast protein (Gtr1) presumably involved in phosphate transport and/or cell growth [5].

Physical interactions of GTR1

• Gtr2p interacts with itself in the presence of Gtr1p [4].
• Gtr1p bound the Ran-binding domain of Yrb2p [1].

Other interactions of GTR1

• S. cerevisiae possesses a novel gene, GTR2, which is homologous to GTR1 [4].
• The other three genes, GTR1, PHO86 and PHO87, are also suggested to be involved in the P(i) uptake system [6].
• Furthermore, gtr1-11 suppressed the rna1-1, temperature-sensitive mutant of the Gsp1p GTPase-activating protein, but not the srp1-31, temperature-sensitive mutant of the S. cerevisiae importin alpha homologue. mtr1-2, srm1-1 and prp20-1 were also suppressed by overexpression of the mutated Gtr1p, Gtr1-11p [7].
• The association of Gtr1p with Rpc19p occurred in a GTP-form-specific manner [8].
• This genetic system has also led us to identify Gtr1 as an Meh1 interacting protein [9].

References