TPO1/YLL028W Summary Help

Standard Name TPO1 1
Systematic Name YLL028W
Feature Type ORF, Verified
Description Polyamine transporter of the major facilitator superfamily; member of the 12-spanner drug:H(+) antiporter DHA1 family; recognizes spermine, putrescine, and spermidine; catalyzes uptake of polyamines at alkaline pH and excretion at acidic pH; during oxidative stress exports spermine, spermidine from the cell, which controls timing of expression of stress-responsive genes; phosphorylation enhances activity and sorting to the plasma membrane (1, 2, 3, 4, 5 and see Summary Paragraph)
Name Description Transporter of POlyamines 1
Chromosomal Location
ChrXII:84804 to 86564 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All TPO1 GO evidence and references
  View Computational GO annotations for TPO1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 2 genes
Resources
Classical genetics
null
overexpression
reduction of function
unspecified
Large-scale survey
null
overexpression
Resources
91 total interaction(s) for 80 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 2
  • Affinity Capture-RNA: 1
  • Biochemical Activity: 4
  • PCA: 64
  • Protein-RNA: 1
  • Two-hybrid: 1

Genetic Interactions
  • Negative Genetic: 8
  • Phenotypic Enhancement: 1
  • Positive Genetic: 8
  • Synthetic Growth Defect: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 586
Molecular Weight (Da) 64,272
Isoelectric Point (pI) 6.86
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXII:84804 to 86564 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1761 84804..86564 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | TCDB | UniProtKB
Primary SGDIDS000003951
SUMMARY PARAGRAPH for TPO1

The widespread biological phenomenon of multidrug resistance (MDR) poses serious challenges for the treatment of human cancers, and also of bacterial and fungal infections. MDR is typically associated with transport systems that catalyze the efflux of various compounds out of the cell. Among the most important MDR transporters are those belonging to the major facilitator superfamily (MFS). MFS-MDR transporters are found in Eucarya, Bacteria, and Archaea, and have been classified into two families based on the number of predicted transmembrane spans: The Drug:H+ Antiporter-1 (12-Spanner; DHA1) Family, TC 2.A.1.2, and the Drug:H+ Antiporter-2 (14-Spanner; DHA2) Family, TC 2.A.1.3 (6).

In S. cerevisiae, the DHA1 family comprises 12 genes involved in various biological processes: AQR1, QDR1, QDR2, QDR3, FLR1, DTR1, TPO1, TPO2, TPO3, TPO4, HOL1, and YHK8 (6). Aqr1p, Qdr1-3p, and Flr1p are plasma membrane proteins that serve as multidrug transporters (7, 8, 9, 10, 11, 12, 13). Aqr1p has also been implicated in the excretion of excess amino acids, and Qdr2p in the import of potassium ions (14, 15). Dtr1p, a putative dityrosine transporter, resides in the prospore membrane and functions in spore wall synthesis (16, 17). Tpo1-4p are membrane proteins involved in the export of polyamines, including spermine, spermidine, and putrescine (2, 18). Hol1p participates in cation and alcohol transport (19, 20), and Yhk8p is a putative drug transporter requiring further experimental characterization (11, 21).

The 12 DHA1 family genes of S. cerevisiae are similar to several ion and amine transporters in human, including SLC22A5, SLC22A11, SLC22A13, SLC22A14, and SLC22A3, which function primarily in the elimination of drugs and other xenobiotics from various tissues. Mutations in the human genes have been implicated in Crohn's disease, hypoglycemia, and various myopathies.

Last updated: 2008-02-08 Contact SGD

References cited on this page View Complete Literature Guide for TPO1
1) Tomitori H, et al.  (1999) Identification of a gene for a polyamine transport protein in yeast. J Biol Chem 274(6):3265-7
2) Tomitori H, et al.  (2001) Multiple polyamine transport systems on the vacuolar membrane in yeast. Biochem J 353(Pt 3):681-8
3) Uemura T, et al.  (2005) Characteristics of the polyamine transporter TPO1 and regulation of its activity and cellular localization by phosphorylation. J Biol Chem 280(10):9646-52
4) Dias PJ, et al.  (2010) Evolution of the 12-Spanner Drug:H+ Antiporter DHA1 Family in Hemiascomycetous Yeasts. OMICS 14(6):701-10
5) Kruger A, et al.  (2013) Tpo1-mediated spermine and spermidine export controls cell cycle delay and times antioxidant protein expression during the oxidative stress response. EMBO Rep 14(12):1113-9
6) Gbelska Y, et al.  (2006) Evolution of gene families: the multidrug resistance transporter genes in five related yeast species. FEMS Yeast Res 6(3):345-55
7) Tenreiro S, et al.  (2002) AQR1 gene (ORF YNL065w) encodes a plasma membrane transporter of the major facilitator superfamily that confers resistance to short-chain monocarboxylic acids and quinidine in Saccharomyces cerevisiae. Biochem Biophys Res Commun 292(3):741-8
8) Nunes PA, et al.  (2001) Resistance and adaptation to quinidine in Saccharomyces cerevisiae: role of QDR1 (YIL120w), encoding a plasma membrane transporter of the major facilitator superfamily required for multidrug resistance. Antimicrob Agents Chemother 45(5):1528-34
9) Tenreiro S, et al.  (2005) The yeast multidrug transporter Qdr3 (Ybr043c): localization and role as a determinant of resistance to quinidine, barban, cisplatin, and bleomycin. Biochem Biophys Res Commun 327(3):952-9
10) Vargas RC, et al.  (2004) Saccharomyces cerevisiae multidrug transporter Qdr2p (Yil121wp): localization and function as a quinidine resistance determinant. Antimicrob Agents Chemother 48(7):2531-7
11) Goffeau A, et al.  (1997) Multidrug-resistant transport proteins in yeast: complete inventory and phylogenetic characterization of yeast open reading frames with the major facilitator superfamily. Yeast 13(1):43-54
12) Alarco AM, et al.  (1997) AP1-mediated multidrug resistance in Saccharomyces cerevisiae requires FLR1 encoding a transporter of the major facilitator superfamily. J Biol Chem 272(31):19304-13
13) Broco N, et al.  (1999) FLR1 gene (ORF YBR008c) is required for benomyl and methotrexate resistance in Saccharomyces cerevisiae and its benomyl-induced expression is dependent on pdr3 transcriptional regulator. Yeast 15(15):1595-608
14) Velasco I, et al.  (2004) Saccharomyces cerevisiae Aqr1 is an internal-membrane transporter involved in excretion of amino acids. Eukaryot Cell 3(6):1492-503
15) Vargas RC, et al.  (2007) Saccharomyces cerevisiae Multidrug Resistance Transporter Qdr2 Is Implicated in Potassium Uptake, Providing a Physiological Advantage to Quinidine-Stressed Cells. Eukaryot Cell 6(2):134-42
16) Felder T, et al.  (2002) Dtrlp, a multidrug resistance transporter of the major facilitator superfamily, plays an essential role in spore wall maturation in Saccharomyces cerevisiae. Eukaryot Cell 1(5):799-810
17) Iwamoto MA, et al.  (2005) Saccharomyces cerevisiae Sps1p regulates trafficking of enzymes required for spore wall synthesis. Eukaryot Cell 4(3):536-44
18) Albertsen M, et al.  (2003) Localization and function of the yeast multidrug transporter Tpo1p. J Biol Chem 278(15):12820-5
19) Gaber RF, et al.  (1990) HOL1 mutations confer novel ion transport in Saccharomyces cerevisiae. Mol Cell Biol 10(2):643-52
20) Wright MB, et al.  (1996) Amino acid substitutions in membrane-spanning domains of Hol1, a member of the major facilitator superfamily of transporters, confer nonselective cation uptake in Saccharomyces cerevisiae. J Bacteriol 178(24):7197-205
21) Barker KS, et al.  (2003) Identification of genes differentially expressed in association with reduced azole susceptibility in Saccharomyces cerevisiae. J Antimicrob Chemother 51(5):1131-40