TPI1/YDR050C Summary Help

Standard Name TPI1 1
Systematic Name YDR050C
Feature Type ORF, Verified
Description Triose phosphate isomerase, abundant glycolytic enzyme; mRNA half-life is regulated by iron availability; transcription is controlled by activators Reb1p, Gcr1p, and Rap1p through binding sites in the 5' non-coding region; inhibition of Tpi1p activity by PEP (phosphoenolpyruvate) stimulates redox metabolism in respiring cells; E104D mutation in human TPI causes a rare autosomal disease (1, 2, 3, 4, 5 and see Summary Paragraph)
Name Description Triose-Phosphate Isomerase 1
Chromosomal Location
ChrIV:556472 to 555726 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All TPI1 GO evidence and references
  View Computational GO annotations for TPI1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 23 genes
Classical genetics
Large-scale survey
reduction of function
65 total interaction(s) for 52 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 25
  • Affinity Capture-RNA: 11
  • Affinity Capture-Western: 2
  • Co-crystal Structure: 2
  • Co-purification: 1
  • PCA: 7
  • Reconstituted Complex: 2
  • Two-hybrid: 1

Genetic Interactions
  • Negative Genetic: 8
  • Synthetic Growth Defect: 3
  • Synthetic Lethality: 3

Expression Summary
Length (a.a.) 248
Molecular Weight (Da) 26,795
Isoelectric Point (pI) 5.86
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrIV:556472 to 555726 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..747 556472..555726 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000002457

Glycolysis is the lysis, or splitting, of one molecule of glucose into two molecules of pyruvate, producing a net gain of two ATP molecules. Pyruvate can then be used in anaerobic (fermentation) or aerobic (respiration) metabolism. The glycolysis pathway and the genes involved are illustrated here.

During glycolysis, Tpi1p (triose phosphate isomerase) catalyzes the reversible interconversion of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (1, 6). It is required for growth on glucose as the sole carbon source (6). In Saccharomyces cerevisiae, Tpi1p is an abundant glycolytic enzyme that makes up about 2% of the soluble cellular protein (3).

Tpi1p functions as a homodimer (7) and the active site residues include Glu165, His95, and Lys12. The catalytic site Glu and His residues are thought to extract and donate protons during catalysis (7, 8). The sequence around the active site residues is fully conserved in a number of organisms including chicken, yeast and Trypanosoma brucei (9).

The expression of TPI1 may be regulated by the transcriptional activators Reb1p, Rap1p, and Gcr1p that bind sites in the 5' non-coding region of TPI1. However, Gcr1p is able to activate gene expression in the absence of Reb1p or Rap1p. Therefore, it has been suggested that Gcr1p is required for activation of TPI1 and that the role of Reb1p and Rap1p, which bind adjacent to Gcr1p-binding sites, may be to facilitate or modulate Gcr1p binding in vivo (3).

In humans, deficiency of triosephosphate isomerase (TPI1) (OMIM) causes haemolytic anaemia coupled with progressive, severe neurological disorder (10).

Last updated: 2005-08-09 Contact SGD

References cited on this page View Complete Literature Guide for TPI1
1) Alber T and Kawasaki G  (1982) Nucleotide sequence of the triose phosphate isomerase gene of Saccharomyces cerevisiae. J Mol Appl Genet 1(5):419-34
2) Krieger K and Ernst JF  (1994) Iron regulation of triosephosphate isomerase transcript stability in the yeast Saccharomyces cerevisiae. Microbiology 140 ( Pt 5)():1079-84
3) Scott EW and Baker HV  (1993) Concerted action of the transcriptional activators REB1, RAP1, and GCR1 in the high-level expression of the glycolytic gene TPI. Mol Cell Biol 13(1):543-50
4) Gruning NM, et al.  (2011) Pyruvate Kinase Triggers a Metabolic Feedback Loop that Controls Redox Metabolism in Respiring Cells. Cell Metab 14(3):415-27
5) Rodriguez-Almazan C, et al.  (2008) Structural basis of human triosephosphate isomerase deficiency: mutation E104D is related to alterations of a conserved water network at the dimer interface. J Biol Chem 283(34):23254-63
6) Compagno C, et al.  (2001) Alterations of the glucose metabolism in a triose phosphate isomerase-negative Saccharomyces cerevisiae mutant. Yeast 18(7):663-70
7) Lolis E, et al.  (1990) Structure of yeast triosephosphate isomerase at 1.9-A resolution. Biochemistry 29(28):6609-18
8) Joseph-McCarthy D, et al.  (1994) Crystal structure of the mutant yeast triosephosphate isomerase in which the catalytic base glutamic acid 165 is changed to aspartic acid. Biochemistry 33(10):2824-9
9) Wierenga RK, et al.  (1992) Comparison of the refined crystal structures of liganded and unliganded chicken, yeast and trypanosomal triosephosphate isomerase. J Mol Biol 224(4):1115-26
10) Olah J, et al.  (2002) Triosephosphate isomerase deficiency: a neurodegenerative misfolding disease. Biochem Soc Trans 30(2):30-8