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Gene Review

TFS1  -  Tfs1p

Saccharomyces cerevisiae S288c

Synonyms: CDC25 suppressor 1, CPY inhibitor, Carboxypeptidase Y inhibitor, DKA1, I(C), ...
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Disease relevance of TFS1


High impact information on TFS1

  • The molecular analysis of the NSP1 protein points to a two domain model: a nonessential domain (the first 603 amino acids) composed of repetitive sequences common to other nuclear proteins and an essential, carboxy-terminal domain (residues 604-823) mediating the vital function of NSP1 [3].
  • The affinity-purified antibody against the yeast NSP1 protein stained the nucleus and centrosomes of mammalian MDCK (Madin Darby canine kidney) cells in indirect immunofluorescence [4].
  • The N-terminal acetylation status of Tfs1p, Act1p, and Rnr4p in both wild type and nat3Delta was confirmed by tandem mass spectrometry [5].
  • The involvement of Nat3p and Tfs1p in PKA signaling was supported by caffeine growth inhibition studies [5].
  • We conclude that the NatB-dependent acetylation of Tfs1p appears to be essential for its inhibitory activity on CPY as well its role in regulating the PKA pathway [5].

Biological context of TFS1


Anatomical context of TFS1

  • Consistent with a cytoplasmic localization, Ic is soluble and contains no sequences which could serve as potential signals for transport into the endoplasmic reticulum [9].
  • Only one form of active carboxypeptidase Y is found to be present in the proteolytically activated extracts, i.e., no polypeptide fragments of carboxypeptidase Y-inhibitor remain bound to the enzyme after it has been activated by proteinase B. In vacuoles prepared from spheroplasts no inactive carboxypeptidase Y can be detected [10].

Associations of TFS1 with chemical compounds

  • The stress-induced carboxypeptidase Y (CPY) inhibitor and phosphatidylethanolamine-binding protein family member Tfs1p was identified as a novel NatB substrate [5].
  • Furthermore it was found that unacetylated Tfs1p expressed in nat3Delta showed an approximately 100-fold decrease in CPY inhibition compared with the acetylated form, indicating that the N-terminal acetyl group is essential for CPY inhibition by Tfs1p [5].
  • Considering their homology to Ic, it is tempting to speculate that they may also be inhibitors of serine carboxypeptidases [9].
  • However, deletion of tfs1 results in slow growth and increased sensitivity to the drug 6-azauracil, a phenotype similar to that of a S. cerevisiae strain deleted for the gene encoding TFIIS [8].

Regulatory relationships of TFS1

  • The ability of TFS1 to suppress cdc25 is allele specific: the temperature-sensitive cdc25-1 mutation is suppressed efficiently but the cdc25-5 mutation and two disruption mutations are only partially suppressed [6].
  • At pH 5, the carboxypeptidase Y-inhibitor complex is activated both by proteinase A (EC and B. Yeast proteinases are activated in a crude extract by incubation at pH 5 [3] [10].

Other interactions of TFS1


Analytical, diagnostic and therapeutic context of TFS1

  • Sequence analysis of the cloned NSP1 locus suggests that the NSP1 product contains 269 amino acids and has a membrane-spanning domain at its carboxyl terminus [11].


  1. Tfs1p, a member of the PEBP family, inhibits the Ira2p but not the Ira1p Ras GTPase-activating protein in Saccharomyces cerevisiae. Chautard, H., Jacquet, M., Schoentgen, F., Bureaud, N., Bénédetti, H. Eukaryotic Cell (2004) [Pubmed]
  2. From structure to function: possible biological roles of a new widespread protein family binding hydrophobic ligands and displaying a nucleotide binding site. Schoentgen, F., Jollès, P. FEBS Lett. (1995) [Pubmed]
  3. NSP1: a yeast nuclear envelope protein localized at the nuclear pores exerts its essential function by its carboxy-terminal domain. Nehrbass, U., Kern, H., Mutvei, A., Horstmann, H., Marshallsay, B., Hurt, E.C. Cell (1990) [Pubmed]
  4. A novel nucleoskeletal-like protein located at the nuclear periphery is required for the life cycle of Saccharomyces cerevisiae. Hurt, E.C. EMBO J. (1988) [Pubmed]
  5. The stress-induced Tfs1p requires NatB-mediated acetylation to inhibit carboxypeptidase Y and to regulate the protein kinase A pathway. Caesar, R., Blomberg, A. J. Biol. Chem. (2004) [Pubmed]
  6. TFS1: a suppressor of cdc25 mutations in Saccharomyces cerevisiae. Robinson, L.C., Tatchell, K. Mol. Gen. Genet. (1991) [Pubmed]
  7. The multiple site binding of carboxypeptidase Y inhibitor (IC) to the cognate proteinase. Implications for the biological roles of the phosphatidylethanolamine-binding protein. Mima, J., Narita, Y., Chiba, H., Hayashi, R. J. Biol. Chem. (2003) [Pubmed]
  8. Isolation and characterization of the Schizosaccharomyces pombe gene encoding transcript elongation factor TFIIS. Williams, L.A., Kane, C.M. Yeast (1996) [Pubmed]
  9. A high-affinity inhibitor of yeast carboxypeptidase Y is encoded by TFS1 and shows homology to a family of lipid binding proteins. Bruun, A.W., Svendsen, I., Sørensen, S.O., Kielland-Brandt, M.C., Winther, J.R. Biochemistry (1998) [Pubmed]
  10. Interaction of proteinases and their inhibitors from yeast. Activation of carboxypeptidase Y. Fischer, E.P., Holzer, H. Biochim. Biophys. Acta (1980) [Pubmed]
  11. Cloning and characterization of NSP1, a locus encoding a component of a CDC25-dependent, nutrient-responsive pathway in Saccharomyces cerevisiae. Tripp, M.L., Bouchard, R.A., Piñón, R. Mol. Microbiol. (1989) [Pubmed]
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