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Gene Review

AKR1  -  Akr1p

Saccharomyces cerevisiae S288c

Synonyms: Ankyrin repeat-containing protein AKR1, D9954.9, Palmitoyltransferase AKR1, YD9230B.03C, YDR264C
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High impact information on AKR1

  • Identification of the protein acyltransferases Erf2/Erf4 and Akr1 in yeast has provided new insight into the palmitoylation reaction [1].
  • Akr1p, purified to near homogeneity from yeast membranes, catalyzes Yck2p palmitoylation in vitro, indicating that Akr1p is itself a PTase [2].
  • Mutations introduced into the Akr1p DHHC-CRD eliminate both the trans- and autopalmitoylation activities, indicating a central participation of this conserved sequence in the enzymatic reaction [2].
  • The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase [2].
  • Interestingly, Iqg1p shows two-hybrid interactions with the ankyrin repeat-containing protein, Akr1p (Kao, L.-R., J. Peterson, J. Ruiru, L. Bender, and A. Bender. 1996. Mol. Cell. Biol. 16:168-178), which inhibits pheromone signaling and appears to promote cytokinesis and/or trafficking [3].

Biological context of AKR1


Anatomical context of AKR1

  • First, when receptor synthesis is shut off, akr1 delta cells retain the ability to mate longer than do AKR1 cells [8].

Associations of AKR1 with chemical compounds


Regulatory relationships of AKR1

  • We therefore propose that Akr1p negatively affects the activity of a protein that both controls cell shape and contributes to the pheromone response pathway upstream of Ste20p but downstream of G beta gamma [4].

Other interactions of AKR1

  • Although the elevated signalling is eliminated by deletion of Ste20p (or components downstream of Ste20p), the growth and morphological abnormalities of cells lacking Akr1p are not rescued by deletion of any of the known pheromone response pathway components [4].
  • Cells from which AKR1 had been deleted were alive but misshapen at 30 degrees C and inviable at 37 degrees C. During a screen for mutants that required one or more copies of wild-type AKR1 for survival at 30 degrees C, we isolated mutations in GPA1, which encodes the G alpha subunit of the pheromone receptor-coupled G protein [5].
  • Second, Ste3p half-life is increased by greater than 5-fold in akr1 delta cells compared with AKR1 cells [8].
  • In contrast, akr1 delta cells cannot carry out ligand-mediated endocytosis of Ste2p [8].
  • In vitro experiments revealed that Akr1 indeed acts as a protein acyltransferase for Lcb4 [7].

Analytical, diagnostic and therapeutic context of AKR1


  1. Palmitoylation of intracellular signaling proteins: regulation and function. Smotrys, J.E., Linder, M.E. Annu. Rev. Biochem. (2004) [Pubmed]
  2. The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase. Roth, A.F., Feng, Y., Chen, L., Davis, N.G. J. Cell Biol. (2002) [Pubmed]
  3. Iqg1p, a yeast homologue of the mammalian IQGAPs, mediates cdc42p effects on the actin cytoskeleton. Osman, M.A., Cerione, R.A. J. Cell Biol. (1998) [Pubmed]
  4. AKR1 encodes a candidate effector of the G beta gamma complex in the Saccharomyces cerevisiae pheromone response pathway and contributes to control of both cell shape and signal transduction. Pryciak, P.M., Hartwell, L.H. Mol. Cell. Biol. (1996) [Pubmed]
  5. Interactions between the ankyrin repeat-containing protein Akr1p and the pheromone response pathway in Saccharomyces cerevisiae. Kao, L.R., Peterson, J., Ji, R., Bender, L., Bender, A. Mol. Cell. Biol. (1996) [Pubmed]
  6. Akr1p and the type I casein kinases act prior to the ubiquitination step of yeast endocytosis: Akr1p is required for kinase localization to the plasma membrane. Feng, Y., Davis, N.G. Mol. Cell. Biol. (2000) [Pubmed]
  7. Long-chain base kinase Lcb4 Is anchored to the membrane through its palmitoylation by Akr1. Kihara, A., Kurotsu, F., Sano, T., Iwaki, S., Igarashi, Y. Mol. Cell. Biol. (2005) [Pubmed]
  8. The ankyrin repeat-containing protein Akr1p is required for the endocytosis of yeast pheromone receptors. Givan, S.A., Sprague, G.F. Mol. Biol. Cell (1997) [Pubmed]
  9. The aldo-keto reductase superfamily homepage. Hyndman, D., Bauman, D.R., Heredia, V.V., Penning, T.M. Chem. Biol. Interact. (2003) [Pubmed]
  10. Transmembrane topology of the protein palmitoyl transferase Akr1. Politis, E.G., Roth, A.F., Davis, N.G. J. Biol. Chem. (2005) [Pubmed]
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