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Gene Review

MID2  -  Mid2p

Saccharomyces cerevisiae S288c

Synonyms: Cell wall integrity sensor MID2, KAI1, L8543.19, Mating pheromone-induced death protein 2, Protein kinase A interference protein 1, ...
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Disease relevance of MID2


High impact information on MID2

  • No genetic interactions were found between mid2 and the related gene mid1 [2].
  • Here, we identified a protein Mid2p on the basis of its sequence similarity to S. pombe Mid1p, Saccharomyces cerevisiae Bud4p, and Candida albicans Int1p [2].
  • Our data suggest that in yeast, O mannosylation increases the activity of Wsc1p, Wsc2p, and Mid2p by enhancing their stability [3].
  • Aberrant processing of the WSC family and Mid2p cell surface sensors results in cell death of Saccharomyces cerevisiae O-mannosylation mutants [3].
  • We demonstrate that Mid2 is not mannosylated in a pmt2 mutant and that this modification is important for signaling by Mid2 [4].

Biological context of MID2

  • A role for MID2 in the cell integrity pathway is further supported by the finding that MID2 is required for induction of Mpk1p tyrosine phosphorylation during exposure to alpha-factor, calcofluor white, or high temperature [5].
  • In addition, we have identified an open reading frame, MTL1, which encodes a protein with both structural and functional similarity to Mid2p [5].
  • We conclude that Hcs77 is dedicated to signaling cell wall stress during vegetative growth and that Mid2 participates in this signaling, but its primary role is in signaling wall stress during pheromone-induced morphogenesis [6].
  • Overexpression of MID2 suppresses the profilin-deficient phenotype of yeast cells [7].
  • A high-copy-number plasmid containing MID2, which encodes a potential transmembrane protein involved in cell cycle control, suppresses the abnormal growth, actin distribution, alpha-factor maturation and the accumulation of intracellular membranous structures in pfy1delta cells [7].

Anatomical context of MID2


Associations of MID2 with chemical compounds


Physical interactions of MID2


Regulatory relationships of MID2


Other interactions of MID2

  • It has been proposed that Wsc1p and Mid2p act upstream of the protein kinase C (PKC) pathway to function as mechanosensors of cell wall stress [8].
  • The slight viability defect of rgd1 in minimal medium, which was exacerbated by mid2, was not osmoremediated [11].
  • To further explore Mid2p signalling a two-hybrid screen was done using the cytoplasmic tail of Mid2p; this identified ZEO1 (YOL109w), encoding a 12 kDa peripheral membrane protein that localizes to the plasma membrane [13].
  • Our data are consistent with a role for Mid2p in sensing cell wall stress and in activation of a response that includes both increased chitin synthesis and the Mpk1p mitogen-activated protein kinase cell integrity pathway [5].
  • MID2 was isolated as a multicopy activator of the Skn7p transcription factor [5].

Analytical, diagnostic and therapeutic context of MID2

  • Northern blot analysis showed that the expression of MID2 is stimulated threefold by mating pheromone [14].
  • Downregulation of KAI1 has been found to be clinically associated with metastatic progression in a variety of cancers, whereas overexpression of CD82 specifically suppresses tumor metastasis in various animal models [1].


  1. Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Bandyopadhyay, S., Zhan, R., Chaudhuri, A., Watabe, M., Pai, S.K., Hirota, S., Hosobe, S., Tsukada, T., Miura, K., Takano, Y., Saito, K., Pauza, M.E., Hayashi, S., Wang, Y., Mohinta, S., Mashimo, T., Iiizumi, M., Furuta, E., Watabe, K. Nat. Med. (2006) [Pubmed]
  2. Mid2p stabilizes septin rings during cytokinesis in fission yeast. Berlin, A., Paoletti, A., Chang, F. J. Cell Biol. (2003) [Pubmed]
  3. Aberrant processing of the WSC family and Mid2p cell surface sensors results in cell death of Saccharomyces cerevisiae O-mannosylation mutants. Lommel, M., Bagnat, M., Strahl, S. Mol. Cell. Biol. (2004) [Pubmed]
  4. Wsc1 and Mid2 are cell surface sensors for cell wall integrity signaling that act through Rom2, a guanine nucleotide exchange factor for Rho1. Philip, B., Levin, D.E. Mol. Cell. Biol. (2001) [Pubmed]
  5. Saccharomyces cerevisiae mid2p is a potential cell wall stress sensor and upstream activator of the PKC1-MPK1 cell integrity pathway. Ketela, T., Green, R., Bussey, H. J. Bacteriol. (1999) [Pubmed]
  6. Mid2 is a putative sensor for cell integrity signaling in Saccharomyces cerevisiae. Rajavel, M., Philip, B., Buehrer, B.M., Errede, B., Levin, D.E. Mol. Cell. Biol. (1999) [Pubmed]
  7. Overexpression of MID2 suppresses the profilin-deficient phenotype of yeast cells. Marcoux, N., Bourbonnais, Y., Charest, P.M., Pallotta, D. Mol. Microbiol. (1998) [Pubmed]
  8. The Rho3 and Rho4 small GTPases interact functionally with Wsc1p, a cell surface sensor of the protein kinase C cell-integrity pathway in Saccharomyces cerevisiae. Fernandes, H., Roumanie, O., Claret, S., Gatti, X., Thoraval, D., Doignon, F., Crouzet, M. Microbiology (Reading, Engl.) (2006) [Pubmed]
  9. Regulatory mechanisms for modulation of signaling through the cell integrity Slt2-mediated pathway in Saccharomyces cerevisiae. Martín, H., Rodríguez-Pachón, J.M., Ruiz, C., Nombela, C., Molina, M. J. Biol. Chem. (2000) [Pubmed]
  10. Cell integrity signaling activation in response to hyperosmotic shock in yeast. García-Rodríguez, L.J., Valle, R., Durán, A., Roncero, C. FEBS Lett. (2005) [Pubmed]
  11. RGD1 genetically interacts with MID2 and SLG1, encoding two putative sensors for cell integrity signalling in Saccharomyces cerevisiae. de Bettignies, G., Barthe, C., Morel, C., Peypouquet, M.F., Doignon, F., Crouzet, M. Yeast (1999) [Pubmed]
  12. The Rgd1p Rho GTPase-activating protein and the Mid2p cell wall sensor are required at low pH for protein kinase C pathway activation and cell survival in Saccharomyces cerevisiae. Claret, S., Gatti, X., Doignon, F., Thoraval, D., Crouzet, M. Eukaryotic Cell (2005) [Pubmed]
  13. A synthetic analysis of the Saccharomyces cerevisiae stress sensor Mid2p, and identification of a Mid2p-interacting protein, Zeo1p, that modulates the PKC1-MPK1 cell integrity pathway. Green, R., Lesage, G., Sdicu, A.M., Ménard, P., Bussey, H. Microbiology (Reading, Engl.) (2003) [Pubmed]
  14. The MID2 gene encodes a putative integral membrane protein with a Ca(2+)-binding domain and shows mating pheromone-stimulated expression in Saccharomyces cerevisiae. Ono, T., Suzuki, T., Anraku, Y., Iida, H. Gene (1994) [Pubmed]
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