The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

HMG2  -  hydroxymethylglutaryl-CoA reductase...

Saccharomyces cerevisiae S288c

Synonyms: 3-hydroxy-3-methylglutaryl-coenzyme A reductase 2, HMG-CoA reductase 2, L9324.2, YLR450W
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

High impact information on HMG2

  • The effect is reversible, biologically relevant by numerous criteria, highly specific for farnesol structure, and requires an intact Hmg2p sterol-sensing domain [1].
  • Using in vitro structural assays, we now show that the pathway derivative farnesol causes Hmg2p to undergo a change to a less folded structure [1].
  • Our data suggested that Cod1p is a calcium transporter required for regulating Hmg2p degradation [2].
  • The yeast HMG-CoA reductase isozyme Hmg2p undergoes stringently regulated degradation by machinery that is also required for ER quality control [3].
  • One signal for degradation of Hmg2p was a nonsterol, mevalonate-derived molecule produced before the synthesis of squalene [4].

Biological context of HMG2


Anatomical context of HMG2

  • The predicted amino acid sequence of ABF2 is closely related to the high-mobility group proteins HMG1 and HMG2 from vertebrate cell nuclei and to several other DNA-binding proteins [8].
  • Overproduction of chimeric proteins containing the HMG2/1 peptide, which comprises the seven transmembrane domains of Saccharomyces cerevisiae 3-hydroxy-3-methylglutaryl-CoA reductase isozymes 1 and 2, has previously been observed to induce the proliferation of internal endoplasmic reticulum-like membranes [9].
  • We show the association of mammalian p97 and its yeast homologue Cdc48p in complexes with two respective ERAD substrates, secretory immunoglobulin M in B lymphocytes and 6myc-Hmg2p in yeast [10].
  • Specifically, increased levels of Hmg1p were concentrated in the nuclear envelope, whereas increased levels of Hmg2p were concentrated in the peripheral ER [11].

Associations of HMG2 with chemical compounds

  • However, cells containing a mutant allele of either HMG1 or HMG2 are viable but are more sensitive to compactin, a competitive inhibitor of HMG-CoA reductase, than are wild-type cells [12].
  • The two yeast genes for 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, HMG1 and HMG2, each encode a functional isozyme [6].
  • Decreased mevalonate pathway flux resulted in decreased degradation of Hmg2p [4].
  • Finally, our data indicated that the feedback signal controlling Hmg2p ubiquitination and degradation was derived from farnesyl diphosphate, and thus implied conservation of an HMG-R degradation signal between yeast and mammals [13].
  • Our studies with the sterol pathway-regulated ERAD substrate Hmg2p, an isozyme of the yeast cholesterol biosynthetic enzyme HMG-coenzyme A reductase (HMGR), indicated that the HRD complex discerns between a degradation-competent "misfolded" state and a stable, tightly folded state [14].

Other interactions of HMG2

  • Cells containing mutant alleles of both HMG1 and HMG2 are unable to undergo spore germination and vegetative growth [12].
  • The overexpression of EKS1/HRD3, which stabilizes Hmg2p, did not affect the stability of wild-type or mutant Sar1p or any early Sec proteins we examined [15].
  • In contrast to Hmg2p-degradation, that of native CYP3A4 does not appear to absolutely require Hrd1p, another component of the ER-associated Ub-ligase complex [16].
  • EKS1 turns out to be identical to HRD3, which was independently isolated as a gene implicated in the degradation of an HMG-CoA reductase isozyme, Hmg2p [15].
  • DNA sequencing and Northern (RNA) blot analysis revealed that one gene, called ACP2 (acidic protein 2), synthesizes a poly(A)+ RNA in S. cerevisiae which encodes a 27,000-molecular-weight protein whose amino acid sequence is homologous to those of calf HMG1 and HMG2 and trout HMGT proteins [17].


  1. Lipid-mediated, reversible misfolding of a sterol-sensing domain protein. Shearer, A.G., Hampton, R.Y. EMBO J. (2005) [Pubmed]
  2. Regulation of HMG-CoA reductase degradation requires the P-type ATPase Cod1p/Spf1p. Cronin, S.R., Khoury, A., Ferry, D.K., Hampton, R.Y. J. Cell Biol. (2000) [Pubmed]
  3. A 'distributed degron' allows regulated entry into the ER degradation pathway. Gardner, R.G., Hampton, R.Y. EMBO J. (1999) [Pubmed]
  4. Regulated degradation of HMG-CoA reductase, an integral membrane protein of the endoplasmic reticulum, in yeast. Hampton, R.Y., Rine, J. J. Cell Biol. (1994) [Pubmed]
  5. Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis. Basson, M.E., Thorsness, M., Finer-Moore, J., Stroud, R.M., Rine, J. Mol. Cell. Biol. (1988) [Pubmed]
  6. Identifying mutations in duplicated functions in Saccharomyces cerevisiae: recessive mutations in HMG-CoA reductase genes. Basson, M.E., Moore, R.L., O'Rear, J., Rine, J. Genetics (1987) [Pubmed]
  7. Mutations that affect vacuole biogenesis inhibit proliferation of the endoplasmic reticulum in Saccharomyces cerevisiae. Koning, A.J., Larson, L.L., Cadera, E.J., Parrish, M.L., Wright, R.L. Genetics (2002) [Pubmed]
  8. A close relative of the nuclear, chromosomal high-mobility group protein HMG1 in yeast mitochondria. Diffley, J.F., Stillman, B. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  9. Targeting of heterologous membrane proteins into proliferated internal membranes in Saccharomyces cerevisiae. Wittekindt, N.E., Würgler, F.E., Sengstag, C. Yeast (1995) [Pubmed]
  10. AAA-ATPase p97/Cdc48p, a cytosolic chaperone required for endoplasmic reticulum-associated protein degradation. Rabinovich, E., Kerem, A., Fröhlich, K.U., Diamant, N., Bar-Nun, S. Mol. Cell. Biol. (2002) [Pubmed]
  11. Different subcellular localization of Saccharomyces cerevisiae HMG-CoA reductase isozymes at elevated levels corresponds to distinct endoplasmic reticulum membrane proliferations. Koning, A.J., Roberts, C.J., Wright, R.L. Mol. Biol. Cell (1996) [Pubmed]
  12. Saccharomyces cerevisiae contains two functional genes encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Basson, M.E., Thorsness, M., Rine, J. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  13. Ubiquitin-mediated regulation of 3-hydroxy-3-methylglutaryl-CoA reductase. Hampton, R.Y., Bhakta, H. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  14. In vivo action of the HRD ubiquitin ligase complex: mechanisms of endoplasmic reticulum quality control and sterol regulation. Gardner, R.G., Shearer, A.G., Hampton, R.Y. Mol. Cell. Biol. (2001) [Pubmed]
  15. Identification of SEC12, SED4, truncated SEC16, and EKS1/HRD3 as multicopy suppressors of ts mutants of Sar1 GTPase. Saito, Y., Yamanushi, T., Oka, T., Nakano, A. J. Biochem. (1999) [Pubmed]
  16. Ubiquitin-dependent 26S proteasomal pathway: a role in the degradation of native human liver CYP3A4 expressed in Saccharomyces cerevisiae? Murray, B.P., Correia, M.A. Arch. Biochem. Biophys. (2001) [Pubmed]
  17. The Saccharomyces cerevisiae ACP2 gene encodes an essential HMG1-like protein. Haggren, W., Kolodrubetz, D. Mol. Cell. Biol. (1988) [Pubmed]
WikiGenes - Universities