UbiProt Database - proteins_show

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Protein information

Protein name 3-hydroxy-3-methylglutaryl-coenzyme A reductase 2 
Synonyms EC 1.1.1.34
HMG-CoA reductase 2
HMGR
Gene name HMG2 , YLR450W , L9324.2 .
Source Saccharomyces cerevisiae (Baker's yeast)
Expression system Saccharomyces cerevisiae (Baker's yeast)
Full length  1045
Precursor  no
Mature form length  1045
Molecular weight (Da)  115692
Swiss-Prot Sequence Version  October 1, 1989 (Sequence version 1)
Comments  HMGR is a key enzyme in the mevalonate pathway by which isoprenoids and sterols are synthesized [1]. HMGR is an integral endoplasmic reticulum (ER) membrane protein [2].

Cross-references

Swiss-Prot/TrEMBL HMDH2_YEAST
PDB 1DQA .

Ubiquitylation features

Ubiquitylation site  
 

Ubiquitylation type Multiple ubiquitylation
Features In yeast isoform 1 of HMGR is stable, while isoform 2 is rapidly degraded [1]. Farnesyl diphosphate (FPP) serves as a positive signal for HMGR degradation both in yeast and in mammals [2]. This process is mediated by ubiquitylation and proteasomal degradation [3].

Ubiquitylation/deubiquitylation machinery

E2 Ubc7
E3 HRD
E4/AP Not determined
DUB Not determined
Comments Ubiquitylation is facilitated by RING-H2 ubiquitin ligase complex HRD, composed of ER proteins Hrd1p and Hrd3p, and responcible for quality control in ER-associated degradation [4].

References

[1]Hampton RY, Rine J.
Regulated degradation of HMG-CoA reductase, an integral membrane protein of the endoplasmic reticulum, in yeast. J Cell Biol. 125(2):299-312 (1994).
[8163547]
[2]Gardner RG, Hampton RY.
A highly conserved signal controls degradation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase in eukaryotes. J Biol Chem. 274(44):31671-8 (1998).
[10531376]
[3]Hampton RY, Bhakta H.
Ubiquitin-mediated regulation of 3-hydroxy-3-methylglutaryl-CoA reductase. Proc Natl Acad Sci U S A. 94(24):12944-8 (1997).
[9371780]
[4]Gardner RG, Shearer AG, Hampton RY.
In vivo action of the HRD ubiquitin ligase complex: mechanisms of endoplasmic reticulum quality control and sterol regulation. Mol Cell Biol. 21(13):4276-91 (2001).
[11390656]
[5]Bays NW, Gardner RG, Seelig LP, Joazeiro CA, Hampton RY:
Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation. Nat.Cell Biol. 2001, 3:24-29.
[11146622]
 

Ubiquitylation type Lys48-linked multi-ubiquitin chain
Features ND

Ubiquitylation/deubiquitylation machinery

E2 UBC7_YEAST
E3 HRD1_YEAST
E4/AP ND
DUB ND
Comments ND

References

[1]Bays NW, Gardner RG, Seelig LP, Joazeiro CA, Hampton RY:
Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation. Nat.Cell Biol. 2001, 3:24-29.
[11146622]
[2]Hampton RY, Bhakta H.
Ubiquitin-mediated regulation of 3-hydroxy-3-methylglutaryl-CoA reductase. Proc Natl Acad Sci U S A. 94(24):12944-8 (1997).
[9371780]

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