3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase (HMGCR)

HMG-CoA Reductase; Hydroxymethylglutaryl-CoA Reductase

SPN	T098
HGNC	5006
MGI	96159
PubMed	21355415
RGD	2803
UniProt	P04035
Wiki	HMGCR

HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase.

Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of low density lipoprotein (LDL) via the LDL receptor as well as oxidized species of cholesterol. Competitive inhibitors of the reductase induce the expression of LDL receptors in the liver, which in turn increases the catabolism of plasma LDL and lowers the plasma concentration of cholesterol, an important determinant of atherosclerosis.

Reference

"Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation."
J. Biol. Chem. 260:10271-10277(1985) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and comparative analysis of human chromosome 5."
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth."
J. Lipid Res. 21:505-517(1980) [PubMed] [Europe PMC] [Abstract]

"Accelerated degradation of HMG CoA reductase mediated by binding of insig-1 to its sterol-sensing domain."
Mol. Cell 11:25-33(2003) [PubMed] [Europe PMC] [Abstract]

"Dislocation of HMG-CoA reductase and Insig-1, two polytopic endoplasmic reticulum proteins, en route to proteasomal degradation."
Mol. Biol. Cell 20:3330-3341(2009) [PubMed] [Europe PMC] [Abstract]

"Metabolically regulated endoplasmic reticulum-associated degradation of 3-hydroxy-3-methylglutaryl-CoA reductase: evidence for requirement of a geranylgeranylated protein."
J. Biol. Chem. 286:32150-32161(2011) [PubMed] [Europe PMC] [Abstract]

"A novel 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) splice variant with an alternative exon 1 potentially encoding an extended N-terminus."
BMC Mol. Biol. 13:29-29(2012) [PubMed] [Europe PMC] [Abstract]

"The UBIAD1 prenyltransferase links menaquione-4 synthesis to cholesterol metabolic enzymes."
Hum. Mutat. 34:317-329(2013) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis."
EMBO J. 19:819-830(2000) [PubMed] [Europe PMC] [Abstract]

"Structural mechanism for statin inhibition of HMG-CoA reductase."
Science 292:1160-1164(2001) [PubMed] [Europe PMC] [Abstract]

"Thermodynamic and structure guided design of statin based inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase."
J. Med. Chem. 51:3804-3813(2008) [PubMed] [Europe PMC] [Abstract]

"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]

Erratum
Nat. Genet. 23:373-373(1999)