3-hydroxy-3-methylglutaryl-coenzyme A reductase

UniProt P04035 Organism Homo sapiens Gene HMGCR EC 1.1.1.34

Also known as: HMGCR

Function

Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis. HMGCR is the main target of statins, a class of cholesterol-lowering drugs.

Classification

Family (Pfam): PF00368 HMG-CoA_red, PF12349 Sterol-sensing
InterPro: HMG_CoA_Rdtase, HMG_CoA_Rdtase_cat_sf, HMG_CoA_Rdtase_CS, HMG_CoA_Rdtase_eu_arc, HMG_CoA_Rdtase_metazoan, HMG_CoA_Rdtase_N, HMG_CoA_Rdtase_NAD(P)-bd_sf, HMG_CoA_Rdtase_sub-bd_dom_sf, HMGCR/SNAP/NPC1-like_SSD, SSD
Functional cluster: Ribosomal Protein S5 & Biosynthetic Enzymes

Experimental structures · PDB · 24

1DQ8 X-ray 2.10A
1DQ9 X-ray 2.80A
1DQA X-ray 2.00A
1HW8 X-ray 2.10A
1HW9 X-ray 2.33A
1HWI X-ray 2.30A
1HWJ X-ray 2.26A
1HWK X-ray 2.22A
1HWL X-ray 2.10A
2Q1L X-ray 2.05A
2Q6B X-ray 2.00A
2Q6C X-ray 2.00A
… and 12 more

A predicted model is available from AlphaFold.

Gene Ontology · 21

Disease associations

muscular dystrophy, limb-girdle, autosomal recessive 28 MONDO:0957270
OMIM:620410 RAW:OMIM_620410

Drugs targeting this protein · 10

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

UbiA prenyltransferase domain-containing protein 1 1 shared papers
Insulin-induced gene 1 protein 2 shared papers
Phospholipid-transporting ATPase ABCA1 1 shared papers
Sterol O-acyltransferase 1 1 shared papers
Scavenger receptor class B member 1 1 shared papers
Apolipoprotein B-100 1 shared papers
E3 ubiquitin-protein ligase RNF139 1 shared papers
Sortilin 1 shared papers
Insulin-induced gene 2 protein 1 shared papers
E3 ubiquitin-protein ligase AMFR 1 shared papers

Literature · 24 cited papers

Bi-allelic variants in HMGCR cause an autosomal-recessive progressive limb-girdle muscular dystrophy. Am. J. Hum. Genet. · 2023
Limb girdle muscular disease caused by HMGCR mutation and statin myopathy treatable with mevalonolactone. Proc. Natl. Acad. Sci. U.S.A. · 2023
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
The UBIAD1 prenyltransferase links menaquione-4 synthesis to cholesterol metabolic enzymes. Hum. Mutat. · 2013
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. · 2012
Sterol-induced degradation of HMG CoA reductase depends on interplay of two Insigs and two ubiquitin ligases, gp78 and Trc8. Proc. Natl. Acad. Sci. U.S.A. · 2011
Metabolically regulated endoplasmic reticulum-associated degradation of 3-hydroxy-3-methylglutaryl-CoA reductase: evidence for requirement of a geranylgeranylated protein. J. Biol. Chem. · 2011
Epigallocatechin-3-gallate potently inhibits the in vitro activity of hydroxy-3-methyl-glutaryl-CoA reductase. J. Lipid Res. · 2011
Biological, clinical and population relevance of 95 loci for blood lipids. Nature · 2010
Dislocation of HMG-CoA reductase and Insig-1, two polytopic endoplasmic reticulum proteins, en route to proteasomal degradation. Mol. Biol. Cell · 2009
Thermodynamic and structure guided design of statin based inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase. J. Med. Chem. · 2008
… and 12 more in the literature graph

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