Names & Taxonomy
- Uniprot ID:
- P04035
- Entry Name:
- HMDH_HUMAN
- Status:
- reviewed
- Protein Names:
- 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) (EC 1.1.1.34)
- Gene Names:
- HMGCR
- Gene Names Primary:
- HMGCR
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 888
- Sequence:
- MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSSDIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTGLNEALPFFLLLIDLSRASTLAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIGVGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFARVLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTADTSKVSLGLDENVSKRIEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQTETESTLSLKNPITSPVVTQKKVPDNCCRREPMLVRNNQKCDSVEEETGINRERKVEVIKPLVAETDTPNRATFVVGNSSLLDTSSVLVTQEPEIELPREPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYKLETLMETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGVAGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRACDSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMISKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREVLKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITLMEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLARIVCGTVMAGELSLMAALAAGHLVKSHMIHNRSKINLQDLQGACTKKTA
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Endoplasmic reticulum membrane; Multi-pass membrane protein.
Function
- Function:
- Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.
- Pathway:
- Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
- Catalytic Activity:
- (R)-mevalonate + CoA + 2 NADP(+) = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH.
- Enzyme Regulation:
- ENZYME REGULATION: Regulated by a negative feedback mechanism through sterols and non-sterol metabolites derived from mevalonate. Inhibited by statins, a class of hypolipidemic agents used as pharmaceuticals to lower cholesterol levels in individuals at risk from cardiovascular disease due to hypercholesterolemia. Inhibition of HMGCR in the liver stimulates the LDL-receptors, which results in an increased clearance of LDL from the bloodstream and a decrease in blood cholesterol levels. The first results can be seen after one week of statin use and the effect is maximal after four to six weeks.
- Active Site:
- ACT_SITE 559 559 Charge relay system.; ACT_SITE 691 691 Charge relay system.; ACT_SITE 767 767 Charge relay system.; ACT_SITE 866 866 Proton donor.
- Cross Reference Drug Bank:
- DB01076 DB01095 DB00227 DB08860 DB00175 DB01098 DB00641
- Gene Ontology Go:
- endoplasmic reticulum
endoplasmic reticulum membrane
integral component of membrane
peroxisomal membrane
coenzyme binding
hydroxymethylglutaryl-CoA reductase (NADPH) activity
hydroxymethylglutaryl-CoA reductase activity
NADPH binding
aging
cellular lipid metabolic process
cholesterol biosynthetic process
coenzyme A metabolic process
isoprenoid biosynthetic process
myoblast differentiation
negative regulation of insulin secretion involved in cellular response to glucose stimulus
negative regulation of MAP kinase activity
negative regulation of striated muscle cell apoptotic process
negative regulation of vasodilation
negative regulation of wound healing
positive regulation of cardiac muscle cell apoptotic process
positive regulation of ERK1 and ERK2 cascade
positive regulation of skeletal muscle tissue development
positive regulation of smooth muscle cell proliferation
positive regulation of stress-activated MAPK cascade
protein tetramerization
response to ethanol
response to nutrient
small molecule metabolic process
ubiquinone metabolic process
visual learning - Gene Ontology Biological Process:
- aging
cellular lipid metabolic process
cholesterol biosynthetic process
coenzyme A metabolic process
isoprenoid biosynthetic process
myoblast differentiation
negative regulation of insulin secretion involved in cellular response to glucose stimulus
negative regulation of MAP kinase activity
negative regulation of striated muscle cell apoptotic process
negative regulation of vasodilation
negative regulation of wound healing
positive regulation of cardiac muscle cell apoptotic process
positive regulation of ERK1 and ERK2 cascade
positive regulation of skeletal muscle tissue development
positive regulation of smooth muscle cell proliferation
positive regulation of stress-activated MAPK cascade
protein tetramerization
response to ethanol
response to nutrient
small molecule metabolic process
ubiquinone metabolic process
visual learning - Gene Ontology Molecular Function:
- coenzyme binding
hydroxymethylglutaryl-CoA reductase (NADPH) activity
hydroxymethylglutaryl-CoA reductase activity
NADPH binding - Gene Ontology Cellular Component:
- endoplasmic reticulum
endoplasmic reticulum membrane
integral component of membrane
peroxisomal membrane - Keywords:
- 3D-structure
Alternative splicing
Cholesterol biosynthesis
Cholesterol metabolism
Complete proteome
Endoplasmic reticulum
Glycoprotein
Isopeptide bond
Lipid biosynthesis
Lipid metabolism
Membrane
NADP
Oxidoreductase
Phosphoprotein
Polymorphism
Reference proteome
Steroid biosynthesis
Steroid metabolism
Sterol biosynthesis
Sterol metabolism
Transmembrane
Transmembrane helix
Ubl conjugation - Interacts With:
- Q9Y5Z9; Q9Y5Z9-1