Hmgcr
entrez
15357
canonical
uniprot
Q01237
canonical
ensembl
ENSMUSG00000021670
resolver
ensp
ENSMUSP00000022176
resolver
ensp
ENSMUSP00000190927
resolver
enst
ENSMUST00000022176
resolver
genesymbol
Hmgcr
resolver
uniprot
G3X8U5
resolver
uniprot
Q5U4I2
resolver
uniprot
Q8BV96
resolver
uniprot_entry
HMDH_MOUSE
resolver
uniprot_entry
Q8BV96_MOUSE
resolver
uniprot_sec
G3X8U5
resolver
uniprot_sec
Q5U4I2
resolver
activity_regulation
ACTIVITY REGULATION: Regulated by a negative feedback mechanism through sterols and non-sterol metabolites derived from mevalonate (By similarity). Phosphorylation at Ser-871 down-regulates the catalytic activity (By similarity). {ECO:0000250|UniProtKB:P00347, ECO:0000250|UniProtKB:P04035}.
uniprot
proteins
amino_acid_sequence
MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSSDIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTGLNEALPFFLLLIDLSRASALAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIGVGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFARVLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTAEQAKVSLGLDEDVSKRIEPSVSLWQFYLSKMISMDIEQVITLSLAFLLAVKYIFFEQAETESTLSLKNPITSPVVTSKKAQDNCCRREPLLVRRNQKLSSVEEDPGANQERKVEVIKPLVVEAETTSRATFVLGASVASPPSALGTQEPGIELPIEPRPNEECLQILENAEKGAKFLSDAEIIQLVNAKHIPAYKLETLMETHERGVSIRRQLLSTKLAEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGVAGPLCLDGKEYQVPMATTEGCLVASTNRGCRAISLGGGASSRVLADGMTRGPVVRLPRACDSAEVKTWLETPEGFAVIKEAFDSTSRFARLQKLHVTMAGRNLYIRFQSRTGDAMGMNMISKGTEKALLKLQEFFPDMQILAVSGNYCTDKKPAAINWIEGRGKTVVCEAVIPAKVVREVLKTTTEAMVDVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITLMEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLARIVCGTVMAGELSLMAALAAGHLVRSHMVHNRSKINLQDLQGTCTKKAA
uniprot
proteins
ec_number
1.1.1.34
uniprot
proteins
function
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. {ECO:0000269|PubMed:16100574}.
uniprot
proteins
mass_dalton
97040
uniprot
proteins
pathway_participation
PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
uniprot
proteins
post_translational_modification
PTM: Undergoes sterol-mediated ubiquitination and ER-associated degradation (ERAD). Accumulation of sterols in the endoplasmic reticulum (ER) membrane, triggers binding of the reductase to the ER membrane protein INSIG1 or INSIG2. The INSIG1 binding leads to the recruitment of the ubiquitin ligase, AMFR/gp78, RNF139 or RNF145, initiating ubiquitination of the reductase. The ubiquitinated reductase is then extracted from the ER membrane and delivered to cytosolic 26S proteosomes by a mechanism probably mediated by the ATPase Valosin-containing protein VCP/p97. The INSIG2-binding leads to the recruitment of the ubiquitin ligase RNF139, initiating ubiquitination of the reductase. Lys-248 is the main site of ubiquitination. Ubiquitination is enhanced by the presence of a geranylgeranylated protein. {ECO:0000250|UniProtKB:P04035}.; PTM: N-glycosylated. Deglycosylated by NGLY1 on release from the endoplasmic reticulum (ER) in a sterol-mediated manner. {ECO:0000250|UniProtKB:P04035}.; PTM: Phosphorylated. Phosphorylation at Ser-871 reduces the catalytic activity. {ECO:0000250|UniProtKB:P00347}.
uniprot
proteins
protein_family
HMG-CoA reductase family
uniprot
proteins
pubmed
12920113
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16100574
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
2258621
uniprot
proteins
sequence_length
887
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P04035}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P00347}. Peroxisome membrane {ECO:0000250|UniProtKB:P04035}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P00347}.
uniprot
proteins
transmembrane_region
TRANSMEM 10..39; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P00347"; TRANSMEM 57..78; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P00347"; TRANSMEM 90..114; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P00347"; TRANSMEM 124..149; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P00347"; TRANSMEM 160..187; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P00347"; TRANSMEM 192..220; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P00347"; TRANSMEM 249..275; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P00347"; TRANSMEM 315..339; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P00347
uniprot
proteins