Hmgcr
entrez
25675
canonical
uniprot
P51639
canonical
ensembl
ENSRNOG00000016122
resolver
ensp
ENSRNOP00000087297
resolver
ensp
ENSRNOP00000096084
resolver
ensp
ENSRNOP00000097467
resolver
enst
ENSRNOT00000096437
resolver
enst
ENSRNOT00000101787
resolver
enst
ENSRNOT00000112347
resolver
genesymbol
Hmgcr
resolver
uniprot
A0A8I6A6Z9
resolver
uniprot
A0A8I6AUL2
resolver
uniprot
A0A8I6AV02
resolver
uniprot
Q64601
resolver
uniprot
Q6P2A6
resolver
uniprot_entry
A0A8I6A6Z9_RAT
resolver
uniprot_entry
A0A8I6AV02_RAT
resolver
uniprot_entry
HMDH_RAT
resolver
uniprot_sec
A0A8I6AUL2
resolver
uniprot_sec
Q64601
resolver
uniprot_sec
Q6P2A6
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
MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSSDIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTGLNEALPFFLLLIDLSRASALAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIGVGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFARVLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTAEQSKVSLGLAEDVSKRIEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQAETESTLSLKNPITSPVVTPKKAQDNCCRREPLLVRRNQKLSSVEEDPGVNQDRKVEVIKPLVAEAETSGRATFVLGASAASPPLALGAQEPGIELPSEPRPNEECLQILESAEKGAKFLSDAEIIQLVNAKHIPAYKLETLMETHERGVSIRRQLLSAKLAEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGVAGPLCLDGKEYQVPMATTEGCLVASTNRGCRAISLGGGASSRVLADGMSRGPVVRLPRACDSAEVKSWLETPEGFAVVKEAFDSTSRFARLQKLHVTLAGRNLYIRLQSKTGDAMGMNMISKGTEKALLKLQEFFPELQILAVSGNYCTDKKPAAINWIEGRGKTVVCEAVIPAKVVREVLKTTTEAMVDVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITLMEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLARIVCGTVMAGELSLMAALAAGHLVRSHMVHNRSKINLQDLQGTCTKKAA
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:4019513}.
uniprot
proteins
mass_dalton
96688
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
15489334
uniprot
proteins
pubmed
1628744
uniprot
proteins
pubmed
2369897
uniprot
proteins
pubmed
4019513
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