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Details on Person UniProt:A7Z064 HMGCR
| Class:Id | ReferenceGeneProduct:2455458 |
|---|---|
| _chainChangeLog | chain:1-888 added on Fri February 6 2015 |
| _displayName | UniProt:A7Z064 HMGCR |
| _timestamp | 2025-02-21 18:47:28 |
| chain | chain:1-888 |
| checksum | 16CFA777C3AA9D1A |
| comment | 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.CATALYTIC ACTIVITY (R)-mevalonate + 2 NADP(+) + CoA = (3S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H(+)ACTIVITY REGULATION Regulated by a negative feedback mechanism through sterols and non-sterol metabolites derived from mevalonate (By similarity). Phosphorylation at Ser-872 down-regulates the catalytic activity (By similarity).PATHWAY Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.SUBUNIT Homotetramer. Homodimer (By similarity). Interacts (via its SSD) with INSIG1; the interaction, accelerated by sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its ubiquitination by the sterol-mediated ERAD pathway. Interacts with UBIAD1 (By similarity).SUBCELLULAR LOCATION 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.PTM N-glycosylated. Deglycosylated by NGLY1 on release from the endoplasmic reticulum (ER) in a sterol-mediated manner.PTM Phosphorylated. Phosphorylation at Ser-872 reduces the catalytic activity.SIMILARITY Belongs to the HMG-CoA reductase family. |
| created | [InstanceEdit:2455454] Weiser, JD |
| description | recommendedName: 3-hydroxy-3-methylglutaryl-coenzyme A reductase shortName: HMG-CoA reductase ecNumber evidence="2"1.1.1.34 |
| geneName | HMGCR |
| identifier | A7Z064 |
| isSequenceChanged | FALSE |
| keyword | Cholesterol biosynthesis Cholesterol metabolism Endoplasmic reticulum Glycoprotein Isopeptide bond Lipid biosynthesis Lipid metabolism Membrane NADP Oxidoreductase Peroxisome Phosphoprotein Reference proteome Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism Transmembrane Transmembrane helix Ubl conjugation |
| modified | [InstanceEdit:2587579] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9607352] Weiser, JD [InstanceEdit:9627708] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9698430] Weiser, JD [InstanceEdit:9706439] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | HMGCR |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | HMDH_BOVIN F1MMP6 |
| sequenceLength | 888 |
| species | [Species:48898] Bos taurus |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:A7Z064 HMGCR (2455458)
