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FLASH GENE
Symbol HMGCR contributors: mct/ - updated : 28-01-2020
HGNC name 3-hydroxy-3-methylglutaryl-Coenzyme A reductase
HGNC id 5006
PROTEIN
PHYSICAL PROPERTIES Hydrophobic
STRUCTURE
motifs/domains
  • a N terminal hydrophobic membrane-bound domain
  • a five spanning transmembrane sterol sensing domain (SSD), TM2-6
  • a flexible linker domain
  • a catalytic domain
    • HOMOLOGY
    intraspecies homolog to NPC1L1
    Homologene
    FAMILY
  • Patched family
  • HMG-CoA reductase family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,peroxisome
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • catalyzing a rate-limiting step in cholesterol biosynthesis (conversion of HMG-CoA to mevalonate)
  • membrane-bound enzyme, catalyzing a rate-limiting step in sterol and isoprenoid biosynthesis and being the primary target of hypocholesterolemic drug therapy
  • oncogenic roles of HMGCR in glioblastoma cells
  • promotes protein prenylation and therefore is indispensible for T-cell survival
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • is a critical regulator of MYC phosphorylation, activation, and tumorigenic properties
  • ubiquitin ligase (E3) AMFR has been implicated in the sterol-regulated degradation of HMGCR and INSIG1 through ER-associated degradation (ERAD)
  • HNRNPA1 regulates HMGCR alternative splicing and modulates cellular cholesterol metabolism
  • MARCHF6 controls abundance of both SQLE and HMGCR, establishing it as a major regulator of flux through the cholesterol synthesis pathway
  • TSH could regulate the phosphorylation of HMGCR via AMPK, which established a potential mechanism for hypercholesterolemia involved in a direct action of the TSH in the liver
  • HMGCR is a target gene of SREBF2 and luteolin modulates HMGCR transcription by decreasing the expression and nuclear translocation of SREBF2
  • FAF2 is an essential determinant of metabolically stimulated degradation of HMGCR and of cholesterol biosynthesis in multiple cell types
  • HSP90AA1 interacted with HMGCR, the rate&
    • 8209;limiting enzyme of mevalonate pathway, and regulated its protein expression level by inhibiting protein degradation
  • stabilization of HMGCR by UBIAD1 increases cholesterol biosynthesis and eventually causes cholesterol accumulation in the cornea
    • cell & other
    REGULATION
    inhibited by maybe degradated by the p97 subunit of 265 proteasome (see PSMD2)
    Other regulated by phosphorylation/dephosphorylation and by a negative feedback mechanism mediated by sterols (cholesterol) and non sterol metabolites derived from mevalonate
    ASSOCIATED DISORDERS
    corresponding disease(s) LGMDR28
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in gastric cancer and promotes the growth and migration of the cancer cells
    Susceptibility to Alzheimer disease (AD)
    Variant & Polymorphism SNP
  • HMGCR (rs3846662) plays a vital role in AD pathology mainly by influencing brain structure and glucose metabolism during AD progression
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivestomach
    is a promising therapeutic targetin gastric cancer
    ANIMAL & CELL MODELS