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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
Location 5q13.3      Physical location : 74.632.992 - 74.657.924
Synonym name
  • HMG CoA reductase
  • 3-hydroxy-3-methylglutaryl CoA reductase (NADPH)
  • Synonym symbol(s) EVI19, LDLCQ3, HMGR
    EC.number 1.1.1.88, 1.1.1.34
    DNA
    TYPE functioning gene
    STRUCTURE 25.78 kb     20 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • two sterol-regulatory elements (SREs) in close proximity in both the human HMGCR and SQLE promoters, as well as one NF-Y site in HMGCR and two in SQLE
  • MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    20 - 4589 - 888 - 2019 30483734
    19 - 4430 - 835 - 2019 30483734
    20 - 4507 - 888 - 2019 30483734
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly
    Reproductivemale system   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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)
    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