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    HMGCR 3-hydroxy-3-methylglutaryl-CoA reductase [ Homo sapiens ]

    Gene ID: 3156, updated on 29-Jan-2012
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    Summary

    Official Symbol
    HMGCRprovided by HGNC
    Official Full Name
    3-hydroxy-3-methylglutaryl-CoA reductaseprovided by HGNC
    Primary source
    HGNC:5006
    See related
    Ensembl:ENSG00000113161; HPRD:00836; MIM:142910; Vega:OTTHUMG00000102069
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    LDLCQ3
    Summary
    HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase. Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of low density lipoprotein (LDL) via the LDL receptor. Competitive inhibitors of the reductase induce the expression of LDL receptors in the liver, which in turn increases the catabolism of plasma LDL and lowers the plasma concentration of cholesterol, an important determinant of atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
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    Genomic context

    Location :
    5q13.3-q14
    Sequence :
    Chromosome: 5; NC_000005.9 (74632993..74657926)
    See HMGCR in Epigenomics, MapViewer

    Chromosome 5 - NC_000005.9Genomic Context describing neighboring genes Neighboring gene glucosaminyl (N-acetyl) transferase 4, core 2 Neighboring gene ankyrin repeat domain 31 Neighboring gene SMT3 suppressor of mif two 3 homolog 2 (S. cerevisiae) pseudogene 5 Neighboring gene collagen, type IV, alpha 3 (Goodpasture antigen) binding protein Neighboring gene ribosomal protein S26 pseudogene 26 Neighboring gene polymerase (DNA directed) kappa

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Linalool reduces the expression of 3-hydroxy-3-methylglutaryl CoA reductase via sterol regulatory element binding protein-2- and ubiquitin-dependent mechanisms. Cho SY, et al. FEBS Lett, 2011 Oct 20. PMID 21944868.
    2. Regulation of HMG-CoA reductase in mammals and yeast. Burg JS, et al. Prog Lipid Res, 2011 Oct. PMID 21801748.
    3. HMG-CoA reductase activation and urinary pellet cholesterol elevations in acute kidney injury. Johnson AC, et al. Clin J Am Soc Nephrol, 2011 Sep. PMID 21799150.
    4. Metabolically regulated endoplasmic reticulum-associated degradation of 3-hydroxy-3-methylglutaryl-CoA reductase: evidence for requirement of a geranylgeranylated protein. Leichner GS, et al. J Biol Chem, 2011 Sep 16. PMID 21778231.
    5. Short- and long-term regulation of 3-hydroxy 3-methylglutaryl coenzyme A reductase by a 4-methylcoumarin. Trapani L, et al. Biochimie, 2011 Jul. PMID 21530605.

    See all (120) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. HMG-CoA reductase activation and urinary pellet cholesterol elevations in acute kidney injury.
      Title: HMG-CoA reductase activation and urinary pellet cholesterol elevations in acute kidney injury.
    2. HMG-CoA reductase regulation takes place at the levels of transcription, translation, post-translational modification and degradation. (Review)
      Title: Regulation of HMG-CoA reductase in mammals and yeast.
    3. Linalool reduces the expression of 3-hydroxy-3-methylglutaryl CoA reductase via sterol regulatory element binding protein-2- and ubiquitin-dependent mechanisms.
      Title: Linalool reduces the expression of 3-hydroxy-3-methylglutaryl CoA reductase via sterol regulatory element binding protein-2- and ubiquitin-dependent mechanisms.
    4. inhibition of protein geranylgeranylation markedly attenuated ubiquitylation and dislocation, implicating for the first time a geranylgeranylated protein(s) in the metabolically regulated ERAD of HMGR.
      Title: Metabolically regulated endoplasmic reticulum-associated degradation of 3-hydroxy-3-methylglutaryl-CoA reductase: evidence for requirement of a geranylgeranylated protein.
    5. Data show that the antioxidant property of 4-methylesculetin led to the reduction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activation state through the increase of the enzyme phosphorylation.
      Title: Short- and long-term regulation of 3-hydroxy 3-methylglutaryl coenzyme A reductase by a 4-methylcoumarin.
    6. Data show that the inhibition of HMG-CoA reductase may be a useful target for the treatment of MYC-associated HCC as well as other tumors.
      Title: MYC phosphorylation, activation, and tumorigenic potential in hepatocellular carcinoma are regulated by HMG-CoA reductase.
    7. Studies indicate that the HMGR active site contains a region capable of binding NADPH, a substrate necessary for the reduction of HMG-CoA, the first step in this multistep catalytic process.
      Title: Proteopedia entry: HMG-CoA reductase.
    8. identify two ER membrane proteins, SPFH2 and TMUB1, as associated proteins of gp78, a membrane-bound ubiquitin ligase that mediates sterol-accelerated ERAD of the cholesterol biosynthetic enzyme HMG-CoA reductase.
      Title: Membrane-associated ubiquitin ligase complex containing gp78 mediates sterol-accelerated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
    9. To examine if a statin-resistant, catalytically-active isoform of HMGCR could be generated, we altered the protein to include additional residues in the flap domain, which has a role in statin binding.
      Title: Human hydroxymethylglutaryl-coenzyme A reductase (HMGCR) and statin sensitivity.
    10. In this age and sex matched case-control study, the genotype distribution and allele frequency of this polymorphism of HMGCR were not associated with Alzheimer disease.
      Title: A functional polymorphism in the HMGCR promoter affects transcriptional activity but not the risk for Alzheimer disease in Swedish populations.
    Submit: New GeneRIF Correction See all (53)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

    Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13.

    Common variants at 30 loci contribute to polygenic dyslipidemia.

    Genetic variants influencing circulating lipid levels and risk of coronary artery disease.

    Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.

    Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.

    Low density lipoprotein cholesterol level QTL 3

    Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.

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    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    Nef nef HIV-1 Nef modulates expression of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGCR) in Jurkat cells PubMed

    Go to the HIV-1, Human Protein Interaction Database

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_000850.1 NP_821074.1 STARD13    BIND  PubMed STARD13 (RhoGAP) interacts with HMGCR (HMG CoA reductase). 
    P04035 Q07960 ARHGAP1    HPRD  PubMed  
    P04035 P04035 HMGCR    HPRD  PubMed  
    P04035 O15503 INSIG1    HPRD  PubMed  
    P04035 P17612 PRKACA    HPRD  PubMed  
    P04035 Q9Y3M8 STARD13    HPRD  PubMed  
    BioGRID:109399 BioGRID:106764 AMFR    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109399 BioGRID:116331 ERLIN2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109399 BioGRID:109850 INSIG1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109399 BioGRID:124744 STARD13    BioGRID  PubMed Two-hybrid 
    BioGRID:109399 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:109399 BioGRID:113258 VCP    BioGRID  PubMed Affinity Capture-Western 
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    General gene information

    Markers

    Genotypes

    Homology

    • Homologs of the HMGCR gene: The HMGCR gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.pombe, S.cerevisiae, K.lactis, E.gossypii, M.grisea, N.crassa, A.thaliana, and rice.
    • Map Viewer (Mouse, Rat)

    Pathways from BioSystems

    • Bile secretion, organism-specific biosystem (from KEGG)
      Bile secretion, organism-specific biosystemBile is a vital secretion, essential for digestion and absorption of fats and fat-soluble vitamins in the small intestine. Moreover, bile is an important route of elimination for excess cholesterol a...
    • Bile secretion, conserved biosystem (from KEGG)
      Bile secretion, conserved biosystemBile is a vital secretion, essential for digestion and absorption of fats and fat-soluble vitamins in the small intestine. Moreover, bile is an important route of elimination for excess cholesterol a...
    • C5 isoprenoid biosynthesis, mevalonate pathway, organism-specific biosystem (from KEGG)
      C5 isoprenoid biosynthesis, mevalonate pathway, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Terpenoid backbone biosynthesis
    • C5 isoprenoid biosynthesis, mevalonate pathway, conserved biosystem (from KEGG)
      C5 isoprenoid biosynthesis, mevalonate pathway, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Terpenoid backbone biosynthesis
    • Cholesterol Biosynthesis, organism-specific biosystem (from WikiPathways)
      Cholesterol Biosynthesis, organism-specific biosystemCholesterol is a waxy steroid metabolite found in the cell membranes and transported in the blood plasma of all animals. It is an essential structural component of mammalian cell membranes, where it ...
    • Cholesterol biosynthesis, organism-specific biosystem (from REACTOME)
      Cholesterol biosynthesis, organism-specific biosystemCholesterol is synthesized de novo from from acetyl CoA. The overall synthetic process is outlined in the figure below. Enzymes whose regulation plays a major role in determining the rate of choleste...
    • Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystem (from REACTOME)
      Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystemThe reactions involved in the metabolism of fatty acids and of the triacylglycerols and ketone bodies derived from them form a closely interrelated, coordinately regulated module that plays a central...
    • Metabolic pathways, organism-specific biosystem (from KEGG)
      Metabolic pathways, organism-specific biosystem
      Metabolic pathways
    • Metabolism, organism-specific biosystem (from REACTOME)
      Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
      Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
    • PPARA Activates Gene Expression, organism-specific biosystem (from REACTOME)
      PPARA Activates Gene Expression, organism-specific biosystemThe set of genes regulated by PPAR-alpha is not fully known in humans, however many examples have been found in mice. Genes directly activated by PPAR-alpha contain peroxisome proliferator receptor e...
    • Regulation of Lipid Metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha), organism-specific biosystem (from REACTOME)
      Regulation of Lipid Metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha), organism-specific biosystemPeroxisome proliferator-activated receptor alpha (PPAR-alpha) is the major regulator of fatty acid oxidation in the liver. PPARalpha is also the target of fibrate drugs used to treat abnormal plasma ...
    • Statin Pathway, organism-specific biosystem (from WikiPathways)
      Statin Pathway, organism-specific biosystemStatins inhibit endogenous cholesterol production by competitive inhibition of HMG-CoA reductase (HMGCR), the enzyme that catalyzes conversion of HMG-CoA to mevalonate, an early rate-limiting step in...
    • Terpenoid backbone biosynthesis, organism-specific biosystem (from KEGG)
      Terpenoid backbone biosynthesis, organism-specific biosystemTerpenoids, also known as isoprenoids, are a large class of natural products consisting of isoprene (C5) units. There are two biosynthetic pathways, the mevalonate pathway [MD:M00095] and the non-mev...
    • Terpenoid backbone biosynthesis, conserved biosystem (from KEGG)
      Terpenoid backbone biosynthesis, conserved biosystemTerpenoids, also known as isoprenoids, are a large class of natural products consisting of isoprene (C5) units. There are two biosynthetic pathways, the mevalonate pathway [MD:M00095] and the non-mev...
    • mevalonate pathway I, organism-specific biosystem (from BIOCYC)
      mevalonate pathway I, organism-specific biosystemGeneral Background The biosynthesis of : DELTA3-ISOPENTENYL-PP (IPP) occurs via the : PWY-922 (MVA pathway, this pathway). IPP is synthesized from the condensation of three acetyl-CoA molecules. ...
    • mevalonate pathway I, conserved biosystem (from BIOCYC)
      mevalonate pathway I, conserved biosystemGeneral Background The biosynthesis of |FRAME: DELTA3-ISOPENTENYL-PP| (IPP) can occur via two distinct routes: the |FRAME: PWY-922| (MVA pathway, this pathway) and the |FRAME:NONMEVIPP-PWY| (MEP pa...
    • superpathway of cholesterol biosynthesis, organism-specific biosystem (from BIOCYC)
      superpathway of cholesterol biosynthesis, organism-specific biosystem
      superpathway of cholesterol biosynthesis
    • superpathway of cholesterol biosynthesis, conserved biosystem (from BIOCYC)
      superpathway of cholesterol biosynthesis, conserved biosystemThe sequence of reactions in the cholesterol biosynthetic pathway may vary. This superpathway gives an overview of three possible routes of cholesterol biosynthesis. These routes exist because redu...
    • superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate), organism-specific biosystem (from BIOCYC)
      superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate), organism-specific biosystem: GERANYLGERANYL-PP (also known as geranylgeranyl pyrophosphate, or GGPP) is a crucial compound involved in the biosynthesis of a variety of terpenes and terpenoids, including central compounds such ...
    • superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate), conserved biosystem (from BIOCYC)
      superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate), conserved biosystem|FRAME: GERANYLGERANYL-PP| (also known as geranylgeranyl pyrophosphate, or GGPP) is a crucial compound involved in the biosynthesis of a variety of terpenes and terpenoids, including central compound...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    NADP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    hydroxymethylglutaryl-CoA reductase (NADPH) activity TAS
    Traceable Author Statement
    more info
    		  
    oxidoreductase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    cellular lipid metabolic process TAS
    Traceable Author Statement
    more info
    		  
    cholesterol biosynthetic process TAS
    Traceable Author Statement
    more info
    		  
    coenzyme A metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    germ cell migration TAS
    Traceable Author Statement
    more info
    		 PubMed 
    gonad development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    isoprenoid biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    small molecule metabolic process TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  
    integral to membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    peroxisomal membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    peroxisome IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    3-hydroxy-3-methylglutaryl-Coenzyme A reductase
    Names
    3-hydroxy-3-methylglutaryl-Coenzyme A reductase
    HMG-CoA reductase
    hydroxymethylglutaryl-CoA reductase
    3-hydroxy-3-methylglutaryl CoA reductase (NADPH)
    NP_000850.1
    NP_001124468.1
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011449.1 RefSeqGene

      Range
      5001..29934
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000859.2 → NP_000850.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AA648735, BC033692, CN278665, M11058, M62627
      Consensus CDS
      CCDS4027.1
      UniProtKB/Swiss-Prot
      P04035
      Related
      ENSP00000287936, OTTHUMP00000128250, ENST00000287936, OTTHUMT00000219877
      Conserved Domains (3) summary
      cd00643
      Location:465 – 871
      Blast Score: 1776
      HMG-CoA_reductase_classI; Class I hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR)
      TIGR00920
      Location:1 – 888
      Blast Score: 3905
      2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      cl14618
      Location:88 – 218
      Blast Score: 139
      SecD_SecF; Protein export membrane protein

    2. NM_001130996.1 → NP_001124468.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame coding exon in the middle region, as compared to variant 1. The resulting isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AA648735, BC033692, CN278665, M62627
      Consensus CDS
      CCDS47234.1
      UniProtKB/Swiss-Prot
      P04035
      Related
      ENSP00000340816, OTTHUMP00000222063, ENST00000343975, OTTHUMT00000369021
      Conserved Domains (4) summary
      cd00643
      Location:522 – 818
      Blast Score: 1379
      HMG-CoA_reductase_classI; Class I hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR)
      TIGR00920
      Location:1 – 835
      Blast Score: 3535
      2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      cl14618
      Location:88 – 218
      Blast Score: 139
      SecD_SecF; Protein export membrane protein
      cl00205
      Location:465 – 520
      Blast Score: 115
      HMG-CoA_reductase; Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR)

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000005.9 Reference GRCh37.p5 Primary Assembly

      Range
      74632993..74657926
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000137.1 Alternate HuRef

      Range
      69838165..69863098
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC008897.7 (39594..64420) None
    genomic AF273765.1 AAG21343.1
    genomic AY321356.1 AAP72015.1
    genomic CH471084.1 EAW95754.1
      EAW95755.1
      EAW95756.1
    genomic HB386655.1 CAZ64465.1
    mRNA AA648735.1 None
    mRNA AK292892.1 BAF85581.1
    mRNA AK296499.1 BAH12375.1
    mRNA AK299655.1 BAG61573.1
    mRNA AK312437.1 BAG35346.1
    mRNA AY429541.1 None
    mRNA AY429542.1 None
    mRNA AY429543.1 None
    mRNA BC024180.1 None
    mRNA BC033692.1 AAH33692.1
    mRNA CN278665.1 None
    mRNA M11058.1 AAA52679.1
    mRNA M62627.1 None
    mRNA M62633.1 None
    other-genetic DQ890855.2 ABM81781.1
    other-genetic DQ894009.2 ABM84935.1
    Protein Accession Links
    GenePept Link UniProtKB Link
    P04035.1 GenPept UniProtKB/Swiss-Prot:P04035
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
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