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HMGCR 3-hydroxy-3-methylglutaryl-CoA reductase [ Homo sapiens (human) ]

Gene ID: 3156, updated on 12-Aug-2018

Summary

Official Symbol
HMGCRprovided by HGNC
Official Full Name
3-hydroxy-3-methylglutaryl-CoA reductaseprovided by HGNC
Primary source
HGNC:HGNC:5006
See related
Ensembl:ENSG00000113161 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]
Expression
Ubiquitous expression in brain (RPKM 31.2), colon (RPKM 23.2) and 25 other tissues See more
Orthologs

Genomic context

See HMGCR in Genome Data Viewer
Location:
5q13.3
Exon count:
22
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 5 NC_000005.10 (75336334..75362101)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (74632159..74657926)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 1336 Neighboring gene ankyrin repeat domain 31 Neighboring gene SUMO2 pseudogene 5 Neighboring gene collagen type IV alpha 3 binding protein Neighboring gene ribosomal protein S26 pseudogene 26 Neighboring gene RNA, U7 small nuclear 175 pseudogene Neighboring gene DNA polymerase kappa

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
A genome wide association study identifies common variants associated with lipid levels in the Chinese population.
NHGRI GWA Catalog
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.
NHGRI GWA Catalog
Biological, clinical and population relevance of 95 loci for blood lipids.
NHGRI GWA Catalog
Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13.
NHGRI GWA Catalog
Common variants at 30 loci contribute to polygenic dyslipidemia.
NHGRI GWA Catalog
Discovery and refinement of loci associated with lipid levels.
NHGRI GWA Catalog
Genetic variants influencing circulating lipid levels and risk of coronary artery disease.
NHGRI GWA Catalog
Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.
NHGRI GWA Catalog
Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits.
NHGRI GWA Catalog
Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.
NHGRI GWA Catalog
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.
NHGRI GWA Catalog

HIV-1 interactions

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 Interaction Database

Pathways from BioSystems

  • AMP-activated Protein Kinase (AMPK) Signaling, organism-specific biosystem (from WikiPathways)
    AMP-activated Protein Kinase (AMPK) Signaling, organism-specific biosystemAMPK signaling pathway, a fuel sensor and regulator, promotes ATP-producing and inhibits ATP-consuming pathways in various tissues. AMPK is a heterotrimer composed of alpha-catalytic and beta and gam...
  • AMPK signaling pathway, organism-specific biosystem (from KEGG)
    AMPK signaling pathway, organism-specific biosystemAMP-activated protein kinase (AMPK) is a serine threonine kinase that is highly conserved through evolution. AMPK system acts as a sensor of cellular energy status. It is activated by increases in th...
  • AMPK signaling pathway, conserved biosystem (from KEGG)
    AMPK signaling pathway, conserved biosystemAMP-activated protein kinase (AMPK) is a serine threonine kinase that is highly conserved through evolution. AMPK system acts as a sensor of cellular energy status. It is activated by increases in th...
  • Activation of gene expression by SREBF (SREBP), organism-specific biosystem (from REACTOME)
    Activation of gene expression by SREBF (SREBP), organism-specific biosystemAfter transiting to the nucleus SREBPs (SREBP1A/1C/2, SREBFs) bind short sequences, sterol regulatory elements (SREs), in the promoters of target genes (reviewed in Eberle et al. 2004, Weber et al. 2...
  • 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...
  • Integrated Breast Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Breast Cancer Pathway, organism-specific biosystemThis pathway incorporates the most important proteins for Breast Cancer. The Rp score from the Connectivity-Maps (C-Maps) webserver was used to determine the rank of the most important proteins in Br...
  • 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 cholesterol biosynthesis by SREBP (SREBF), organism-specific biosystem (from REACTOME)
    Regulation of cholesterol biosynthesis by SREBP (SREBF), organism-specific biosystemSterol regulatory element binding proteins (SREBPs, SREBFs) respond to low cholesterol concentrations by transiting to the nucleus and activating genes involved in cholesterol and lipid biosynthesis ...
  • 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 ...
  • SREBF and miR33 in cholesterol and lipid homeostasis, organism-specific biosystem (from WikiPathways)
    SREBF and miR33 in cholesterol and lipid homeostasis, organism-specific biosystemThis pathway describes transcription factor-microRNA circuits governing cholesterol and lipid homeostasis. It is based on a seminar by Dr. Anders Näär.
  • 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...
  • Sterol Regulatory Element-Binding Proteins (SREBP) signalling, organism-specific biosystem (from WikiPathways)
    Sterol Regulatory Element-Binding Proteins (SREBP) signalling, organism-specific biosystemSterol regulatory element-binding proteins (SREBPs) are membrane-bound proteins that act as transcription factors. They regulate lipid, especially cholesterol, biosynthesis and uptake at a transcript...
  • Target Of Rapamycin (TOR) Signaling, organism-specific biosystem (from WikiPathways)
    Target Of Rapamycin (TOR) Signaling, organism-specific biosystemTOR signaling is responsible for a cellular reaction towards nutrient and energy availability and hypoxia/stress. The mammalian Target Of Rapamycin (mTOR), a serine/threonine kinase, is the central r...
  • 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, organism-specific biosystem (from BIOCYC)
    mevalonate pathway, organism-specific biosystemGeneral Background In humans, this pathway leads to : PWY66-341, : PWY-6061 and all steroid biosynthesis pathways via the formation of : FARNESYL-PP (FPP). The : DELTA3-ISOPENTENYL-PP (IPP) from thi...
  • 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
    superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate)
  • 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...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
NADPH binding IDA
Inferred from Direct Assay
more info
PubMed 
coenzyme binding IDA
Inferred from Direct Assay
more info
PubMed 
hydroxymethylglutaryl-CoA reductase (NADPH) activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
hydroxymethylglutaryl-CoA reductase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
hydroxymethylglutaryl-CoA reductase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IEA
Inferred from Electronic Annotation
more info
 
protein phosphatase 2A binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
aging IEA
Inferred from Electronic Annotation
more info
 
cholesterol biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
coenzyme A metabolic process IEA
Inferred from Electronic Annotation
more info
 
isoprenoid biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
myoblast differentiation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of MAP kinase activity IEA
Inferred from Electronic Annotation
more info
 
negative regulation of blood vessel diameter IEA
Inferred from Electronic Annotation
more info
 
negative regulation of insulin secretion involved in cellular response to glucose stimulus IEA
Inferred from Electronic Annotation
more info
 
negative regulation of striated muscle cell apoptotic process IEA
Inferred from Electronic Annotation
more info
 
negative regulation of wound healing IEA
Inferred from Electronic Annotation
more info
 
oxidation-reduction process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of ERK1 and ERK2 cascade IEA
Inferred from Electronic Annotation
more info
 
positive regulation of cardiac muscle cell apoptotic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of skeletal muscle tissue development IEA
Inferred from Electronic Annotation
more info
 
positive regulation of smooth muscle cell proliferation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of stress-activated MAPK cascade IEA
Inferred from Electronic Annotation
more info
 
protein tetramerization IDA
Inferred from Direct Assay
more info
PubMed 
regulation of cholesterol biosynthetic process TAS
Traceable Author Statement
more info
 
regulation of lipid metabolic process TAS
Traceable Author Statement
more info
 
response to ethanol IEA
Inferred from Electronic Annotation
more info
 
response to nutrient IEA
Inferred from Electronic Annotation
more info
 
sterol biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquinone metabolic process IEA
Inferred from Electronic Annotation
more info
 
visual learning IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
endoplasmic reticulum IDA
Inferred from Direct Assay
more info
PubMed 
endoplasmic reticulum membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
PubMed 
integral component of membrane IEA
Inferred from Electronic Annotation
more info
 
peroxisomal membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
peroxisomal membrane IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
3-hydroxy-3-methylglutaryl-Coenzyme A reductase
Names
3-hydroxy-3-methylglutaryl CoA reductase (NADPH)
HMG-CoA reductase
hydroxymethylglutaryl-CoA reductase
NP_000850.1
NP_001124468.1
XP_011541659.1
XP_011541660.1
XP_011541661.1

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_000859.2NP_000850.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform 1

    See identical proteins and their annotated locations for NP_000850.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Variants 1 and 3 both encode the same isoform (1).
    Source sequence(s)
    AA648735, BC033692, CN278665, M11058, M62627
    Consensus CDS
    CCDS4027.1
    UniProtKB/Swiss-Prot
    P04035
    UniProtKB/TrEMBL
    A0A024RAP2
    Related
    ENSP00000287936.4, OTTHUMP00000128250, ENST00000287936.8, OTTHUMT00000219877
    Conserved Domains (1) summary
    TIGR00920
    Location:1888
    2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
  2. NM_001130996.1NP_001124468.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform 2

    See identical proteins and their annotated locations for NP_001124468.1

    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
    ENSP00000340816.5, OTTHUMP00000222063, ENST00000343975.9, OTTHUMT00000369021
    Conserved Domains (1) summary
    TIGR00920
    Location:1835
    2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
  3. NM_001364187.1NP_001351116.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1 and 3 both encode the same isoform (1).
    Source sequence(s)
    AC008897
    Conserved Domains (1) summary
    TIGR00920
    Location:1888
    2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p12 Primary Assembly

    Range
    75336334..75362101
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011543357.1XP_011541659.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X1

    UniProtKB/Swiss-Prot
    P04035
    Conserved Domains (3) summary
    cd00643
    Location:485891
    HMG-CoA_reductase_classI; Class I hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR)
    TIGR00920
    Location:21908
    2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
    cl21543
    Location:108238
    MMPL; MMPL family
  2. XM_011543359.1XP_011541661.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X3

    Conserved Domains (3) summary
    cd00643
    Location:485838
    HMG-CoA_reductase_classI; Class I hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR)
    TIGR00920
    Location:21855
    2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
    cl21543
    Location:108238
    MMPL; MMPL family
  3. XM_011543358.1XP_011541660.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X2

    See identical proteins and their annotated locations for XP_011541660.1

    UniProtKB/Swiss-Prot
    P04035
    UniProtKB/TrEMBL
    A0A024RAP2
    Conserved Domains (1) summary
    TIGR00920
    Location:1888
    2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
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