HMGCR - 3-hydroxy-3-methylglutaryl-coenzyme A reductase - human protein (Function)
 
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HMGCR »  3-hydroxy-3-methylglutaryl-coenzyme A reductase   [ EC 1.1.1.34 ]  (HMG-CoA reductase)
 
Gene name:  HMGCR
Family name: HMG-CoA reductase
Entry whose protein(s) existence is based on evidence at protein level
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1 84 3
GENE REF ISO

Function

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Overview 
Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.  
  • CuratedUniProtKB
According to TCDB this is a transporter from family:
the resistance-nodulation-cell division (rnd) superfamily  2.A.6.6.5  
GO molecular function 
Coenzyme bindingdefinition[GO:0050662]  
1
  • IDAUniProtKB
Hydroxymethylglutaryl-CoA reductase (NADPH) activitydefinition[GO:0004420]  
  • IEAEC 2 GO
Hydroxymethylglutaryl-CoA reductase activitydefinition[GO:0042282]  
1
  • IDAUniProtKB
NADPH bindingdefinition[GO:0070402]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
1
  • IPIIntAct
Protein homodimerization activitydefinition[GO:0042803] silver  
  • IEAOrtholog Compara
GO biological process 
Agingdefinition[GO:0007568] silver  
  • IEAOrtholog Compara
Coenzyme A metabolic processdefinition[GO:0015936] silver  
  • IEAInterPro 2 GO
Embryo developmentdefinition[GO:0009790] silver  
  • IEAOrtholog Compara
Isoprenoid biosynthetic processdefinition[GO:0008299] silver  
  • IEAOrtholog Compara
Myoblast differentiationdefinition[GO:0045445] silver  
  • IEAOrtholog Compara
Negative regulation of insulin secretion involved in cellular response to glucose stimulusdefinition[GO:0061179] silver  
  • IEAOrtholog Compara
Negative regulation of MAP kinase activitydefinition[GO:0043407] silver  
  • IEAOrtholog Compara
Negative regulation of striated muscle cell apoptotic processdefinition[GO:0010664] silver  
  • IEAOrtholog Compara
Negative regulation of vasodilationdefinition[GO:0045908] silver  
  • IEAOrtholog Compara
Negative regulation of wound healingdefinition[GO:0061045] silver  
  • IEAOrtholog Compara
Oxidation-reduction processdefinition[GO:0055114]  
  • IEAUniProtKB KW
Positive regulation of cardiac muscle cell apoptotic processdefinition[GO:0010666] silver  
  • IEAOrtholog Compara
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374] silver  
  • IEAOrtholog Compara
Positive regulation of skeletal muscle tissue developmentdefinition[GO:0048643] silver  
  • IEAOrtholog Compara
Positive regulation of smooth muscle cell proliferationdefinition[GO:0048661] silver  
  • IEAOrtholog Compara
Positive regulation of stress-activated MAPK cascadedefinition[GO:0032874] silver  
  • IEAOrtholog Compara
Protein tetramerizationdefinition[GO:0051262]  
1
  • IDAUniProtKB
Response to ethanoldefinition[GO:0045471] silver  
  • IEAOrtholog Compara
Response to nutrientdefinition[GO:0007584] silver  
  • IEAOrtholog Compara
Ubiquinone metabolic processdefinition[GO:0006743] silver  
  • IEAOrtholog Compara
Visual learningdefinition[GO:0008542] silver  
  • IEAOrtholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 1.1.1.34: (R)-mevalonate + CoA + 2 NADP(+) (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH.  
  • CuratedUniProtKB
It is regulated in the following manner
Regulated by a negative feedback mechanism through sterols and non-sterol metabolites derived from mevalonate. Inhibited by statins, a class of hypolipidemic agents used as pharmaceuticals to lower cholesterol levels in individuals at risk from cardiovascular disease due to hypercholesterolemia. Inhibition of HMGCR in the liver stimulates the LDL-receptors, which results in an increased clearance of LDL from the bloodstream and a decrease in blood cholesterol levels. The first results can be seen after one week of statin use and the effect is maximal after four to six weeks.  
1
  • CuratedUniProtKB
Pathways 
This protein is involved in the following pathway
According to KEGG, this protein belongs to the following pathways:
Bile secretion  hsa04976+3156  
Metabolic pathways  hsa01100+3156  
Terpenoid backbone biosynthesis  hsa00900+3156  
According to Reactome, this protein belongs to the following pathways:
Activation of gene expression by SREBF (SREBP)  REACT_147904  
Cholesterol biosynthesis  REACT_9405  
PPARA activates gene expression  REACT_116145  
 
More information is available from:
 

Keywords

Biological process 
Cholesterol biosynthesis  definition   [KW-0152]
Cholesterol metabolism  definition   [KW-0153]
Lipid biosynthesis  definition   [KW-0444]
Lipid metabolism  definition   [KW-0443]
Steroid biosynthesis  definition   [KW-0752]
Steroid metabolism  definition   [KW-0753]
Sterol biosynthesis  definition   [KW-0756]
Sterol metabolism  definition   [KW-1207]
Molecular function 
Oxidoreductase  definition   [KW-0560]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Enzyme and pathway databases
SABIO-RK: P04035
Other
GeneWiki: HMG-CoA_reductase
GenomeRNAi: 3156
PRO: PR:P04035
Chemistry
GuidetoPHARMACOLOGY: 639