HMG-CoA reductase

HMGCR
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHMGCR, HMG-CoA reductase, Entrez 3156, LDLCQ3, 3-hydroxy-3-methylglutaryl-CoA reductase, Hydroxymethylglutaryl-CoA reductase
External IDsOMIM: 142910; MGI: 96159; HomoloGene: 30994; GeneCards: HMGCR; OMA:HMGCR - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000859
NM_001130996
NM_001364187

NM_008255
NM_001360165
NM_001360166

RefSeq (protein)

NP_000850
NP_001124468
NP_001351116
NP_000850.1

NP_032281
NP_001347094
NP_001347095

Location (UCSC)Chr 5: 75.34 – 75.36 MbChr 13: 96.79 – 96.81 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
hydroxymethylglutaryl-CoA reductase (NADH)
Identifiers
EC no.1.1.1.88
CAS no.37250-24-1
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
hydroxymethylglutaryl-CoA reductase (NADPH)
HMG-CoA reductase (NADPH), Human
Identifiers
EC no.1.1.1.34
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, official symbol HMGCR) is the rate-controlling enzyme (NADH-dependent, EC 1.1.1.88; NADPH-dependent, EC 1.1.1.34) of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids. HMGCR catalyzes the conversion of HMG-CoA to mevalonic acid, a necessary step in the biosynthesis of cholesterol. Normally in mammalian cells this enzyme is competitively suppressed so that its effect is controlled. This enzyme is the target of the widely available cholesterol-lowering drugs known collectively as the statins, which help treat dyslipidemia.

HMG-CoA reductase is anchored in the membrane of the endoplasmic reticulum, and was long regarded as having seven transmembrane domains, with the active site located in a long carboxyl terminal domain in the cytosol. More recent evidence shows it to contain eight transmembrane domains.[5]

In humans, the gene for HMG-CoA reductase (NADPH) is located on the long arm of the fifth chromosome (5q13.3-14).[6] Related enzymes having the same function are also present in other animals, plants and bacteria.

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000113161Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021670Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Roitelman J, Olender EH, Bar-Nun S, Dunn WA, Simoni RD (June 1992). "Immunological evidence for eight spans in the membrane domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase: implications for enzyme degradation in the endoplasmic reticulum". The Journal of Cell Biology. 117 (5): 959–973. doi:10.1083/jcb.117.5.959. PMC 2289486. PMID 1374417.
  6. ^ Lindgren V, Luskey KL, Russell DW, Francke U (December 1985). "Human genes involved in cholesterol metabolism: chromosomal mapping of the loci for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase with cDNA probes". Proceedings of the National Academy of Sciences of the United States of America. 82 (24): 8567–8571. Bibcode:1985PNAS...82.8567L. doi:10.1073/pnas.82.24.8567. PMC 390958. PMID 3866240.