Gene/Proteome Database (LMPD)

LMPD ID
LMP002414
Gene ID
15357
Species
Mus musculus (Mouse)
Gene Name
3-hydroxy-3-methylglutaryl-Coenzyme A reductase
Gene Symbol
Hmgcr
Synonyms
HMG-CoAR; Red
Alternate Names
3-hydroxy-3-methylglutaryl-coenzyme A reductase; HMG-CoA reductase; 3-hydroxy-3-methylglutaryl-CoA reductase
Chromosome
13
Map Location
13 D1|13 50.65 cM
EC Number
1.1.1.34

Proteins

3-hydroxy-3-methylglutaryl-coenzyme A reductase
Refseq ID NP_032281
Protein GI 160358778
UniProt ID Q01237
mRNA ID NM_008255
Length 887
RefSeq Status VALIDATED
MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSSDIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTGLNEALPFFLLLIDLSRASALAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIGVGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFARVLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTAEQAKVSLGLDEDVSKRIEPSVSLWQFYLSKMISMDIEQVITLSLAFLLAVKYIFFEQAETESTLSLKNPITSPVVTSKKAQDNCCRREPLLVRRNQKLSSVEEDPGANQERKVEVIKPLVVEAETTSRATFVLGASVASPPSALGTQEPGIELPIEPRPNEECLQILENAEKGAKFLSDAEIIQLVNAKHIPAYKLETLMETHERGVSIRRQLLSTKLAEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGVAGPLCLDGKEYQVPMATTEGCLVASTNRGCRAISLGGGASSRVLADGMTRGPVVRLPRACDSAEVKTWLETPEGFAVIKEAFDSTSRFARLQKLHVTMAGRNLYIRFQSRTGDAMGMNMISKGTEKALLKLQEFFPDMQILAVSGNYCTDKKPAAINWIEGRGKTVVCEAVIPAKVVREVLKTTTEAMVDVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITLMEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLARIVCGTVMAGELSLMAALAAGHLVRSHMVHNRSKINLQDLQGTCTKKAA

Gene Information

Entrez Gene ID
15357
Gene Name
3-hydroxy-3-methylglutaryl-Coenzyme A reductase
Gene Symbol
Hmgcr
Species
Mus musculus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005789 IEA:InterPro C endoplasmic reticulum membrane
GO:0016021 IEA:UniProtKB-KW C integral component of membrane
GO:0005778 IEA:Ensembl C peroxisomal membrane
GO:0070402 IEA:Ensembl F NADPH binding
GO:0004420 IDA:MGI F hydroxymethylglutaryl-CoA reductase (NADPH) activity
GO:0042282 IEA:Ensembl F hydroxymethylglutaryl-CoA reductase activity
GO:0007568 IEA:Ensembl P aging
GO:0006695 IDA:MGI P cholesterol biosynthetic process
GO:0015936 IEA:InterPro P coenzyme A metabolic process
GO:0008299 IEA:Ensembl P isoprenoid biosynthetic process
GO:0045445 IEA:Ensembl P myoblast differentiation
GO:0043407 IGI:MGI P negative regulation of MAP kinase activity
GO:0061179 IEA:Ensembl P negative regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0010664 IEA:Ensembl P negative regulation of striated muscle cell apoptotic process
GO:0045908 IEA:Ensembl P negative regulation of vasodilation
GO:0061045 IEA:Ensembl P negative regulation of wound healing
GO:0070374 IEA:Ensembl P positive regulation of ERK1 and ERK2 cascade
GO:0010666 IEA:Ensembl P positive regulation of cardiac muscle cell apoptotic process
GO:0048643 IEA:Ensembl P positive regulation of skeletal muscle tissue development
GO:0048661 IEA:Ensembl P positive regulation of smooth muscle cell proliferation
GO:0032874 IEA:Ensembl P positive regulation of stress-activated MAPK cascade
GO:0051262 IEA:Ensembl P protein tetramerization
GO:0045471 IEA:Ensembl P response to ethanol
GO:0007584 IEA:Ensembl P response to nutrient
GO:0006743 IEA:Ensembl P ubiquinone metabolic process
GO:0008542 IGI:MGI P visual learning

KEGG Pathway Links

KEGG Pathway ID Description
mmu04152 AMPK signaling pathway
mmu04976 Bile secretion

Domain Information

InterPro Annotations

Accession Description
IPR023282 Hydroxymethylglutaryl-CoA reductase, N-terminal
IPR002202 Hydroxymethylglutaryl-CoA reductase, class I/II
IPR009023 Hydroxymethylglutaryl-CoA reductase, class I/II, NAD/NADP-binding domain
IPR023074 Hydroxymethylglutaryl-CoA reductase, class I/II, catalytic domain
IPR023076 Hydroxymethylglutaryl-CoA reductase, class I/II, conserved site
IPR009029 Hydroxymethylglutaryl-CoA reductase, class I/II, substrate-binding domain
IPR004554 Hydroxymethylglutaryl-CoA reductase, eukaryotic/arcaheal type
IPR004816 Hydroxymethylglutaryl-CoA reductase, metazoan
IPR000731 Sterol-sensing domain

UniProt Annotations

Entry Information

Gene Name
3-hydroxy-3-methylglutaryl-Coenzyme A reductase
Protein Entry
HMDH_MOUSE
UniProt ID
Q01237
Species
Mouse

Comments

Comment Type Description
Catalytic Activity (R)-mevalonate + CoA + 2 NADP(+) = (S)-3- hydroxy-3-methylglutaryl-CoA + 2 NADPH. {ECO:0000255|PROSITE- ProRule:PRU10003}.
Enzyme Regulation Regulated by a negative feedback mechanism through sterols and non-sterol metabolites derived from mevalonate.
Function 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.
Pathway Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
Ptm N-glycosylated. Deglycosylated by NGLY1 on release from the endoplasmic reticulum (ER) in a sterol-mediated manner. {ECO:0000250}.
Ptm Undergoes sterol-mediated ubiquitination and ER-association degradation (ERAD). Accumulation of sterols in the endoplasmic reticulum (ER) membrane, triggers binding of the reductase to the ER membrane protein INSIG1. This INSIG binding leads to the recruitment of the ubiquitin ligase, AMFR/gp78, initiating ubiquitination of the reductase. The ubiquitinated reductase is then extracted from the ER membrane and delivered to cytosolic 26S proteosomes by a mechanism probably mediated by the ATPase Valosin-containing protein VCP/p97. Lys-248 is the main site of ubiquitination. Ubiquitination is enhanced by the presence of a geranylgeranylated protein (By similarity). {ECO:0000250}.
Similarity Belongs to the HMG-CoA reductase family. {ECO:0000305}.
Similarity Contains 1 SSD (sterol-sensing) domain. {ECO:0000255|PROSITE-ProRule:PRU00199}.
Subcellular Location Endoplasmic reticulum membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}.
Subunit Homodimer. Interacts with INSIG1 (via its SSD); the interaction, accelerated by sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its ubiquitination by the sterol-mediated ERAD pathway. Interacts with UBIAD1 (By similarity). {ECO:0000250}.

Identical and Related Proteins

Unique RefSeq proteins for LMP002414 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
160358778 RefSeq NP_032281 887 3-hydroxy-3-methylglutaryl-coenzyme A reductase

Identical Sequences to LMP002414 proteins

Reference Database Accession Length Protein Name
GI:160358778 GenBank EDL00884.1 887 3-hydroxy-3-methylglutaryl-Coenzyme A reductase [Mus musculus]
GI:160358778 RefSeq XP_006517594.1 887 PREDICTED: 3-hydroxy-3-methylglutaryl-coenzyme A reductase isoform X2 [Mus musculus]
GI:160358778 RefSeq XP_006517595.1 887 PREDICTED: 3-hydroxy-3-methylglutaryl-coenzyme A reductase isoform X3 [Mus musculus]
GI:160358778 SwissProt Q01237.3 887 RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase; Short=HMG-CoA reductase [Mus musculus]

Related Sequences to LMP002414 proteins

Reference Database Accession Length Protein Name
GI:160358778 GenBank AAH85083.1 887 3-hydroxy-3-methylglutaryl-Coenzyme A reductase [Mus musculus]
GI:160358778 GenBank AAH91631.1 881 Unknown (protein for IMAGE:7197923), partial [Xenopus laevis]
GI:160358778 GenBank EDM10120.1 887 3-hydroxy-3-methylglutaryl-Coenzyme A reductase [Rattus norvegicus]
GI:160358778 RefSeq NP_037266.2 887 3-hydroxy-3-methylglutaryl-coenzyme A reductase [Rattus norvegicus]
GI:160358778 RefSeq XP_006517593.1 897 PREDICTED: 3-hydroxy-3-methylglutaryl-coenzyme A reductase isoform X1 [Mus musculus]
GI:160358778 SwissProt P51639.2 887 RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase; Short=HMG-CoA reductase [Rattus norvegicus]