Gene/Proteome Database (LMPD)

LMPD ID
LMP012544
Gene ID
25675
Species
Rattus norvegicus (Rat)
Gene Name
3-hydroxy-3-methylglutaryl-CoA reductase
Gene Symbol
Hmgcr
Synonyms
3H3M;
Alternate Names
3-hydroxy-3-methylglutaryl-coenzyme A reductase; HMG-CoA reductase;
Chromosome
2
Map Location
2q12
EC Number
1.1.1.34;
Summary
enzyme involved in mevalonate synthesis [RGD, Feb 2006]
Orthologs
View orthologs and multiple alignments for Hmgcr

Proteins

3-hydroxy-3-methylglutaryl-coenzyme A reductase
Refseq ID NP_037266
Protein GI 40538852
UniProt ID P51639
mRNA ID NM_013134
Length 887
MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSSDIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTGLNEALPFFLLLIDLSRASALAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIGVGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFARVLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTAEQSKVSLGLAEDVSKRIEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQAETESTLSLKNPITSPVVTPKKAQDNCCRREPLLVRRNQKLSSVEEDPGVNQDRKVEVIKPLVAEAETSGRATFVLGASAASPPLALGAQEPGIELPSEPRPNEECLQILESAEKGAKFLSDAEIIQLVNAKHIPAYKLETLMETHERGVSIRRQLLSAKLAEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGVAGPLCLDGKEYQVPMATTEGCLVASTNRGCRAISLGGGASSRVLADGMSRGPVVRLPRACDSAEVKSWLETPEGFAVVKEAFDSTSRFARLQKLHVTLAGRNLYIRLQSKTGDAMGMNMISKGTEKALLKLQEFFPELQILAVSGNYCTDKKPAAINWIEGRGKTVVCEAVIPAKVVREVLKTTTEAMVDVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITLMEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLARIVCGTVMAGELSLMAALAAGHLVRSHMVHNRSKINLQDLQGTCTKKAA

Gene Information

Entrez Gene ID
25675
Gene Name
3-hydroxy-3-methylglutaryl-CoA reductase
Gene Symbol
Hmgcr
Species
Rattus norvegicus

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:0043231 IDA:RGD C intracellular membrane-bounded organelle
GO:0005778 IEA:Ensembl C peroxisomal membrane
GO:0070402 IEA:Ensembl F NADPH binding
GO:0004420 IEA:UniProtKB-EC F hydroxymethylglutaryl-CoA reductase (NADPH) activity
GO:0042282 IDA:RGD F hydroxymethylglutaryl-CoA reductase activity
GO:0042803 IDA:RGD F protein homodimerization activity
GO:0051721 IPI:RGD F protein phosphatase 2A binding
GO:0007568 IEP:RGD P aging
GO:0006695 IDA:RGD P cholesterol biosynthetic process
GO:0015936 IEA:InterPro P coenzyme A metabolic process
GO:0010142 TAS:RGD P farnesyl diphosphate biosynthetic process, mevalonate pathway
GO:0008299 IDA:RGD P isoprenoid biosynthetic process
GO:0045445 IEP:RGD P myoblast differentiation
GO:0043407 IEA:Ensembl P negative regulation of MAP kinase activity
GO:0043066 IMP:RGD P negative regulation of apoptotic process
GO:0061179 IMP:RGD P negative regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0010664 IMP:RGD P negative regulation of striated muscle cell apoptotic process
GO:0045908 IMP:RGD P negative regulation of vasodilation
GO:0061045 IMP:RGD P negative regulation of wound healing
GO:0070374 IMP:RGD P positive regulation of ERK1 and ERK2 cascade
GO:0010666 IMP:RGD P positive regulation of cardiac muscle cell apoptotic process
GO:0008284 IMP:RGD P positive regulation of cell proliferation
GO:0048643 IMP:RGD P positive regulation of skeletal muscle tissue development
GO:0048661 IMP:RGD P positive regulation of smooth muscle cell proliferation
GO:0032874 IMP:RGD P positive regulation of stress-activated MAPK cascade
GO:0051262 IEA:Ensembl P protein tetramerization
GO:0045471 IEP:RGD P response to ethanol
GO:0007584 IEP:RGD P response to nutrient
GO:0006743 IMP:RGD P ubiquinone metabolic process
GO:0008542 IEA:Ensembl P visual learning

KEGG Pathway Links

KEGG Pathway ID Description
ko04152 AMPK signaling pathway
rno04152 AMPK signaling pathway
ko04976 Bile secretion
rno04976 Bile secretion
M00095 C5 isoprenoid biosynthesis, mevalonate pathway
rno01100 Metabolic pathways
ko00900 Terpenoid backbone biosynthesis
rno00900 Terpenoid backbone biosynthesis

REACTOME Pathway Links

REACTOME Pathway ID Description
5954496 Activation of gene expression by SREBF (SREBP)
5953924 Cholesterol biosynthesis
5953288 Fatty acid, triacylglycerol, and ketone body metabolism
5953250 Metabolism
5953289 Metabolism of lipids and lipoproteins
5954333 PPARA activates gene expression
5954497 Regulation of cholesterol biosynthesis by SREBP (SREBF)
5954222 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)

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-CoA reductase
Protein Entry
HMDH_RAT
UniProt ID
P51639
Species
Rat

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
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)
Similarity Belongs to the HMG-CoA reductase family
Similarity Contains 1 SSD (sterol-sensing) domain
Subcellular Location Endoplasmic reticulum membrane; Multi-pass membrane protein.
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)

Identical and Related Proteins

Unique RefSeq proteins for LMP012544 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
40538852 RefSeq NP_037266 887 3-hydroxy-3-methylglutaryl-coenzyme A reductase

Identical Sequences to LMP012544 proteins

Reference Database Accession Length Protein Name
GI:40538852 GenBank AAH64654.1 887 3-hydroxy-3-methylglutaryl-Coenzyme A reductase [Rattus norvegicus]
GI:40538852 GenBank EDM10120.1 887 3-hydroxy-3-methylglutaryl-Coenzyme A reductase [Rattus norvegicus]
GI:40538852 SwissProt P51639.2 887 RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase; Short=HMG-CoA reductase [Rattus norvegicus]

Related Sequences to LMP012544 proteins

Reference Database Accession Length Protein Name
GI:40538852 GenBank AAH64654.1 887 3-hydroxy-3-methylglutaryl-Coenzyme A reductase [Rattus norvegicus]
GI:40538852 GenBank EDM10120.1 887 3-hydroxy-3-methylglutaryl-Coenzyme A reductase [Rattus norvegicus]
GI:40538852 SwissProt P51639.2 887 RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase; Short=HMG-CoA reductase [Rattus norvegicus]