HMG2 hydroxymethylglutaryl-CoA reductase (NADPH) HMG2 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Gene symbol: HMG2
Gene description: hydroxymethylglutaryl-CoA reductase (NADPH) HMG2
Primary source: FungiDB:YLR450W
Locus tag: YLR450W
See related: SGD:S000004442; AllianceGenome:SGD:S000004442
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Saccharomyces cerevisiae S288C (strain: S288C)
Lineage: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces
Summary: Enables hydroxymethylglutaryl-CoA reductase (NADPH) activity. Predicted to be involved in ergosterol biosynthetic process and isoprenoid biosynthetic process. Located in endoplasmic reticulum membrane and nuclear envelope. Part of proteasome complex. Human ortholog(s) of this gene implicated in several diseases, including asthma; coronary artery disease (multiple); dementia; diabetes mellitus (multiple); and neurodegenerative disease (multiple). Orthologous to human HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase). [provided by Alliance of Genome Resources, Apr 2022]
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Genomic context

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See HMG2 in Genome Data Viewer

Location:: chromosome: XII

Exon count:: 1

Sequence:: Chromosome: XII; NC_001144.5 (1032627..1035764)

Chromosome XII - NC_001144.5 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001144.5

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

An autonomous, but INSIG-modulated, role for the sterol sensing domain in mallostery-regulated ERAD of yeast HMG-CoA reductase.
Title: An autonomous, but INSIG-modulated, role for the sterol sensing domain in mallostery-regulated ERAD of yeast HMG-CoA reductase.
Nsg1-mediated stabilization of Hmg2 and the Nsg1-Hmg2 interaction required the early sterol lanosterol.
Title: Insulin-induced gene protein (INSIG)-dependent sterol regulation of Hmg2 endoplasmic reticulum-associated degradation (ERAD) in yeast.
The sterol-sensing domain (SSD) directly mediates signal-regulated endoplasmic reticulum-associated degradation (ERAD) of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase isozyme Hmg2.
Title: The sterol-sensing domain (SSD) directly mediates signal-regulated endoplasmic reticulum-associated degradation (ERAD) of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase isozyme Hmg2.
In the K6R substituted Hmg2 mutant, the squalene content was approximately 20-fold higher than in the wild-type EGY48 parental strain and ERG6 deletion did not further enhance squalene accumulation.
Title: Observations on squalene accumulation in Saccharomyces cerevisiae due to the manipulation of HMG2 and ERG6.
GGPP is the FPP-derived regulator of Hmg2p ubiquitination.
Title: Geranylgeranyl pyrophosphate is a potent regulator of HRD-dependent 3-Hydroxy-3-methylglutaryl-CoA reductase degradation in yeast.
Hrd1p was rate-limiting for Hmg2p-GFP retrotranslocation, which required ATP, the AAA-ATPase Cdc48p, and its receptor Ubx2p.
Title: In vitro analysis of Hrd1p-mediated retrotranslocation of its multispanning membrane substrate 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase.
although related, Hmg2p- and Hmg1p-induced ER remodeling are mechanistically distinct
Title: Genetic and structural analysis of Hmg2p-induced endoplasmic reticulum remodeling in Saccharomyces cerevisiae.
results show that farnesol causes Hmg2p to undergo a change to a less folded structure
Title: Lipid-mediated, reversible misfolding of a sterol-sensing domain protein.

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Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Orthologs from OrthoDB

Gene Ontology Provided by SGD

Function	Evidence Code	Pubs
enables hydroxymethylglutaryl-CoA reductase (NADPH) activity	IBA Inferred from Biological aspect of Ancestor more info
enables hydroxymethylglutaryl-CoA reductase (NADPH) activity	IDA Inferred from Direct Assay more info	PubMed
enables hydroxymethylglutaryl-CoA reductase (NADPH) activity	IEA Inferred from Electronic Annotation more info
enables hydroxymethylglutaryl-CoA reductase (NADPH) activity	IGI Inferred from Genetic Interaction more info	PubMed
enables oxidoreductase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in coenzyme A metabolic process	IEA Inferred from Electronic Annotation more info
involved_in ergosterol biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in ergosterol biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in ergosterol biosynthetic process	ISA Inferred from Sequence Alignment more info	PubMed
involved_in isoprenoid biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in isoprenoid biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in sterol biosynthetic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in endoplasmic reticulum	HDA more info	PubMed
is_active_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
is_active_in endoplasmic reticulum membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in nuclear envelope	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear envelope	IEA Inferred from Electronic Annotation more info
located_in nuclear periphery	HDA more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
is_active_in peroxisomal membrane	IBA Inferred from Biological aspect of Ancestor more info
part_of proteasome complex	IPI Inferred from Physical Interaction more info	PubMed

General protein information

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Preferred Names: hydroxymethylglutaryl-CoA reductase (NADPH) HMG2

NP_013555.1

EC 1.1.1.34

HMG-CoA reductase; converts HMG-CoA to mevalonate, a rate-limiting step in sterol biosynthesis; one of two isozymes; overproduction induces assembly of peripheral ER membrane arrays and short nuclear-associated membrane stacks; forms foci at nuclear periphery upon DNA replication stress; primarily expressed on the peri-membrane side of the ER; human homolog HMGCR can complement yeast hmg2 mutant

NCBI Reference Sequences (RefSeq)

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Genome Annotation

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

Reference assembly

Genomic

NC_001144.5 Reference assembly

Range

1032627..1035764

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001182338.1 → NP_013555.1 TPA: hydroxymethylglutaryl-CoA reductase (NADPH) HMG2 [Saccharomyces cerevisiae S288C]

See identical proteins and their annotated locations for NP_013555.1

Status: REVIEWED

UniProtKB/Swiss-Prot

D6VZ84, E9P8X3, P12684

UniProtKB/TrEMBL

A0A8H4BXL6, A7A1W9, C8ZE57, N1P0A7

Conserved Domains (3) summary

TIGR00533
Location:612 → 1021

HMG_CoA_R_NADP; 3-hydroxy-3-methylglutaryl Coenzyme A reductase, hydroxymethylglutaryl-CoA reductase (NADP)

TIGR00920
Location:195 → 1030

2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase

pfam13323
Location:10 → 159

HPIH; N-terminal domain with HPIH motif