Hmgcs2 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Hmgcs2provided by MGI
Official Full Name: 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2provided by MGI
Primary source: MGI:MGI:101939
See related: Ensembl:ENSMUSG00000027875 AllianceGenome:MGI:101939
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: mHS; 1300002P16
Summary: Enables hydroxymethylglutaryl-CoA synthase activity. Predicted to be involved in acetyl-CoA metabolic process; farnesyl diphosphate biosynthetic process, mevalonate pathway; and ketone body biosynthetic process. Located in mitochondrion. Is expressed in several structures, including alimentary system; cardiovascular system; facial bone primordium; nervous system; and reproductive system. Used to study HMG-CoA synthase 2 deficiency. Human ortholog(s) of this gene implicated in HMG-CoA synthase 2 deficiency. Orthologous to human HMGCS2 (3-hydroxy-3-methylglutaryl-CoA synthase 2). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in liver E18 (RPKM 447.3), liver adult (RPKM 391.9) and 3 other tissues See more
Orthologs: human all
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Genomic context

Location:: 3 F2.2; 3 42.74 cM

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	3	NC_000069.7 (98187747..98218054)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	3	NC_000069.6 (98280431..98310738)

Chromosome 3 - NC_000069.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Downregulation of HMGCS2 mediated AECIIs lipid metabolic alteration promotes pulmonary fibrosis by activating fibroblasts.
Title: Downregulation of HMGCS2 mediated AECIIs lipid metabolic alteration promotes pulmonary fibrosis by activating fibroblasts.
Liver-Derived Ketogenesis via Overexpressing HMGCS2 Promotes the Recovery of Spinal Cord Injury.
Title: Liver-Derived Ketogenesis via Overexpressing HMGCS2 Promotes the Recovery of Spinal Cord Injury.
Hmgcs2 regulates M2 polarization of macrophages to repair myocardial injury induced by sepsis.
Title: Hmgcs2 regulates M2 polarization of macrophages to repair myocardial injury induced by sepsis.
LONP1 targets HMGCS2 to protect mitochondrial function and attenuate chronic kidney disease.
Title: LONP1 targets HMGCS2 to protect mitochondrial function and attenuate chronic kidney disease.
To test if Hmgcs2 is important for gonad development in mammals, we pursued two lines of investigations. Firstly, we generated Hmgcs2-null mice using CRISPR/Cas9 and found that these mice had gonads that developed normally even on a sensitized background
Title: The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice.
To elucidate the relationship between HMGCS2 and NF-kB, we tested inhibited and over-expressed NF-kB. We found that NF-kB acted as a positive regulator for HMGCS2 under ketosis treatment conditions.
Title: Silibinin inhibits in vitro ketosis by regulating HMGCS2 and NF-kB: elucidation of signaling molecule relationship under ketotic conditions.
It is a key enzyme for catalyzing b-hydroxybutyric acid production, and observed in early Alzheimer's disease.And a hepatic inflammatory factor, IL-6 enhances ketogenesis through HMGCS2 signaling activation by p38/NF-kB p65.
Title: Early interleukin-6 enhances hepatic ketogenesis in APP(SWE)/PSEN1dE9 mice via 3-hydroxy-3-methylglutary-CoA synthase 2 signaling activation by p38/nuclear factor κB p65.
Using in vitro ketosis model by glucose starvation, studied inhibition of ketosis by momilactone B. Found momilactone B could regulate the angiopoietin-like-3 (ANGPTL3)-lipoprotein lipase (LPL)pathway, and suppressed the expression of HMGCS2 through the increased expression of STAT5b.
Title: Momilactone B Inhibits Ketosis In Vitro by Regulating the ANGPTL3-LPL Pathway and Inhibiting HMGCS2.
HMGCS2 was identified as a major down-regulated protein in colonic crypts isolated from Keratin 8-/- mice.
Title: Keratin 8 absence down-regulates colonocyte HMGCS2 and modulates colonic ketogenesis and energy metabolism.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (10) 1 citation
Targeted (3) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Hmgcs2 (e-PCR), detects polymorphism
- UniSTS:527387

U12791 (e-PCR)
- UniSTS:125673

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables hydroxymethylglutaryl-CoA synthase activity	IBA Inferred from Biological aspect of Ancestor more info
enables hydroxymethylglutaryl-CoA synthase activity	IDA Inferred from Direct Assay more info	PubMed
enables hydroxymethylglutaryl-CoA synthase activity	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in acetyl-CoA metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in acetyl-CoA metabolic process	IEA Inferred from Electronic Annotation more info
involved_in acetyl-CoA metabolic process	ISO Inferred from Sequence Orthology more info
involved_in adipose tissue development	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amino acid stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to fatty acid	IEA Inferred from Electronic Annotation more info
involved_in cellular response to glucocorticoid stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to insulin stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in cholesterol biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in farnesyl diphosphate biosynthetic process, mevalonate pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in farnesyl diphosphate biosynthetic process, mevalonate pathway	IEA Inferred from Electronic Annotation more info
involved_in ketone body biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in ketone body biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in kidney development	IEA Inferred from Electronic Annotation more info
involved_in liver development	IEA Inferred from Electronic Annotation more info
involved_in lung development	IEA Inferred from Electronic Annotation more info
involved_in midgut development	IEA Inferred from Electronic Annotation more info
involved_in multicellular organismal response to stress	IEA Inferred from Electronic Annotation more info
involved_in response to cAMP	IEA Inferred from Electronic Annotation more info
involved_in response to ethanol	IEA Inferred from Electronic Annotation more info
involved_in response to glucagon	IEA Inferred from Electronic Annotation more info
involved_in response to growth hormone	IEA Inferred from Electronic Annotation more info
involved_in response to linoleic acid	IEA Inferred from Electronic Annotation more info
involved_in response to metal ion	IEA Inferred from Electronic Annotation more info
involved_in response to monosaccharide	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient	IEA Inferred from Electronic Annotation more info
involved_in response to prostaglandin F	IEA Inferred from Electronic Annotation more info
involved_in response to starvation	IEA Inferred from Electronic Annotation more info
involved_in response to temperature stimulus	IEA Inferred from Electronic Annotation more info
involved_in response to testosterone	IEA Inferred from Electronic Annotation more info
involved_in response to triglyceride	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in mitochondrial inner membrane	HDA more info	PubMed
located_in mitochondrial matrix	IEA Inferred from Electronic Annotation more info
located_in mitochondrial matrix	ISO Inferred from Sequence Orthology more info
located_in mitochondrion	HDA more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: hydroxymethylglutaryl-CoA synthase, mitochondrial

Names: 3-hydroxy-3-methylglutaryl coenzyme A synthase; HMG-CoA synthase

NP_032282.2

EC 2.3.3.10

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_008256.4 → NP_032282.2 hydroxymethylglutaryl-CoA synthase, mitochondrial precursor

See identical proteins and their annotated locations for NP_032282.2

Status: VALIDATED

Source sequence(s)

AC121771, AC147476, AK004865

Consensus CDS

CCDS17662.1

UniProtKB/Swiss-Prot

P54869, Q64740, Q9DBK1, Q9DBM4

UniProtKB/TrEMBL

Q8N7N8

Related

ENSMUSP00000088249.3, ENSMUST00000090746.3

Conserved Domains (3) summary

TIGR01833
Location:50 → 505

HMG-CoA-S_euk; 3-hydroxy-3-methylglutaryl-CoA-synthase, eukaryotic clade

pfam01154
Location:53 → 223

HMG_CoA_synt_N; Hydroxymethylglutaryl-coenzyme A synthase N terminal

pfam08540
Location:224 → 505

HMG_CoA_synt_C; Hydroxymethylglutaryl-coenzyme A synthase C terminal