HMGCS2 3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial) [Homo sapiens] - Gene

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Summary

Official Symbol: HMGCS2provided by HGNC
Official Full Name: 3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)provided by HGNC
Primary source: HGNC:5008
See related: Ensembl:ENSG00000134240; HPRD:02580; MIM:600234; Vega:OTTHUMG00000012101
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: The protein encoded by this gene belongs to the HMG-CoA synthase family. It is a mitochondrial enzyme that catalyzes the first reaction of ketogenesis, a metabolic pathway that provides lipid-derived energy for various organs during times of carbohydrate deprivation, such as fasting. Mutations in this gene are associated with HMG-CoA synthase deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

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Genomic context

Location :: 1p13-p12

Sequence :: Chromosome: 1; NC_000001.10 (120290619..120311555, complement)

See HMGCS2 in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Human HMGCS2 regulates mitochondrial fatty acid oxidation and FGF21 expression
Title: Human HMGCS2 regulates mitochondrial fatty acid oxidation and FGF21 expression in HepG2 cell line.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
Title: Genome-wide searching of rare genetic variants in WTCCC data.
The authors report high-resolution crystal structures of the human cytosolic (hHMGCS1) and mitochondrial (hHMGCS2) isoforms in binary product complexes.
Title: Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
Ketogenesis is an undesirable metabolic characteristic of the proliferating cell, which is down-regulated through c-Myc-mediated repression of the key metabolic gene HMGCS2.
Title: Ketogenic HMGCS2 Is a c-Myc target gene expressed in differentiated cells of human colonic epithelium and down-regulated in colon cancer.

Submit: New GeneRIF Correction

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Products	Interactant	Other Gene	Complex	Source	Pubs	Description
BioGRID:109401	BioGRID:113164	UBC		BioGRID	PubMed	Affinity Capture-MS
BioGRID:109401	BioGRID:116168	YWHAQ		BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
hydroxymethylglutaryl-CoA synthase activity	IEA Inferred from Electronic Annotation more info
transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
adipose tissue development	IEA Inferred from Electronic Annotation more info
brain development	IEA Inferred from Electronic Annotation more info
cellular ketone body metabolic process	TAS Traceable Author Statement more info
cellular lipid metabolic process	TAS Traceable Author Statement more info
cellular response to amino acid stimulus	IEA Inferred from Electronic Annotation more info
cellular response to fatty acid	IEA Inferred from Electronic Annotation more info
cellular response to glucocorticoid stimulus	IEA Inferred from Electronic Annotation more info
cellular response to hormone stimulus	IEA Inferred from Electronic Annotation more info
cellular response to insulin stimulus	IEA Inferred from Electronic Annotation more info
cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
cellular response to organic cyclic compound	IEA Inferred from Electronic Annotation more info
cholesterol biosynthetic process	IEA Inferred from Electronic Annotation more info
isoprenoid biosynthetic process	IEA Inferred from Electronic Annotation more info
ketone body biosynthetic process	TAS Traceable Author Statement more info
kidney development	IEA Inferred from Electronic Annotation more info
liver development	IEA Inferred from Electronic Annotation more info
lung development	IEA Inferred from Electronic Annotation more info
midgut development	IEA Inferred from Electronic Annotation more info
multicellular organismal response to stress	IEA Inferred from Electronic Annotation more info
response to bacterium	IEA Inferred from Electronic Annotation more info
response to cAMP	IEA Inferred from Electronic Annotation more info
response to drug	IEA Inferred from Electronic Annotation more info
response to ethanol	IEA Inferred from Electronic Annotation more info
response to glucagon stimulus	IEA Inferred from Electronic Annotation more info
response to growth hormone stimulus	IEA Inferred from Electronic Annotation more info
response to linoleic acid	IEA Inferred from Electronic Annotation more info
response to metal ion	IEA Inferred from Electronic Annotation more info
response to monosaccharide stimulus	IEA Inferred from Electronic Annotation more info
response to nutrient	IEA Inferred from Electronic Annotation more info
response to prostaglandin F stimulus	IEA Inferred from Electronic Annotation more info
response to starvation	IEA Inferred from Electronic Annotation more info
response to temperature stimulus	IEA Inferred from Electronic Annotation more info
response to testosterone stimulus	IEA Inferred from Electronic Annotation more info
response to triglyceride	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
mitochondrial inner membrane	IEA Inferred from Electronic Annotation more info
mitochondrial matrix	TAS Traceable Author Statement more info
mitochondrion	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: hydroxymethylglutaryl-CoA synthase, mitochondrial

Names: hydroxymethylglutaryl-CoA synthase, mitochondrial; HMG-CoA synthase; 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (mitochondrial)

NP_001159579.1

EC 2.3.3.10

NP_005509.1

EC 2.3.3.10

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NCBI Reference Sequences (RefSeq)

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.

Genomic

NG_013348.1 RefSeqGene

Range

5001..25937

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001166107.1 → NP_001159579.1 hydroxymethylglutaryl-CoA synthase, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) is missing an in-frame coding exon compared to variant 1. This results in a shorter isoform (2) lacking an internal protein segment compared to isoform 1.

Source sequence(s)

AI215948, AK303777, BC044217, BP420631, BX104280

Consensus CDS

CCDS53353.1

UniProtKB/Swiss-Prot

P54868

Related

ENSP00000439495, OTTHUMP00000243996, ENST00000544913, OTTHUMT00000409524

Conserved Domains (2) summary

cd00827
Location:53 – 381
Blast Score: 482

init_cond_enzymes; "initiating" condensing enzymes are a subclass of decarboxylating condensing enzymes, including beta-ketoacyl [ACP] synthase, type III and polyketide synthases, type III, which include chalcone synthase and related enzymes. They are characterized by the ...

TIGR01833
Location:50 – 464
Blast Score: 1985

HMG-CoA-S_euk; 3-hydroxy-3-methylglutaryl-CoA-synthase, eukaryotic clade
NM_005518.3 → NP_005509.1 hydroxymethylglutaryl-CoA synthase, mitochondrial isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AI215948, BC044217, BP420631, BX104280

Consensus CDS

CCDS905.1

UniProtKB/Swiss-Prot

P54868

Related

ENSP00000358414, OTTHUMP00000013928, ENST00000369406, OTTHUMT00000033469

Conserved Domains (2) summary

cd00827
Location:53 – 423
Blast Score: 611

init_cond_enzymes; "initiating" condensing enzymes are a subclass of decarboxylating condensing enzymes, including beta-ketoacyl [ACP] synthase, type III and polyketide synthases, type III, which include chalcone synthase and related enzymes. They are characterized by the ...

TIGR01833
Location:50 – 506
Blast Score: 2271

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

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000001.10 Reference GRCh37.p5 Primary Assembly

Range

120290619..120311555, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

118149159..118170093, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AL589734.5	CAI22408.1
genomic	CH471122.1	EAW56709.1
		EAW56710.1
genomic	U81859.1	AAB72036.1
mRNA	AI215948.1	None
mRNA	AK301594.1	BAH13520.1
mRNA	AK302276.1	BAH13664.1
mRNA	AK303777.1	BAH14049.1
mRNA	AK313590.1	None
mRNA	BC044217.1	AAH44217.1
mRNA	BF964973.1	None
mRNA	BP420631.1	None
mRNA	BX104280.1	None
mRNA	CR456850.1	CAG33131.1
mRNA	GU433940.1	ADD21696.1
mRNA	U12788.1	AAA92673.1
mRNA	U12789.1	AAA92674.1
mRNA	X83618.1	CAA58593.1