Gene/Proteome Database (LMPD)
LMPD ID
LMP002585
Gene ID
Species
Homo sapiens (Human)
Gene Name
3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)
Gene Symbol
Synonyms
-
Alternate Names
hydroxymethylglutaryl-CoA synthase, mitochondrial; HMG-CoA synthase; 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (mitochondrial)
Chromosome
1
Map Location
1p13-p12
EC Number
2.3.3.10
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]
Orthologs
Proteins
| hydroxymethylglutaryl-CoA synthase, mitochondrial isoform 1 precursor | |
|---|---|
| Refseq ID | NP_005509 |
| Protein GI | 5031751 |
| UniProt ID | P54868 |
| mRNA ID | NM_005518 |
| Length | 508 |
| RefSeq Status | REVIEWED |
| MQRLLTPVKRILQLTRAVQETSLTPARLLPVAHQRFSTASAVPLAKTDTWPKDVGILALEVYFPAQYVDQTDLEKYNNVEAGKYTVGLGQTRMGFCSVQEDINSLCLTVVQRLMERIQLPWDSVGRLEVGTETIIDKSKAVKTVLMELFQDSGNTDIEGIDTTNACYGGTASLFNAANWMESSSWDGRYAMVVCGDIAVYPSGNARPTGGAGAVAMLIGPKAPLALERGLRGTHMENVYDFYKPNLASEYPIVDGKLSIQCYLRALDRCYTSYRKKIQNQWKQAGSDRPFTLDDLQYMIFHTPFCKMVQKSLARLMFNDFLSASSDTQTSLYKGLEAFGGLKLEDTYTNKDLDKALLKASQDMFDKKTKASLYLSTHNGNMYTSSLYGCLASLLSHHSAQELAGSRIGAFSYGSGLAASFFSFRVSQDAAPGSPLDKLVSSTSDLPKRLASRKCVSPEEFTEIMNQREQFYHKVNFSPPGDTNSLFPGTWYLERVDEQHRRKYARRPV | |
| transit_peptide: 1..37 calculated_mol_wt: 4270 peptide sequence: MQRLLTPVKRILQLTRAVQETSLTPARLLPVAHQRFS mat_peptide: 38..466 product: hydroxymethylglutaryl-CoA synthase, mitochondrial isoform 2 calculated_mol_wt: 48230 peptide sequence: TASAVPLAKTDTWPKDVGILALEVYFPAQYVDQTDLEKYNNVEAGKYTVGLGQTRMGFCSVQEDINSLCLTVVQRLMERIQLPWDSVGRLEVGTETIIDKSKAVKTVLMELFQDSGNTDIEGIDTTNACYGGTASLFNAANWMESSSWDGLRGTHMENVYDFYKPNLASEYPIVDGKLSIQCYLRALDRCYTSYRKKIQNQWKQAGSDRPFTLDDLQYMIFHTPFCKMVQKSLARLMFNDFLSASSDTQTSLYKGLEAFGGLKLEDTYTNKDLDKALLKASQDMFDKKTKASLYLSTHNGNMYTSSLYGCLASLLSHHSAQELAGSRIGAFSYGSGLAASFFSFRVSQDAAPGSPLDKLVSSTSDLPKRLASRKCVSPEEFTEIMNQREQFYHKVNFSPPGDTNSLFPGTWYLERVDEQHRRKYARRPV transit_peptide: 1..37 calculated_mol_wt: 4270 peptide sequence: MQRLLTPVKRILQLTRAVQETSLTPARLLPVAHQRFS mat_peptide: 38..508 product: hydroxymethylglutaryl-CoA synthase, mitochondrial isoform 1 calculated_mol_wt: 52384 peptide sequence: TASAVPLAKTDTWPKDVGILALEVYFPAQYVDQTDLEKYNNVEAGKYTVGLGQTRMGFCSVQEDINSLCLTVVQRLMERIQLPWDSVGRLEVGTETIIDKSKAVKTVLMELFQDSGNTDIEGIDTTNACYGGTASLFNAANWMESSSWDGRYAMVVCGDIAVYPSGNARPTGGAGAVAMLIGPKAPLALERGLRGTHMENVYDFYKPNLASEYPIVDGKLSIQCYLRALDRCYTSYRKKIQNQWKQAGSDRPFTLDDLQYMIFHTPFCKMVQKSLARLMFNDFLSASSDTQTSLYKGLEAFGGLKLEDTYTNKDLDKALLKASQDMFDKKTKASLYLSTHNGNMYTSSLYGCLASLLSHHSAQELAGSRIGAFSYGSGLAASFFSFRVSQDAAPGSPLDKLVSSTSDLPKRLASRKCVSPEEFTEIMNQREQFYHKVNFSPPGDTNSLFPGTWYLERVDEQHRRKYARRPV | |
| hydroxymethylglutaryl-CoA synthase, mitochondrial isoform 2 precursor | |
|---|---|
| Refseq ID | NP_001159579 |
| Protein GI | 260656028 |
| UniProt ID | P54868 |
| mRNA ID | NM_001166107 |
| Length | 466 |
| RefSeq Status | REVIEWED |
| MQRLLTPVKRILQLTRAVQETSLTPARLLPVAHQRFSTASAVPLAKTDTWPKDVGILALEVYFPAQYVDQTDLEKYNNVEAGKYTVGLGQTRMGFCSVQEDINSLCLTVVQRLMERIQLPWDSVGRLEVGTETIIDKSKAVKTVLMELFQDSGNTDIEGIDTTNACYGGTASLFNAANWMESSSWDGLRGTHMENVYDFYKPNLASEYPIVDGKLSIQCYLRALDRCYTSYRKKIQNQWKQAGSDRPFTLDDLQYMIFHTPFCKMVQKSLARLMFNDFLSASSDTQTSLYKGLEAFGGLKLEDTYTNKDLDKALLKASQDMFDKKTKASLYLSTHNGNMYTSSLYGCLASLLSHHSAQELAGSRIGAFSYGSGLAASFFSFRVSQDAAPGSPLDKLVSSTSDLPKRLASRKCVSPEEFTEIMNQREQFYHKVNFSPPGDTNSLFPGTWYLERVDEQHRRKYARRPV | |
Gene Information
Entrez Gene ID
Gene Name
3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)
Gene Symbol
Species
Homo sapiens
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005743 | IEA:Ensembl | C | mitochondrial inner membrane |
| GO:0005759 | TAS:Reactome | C | mitochondrial matrix |
| GO:0005739 | TAS:ProtInc | C | mitochondrion |
| GO:0004421 | IEA:UniProtKB-EC | F | hydroxymethylglutaryl-CoA synthase activity |
| GO:0046950 | TAS:Reactome | P | cellular ketone body metabolic process |
| GO:0044255 | TAS:Reactome | P | cellular lipid metabolic process |
| GO:0006695 | IEA:UniProtKB-KW | P | cholesterol biosynthetic process |
| GO:0008299 | IEA:InterPro | P | isoprenoid biosynthetic process |
| GO:0046951 | TAS:Reactome | P | ketone body biosynthetic process |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| hsa03320 | PPAR signaling pathway |
| hsa00900 | Terpenoid backbone biosynthesis |
BIOCYC Pathway Links
| BIOCYC Pathway ID | Description |
|---|---|
| PWY66-367 | ketogenesis |
Domain Information
InterPro Annotations
| Accession | Description |
|---|---|
| IPR010122 | Hydroxymethylglutaryl-CoA synthase, eukaryotic |
| IPR013746 | Hydroxymethylglutaryl-coenzyme A synthase C-terminal domain |
| IPR013528 | Hydroxymethylglutaryl-coenzyme A synthase, N-terminal |
| IPR000590 | Hydroxymethylglutaryl-coenzyme A synthase, active site |
| IPR016039 | Thiolase-like |
| IPR016038 | Thiolase-like, subgroup |
UniProt Annotations
Entry Information
Gene Name
3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)
Protein Entry
HMCS2_HUMAN
UniProt ID
Species
Human
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=P54868-1; Sequence=Displayed; Name=2; IsoId=P54868-2; Sequence=VSP_042892; Note=No experimental confirmation available.; Name=3; Synonyms=HMGCS2delta4; IsoId=P54868-3; Sequence=VSP_047445; |
| Catalytic Activity | Acetyl-CoA + H(2)O + acetoacetyl-CoA = (S)-3- hydroxy-3-methylglutaryl-CoA + CoA. {ECO |
| Disease | HMG-CoA synthase deficiency (HMGCS deficiency) [MIM |
| Function | This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase. |
| Pathway | Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA |
| Similarity | Belongs to the HMG-CoA synthase family. |
| Subcellular Location | Mitochondrion. |
| Subunit | Homodimer. |
| Tissue Specificity | Expression in liver is 200-fold higher than in any other tissue. Low expression in colon, kidney, testis, and pancreas. Very low expression in heart and skeletal muscle. Not detected in brain. The relative expression of isoform 3 (at mRNA level) is highest in heart (70%) and skeletal muscle (60%). {ECO |
Identical and Related Proteins
Unique RefSeq proteins for LMP002585 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 5031751 | RefSeq | NP_005509 | 508 | hydroxymethylglutaryl-CoA synthase, mitochondrial isoform 1 precursor |
| 260656028 | RefSeq | NP_001159579 | 466 | hydroxymethylglutaryl-CoA synthase, mitochondrial isoform 2 precursor |
Identical Sequences to LMP002585 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:260656028 | DBBJ | BAH14049.1 | 466 | unnamed protein product [Homo sapiens] |
| GI:5031751 | GenBank | ADR87073.1 | 508 | Sequence 320 from patent US 7740664 |
| GI:5031751 | GenBank | ADT49794.1 | 508 | Sequence 1811 from patent US 7842467 |
| GI:5031751 | GenBank | ADT49796.1 | 508 | Sequence 1813 from patent US 7842467 |
| GI:5031751 | GenBank | AEP61176.1 | 508 | Sequence 170 from patent US 8026065 |
| GI:5031751 | GenBank | AHE01227.1 | 508 | Sequence 56143 from patent US 8586006 |
| GI:5031751 | GenBank | AIC48949.1 | 508 | HMGCS2, partial [synthetic construct] |
Related Sequences to LMP002585 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:260656028 | EMBL | CAA58593.1 | 508 | hydroxymethylglutaryl-CoA synthase [Homo sapiens] |
| GI:5031751 | EMBL | CAG33131.1 | 508 | HMGCS2 [Homo sapiens] |
| GI:260656028 | GenBank | AAB72036.1 | 508 | 3-hydroxy-3-methylglutaryl CoA synthase [Homo sapiens] |
| GI:260656028 | GenBank | AHE01227.1 | 508 | Sequence 56143 from patent US 8586006 |
| GI:5031751 | RefSeq | XP_513693.1 | 508 | PREDICTED: hydroxymethylglutaryl-CoA synthase, mitochondrial [Pan troglodytes] |
| GI:5031751 | RefSeq | XP_003268112.1 | 508 | PREDICTED: hydroxymethylglutaryl-CoA synthase, mitochondrial [Nomascus leucogenys] |
| GI:260656028 | RefSeq | XP_003775642.1 | 466 | PREDICTED: hydroxymethylglutaryl-CoA synthase, mitochondrial isoform X2 [Pongo abelii] |
| GI:5031751 | RefSeq | XP_003806352.1 | 508 | PREDICTED: hydroxymethylglutaryl-CoA synthase, mitochondrial [Pan paniscus] |
| GI:260656028 | RefSeq | XP_004026496.1 | 466 | PREDICTED: hydroxymethylglutaryl-CoA synthase, mitochondrial isoform 2 [Gorilla gorilla gorilla] |
| GI:5031751 | RefSeq | XP_008950396.1 | 508 | PREDICTED: hydroxymethylglutaryl-CoA synthase, mitochondrial [Pan paniscus] |
| GI:5031751 | RefSeq | XP_009426430.1 | 508 | PREDICTED: hydroxymethylglutaryl-CoA synthase, mitochondrial [Pan troglodytes] |
| GI:260656028 | SwissProt | P54868.1 | 508 | RecName: Full=Hydroxymethylglutaryl-CoA synthase, mitochondrial; Short=HMG-CoA synthase; AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase; Flags: Precursor [Homo sapiens] |