Gene/Proteome Database (LMPD)
LMPD ID
LMP002403
Gene ID
Species
Homo sapiens (Human)
Gene Name
3-hydroxymethyl-3-methylglutaryl-CoA lyase
Gene Symbol
Synonyms
HL
Alternate Names
hydroxymethylglutaryl-CoA lyase, mitochondrial; HMG-CoA lyase; hydroxymethylglutaricaciduria; 3-hydroxy-3-methylglutaryl-CoA lyase; 3-hydroxy-3-methylglutarate-CoA lyase; 3-hydroxymethyl-3-methylglutaryl-Coenzyme A lyase; mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase
Chromosome
1
Map Location
1p36.1-p35
EC Number
4.1.3.4
Summary
The protein encoded by this gene belongs to the HMG-CoA lyase family. It is a mitochondrial enzyme that catalyzes the final step of leucine degradation and plays a key role in ketone body formation. Mutations in this gene are associated with HMG-CoA lyase deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
Orthologs
Proteins
| hydroxymethylglutaryl-CoA lyase, mitochondrial isoform 1 precursor | |
|---|---|
| Refseq ID | NP_000182 |
| Protein GI | 62198232 |
| UniProt ID | P35914 |
| mRNA ID | NM_000191 |
| Length | 325 |
| RefSeq Status | REVIEWED |
| MAAMRKALPRRLVGLASLRAVSTSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFEAAVAAGAKEVVIFGAASELFTKKNINCSIEESFQRFDAILKAAQSANISVRGYVSCALGCPYEGKISPAKVAEVTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL | |
| hydroxymethylglutaryl-CoA lyase, mitochondrial isoform 2 precursor | |
|---|---|
| Refseq ID | NP_001159531 |
| Protein GI | 260654708 |
| UniProt ID | P35914 |
| mRNA ID | NM_001166059 |
| Length | 254 |
| RefSeq Status | REVIEWED |
| MAAMRKALPRRLVGLASLRAVSTSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFEAAVTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL | |
| transit_peptide: 1..27 calculated_mol_wt: 2831 peptide sequence: MAAMRKALPRRLVGLASLRAVSTSSMG mat_peptide: 28..325 product: hydroxymethylglutaryl-CoA lyase, mitochondrial isoform 1 calculated_mol_wt: 31547 peptide sequence: TLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFEAAVAAGAKEVVIFGAASELFTKKNINCSIEESFQRFDAILKAAQSANISVRGYVSCALGCPYEGKISPAKVAEVTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL transit_peptide: 1..27 calculated_mol_wt: 2831 peptide sequence: MAAMRKALPRRLVGLASLRAVSTSSMG mat_peptide: 28..254 product: hydroxymethylglutaryl-CoA lyase, mitochondrial isoform 2 calculated_mol_wt: 24096 peptide sequence: TLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFEAAVTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL | |
Gene Information
Entrez Gene ID
Gene Name
3-hydroxymethyl-3-methylglutaryl-CoA lyase
Gene Symbol
Species
Homo sapiens
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005743 | IEA:Ensembl | C | mitochondrial inner membrane |
| GO:0005759 | NAS:UniProtKB | C | mitochondrial matrix |
| GO:0005739 | IDA:UniProtKB | C | mitochondrion |
| GO:0005777 | IDA:UniProtKB | C | peroxisome |
| GO:0031406 | IEA:Ensembl | F | carboxylic acid binding |
| GO:0000062 | IEA:Ensembl | F | fatty-acyl-CoA binding |
| GO:0004419 | IDA:UniProtKB | F | hydroxymethylglutaryl-CoA lyase activity |
| GO:0000287 | IDA:UniProtKB | F | magnesium ion binding |
| GO:0030145 | IDA:UniProtKB | F | manganese ion binding |
| GO:0046872 | IDA:UniProtKB | F | metal ion binding |
| GO:0042803 | IDA:UniProtKB | F | protein homodimerization activity |
| GO:0005102 | IPI:UniProtKB | F | receptor binding |
| GO:0006637 | IEA:Ensembl | P | acyl-CoA metabolic process |
| GO:0046950 | TAS:Reactome | P | cellular ketone body metabolic process |
| GO:0044255 | TAS:Reactome | P | cellular lipid metabolic process |
| GO:0046951 | IDA:UniProtKB | P | ketone body biosynthetic process |
| GO:0006552 | NAS:UniProtKB | P | leucine catabolic process |
| GO:0001889 | IEA:Ensembl | P | liver development |
| GO:0007005 | IEA:Ensembl | P | mitochondrion organization |
| GO:0051262 | IDA:UniProtKB | P | protein tetramerization |
| GO:0070542 | IEA:Ensembl | P | response to fatty acid |
| GO:0007584 | IEA:Ensembl | P | response to nutrient |
| GO:0042594 | IEA:Ensembl | P | response to starvation |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| hsa04146 | Peroxisome |
REACTOME Pathway Links
| REACTOME Pathway ID | Description |
|---|---|
| REACT_1464 | Synthesis of Ketone Bodies |
Domain Information
UniProt Annotations
Entry Information
Gene Name
3-hydroxymethyl-3-methylglutaryl-CoA lyase
Protein Entry
HMGCL_HUMAN
UniProt ID
Species
Human
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=P35914-1; Sequence=Displayed; Name=2; Synonyms=HMGCS2delta5,6; IsoId=P35914-2; Sequence=VSP_047444; Note=The transcript is not translated, but would result in a catatically impaired product if it was.; Name=3; Synonyms=HMGCS2delta5,6,7; IsoId=P35914-3; Sequence=VSP_047444, VSP_043788; Note=Very low expression. The transcript is not translated, but would result in a catatically inactive product if it was.; |
| Biophysicochemical Properties | Kinetic parameters: KM=200 uM for magnesium ion {ECO |
| Catalytic Activity | (S)-3-hydroxy-3-methylglutaryl-CoA = acetyl- CoA + acetoacetate. {ECO |
| Cofactor | Name=a divalent metal cation; Xref=ChEBI |
| Disease | 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) [MIM |
| Enzyme Regulation | Stimulated by reducing agents such as dithiothreitol (DTT). |
| Function | Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism. Ketone bodies (beta- hydroxybutyrate, acetoacetate and acetone) are essential as an alternative source of energy to glucose, as lipid precursors and as regulators of metabolism. {ECO |
| Pathway | Metabolic intermediate metabolism; (S)-3-hydroxy-3- methylglutaryl-CoA degradation; acetoacetate from (S)-3-hydroxy-3- methylglutaryl-CoA |
| Similarity | Belongs to the HMG-CoA lyase family. |
| Subcellular Location | Mitochondrion matrix. Peroxisome. Note=Unprocessed form is peroxisomal. |
| Subunit | Homodimer; disulfide-linked. Can also form homotetramers. |
| Tissue Specificity | Highest expression in liver. Expressed in pancreas, kidey, intestine, testis, fibroblasts and lymphoblasts. Very low expression in brain and skeletal muscle. The relative expression of isoform 2 (at mRNA level) is highest in heart (30%), skeletal muscle (22%), and brain (14%). |
Identical and Related Proteins
Unique RefSeq proteins for LMP002403 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 62198232 | RefSeq | NP_000182 | 325 | hydroxymethylglutaryl-CoA lyase, mitochondrial isoform 1 precursor |
| 260654708 | RefSeq | NP_001159531 | 254 | hydroxymethylglutaryl-CoA lyase, mitochondrial isoform 2 precursor |
Identical Sequences to LMP002403 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:260654708 | DBBJ | BAG62406.1 | 254 | unnamed protein product [Homo sapiens] |
| GI:62198232 | GenBank | AGO72367.1 | 325 | Sequence 44 from patent US 8470972 |
| GI:62198232 | GenBank | AGU32358.1 | 325 | Sequence 44 from patent US 8507277 |
| GI:62198232 | GenBank | AGX48262.1 | 325 | Sequence 44 from patent US 8541550 |
| GI:62198232 | GenBank | AHD74276.1 | 325 | Sequence 13642 from patent US 8586006 |
| GI:62198232 | GenBank | AIC54559.1 | 325 | HMGCL, partial [synthetic construct] |
| GI:62198232 | RefSeq | XP_008961375.1 | 325 | PREDICTED: hydroxymethylglutaryl-CoA lyase, mitochondrial isoform X1 [Pan paniscus] |
Related Sequences to LMP002403 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:62198232 | GenBank | AAA92733.1 | 325 | hydroxymethylglutaryl-CoA lyase [Homo sapiens] |
| GI:62198232 | GenBank | JAA14187.1 | 325 | 3-hydroxymethyl-3-methylglutaryl-CoA lyase [Pan troglodytes] |
| GI:62198232 | GenBank | JAA23443.1 | 325 | 3-hydroxymethyl-3-methylglutaryl-CoA lyase [Pan troglodytes] |
| GI:62198232 | RefSeq | XP_001166273.1 | 325 | PREDICTED: hydroxymethylglutaryl-CoA lyase, mitochondrial isoform X1 [Pan troglodytes] |
| GI:62198232 | RefSeq | NP_001127443.1 | 325 | hydroxymethylglutaryl-CoA lyase, mitochondrial precursor [Pongo abelii] |
| GI:260654708 | RefSeq | XP_003307921.1 | 254 | PREDICTED: hydroxymethylglutaryl-CoA lyase, mitochondrial isoform X5 [Pan troglodytes] |
| GI:260654708 | RefSeq | XP_003364485.1 | 254 | PREDICTED: hydroxymethylglutaryl-CoA lyase, mitochondrial isoformX2 [Equus caballus] |
| GI:62198232 | RefSeq | XP_004024945.1 | 325 | PREDICTED: hydroxymethylglutaryl-CoA lyase, mitochondrial isoform 1 [Gorilla gorilla gorilla] |
| GI:260654708 | RefSeq | XP_004024946.1 | 254 | PREDICTED: hydroxymethylglutaryl-CoA lyase, mitochondrial isoform 2 [Gorilla gorilla gorilla] |
| GI:260654708 | RefSeq | XP_005317655.1 | 254 | PREDICTED: hydroxymethylglutaryl-CoA lyase, mitochondrial isoform X2 [Ictidomys tridecemlineatus] |
| GI:260654708 | RefSeq | XP_005394832.1 | 254 | PREDICTED: hydroxymethylglutaryl-CoA lyase, mitochondrial isoform X3 [Chinchilla lanigera] |
| GI:260654708 | RefSeq | XP_006883583.1 | 254 | PREDICTED: hydroxymethylglutaryl-CoA lyase, mitochondrial isoform X2 [Elephantulus edwardii] |