InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: HMGCL

Summary

InnateDB Protein

IDBP-375141.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

HMGCL

Protein Name

3-hydroxymethyl-3-methylglutaryl-CoA lyase

Synonyms

HL;

Species

Homo sapiens

Ensembl Protein

ENSP00000389281

InnateDB Gene

IDBG-94034 (HMGCL)

Protein Structure

UniProt Annotation

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:0000269PubMed:22847177, ECO:0000269PubMed:22865860, ECO:0000269PubMed:8566388}.

Subcellular Localization

Mitochondrion matrix. Peroxisome. Note=Unprocessed form is peroxisomal.

Disease Associations

3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) [MIM:246450]: An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases. {ECO:0000269PubMed:11129331, ECO:0000269PubMed:12746442, ECO:0000269PubMed:16601870, ECO:0000269PubMed:17173698, ECO:0000269PubMed:17459752, ECO:0000269PubMed:19036343, ECO:0000269PubMed:19177531, ECO:0000269PubMed:8798725, ECO:0000269PubMed:9463337, ECO:0000269PubMed:9784232}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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%). {ECO:0000269PubMed:21952825}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 14 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	14 [view]
Protein-Protein	14 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0003824	catalytic activity
GO:0004419	hydroxymethylglutaryl-CoA lyase activity
GO:0005102	receptor binding
GO:0030145	manganese ion binding
GO:0042803	protein homodimerization activity
GO:0046872	metal ion binding

Biological Process

GO:0006552	leucine catabolic process
GO:0044255	cellular lipid metabolic process
GO:0044281	small molecule metabolic process
GO:0046950	cellular ketone body metabolic process
GO:0046951	ketone body biosynthetic process
GO:0051262	protein tetramerization