HMGCL
entrez
3155
canonical
uniprot
P35914
canonical
ensembl
ENSG00000117305
resolver
ensp
ENSP00000363614
resolver
ensp
ENSP00000389281
resolver
genesymbol
HMGCL
resolver
hgnc
HGNC:5005
resolver
uniprot
B4DUP4
resolver
uniprot
B7UCC6
resolver
uniprot
D3Y5K7
resolver
uniprot
Q6IBC0
resolver
uniprot
Q96FP8
resolver
uniprot_entry
HMGCL_HUMAN
resolver
uniprot_sec
B4DUP4
resolver
uniprot_sec
B7UCC6
resolver
uniprot_sec
D3Y5K7
resolver
uniprot_sec
Q6IBC0
resolver
uniprot_sec
Q96FP8
resolver
activity_regulation
ACTIVITY REGULATION: Stimulated by reducing agents such as dithiothreitol (DTT). {ECO:0000269|PubMed:12874287}.
uniprot
proteins
amino_acid_sequence
MAAMRKALPRRLVGLASLRAVSTSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFEAAVAAGAKEVVIFGAASELFTKKNINCSIEESFQRFDAILKAAQSANISVRGYVSCALGCPYEGKISPAKVAEVTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL
uniprot
proteins
disease_involvement
DISEASE: 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:0000269|PubMed:11129331, ECO:0000269|PubMed:12746442, ECO:0000269|PubMed:16601870, ECO:0000269|PubMed:17173698, ECO:0000269|PubMed:17459752, ECO:0000269|PubMed:19036343, ECO:0000269|PubMed:19177531, ECO:0000269|PubMed:8798725, ECO:0000269|PubMed:9463337, ECO:0000269|PubMed:9784232}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
4.1.3.4
uniprot
proteins
function
FUNCTION: Mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis. 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:0000269|PubMed:22847177, ECO:0000269|PubMed:22865860, ECO:0000269|PubMed:8566388}.
uniprot
proteins
mass_dalton
34360
uniprot
proteins
mutagenesis
MUTAGEN 37; /note="E->D: Normal activity."; /evidence="ECO:0000269|PubMed:12874287"; MUTAGEN 41; /note="R->M: Reduced activity, and loss of proton exchange."; /evidence="ECO:0000269|PubMed:15122894"; MUTAGEN 42; /note="D->A,N: Loss of activity, and reduced proton exchange rate."; /evidence="ECO:0000269|PubMed:12874287, ECO:0000269|PubMed:15122894"; MUTAGEN 72; /note="E->A: Loss of activity, and reduced affinity for metal cofactor and substrate."; /evidence="ECO:0000269|PubMed:12874287"; MUTAGEN 204; /note="D->A: Reduced activity, and reduced affinity for metal cofactor and substrate."; /evidence="ECO:0000269|PubMed:12874287"; MUTAGEN 233; /note="H->A: Loss of activity, and reduced proton exchange rate."; /evidence="ECO:0000269|PubMed:12874287, ECO:0000269|PubMed:15122894"; MUTAGEN 266; /note="C->A: Loss of activity."; MUTAGEN 279; /note="E->A: Reduced thermal stability, but normal activity."; /evidence="ECO:0000269|PubMed:12874287"; MUTAGEN 280; /note="D->A: Normal activity."; /evidence="ECO:0000269|PubMed:12874287"; MUTAGEN 323; /note="C->S: Abolishes interchain homodimerization. Exhibits no DTT stimulated activity."; /evidence="ECO:0000269|PubMed:12464283, ECO:0000269|PubMed:22865860
uniprot
proteins
pathway_participation
PATHWAY: Metabolic intermediate metabolism; (S)-3-hydroxy-3-methylglutaryl-CoA degradation; acetoacetate from (S)-3-hydroxy-3-methylglutaryl-CoA: step 1/1.
uniprot
proteins
protein_family
HMG-CoA lyase family
uniprot
proteins
pubmed
11129331
uniprot
proteins
pubmed
12464283
uniprot
proteins
pubmed
12746442
uniprot
proteins
pubmed
12874287
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15122894
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16330550
uniprot
proteins
pubmed
16601870
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17173698
uniprot
proteins
pubmed
17459752
uniprot
proteins
pubmed
19036343
uniprot
proteins
pubmed
19177531
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21952825
uniprot
proteins
pubmed
22847177
uniprot
proteins
pubmed
22865860
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
7527399
uniprot
proteins
pubmed
8440722
uniprot
proteins
pubmed
8566388
uniprot
proteins
pubmed
8617516
uniprot
proteins
pubmed
8798725
uniprot
proteins
pubmed
9463337
uniprot
proteins
pubmed
9784232
uniprot
proteins
sequence_length
325
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250|UniProtKB:P38060}. Peroxisome {ECO:0000250|UniProtKB:P38060}. Note=Unprocessed form is peroxisomal. {ECO:0000250|UniProtKB:P38060}.
uniprot
proteins