HMGCL_MACFA
ID HMGCL_MACFA Reviewed; 325 AA.
AC Q8HXZ6;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Hydroxymethylglutaryl-CoA lyase, mitochondrial;
DE Short=HL;
DE Short=HMG-CoA lyase;
DE EC=4.1.3.4 {ECO:0000250|UniProtKB:P35914};
DE AltName: Full=3-hydroxy-3-methylglutarate-CoA lyase;
DE Flags: Precursor;
GN Name=HMGCL; ORFNames=QccE-12283;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RA Kusuda J., Osada N., Hida M., Sugano S., Hashimoto K.;
RT "Isolation and characterization of cDNA for macaque neurological disease
RT genes.";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that
CC catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-
CC methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in
CC ketogenesis. Terminal step in leucine catabolism. Ketone bodies (beta-
CC hydroxybutyrate, acetoacetate and acetone) are essential as an
CC alternative source of energy to glucose, as lipid precursors and as
CC regulators of metabolism. {ECO:0000250|UniProtKB:P35914}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxy-3-methylglutaryl-CoA = acetoacetate + acetyl-CoA;
CC Xref=Rhea:RHEA:24404, ChEBI:CHEBI:13705, ChEBI:CHEBI:43074,
CC ChEBI:CHEBI:57288; EC=4.1.3.4;
CC Evidence={ECO:0000250|UniProtKB:P35914};
CC -!- PATHWAY: Metabolic intermediate metabolism; (S)-3-hydroxy-3-
CC methylglutaryl-CoA degradation; acetoacetate from (S)-3-hydroxy-3-
CC methylglutaryl-CoA: step 1/1.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Can also form homotetramers.
CC {ECO:0000250|UniProtKB:P35914}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P38060}. Peroxisome
CC {ECO:0000250|UniProtKB:P38060}. Note=Unprocessed form is peroxisomal.
CC {ECO:0000250|UniProtKB:P38060}.
CC -!- SIMILARITY: Belongs to the HMG-CoA lyase family. {ECO:0000305}.
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DR EMBL; AB083316; BAC20595.1; -; mRNA.
DR RefSeq; NP_001270179.1; NM_001283250.1.
DR AlphaFoldDB; Q8HXZ6; -.
DR SMR; Q8HXZ6; -.
DR STRING; 9541.XP_005545275.1; -.
DR GeneID; 101926169; -.
DR CTD; 3155; -.
DR eggNOG; KOG2368; Eukaryota.
DR OrthoDB; 1029775at2759; -.
DR UniPathway; UPA00896; UER00863.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005777; C:peroxisome; IEA:UniProtKB-SubCell.
DR GO; GO:0004419; F:hydroxymethylglutaryl-CoA lyase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; ISS:UniProtKB.
DR GO; GO:0046951; P:ketone body biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR000138; HMG_CoA_lyase_AS.
DR InterPro; IPR043594; HMGL.
DR InterPro; IPR000891; PYR_CT.
DR PANTHER; PTHR42738; PTHR42738; 1.
DR Pfam; PF00682; HMGL-like; 1.
DR PROSITE; PS01062; HMG_COA_LYASE; 1.
DR PROSITE; PS50991; PYR_CT; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Disulfide bond; Lipid metabolism; Lyase; Metal-binding;
KW Mitochondrion; Peroxisome; Reference proteome; Transit peptide.
FT TRANSIT 1..27
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 28..325
FT /note="Hydroxymethylglutaryl-CoA lyase, mitochondrial"
FT /id="PRO_0000013479"
FT DOMAIN 33..300
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT MOTIF 323..325
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 266
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10115"
FT BINDING 41
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 42
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 233
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 235
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 275
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT MOD_RES 48
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35914"
FT MOD_RES 48
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT MOD_RES 111
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT MOD_RES 137
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT MOD_RES 137
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT MOD_RES 179
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT MOD_RES 179
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT MOD_RES 324
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT DISULFID 323
FT /note="Interchain"
FT /evidence="ECO:0000250"
SQ SEQUENCE 325 AA; 34274 MW; 1B3F2C90388927E4 CRC64;
MAAMTKALPR RLVGLASLRA VSTSSMDTLP KQVKIVEVGP RDGLQNEKNI VSTPVKIKLI
DMLSEAGLSV IEATSFVSPK WVPQMADHAE VLKGIQKFPG ITYPVLIPNL KGFEAAVAAG
AKEVSIFGAA SELFTKKNVN CSIEESFQRF DAILKAAQSA NISVRGYVSC VLGCPYEGKI
SPAKVAEVTK KFYSMGCYEI SLGDTIGVGT PGIMKDMLSA VMQEVPPAAL AVHCHDTYGQ
ALANTLMALQ MGVSVVDSSV AGLGGCPYAQ GASGNLATED LVYMLEGLGI HTGVNLQKLL
EAGNFICQAL NRKTSSKVAQ ATCKL
