HMGCL_CHICK
ID HMGCL_CHICK Reviewed; 298 AA.
AC P35915;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 120.
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;
GN Name=HMGCL;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-298, AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=8440722; DOI=10.1016/s0021-9258(18)53620-6;
RA Mitchell G.A., Robert M.-F., Hruz P.W., Wang S., Fontaine G., Behnke C.E.,
RA Mende-Mueller L.M., Schappert K., Lee C., Gibson K.M., Miziorko H.M.;
RT "3-hydroxy-3-methylglutaryl coenzyme A lyase (HL). Cloning of human and
RT chicken liver HL cDNAs and characterization of a mutation causing human HL
RT deficiency.";
RL J. Biol. Chem. 268:4376-4381(1993).
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}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA92728.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; L07034; AAA92728.1; ALT_INIT; mRNA.
DR PIR; B45470; B45470.
DR AlphaFoldDB; P35915; -.
DR SMR; P35915; -.
DR IntAct; P35915; 1.
DR STRING; 9031.ENSGALP00000006445; -.
DR PaxDb; P35915; -.
DR PRIDE; P35915; -.
DR VEuPathDB; HostDB:geneid_396316; -.
DR eggNOG; KOG2368; Eukaryota.
DR InParanoid; P35915; -.
DR PhylomeDB; P35915; -.
DR UniPathway; UPA00896; UER00863.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005777; C:peroxisome; IEA:UniProtKB-SubCell.
DR GO; GO:0004419; F:hydroxymethylglutaryl-CoA lyase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; ISS:UniProtKB.
DR GO; GO:0046951; P:ketone body biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006552; P:leucine catabolic process; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; IBA:GO_Central.
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 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Disulfide bond; Lipid metabolism;
KW Lyase; Metal-binding; Mitochondrion; Peroxisome; Reference proteome.
FT CHAIN 1..298
FT /note="Hydroxymethylglutaryl-CoA lyase, mitochondrial"
FT /id="PRO_0000151520"
FT DOMAIN 6..273
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT MOTIF 296..298
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 239
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10115"
FT BINDING 14
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 15
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 206
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 208
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 248
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT MOD_RES 21
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250"
FT DISULFID 296
FT /note="Interchain"
FT /evidence="ECO:0000250"
SQ SEQUENCE 298 AA; 31436 MW; A6FCD9418E30590F CRC64;
AFPQRVKVVE VGPRDGLQNE KSVVPTPVKI RLIDMLSETG LPVIEATSFV SPRWVPQMAD
HAEVMQGINK LPGVSYPVLT PNLKGFQAAV AAGAKEVSIF GAASELFTKK NINCSIEESL
ERFSEVMNAA RAASIPVRGY VSCVLGCPYE GNISAAKVAE VSKKMYSMGC YEISLGDRIG
IGTPGSMKEM LAAVMKEVPV GALAVHCHDT YGQALANILV ALQMGVSVVD ASVAGLGGCP
YAQGASGNVA TEDLVYMLNG LGIHTGVDLQ KLMDTGTFIC NALNRRTNSK VSQAACRL
