HMGCL_RAT
ID HMGCL_RAT Reviewed; 325 AA.
AC P97519;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 144.
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=9425122; DOI=10.1042/bj3290373;
RA Cullingford T.E., Dolphin C.T., Bhakoo K.K., Peuchen S., Canevari L.,
RA Clark J.B.;
RT "Molecular cloning of rat mitochondrial 3-hydroxy-3-methylglutaryl-CoA
RT lyase and detection of the corresponding mRNA and of those encoding the
RT remaining enzymes comprising the ketogenic 3-hydroxy-3-methylglutaryl-CoA
RT cycle in central nervous system of suckling rat.";
RL Biochem. J. 329:373-381(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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 -!- TISSUE SPECIFICITY: In suckling rat, highest levels in liver and in
CC intestine. Lower levels in heart, kidney and cerebellum. Weak
CC expression in brain cortex, medulla and midbrain. Levels decrease
CC slightly during weaning. {ECO:0000269|PubMed:9425122}.
CC -!- SIMILARITY: Belongs to the HMG-CoA lyase family. {ECO:0000305}.
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DR EMBL; Y10054; CAA71148.1; -; mRNA.
DR EMBL; BC061797; AAH61797.1; -; mRNA.
DR RefSeq; NP_077362.1; NM_024386.1.
DR AlphaFoldDB; P97519; -.
DR SMR; P97519; -.
DR IntAct; P97519; 1.
DR STRING; 10116.ENSRNOP00000012853; -.
DR iPTMnet; P97519; -.
DR PhosphoSitePlus; P97519; -.
DR jPOST; P97519; -.
DR PaxDb; P97519; -.
DR PRIDE; P97519; -.
DR GeneID; 79238; -.
DR KEGG; rno:79238; -.
DR UCSC; RGD:620554; rat.
DR CTD; 3155; -.
DR RGD; 620554; Hmgcl.
DR VEuPathDB; HostDB:ENSRNOG00000009422; -.
DR eggNOG; KOG2368; Eukaryota.
DR HOGENOM; CLU_022138_3_2_1; -.
DR InParanoid; P97519; -.
DR OMA; FGGCPMA; -.
DR OrthoDB; 1029775at2759; -.
DR PhylomeDB; P97519; -.
DR TreeFam; TF105363; -.
DR BRENDA; 4.1.3.4; 5301.
DR Reactome; R-RNO-77111; Synthesis of Ketone Bodies.
DR Reactome; R-RNO-9033241; Peroxisomal protein import.
DR UniPathway; UPA00896; UER00863.
DR PRO; PR:P97519; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000009422; Expressed in liver and 19 other tissues.
DR Genevisible; P97519; RN.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005777; C:peroxisome; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0031406; F:carboxylic acid binding; IPI:RGD.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; IPI:RGD.
DR GO; GO:0004419; F:hydroxymethylglutaryl-CoA lyase activity; IDA:RGD.
DR GO; GO:0000287; F:magnesium ion binding; ISO:RGD.
DR GO; GO:0030145; F:manganese ion binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; ISS:UniProtKB.
DR GO; GO:0005198; F:structural molecule activity; ISO:RGD.
DR GO; GO:0006637; P:acyl-CoA metabolic process; IDA:RGD.
DR GO; GO:0046951; P:ketone body biosynthetic process; IDA:RGD.
DR GO; GO:0006552; P:leucine catabolic process; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; ISO:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0007005; P:mitochondrion organization; ISO:RGD.
DR GO; GO:0070542; P:response to fatty acid; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0042594; P:response to starvation; IEP:RGD.
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_0000013482"
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; 34192 MW; 3557684CF457D19E CRC64;
MATVRKAFPQ RLVGLASLRA ASTSSMGTLP KRVKIVEVGP RDGLQNEKSI VPTPVKIKLI
DMLSEAGLPV IEATSFVSPK WVPQMADHSD VLKGIQKFPG INYPVLTPNM KGFEEAVAAG
AKEVSIFGAA SELFTRKNVN CSIEESFQRF DGVMQAARAA SISVRGYVSC ALGCPYEGKV
SPAKVAEVAK KLYSMGCYEI SLGDTIGVGT PGLMKDMLTA VLHEVPVAAL AVHCHDTYGQ
ALANTLVALQ MGVSVVDSSV AGLGGCPYAK GASGNLATED LVYMLTGLGI HTGVNLQKLL
EAGDFICQAL NRKTSSKVAQ ATCKL
