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Hydroxymethylglutaryl-CoA lyase, mitochondrial (HL) (HMG-CoA lyase) (EC 4.1.3.4) (3-hydroxy-3-methylglutarate-CoA lyase)

 HMGCL_RAT               Reviewed;         325 AA.
P97519;
01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
01-MAY-1997, sequence version 1.
23-MAY-2018, entry version 128.
RecName: Full=Hydroxymethylglutaryl-CoA lyase, mitochondrial;
Short=HL;
Short=HMG-CoA lyase;
EC=4.1.3.4;
AltName: Full=3-hydroxy-3-methylglutarate-CoA lyase;
Flags: Precursor;
Name=Hmgcl;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
STRAIN=Wistar; TISSUE=Liver;
PubMed=9425122; DOI=10.1042/bj3290373;
Cullingford T.E., Dolphin C.T., Bhakoo K.K., Peuchen S., Canevari L.,
Clark J.B.;
"Molecular cloning of rat mitochondrial 3-hydroxy-3-methylglutaryl-CoA
lyase and detection of the corresponding mRNA and of those encoding
the remaining enzymes comprising the ketogenic 3-hydroxy-3-
methylglutaryl-CoA cycle in central nervous system of suckling rat.";
Biochem. J. 329:373-381(1998).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Prostate;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
-!- 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 (By similarity). {ECO:0000250,
ECO:0000269|PubMed:9425122}.
-!- CATALYTIC ACTIVITY: (S)-3-hydroxy-3-methylglutaryl-CoA = acetyl-
CoA + acetoacetate. {ECO:0000255|PROSITE-ProRule:PRU10115}.
-!- PATHWAY: Metabolic intermediate metabolism; (S)-3-hydroxy-3-
methylglutaryl-CoA degradation; acetoacetate from (S)-3-hydroxy-3-
methylglutaryl-CoA: step 1/1.
-!- SUBUNIT: Homodimer; disulfide-linked. Can also form homotetramers.
{ECO:0000250}.
-!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250}.
Peroxisome {ECO:0000250}. Note=Unprocessed form is peroxisomal.
{ECO:0000250}.
-!- TISSUE SPECIFICITY: In suckling rat, highest levels in liver and
in intestine. Lower levels in heart, kidney and cerebellum. Weak
expression in brain cortex, medulla and midbrain. Levels decrease
slightly during weaning. {ECO:0000269|PubMed:9425122}.
-!- SIMILARITY: Belongs to the HMG-CoA lyase family. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; Y10054; CAA71148.1; -; mRNA.
EMBL; BC061797; AAH61797.1; -; mRNA.
RefSeq; NP_077362.1; NM_024386.1.
UniGene; Rn.12297; -.
ProteinModelPortal; P97519; -.
SMR; P97519; -.
IntAct; P97519; 1.
STRING; 10116.ENSRNOP00000012853; -.
iPTMnet; P97519; -.
PhosphoSitePlus; P97519; -.
PaxDb; P97519; -.
PRIDE; P97519; -.
Ensembl; ENSRNOT00000012853; ENSRNOP00000012853; ENSRNOG00000009422.
GeneID; 79238; -.
KEGG; rno:79238; -.
UCSC; RGD:620554; rat.
CTD; 3155; -.
RGD; 620554; Hmgcl.
eggNOG; KOG2368; Eukaryota.
eggNOG; COG0119; LUCA.
GeneTree; ENSGT00390000017690; -.
HOGENOM; HOG000219757; -.
HOVERGEN; HBG064656; -.
InParanoid; P97519; -.
KO; K01640; -.
OMA; FGGCPMA; -.
OrthoDB; EOG091G0DA9; -.
PhylomeDB; P97519; -.
TreeFam; TF105363; -.
BRENDA; 4.1.3.4; 5301.
Reactome; R-RNO-77111; Synthesis of Ketone Bodies.
Reactome; R-RNO-9033241; Peroxisomal protein import.
UniPathway; UPA00896; UER00863.
PRO; PR:P97519; -.
Proteomes; UP000002494; Chromosome 5.
Bgee; ENSRNOG00000009422; -.
Genevisible; P97519; RN.
GO; GO:0005739; C:mitochondrion; IDA:RGD.
GO; GO:0005777; C:peroxisome; IEA:UniProtKB-SubCell.
GO; GO:0031406; F:carboxylic acid binding; IPI:RGD.
GO; GO:0000062; F:fatty-acyl-CoA binding; IPI:RGD.
GO; GO:0004419; F:hydroxymethylglutaryl-CoA lyase activity; IDA:RGD.
GO; GO:0000287; F:magnesium ion binding; IEA:Ensembl.
GO; GO:0030145; F:manganese ion binding; IEA:Ensembl.
GO; GO:0046872; F:metal ion binding; ISS:UniProtKB.
GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl.
GO; GO:0006637; P:acyl-CoA metabolic process; IDA:RGD.
GO; GO:0046951; P:ketone body biosynthetic process; IDA:RGD.
GO; GO:0006629; P:lipid metabolic process; IEA:Ensembl.
GO; GO:0001889; P:liver development; IEP:RGD.
GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl.
GO; GO:0051262; P:protein tetramerization; IEA:Ensembl.
GO; GO:0070542; P:response to fatty acid; IEP:RGD.
GO; GO:0007584; P:response to nutrient; IEP:RGD.
GO; GO:0042594; P:response to starvation; IEP:RGD.
Gene3D; 3.20.20.70; -; 1.
InterPro; IPR013785; Aldolase_TIM.
InterPro; IPR000138; HMG_CoA_lyase_AS.
InterPro; IPR000891; PYR_CT.
Pfam; PF00682; HMGL-like; 1.
PROSITE; PS01062; HMG_COA_LYASE; 1.
PROSITE; PS50991; PYR_CT; 1.
2: Evidence at transcript level;
Acetylation; Complete proteome; Disulfide bond; Lyase; Metal-binding;
Mitochondrion; Peroxisome; Reference proteome; Transit peptide.
TRANSIT 1 27 Mitochondrion. {ECO:0000250}.
CHAIN 28 325 Hydroxymethylglutaryl-CoA lyase,
mitochondrial.
/FTId=PRO_0000013482.
DOMAIN 33 300 Pyruvate carboxyltransferase.
{ECO:0000255|PROSITE-ProRule:PRU01151}.
MOTIF 323 325 Microbody targeting signal.
{ECO:0000255}.
ACT_SITE 266 266 {ECO:0000255|PROSITE-ProRule:PRU10115}.
METAL 42 42 Divalent metal cation. {ECO:0000250}.
METAL 233 233 Divalent metal cation. {ECO:0000250}.
METAL 235 235 Divalent metal cation. {ECO:0000250}.
METAL 275 275 Divalent metal cation. {ECO:0000250}.
BINDING 41 41 Substrate. {ECO:0000250}.
MOD_RES 48 48 N6-acetyllysine; alternate.
{ECO:0000250|UniProtKB:P35914}.
MOD_RES 48 48 N6-succinyllysine; alternate.
{ECO:0000250|UniProtKB:P38060}.
MOD_RES 111 111 N6-acetyllysine.
{ECO:0000250|UniProtKB:P38060}.
MOD_RES 137 137 N6-acetyllysine; alternate.
{ECO:0000250|UniProtKB:P38060}.
MOD_RES 137 137 N6-succinyllysine; alternate.
{ECO:0000250|UniProtKB:P38060}.
MOD_RES 179 179 N6-acetyllysine; alternate.
{ECO:0000250|UniProtKB:P38060}.
MOD_RES 179 179 N6-succinyllysine; alternate.
{ECO:0000250|UniProtKB:P38060}.
MOD_RES 324 324 N6-acetyllysine.
{ECO:0000250|UniProtKB:P38060}.
DISULFID 323 323 Interchain. {ECO:0000250}.
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


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