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Protein

Hydroxymethylglutaryl-CoA lyase, mitochondrial

Gene

Hmgcl

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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).By similarity1 Publication

Catalytic activityi

(S)-3-hydroxy-3-methylglutaryl-CoA = acetyl-CoA + acetoacetate.PROSITE-ProRule annotation

Pathwayi: (S)-3-hydroxy-3-methylglutaryl-CoA degradation

This protein is involved in step 1 of the subpathway that synthesizes acetoacetate from (S)-3-hydroxy-3-methylglutaryl-CoA.
Proteins known to be involved in this subpathway in this organism are:
  1. 3-hydroxymethyl-3-methylglutaryl-CoA lyase, cytoplasmic (Hmgcll1), Hydroxymethylglutaryl-CoA lyase, mitochondrial (Hmgcl)
This subpathway is part of the pathway (S)-3-hydroxy-3-methylglutaryl-CoA degradation, which is itself part of Metabolic intermediate metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes acetoacetate from (S)-3-hydroxy-3-methylglutaryl-CoA, the pathway (S)-3-hydroxy-3-methylglutaryl-CoA degradation and in Metabolic intermediate metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei41 – 411SubstrateBy similarity
Metal bindingi42 – 421Divalent metal cationBy similarity
Metal bindingi233 – 2331Divalent metal cationBy similarity
Metal bindingi235 – 2351Divalent metal cationBy similarity
Active sitei266 – 2661PROSITE-ProRule annotation
Metal bindingi275 – 2751Divalent metal cationBy similarity

GO - Molecular functioni

  • carboxylic acid binding Source: RGD
  • fatty-acyl-CoA binding Source: RGD
  • hydroxymethylglutaryl-CoA lyase activity Source: UniProtKB
  • magnesium ion binding Source: Ensembl
  • manganese ion binding Source: Ensembl
  • metal ion binding Source: UniProtKB

GO - Biological processi

  • acyl-CoA metabolic process Source: RGD
  • ketone body biosynthetic process Source: RGD
  • liver development Source: RGD
  • mitochondrion organization Source: Ensembl
  • protein tetramerization Source: Ensembl
  • response to fatty acid Source: RGD
  • response to nutrient Source: RGD
  • response to starvation Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Ligandi

Metal-binding

Enzyme and pathway databases

BRENDAi4.1.3.4. 5301.
ReactomeiR-RNO-77111. Synthesis of Ketone Bodies.
UniPathwayiUPA00896; UER00863.

Names & Taxonomyi

Protein namesi
Recommended name:
Hydroxymethylglutaryl-CoA lyase, mitochondrial (EC:4.1.3.4)
Short name:
HL
Short name:
HMG-CoA lyase
Alternative name(s):
3-hydroxy-3-methylglutarate-CoA lyase
Gene namesi
Name:Hmgcl
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 5

Organism-specific databases

RGDi620554. Hmgcl.

Subcellular locationi

GO - Cellular componenti

  • mitochondrion Source: RGD
  • peroxisome Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion, Peroxisome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 2727MitochondrionBy similarityAdd
BLAST
Chaini28 – 325298Hydroxymethylglutaryl-CoA lyase, mitochondrialPRO_0000013482Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei48 – 481N6-acetyllysine; alternateBy similarity
Modified residuei48 – 481N6-succinyllysine; alternateBy similarity
Modified residuei111 – 1111N6-acetyllysineBy similarity
Modified residuei137 – 1371N6-acetyllysine; alternateBy similarity
Modified residuei137 – 1371N6-succinyllysine; alternateBy similarity
Modified residuei179 – 1791N6-acetyllysine; alternateBy similarity
Modified residuei179 – 1791N6-succinyllysine; alternateBy similarity
Disulfide bondi323 – 323InterchainBy similarity
Modified residuei324 – 3241N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation, Disulfide bond

Proteomic databases

PaxDbiP97519.
PRIDEiP97519.

PTM databases

iPTMnetiP97519.
PhosphoSiteiP97519.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

GenevisibleiP97519. RN.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Can also form homotetramers.By similarity

Protein-protein interaction databases

IntActiP97519. 1 interaction.
STRINGi10116.ENSRNOP00000012853.

Structurei

3D structure databases

ProteinModelPortaliP97519.
SMRiP97519. Positions 28-323.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi323 – 3253Microbody targeting signalSequence analysis

Sequence similaritiesi

Belongs to the HMG-CoA lyase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2368. Eukaryota.
COG0119. LUCA.
GeneTreeiENSGT00390000017690.
HOGENOMiHOG000219757.
HOVERGENiHBG064656.
InParanoidiP97519.
KOiK01640.
OMAiEAFAQKN.
OrthoDBiEOG73Z2TR.
PhylomeDBiP97519.
TreeFamiTF105363.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR030020. HL.
IPR000138. HMG_CoA_lyase_AS.
IPR000891. PYR_CT.
[Graphical view]
PANTHERiPTHR10277:SF35. PTHR10277:SF35. 1 hit.
PfamiPF00682. HMGL-like. 1 hit.
[Graphical view]
PROSITEiPS01062. HMG_COA_LYASE. 1 hit.
PS50991. PYR_CT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P97519-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATVRKAFPQ RLVGLASLRA ASTSSMGTLP KRVKIVEVGP RDGLQNEKSI
60 70 80 90 100
VPTPVKIKLI DMLSEAGLPV IEATSFVSPK WVPQMADHSD VLKGIQKFPG
110 120 130 140 150
INYPVLTPNM KGFEEAVAAG AKEVSIFGAA SELFTRKNVN CSIEESFQRF
160 170 180 190 200
DGVMQAARAA SISVRGYVSC ALGCPYEGKV SPAKVAEVAK KLYSMGCYEI
210 220 230 240 250
SLGDTIGVGT PGLMKDMLTA VLHEVPVAAL AVHCHDTYGQ ALANTLVALQ
260 270 280 290 300
MGVSVVDSSV AGLGGCPYAK GASGNLATED LVYMLTGLGI HTGVNLQKLL
310 320
EAGDFICQAL NRKTSSKVAQ ATCKL
Length:325
Mass (Da):34,192
Last modified:May 1, 1997 - v1
Checksum:i3557684CF457D19E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y10054 mRNA. Translation: CAA71148.1.
BC061797 mRNA. Translation: AAH61797.1.
RefSeqiNP_077362.1. NM_024386.1.
UniGeneiRn.12297.

Genome annotation databases

EnsembliENSRNOT00000012853; ENSRNOP00000012853; ENSRNOG00000009422.
GeneIDi79238.
KEGGirno:79238.
UCSCiRGD:620554. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y10054 mRNA. Translation: CAA71148.1.
BC061797 mRNA. Translation: AAH61797.1.
RefSeqiNP_077362.1. NM_024386.1.
UniGeneiRn.12297.

3D structure databases

ProteinModelPortaliP97519.
SMRiP97519. Positions 28-323.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP97519. 1 interaction.
STRINGi10116.ENSRNOP00000012853.

PTM databases

iPTMnetiP97519.
PhosphoSiteiP97519.

Proteomic databases

PaxDbiP97519.
PRIDEiP97519.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000012853; ENSRNOP00000012853; ENSRNOG00000009422.
GeneIDi79238.
KEGGirno:79238.
UCSCiRGD:620554. rat.

Organism-specific databases

CTDi3155.
RGDi620554. Hmgcl.

Phylogenomic databases

eggNOGiKOG2368. Eukaryota.
COG0119. LUCA.
GeneTreeiENSGT00390000017690.
HOGENOMiHOG000219757.
HOVERGENiHBG064656.
InParanoidiP97519.
KOiK01640.
OMAiEAFAQKN.
OrthoDBiEOG73Z2TR.
PhylomeDBiP97519.
TreeFamiTF105363.

Enzyme and pathway databases

UniPathwayiUPA00896; UER00863.
BRENDAi4.1.3.4. 5301.
ReactomeiR-RNO-77111. Synthesis of Ketone Bodies.

Miscellaneous databases

PROiP97519.

Gene expression databases

GenevisibleiP97519. RN.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR030020. HL.
IPR000138. HMG_CoA_lyase_AS.
IPR000891. PYR_CT.
[Graphical view]
PANTHERiPTHR10277:SF35. PTHR10277:SF35. 1 hit.
PfamiPF00682. HMGL-like. 1 hit.
[Graphical view]
PROSITEiPS01062. HMG_COA_LYASE. 1 hit.
PS50991. PYR_CT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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."
    Cullingford T.E., Dolphin C.T., Bhakoo K.K., Peuchen S., Canevari L., Clark J.B.
    Biochem. J. 329:373-381(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
    Strain: Wistar.
    Tissue: Liver.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Prostate.

Entry informationi

Entry nameiHMGCL_RAT
AccessioniPrimary (citable) accession number: P97519
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 1, 1997
Last modified: June 8, 2016
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.