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Protein

Hydroxymethylglutaryl-CoA lyase, mitochondrial

Gene

Hmgcl

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 similarity

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. Hydroxymethylglutaryl-CoA lyase, mitochondrial (Hmgcl), 3-hydroxymethyl-3-methylglutaryl-CoA lyase, cytoplasmic (Hmgcll1)
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)DescriptionActionsGraphical viewLength
Binding sitei41SubstrateBy similarity1
Metal bindingi42Divalent metal cationBy similarity1
Metal bindingi233Divalent metal cationBy similarity1
Metal bindingi235Divalent metal cationBy similarity1
Active sitei266PROSITE-ProRule annotation1
Metal bindingi275Divalent metal cationBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Ligandi

Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:96158. Hmgcl.

Subcellular locationi

  • Mitochondrion matrix 1 Publication
  • Peroxisome 1 Publication

  • Note: Unprocessed form is peroxisomal.

GO - Cellular componenti

  • mitochondrial inner membrane Source: MGI
  • mitochondrial matrix Source: UniProtKB-SubCell
  • mitochondrion Source: MGI
  • peroxisome Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion, Peroxisome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 27MitochondrionBy similarityAdd BLAST27
ChainiPRO_000001348028 – 325Hydroxymethylglutaryl-CoA lyase, mitochondrialAdd BLAST298

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei48N6-acetyllysine; alternateCombined sources1
Modified residuei48N6-succinyllysine; alternateCombined sources1
Modified residuei111N6-acetyllysineCombined sources1
Modified residuei137N6-acetyllysine; alternateCombined sources1
Modified residuei137N6-succinyllysine; alternateCombined sources1
Modified residuei179N6-acetyllysine; alternateCombined sources1
Modified residuei179N6-succinyllysine; alternateCombined sources1
Disulfide bondi323InterchainBy similarity
Modified residuei324N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Disulfide bond

Proteomic databases

EPDiP38060.
MaxQBiP38060.
PaxDbiP38060.
PeptideAtlasiP38060.
PRIDEiP38060.

PTM databases

iPTMnetiP38060.
PhosphoSitePlusiP38060.
SwissPalmiP38060.

Expressioni

Gene expression databases

BgeeiENSMUSG00000028672.
CleanExiMM_HMGCL.
GenevisibleiP38060. MM.

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200337. 1 interactor.
IntActiP38060. 1 interactor.
MINTiMINT-1840478.
STRINGi10090.ENSMUSP00000030432.

Structurei

3D structure databases

ProteinModelPortaliP38060.
SMRiP38060.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 300Pyruvate carboxyltransferasePROSITE-ProRule annotationAdd BLAST268

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi323 – 325Microbody targeting signalSequence analysis3

Sequence similaritiesi

Belongs to the HMG-CoA lyase family.Curated
Contains 1 pyruvate carboxyltransferase domain.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2368. Eukaryota.
COG0119. LUCA.
GeneTreeiENSGT00390000017690.
HOGENOMiHOG000219757.
HOVERGENiHBG064656.
InParanoidiP38060.
KOiK01640.
OMAiEAFAQKN.
OrthoDBiEOG091G0DA9.
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.

P38060-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASVRKAFPR RLVGLTSLRA VSTSSMGTLP KQVKIVEVGP RDGLQNEKSI
60 70 80 90 100
VPTPVKIRLI DMLSEAGLPV IEATSFVSPK WVPQMADHSD VLKGIQKFPG
110 120 130 140 150
INYPVLTPNM KGFEEAVAAG AKEVSVFGAV SELFTRKNAN CSIEESFQRF
160 170 180 190 200
AGVMQAAQAA SISVRGYVSC ALGCPYEGKV SPAKVAEVAK KLYSMGCYEI
210 220 230 240 250
SLGDTIGVGT PGLMKDMLTA VMHEVPVTAL AVHCHDTYGQ ALANTLVALQ
260 270 280 290 300
MGVSVVDSSV AGLGGCPYAK GASGNLATED LVYMLNGLGI HTGVNLQKLL
310 320
EAGDFICQAL NRKTSSKVAQ ATCKL
Length:325
Mass (Da):34,239
Last modified:July 27, 2011 - v2
Checksum:iE6A85659EBA1D87F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti62 – 63ML → IV in AAB03107 (PubMed:8617516).Curated2
Sequence conflicti80K → N in AAB27965 (PubMed:8102917).Curated1
Sequence conflicti231A → G in AAB27965 (PubMed:8102917).Curated1
Sequence conflicti238Y → I in AAB27965 (PubMed:8102917).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S65036 mRNA. Translation: AAB27965.1.
U49878
, U49870, U49871, U49872, U49873, U49874, U49875, U49876, U49877 Genomic DNA. Translation: AAB03107.1.
AK132035 mRNA. Translation: BAE20956.1.
AK145251 mRNA. Translation: BAE26328.1.
AK154033 mRNA. Translation: BAE32329.1.
AL672076 Genomic DNA. Translation: CAM15901.1.
CH466552 Genomic DNA. Translation: EDL29963.1.
BC025440 mRNA. Translation: AAH25440.1.
CCDSiCCDS18795.1.
RefSeqiNP_032280.2. NM_008254.2.
UniGeneiMm.482102.

Genome annotation databases

EnsembliENSMUST00000030432; ENSMUSP00000030432; ENSMUSG00000028672.
GeneIDi15356.
KEGGimmu:15356.
UCSCiuc012dnc.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S65036 mRNA. Translation: AAB27965.1.
U49878
, U49870, U49871, U49872, U49873, U49874, U49875, U49876, U49877 Genomic DNA. Translation: AAB03107.1.
AK132035 mRNA. Translation: BAE20956.1.
AK145251 mRNA. Translation: BAE26328.1.
AK154033 mRNA. Translation: BAE32329.1.
AL672076 Genomic DNA. Translation: CAM15901.1.
CH466552 Genomic DNA. Translation: EDL29963.1.
BC025440 mRNA. Translation: AAH25440.1.
CCDSiCCDS18795.1.
RefSeqiNP_032280.2. NM_008254.2.
UniGeneiMm.482102.

3D structure databases

ProteinModelPortaliP38060.
SMRiP38060.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200337. 1 interactor.
IntActiP38060. 1 interactor.
MINTiMINT-1840478.
STRINGi10090.ENSMUSP00000030432.

PTM databases

iPTMnetiP38060.
PhosphoSitePlusiP38060.
SwissPalmiP38060.

Proteomic databases

EPDiP38060.
MaxQBiP38060.
PaxDbiP38060.
PeptideAtlasiP38060.
PRIDEiP38060.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030432; ENSMUSP00000030432; ENSMUSG00000028672.
GeneIDi15356.
KEGGimmu:15356.
UCSCiuc012dnc.1. mouse.

Organism-specific databases

CTDi3155.
MGIiMGI:96158. Hmgcl.

Phylogenomic databases

eggNOGiKOG2368. Eukaryota.
COG0119. LUCA.
GeneTreeiENSGT00390000017690.
HOGENOMiHOG000219757.
HOVERGENiHBG064656.
InParanoidiP38060.
KOiK01640.
OMAiEAFAQKN.
OrthoDBiEOG091G0DA9.
TreeFamiTF105363.

Enzyme and pathway databases

UniPathwayiUPA00896; UER00863.
ReactomeiR-MMU-77111. Synthesis of Ketone Bodies.

Miscellaneous databases

PROiP38060.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028672.
CleanExiMM_HMGCL.
GenevisibleiP38060. MM.

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...

Entry informationi

Entry nameiHMGCL_MOUSE
AccessioniPrimary (citable) accession number: P38060
Secondary accession number(s): Q8QZS6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 130 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.