UniProtKB - P38060 (HMGCL_MOUSE)
Protein
Hydroxymethylglutaryl-CoA lyase, mitochondrial
Gene
Hmgcl
Organism
Mus musculus (Mouse)
Status
Functioni
Mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis. 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
Catalytic activityi
- EC:4.1.3.4By similarity
: (S)-3-hydroxy-3-methylglutaryl-CoA degradation Pathwayi
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:
- Hydroxymethylglutaryl-CoA lyase (Hmgcll1), 3-hydroxy-3-methylglutarate-CoA lyase (Hmgcl), Hydroxymethylglutaryl-CoA lyase (Hmgcll1), Hydroxymethylglutaryl-CoA lyase (Hmgcll1), Hydroxymethylglutaryl-CoA lyase, mitochondrial (Hmgcl), 3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic (Hmgcll1), Hydroxymethylglutaryl-CoA lyase (Hmgcll1)
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 41 | SubstrateBy similarity | 1 | |
Metal bindingi | 42 | Divalent metal cationBy similarity | 1 | |
Metal bindingi | 233 | Divalent metal cationBy similarity | 1 | |
Metal bindingi | 235 | Divalent metal cationBy similarity | 1 | |
Active sitei | 266 | PROSITE-ProRule annotation | 1 | |
Metal bindingi | 275 | Divalent metal cationBy similarity | 1 |
GO - Molecular functioni
- carboxylic acid binding Source: MGI
- fatty-acyl-CoA binding Source: MGI
- hydroxymethylglutaryl-CoA lyase activity Source: UniProtKB
- magnesium ion binding Source: MGI
- manganese ion binding Source: MGI
- metal ion binding Source: UniProtKB
- structural molecule activity Source: MGI
GO - Biological processi
- acyl-CoA metabolic process Source: MGI
- ketone body biosynthetic process Source: UniProtKB
- leucine catabolic process Source: GO_Central
- lipid metabolic process Source: MGI
- liver development Source: Ensembl
- mitochondrion organization Source: MGI
- response to fatty acid Source: Ensembl
- response to nutrient Source: Ensembl
- response to starvation Source: Ensembl
Keywordsi
Molecular function | Lyase |
Ligand | Metal-binding |
Enzyme and pathway databases
Reactomei | R-MMU-77111, Synthesis of Ketone Bodies R-MMU-9033241, Peroxisomal protein import |
UniPathwayi | UPA00896;UER00863 |
Names & Taxonomyi
Protein namesi | Recommended name: Hydroxymethylglutaryl-CoA lyase, mitochondrial (EC:4.1.3.4By similarity)Short name: HL1 Publication Short name: HMG-CoA lyase Alternative name(s): 3-hydroxy-3-methylglutarate-CoA lyase |
Gene namesi | Name:Hmgcl |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:96158, Hmgcl |
Subcellular locationi
Mitochondrion
- Mitochondrion matrix 1 Publication
Peroxisome
- Peroxisome 1 Publication
Note: Unprocessed form is peroxisomal.
Mitochondrion
- mitochondrial inner membrane Source: MGI
- mitochondrial matrix Source: UniProtKB-SubCell
- mitochondrion Source: MGI
Peroxisome
- peroxisome Source: MGI
Other locations
- protein-containing complex Source: MGI
Keywords - Cellular componenti
Mitochondrion, PeroxisomePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 27 | MitochondrionBy similarityAdd BLAST | 27 | |
ChainiPRO_0000013480 | 28 – 325 | Hydroxymethylglutaryl-CoA lyase, mitochondrialAdd BLAST | 298 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 48 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 48 | N6-succinyllysine; alternateCombined sources | 1 | |
Modified residuei | 111 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 137 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 137 | N6-succinyllysine; alternateCombined sources | 1 | |
Modified residuei | 179 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 179 | N6-succinyllysine; alternateCombined sources | 1 | |
Disulfide bondi | 323 | InterchainBy similarity | ||
Modified residuei | 324 | N6-acetyllysineCombined sources | 1 |
Keywords - PTMi
Acetylation, Disulfide bondProteomic databases
EPDi | P38060 |
jPOSTi | P38060 |
MaxQBi | P38060 |
PaxDbi | P38060 |
PeptideAtlasi | P38060 |
PRIDEi | P38060 |
PTM databases
iPTMneti | P38060 |
PhosphoSitePlusi | P38060 |
SwissPalmi | P38060 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000028672, Expressed in liver and 307 other tissues |
Genevisiblei | P38060, MM |
Interactioni
Subunit structurei
Homodimer; disulfide-linked. Can also form homotetramers.
By similarityProtein-protein interaction databases
BioGRIDi | 200337, 3 interactors |
IntActi | P38060, 2 interactors |
MINTi | P38060 |
STRINGi | 10090.ENSMUSP00000030432 |
Miscellaneous databases
RNActi | P38060, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 33 – 300 | Pyruvate carboxyltransferasePROSITE-ProRule annotationAdd BLAST | 268 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 323 – 325 | Microbody targeting signalSequence analysis | 3 |
Sequence similaritiesi
Belongs to the HMG-CoA lyase family.Curated
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG2368, Eukaryota |
GeneTreei | ENSGT00940000158484 |
HOGENOMi | CLU_022138_3_1_1 |
InParanoidi | P38060 |
OMAi | FGGCPMA |
OrthoDBi | 1029775at2759 |
TreeFami | TF105363 |
Family and domain databases
Gene3Di | 3.20.20.70, 1 hit |
InterProi | View protein in InterPro IPR013785, Aldolase_TIM IPR000138, HMG_CoA_lyase_AS IPR043594, HMGL IPR000891, PYR_CT |
PANTHERi | PTHR42738, PTHR42738, 1 hit |
Pfami | View protein in Pfam PF00682, HMGL-like, 1 hit |
PROSITEi | View protein in PROSITE PS01062, HMG_COA_LYASE, 1 hit PS50991, PYR_CT, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P38060-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 62 – 63 | ML → IV in AAB03107 (PubMed:8617516).Curated | 2 | |
Sequence conflicti | 80 | K → N in AAB27965 (PubMed:8102917).Curated | 1 | |
Sequence conflicti | 231 | A → G in AAB27965 (PubMed:8102917).Curated | 1 | |
Sequence conflicti | 238 | Y → I in AAB27965 (PubMed:8102917).Curated | 1 |
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 No translation available. CH466552 Genomic DNA Translation: EDL29963.1 BC025440 mRNA Translation: AAH25440.1 |
CCDSi | CCDS18795.1 |
RefSeqi | NP_032280.2, NM_008254.2 |
Genome annotation databases
Ensembli | ENSMUST00000030432; ENSMUSP00000030432; ENSMUSG00000028672 |
GeneIDi | 15356 |
KEGGi | mmu:15356 |
UCSCi | uc012dnc.1, mouse |
Similar proteinsi
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 No translation available. CH466552 Genomic DNA Translation: EDL29963.1 BC025440 mRNA Translation: AAH25440.1 |
CCDSi | CCDS18795.1 |
RefSeqi | NP_032280.2, NM_008254.2 |
3D structure databases
SMRi | P38060 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 200337, 3 interactors |
IntActi | P38060, 2 interactors |
MINTi | P38060 |
STRINGi | 10090.ENSMUSP00000030432 |
PTM databases
iPTMneti | P38060 |
PhosphoSitePlusi | P38060 |
SwissPalmi | P38060 |
Proteomic databases
EPDi | P38060 |
jPOSTi | P38060 |
MaxQBi | P38060 |
PaxDbi | P38060 |
PeptideAtlasi | P38060 |
PRIDEi | P38060 |
Protocols and materials databases
Antibodypediai | 1373, 319 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000030432; ENSMUSP00000030432; ENSMUSG00000028672 |
GeneIDi | 15356 |
KEGGi | mmu:15356 |
UCSCi | uc012dnc.1, mouse |
Organism-specific databases
CTDi | 3155 |
MGIi | MGI:96158, Hmgcl |
Phylogenomic databases
eggNOGi | KOG2368, Eukaryota |
GeneTreei | ENSGT00940000158484 |
HOGENOMi | CLU_022138_3_1_1 |
InParanoidi | P38060 |
OMAi | FGGCPMA |
OrthoDBi | 1029775at2759 |
TreeFami | TF105363 |
Enzyme and pathway databases
UniPathwayi | UPA00896;UER00863 |
Reactomei | R-MMU-77111, Synthesis of Ketone Bodies R-MMU-9033241, Peroxisomal protein import |
Miscellaneous databases
BioGRID-ORCSi | 15356, 0 hits in 17 CRISPR screens |
ChiTaRSi | Hmgcl, mouse |
PROi | PR:P38060 |
RNActi | P38060, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000028672, Expressed in liver and 307 other tissues |
Genevisiblei | P38060, MM |
Family and domain databases
Gene3Di | 3.20.20.70, 1 hit |
InterProi | View protein in InterPro IPR013785, Aldolase_TIM IPR000138, HMG_CoA_lyase_AS IPR043594, HMGL IPR000891, PYR_CT |
PANTHERi | PTHR42738, PTHR42738, 1 hit |
Pfami | View protein in Pfam PF00682, HMGL-like, 1 hit |
PROSITEi | View protein in PROSITE PS01062, HMG_COA_LYASE, 1 hit PS50991, PYR_CT, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HMGCL_MOUSE | |
Accessioni | P38060Primary (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: | December 2, 2020 | |
This is version 156 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families