P54310 · LIPS_MOUSE
- ProteinHormone-sensitive lipase
- GeneLipe
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids759 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Lipase with broad substrate specificity, catalyzing the hydrolysis of triacylglycerols (TAGs), diacylglycerols (DAGs), monoacylglycerols (MAGs), cholesteryl esters and retinyl esters (PubMed:15550674, PubMed:20625037, PubMed:21454566, PubMed:23066022, PubMed:23291629).
Shows a preferential hydrolysis of DAGs over TAGs and MAGs and of the fatty acid (FA) esters at the sn-1 and sn-2 positions of the glycerol backbone in TAGs (By similarity).
Preferentially hydrolyzes FA esters at the sn-3 position of the glycerol backbone in DAGs (PubMed:23066022).
Catalyzes the hydrolysis of 2-arachidonoylglycerol, an endocannabinoid and of 2-acetyl monoalkylglycerol ether, the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor (PubMed:20625037, PubMed:21454566).
In adipose tissue and heart, it primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production (By similarity).
Shows a preferential hydrolysis of DAGs over TAGs and MAGs and of the fatty acid (FA) esters at the sn-1 and sn-2 positions of the glycerol backbone in TAGs (By similarity).
Preferentially hydrolyzes FA esters at the sn-3 position of the glycerol backbone in DAGs (PubMed:23066022).
Catalyzes the hydrolysis of 2-arachidonoylglycerol, an endocannabinoid and of 2-acetyl monoalkylglycerol ether, the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor (PubMed:20625037, PubMed:21454566).
In adipose tissue and heart, it primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production (By similarity).
Catalytic activity
- a diacylglycerol + H2O = a fatty acid + a monoacylglycerol + H+
- cholesteryl (9Z-octadecenoate) + H2O = (9Z)-octadecenoate + cholesterol + H+This reaction proceeds in the forward direction.
- all-trans-retinyl hexadecanoate + H2O = all-trans-retinol + H+ + hexadecanoateThis reaction proceeds in the forward direction.
- 1,2-di-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + (9Z-octadecenoyl)-glycerol + H+This reaction proceeds in the forward direction.
- 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H+This reaction proceeds in the forward direction.
- 1-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H+This reaction proceeds in the forward direction.
- 2-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H+This reaction proceeds in the forward direction.
- 1-O-hexadecyl-2-acetyl-sn-glycerol + H2O = 1-O-hexadecyl-sn-glycerol + acetate + H+This reaction proceeds in the forward direction.
- 1,2-di-(9Z-octadecenoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + (9Z-octadecenoyl)-glycerol + H+This reaction proceeds in the forward direction.
- 1,3-di-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + 1-(9Z-octadecenoyl)-glycerol + H+This reaction proceeds in the forward direction.
- (9Z)-octadecenoate + 1,2-di-(9Z-octadecenoyl)-glycerol + H+ = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2OThis reaction proceeds in the backward direction.
- 2,3-di-(9Z)-octadecenoyl-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z-octadecenoyl)-glycerol + H+This reaction proceeds in the forward direction.
- 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + di-(9Z)-octadecenoylglycerol + H+This reaction proceeds in the forward direction.
- 1,2-di-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z-octadecenoyl)-glycerol + H+This reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.25 μM | 1-(9Z-octadecenoyl)-glycerol | |||||
0.26 μM | 2-(9Z-octadecenoyl)-glycerol | |||||
0.27 μM | 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol |
Pathway
Glycerolipid metabolism; triacylglycerol degradation.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 423 | |||||
Sequence: S | ||||||
Active site | 694 | |||||
Sequence: D | ||||||
Active site | 724 | |||||
Sequence: H |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameHormone-sensitive lipase
- EC number
- Short namesHSL
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP54310
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Found in the high-density caveolae (By similarity).
Translocates to the cytoplasm from the caveolae upon insulin stimulation (By similarity).
Phosphorylation by AMPK reduces its translocation towards the lipid droplets
Translocates to the cytoplasm from the caveolae upon insulin stimulation (By similarity).
Phosphorylation by AMPK reduces its translocation towards the lipid droplets
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Total acylglycerol levels are unaltered whereas diacylglycerol concentrations are drastically increased in white adipose tissue of knockout mice when compared to wild-type littermates.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 31 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000071548 | 1-759 | Hormone-sensitive lipase | |||
Sequence: MDLRTMTQSLVTLAEDNMAFFSSQGPGETARRLSNVFAGVREQALGLEPTLGQLLGVAHHFDLDTETPANGYRSLVHTARCCLAHLLHKSRYVASNRKSIFFRASHNLAELEAYLAALTQLRAMAYYAQRLLTINRPGVLFFEGDEGLTADFLQEYVTLHKGCFYGRCLGFQFTPAIRPFLQTLSIGLVSFGEHYKRNETGLSVTASSLFTGGRFAIDPELRGAEFERIIQNLDVHFWKAFWNITEIEVLSSLANMASTTVRVSRLLSLPPEAFEMPLTSDPRLTVTISPPLAHTGPAPVLARLISYDLREGQDSKVLNSLAKSEGPRLELRPRPHQAPRSRALVVHIHGGGFVAQTSKSHEPYLKNWAQELGVPIFSIDYSLAPEAPFPRALEECFFAYCWAVKHCDLLGSTGERICLAGDSAGGNLCITVSLRAAAYGVRVPDGIMAAYPVTTLQSSASPSRLLSLMDPLLPLSVLSKCVSAYSGTEAEDHFDSDQKALGVMGLVQRDTSLFLRDLRLGASSWLNSFLELSGRKPQKTTSPTAESVRPTESMRRSVSEAALAQPEGLLGTDTLKKLTIKDLSNSEPSDSPEMSQSMETLGPSTPSDVNFFLRPGNSQEEAEAKDEVRPMDGVPRVRAAFPEGFHPRRSSQGVLHMPLYTSPIVKNPFMSPLLAPDSMLKTLPPVHLVACALDPMLDDSVMFARRLRDLGQPVTLKVVEDLPHGFLSLAALCRETRQATEFCVQRIRLILTPPAAPLN | ||||||
Modified residue | 557 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 559 | Phosphoserine; by AMPK | ||||
Sequence: S | ||||||
Modified residue | 574 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 597 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 618 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 650 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 651 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylation by AMPK reduces its translocation towards the lipid droplets.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Structure
Family & Domains
Features
Showing features for motif, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 349-351 | Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion hole | ||||
Sequence: HGG | ||||||
Region | 534-553 | Disordered | ||||
Sequence: GRKPQKTTSPTAESVRPTES | ||||||
Region | 583-604 | Disordered | ||||
Sequence: LSNSEPSDSPEMSQSMETLGPS |
Sequence similarities
Belongs to the 'GDXG' lipolytic enzyme family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P54310-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length759
- Mass (Da)83,348
- Last updated2006-01-24 v2
- Checksum3419AF52F6C85FF4
P54310-2
- Name2
- Differences from canonical
- 1-1: M → MEPAVESAPVGAQASKQGKEGSKNRSRRRWRKGKIKASAFSHSM
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0U1RPJ0 | A0A0U1RPJ0_MOUSE | Lipe | 24 | ||
E9Q4M2 | E9Q4M2_MOUSE | Lipe | 1072 | ||
A0A0U1RNR0 | A0A0U1RNR0_MOUSE | Lipe | 180 | ||
Q9D4C4 | Q9D4C4_MOUSE | Lipe | 334 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_053335 | 1 | in isoform 2 | |||
Sequence: M → MEPAVESAPVGAQASKQGKEGSKNRSRRRWRKGKIKASAFSHSM | ||||||
Sequence conflict | 113 | in Ref. 3; BAE41414 | ||||
Sequence: A → T | ||||||
Sequence conflict | 311 | in Ref. 3; BAE41414 | ||||
Sequence: E → D | ||||||
Sequence conflict | 330-331 | in Ref. 1; AAC52163 | ||||
Sequence: EL → DV | ||||||
Sequence conflict | 530 | in Ref. 1; AAC52163 | ||||
Sequence: L → P |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U08188 EMBL· GenBank· DDBJ | AAC52163.1 EMBL· GenBank· DDBJ | mRNA | ||
AF179427 EMBL· GenBank· DDBJ | AAC53069.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC162443 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC169209 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AK029984 EMBL· GenBank· DDBJ | BAC26716.1 EMBL· GenBank· DDBJ | mRNA | ||
AK169858 EMBL· GenBank· DDBJ | BAE41414.1 EMBL· GenBank· DDBJ | mRNA | ||
BC021642 EMBL· GenBank· DDBJ | AAH21642.1 EMBL· GenBank· DDBJ | mRNA |