O46647 · LIPL_NEOVI
- ProteinLipoprotein lipase
- GeneLPL
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids475 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Key enzyme in triglyceride metabolism. Catalyzes the hydrolysis of triglycerides from circulating chylomicrons and very low density lipoproteins (VLDL), and thereby plays an important role in lipid clearance from the blood stream, lipid utilization and storage (PubMed:9852258).
Mediates margination of triglyceride-rich lipoprotein particles in capillaries. Recruited to its site of action on the luminal surface of vascular endothelium by binding to GPIHBP1 and cell surface heparan sulfate proteoglycans (By similarity).
Mediates margination of triglyceride-rich lipoprotein particles in capillaries. Recruited to its site of action on the luminal surface of vascular endothelium by binding to GPIHBP1 and cell surface heparan sulfate proteoglycans (By similarity).
Catalytic activity
- a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H+
Activity regulation
The apolipoprotein APOC2 acts as a coactivator of LPL activity (By similarity).
Ca2+ binding promotes protein stability and formation of the active homodimer. Interaction with GPIHBP1 protects LPL against inactivation by ANGPTL4 (By similarity).
Ca2+ binding promotes protein stability and formation of the active homodimer. Interaction with GPIHBP1 protects LPL against inactivation by ANGPTL4 (By similarity).
Features
Showing features for active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 159 | Nucleophile | ||||
Sequence: S | ||||||
Active site | 183 | Charge relay system | ||||
Sequence: D | ||||||
Binding site | 194 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 197 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 199 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 202 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Active site | 268 | Charge relay system | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | chylomicron | |
Cellular Component | extracellular space | |
Cellular Component | plasma membrane | |
Cellular Component | very-low-density lipoprotein particle | |
Molecular Function | apolipoprotein binding | |
Molecular Function | heparan sulfate proteoglycan binding | |
Molecular Function | heparin binding | |
Molecular Function | lipoprotein lipase activity | |
Molecular Function | lipoprotein particle binding | |
Molecular Function | metal ion binding | |
Biological Process | chylomicron remodeling | |
Biological Process | fatty acid biosynthetic process | |
Biological Process | fatty acid metabolic process | |
Biological Process | response to glucose | |
Biological Process | triglyceride catabolic process | |
Biological Process | very-low-density lipoprotein particle remodeling |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameLipoprotein lipase
- EC number
- Short namesLPL
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Carnivora > Caniformia > Musteloidea > Mustelidae > Mustelinae > Neogale
Accessions
- Primary accessionO46647
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
Note: Newly synthesized LPL binds to cell surface heparan proteoglycans and is then released by heparanase. Subsequently, it becomes attached to heparan proteoglycan on endothelial cells. Locates to the plasma membrane of microvilli of hepatocytes with triglyceride-rich lipoproteins (TRL). Some of the bound LPL is then internalized and located inside non-coated endocytic vesicles.
Keywords
- Cellular component
Phenotypes & Variants
Involvement in disease
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | 241 | in chylomicronemia syndrome; no lipase activity | ||||
Sequence: P → L |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1 variant from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-27 | |||||
Sequence: MESKALLLVALGMWFQSLTATRGGVAA | ||||||
Chain | PRO_0000017777 | 28-475 | Lipoprotein lipase | |||
Sequence: ADRGGDFIDIESKFALRTPEDTAEDTCHLIPGVTESVANCHFNHSSKTFVVIHGWTVTGMYESWVPKLVAALYKREPDSNVIVVDWLSRAQQHYPVSAGYTKLVGKDVAKFINWMAEEFHYPLDNVHLLGYSLGAHAAGIAGSLTNKKVNRITGLDPAGPNFEYAEAPSRLSPDDADFVDVLHTFTRGSPGRSIGIQKPVGHVDIYPNGGTFQPGCNIGEAIRVIAERGLGDVDQLVKCSHERSIHLFIDSLLNEENPSKAYRCNSKEAFEKGLCLSCRKNRCNNLGYEINKVRAKRSSKMYLKTRSQMPYKVFHYQVKIHFSGTESDTQTNQAFEISLYGTVAESENIPFTLPEVSANKTYSFLIYTEVDIGELLMLKLKWKSDSYFSWSDWWSSPGFAIEKIRVKAGETQKKVIFCSREKVSHLQKGKASVVFVKCHDKSLNKKSG | ||||||
Disulfide bond | 54↔67 | |||||
Sequence: CHLIPGVTESVANC | ||||||
Glycosylation | 70 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 121 | 3'-nitrotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 191 | 3'-nitrotyrosine | ||||
Sequence: Y | ||||||
Disulfide bond | 243↔266 | |||||
Sequence: CNIGEAIRVIAERGLGDVDQLVKC | ||||||
Disulfide bond | 291↔310 | |||||
Sequence: CNSKEAFEKGLCLSCRKNRC | ||||||
Disulfide bond | 302↔305 | |||||
Sequence: CLSC | ||||||
Modified residue | 343 | 3'-nitrotyrosine | ||||
Sequence: Y | ||||||
Glycosylation | 386 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 445↔465 | |||||
Sequence: CSREKVSHLQKGKASVVFVKC |
Post-translational modification
Tyrosine nitration after lipopolysaccharide (LPS) challenge down-regulates the lipase activity.
Keywords
- PTM
PTM databases
Interaction
Subunit
Homodimer. Interacts with GPIHBP1 with 1:1 stoichiometry (By similarity).
Interacts with APOC2; the interaction activates LPL activity in the presence of lipids (By similarity).
Interaction with heparan sulfate proteoglycans is required to protect LPL against loss of activity. Associates with lipoprotein particles in blood plasma. Interacts with LMF1 and SEL1L; interaction with SEL1L is required to prevent aggregation of newly synthesized LPL in the endoplasmic reticulum (ER), and for normal export of LPL from the ER to the extracellular space (By similarity).
Interacts with SORL1; SORL1 acts as a sorting receptor, promoting LPL localization to endosomes and later to lysosomes, leading to degradation of newly synthesized LPL (By similarity).
Interacts with APOC2; the interaction activates LPL activity in the presence of lipids (By similarity).
Interaction with heparan sulfate proteoglycans is required to protect LPL against loss of activity. Associates with lipoprotein particles in blood plasma. Interacts with LMF1 and SEL1L; interaction with SEL1L is required to prevent aggregation of newly synthesized LPL in the endoplasmic reticulum (ER), and for normal export of LPL from the ER to the extracellular space (By similarity).
Interacts with SORL1; SORL1 acts as a sorting receptor, promoting LPL localization to endosomes and later to lysosomes, leading to degradation of newly synthesized LPL (By similarity).
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 32-53 | Interaction with GPIHBP1 | ||||
Sequence: GDFIDIESKFALRTPEDTAEDT | ||||||
Domain | 341-464 | PLAT | ||||
Sequence: FHYQVKIHFSGTESDTQTNQAFEISLYGTVAESENIPFTLPEVSANKTYSFLIYTEVDIGELLMLKLKWKSDSYFSWSDWWSSPGFAIEKIRVKAGETQKKVIFCSREKVSHLQKGKASVVFVK | ||||||
Region | 417-421 | Important for interaction with lipoprotein particles | ||||
Sequence: WSDWW | ||||||
Region | 430-434 | Important for heparin binding | ||||
Sequence: KIRVK | ||||||
Region | 443-467 | Interaction with GPIHBP1 | ||||
Sequence: IFCSREKVSHLQKGKASVVFVKCHD |
Sequence similarities
Belongs to the AB hydrolase superfamily. Lipase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length475
- Mass (Da)52,968
- Last updated1998-06-01 v1
- Checksum2F2DBF0090F0FB7C
Keywords
- Technical term