O46647 · LIPL_NEOVI

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).

Catalytic activity

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).

Features

Showing features for active site, binding site.

TypeIDPosition(s)Description
Active site159Nucleophile
Active site183Charge relay system
Binding site194Ca2+ (UniProtKB | ChEBI)
Binding site197Ca2+ (UniProtKB | ChEBI)
Binding site199Ca2+ (UniProtKB | ChEBI)
Binding site202Ca2+ (UniProtKB | ChEBI)
Active site268Charge relay system

GO annotations

AspectTerm
Cellular Componentchylomicron
Cellular Componentextracellular space
Cellular Componentplasma membrane
Cellular Componentvery-low-density lipoprotein particle
Molecular Functionapolipoprotein binding
Molecular Functionheparan sulfate proteoglycan binding
Molecular Functionheparin binding
Molecular Functionlipoprotein lipase activity
Molecular Functionlipoprotein particle binding
Molecular Functionmetal ion binding
Biological Processchylomicron remodeling
Biological Processfatty acid biosynthetic process
Biological Processfatty acid metabolic process
Biological Processresponse to glucose
Biological Processtriglyceride catabolic process
Biological Processvery-low-density lipoprotein particle remodeling

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Lipoprotein lipase
  • EC number
  • Short names
    LPL

Gene names

    • Name
      LPL

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Carnivora > Caniformia > Musteloidea > Mustelidae > Mustelinae > Neogale

Accessions

  • Primary accession
    O46647

Proteomes

Subcellular Location

Cell membrane
; Peripheral membrane protein
Secreted
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

Phenotypes & Variants

Involvement in disease

  • Defects in LPL are a cause of chylomicronemia syndrome, also known as type I hyperlipoproteinemia

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variant241in chylomicronemia syndrome; no lipase activity

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.

Go to variant viewer

Keywords

PTM/Processing

Features

Showing features for signal, chain, disulfide bond, glycosylation, modified residue.

TypeIDPosition(s)Description
Signal1-27
ChainPRO_000001777728-475Lipoprotein lipase
Disulfide bond54↔67
Glycosylation70N-linked (GlcNAc...) asparagine
Modified residue1213'-nitrotyrosine
Modified residue1913'-nitrotyrosine
Disulfide bond243↔266
Disulfide bond291↔310
Disulfide bond302↔305
Modified residue3433'-nitrotyrosine
Glycosylation386N-linked (GlcNAc...) asparagine
Disulfide bond445↔465

Post-translational modification

Tyrosine nitration after lipopolysaccharide (LPS) challenge down-regulates the lipase activity.

Keywords

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).

Structure

Family & Domains

Features

Showing features for region, domain.

TypeIDPosition(s)Description
Region32-53Interaction with GPIHBP1
Domain341-464PLAT
Region417-421Important for interaction with lipoprotein particles
Region430-434Important for heparin binding
Region443-467Interaction with GPIHBP1

Sequence similarities

Belongs to the AB hydrolase superfamily. Lipase family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    475
  • Mass (Da)
    52,968
  • Last updated
    1998-06-01 v1
  • Checksum
    2F2DBF0090F0FB7C
MESKALLLVALGMWFQSLTATRGGVAAADRGGDFIDIESKFALRTPEDTAEDTCHLIPGVTESVANCHFNHSSKTFVVIHGWTVTGMYESWVPKLVAALYKREPDSNVIVVDWLSRAQQHYPVSAGYTKLVGKDVAKFINWMAEEFHYPLDNVHLLGYSLGAHAAGIAGSLTNKKVNRITGLDPAGPNFEYAEAPSRLSPDDADFVDVLHTFTRGSPGRSIGIQKPVGHVDIYPNGGTFQPGCNIGEAIRVIAERGLGDVDQLVKCSHERSIHLFIDSLLNEENPSKAYRCNSKEAFEKGLCLSCRKNRCNNLGYEINKVRAKRSSKMYLKTRSQMPYKVFHYQVKIHFSGTESDTQTNQAFEISLYGTVAESENIPFTLPEVSANKTYSFLIYTEVDIGELLMLKLKWKSDSYFSWSDWWSSPGFAIEKIRVKAGETQKKVIFCSREKVSHLQKGKASVVFVKCHDKSLNKKSG

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AJ223493
EMBL· GenBank· DDBJ
CAA11411.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

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