ANGPTL3

Angiopoietin-like 3, also known as ANGPTL3, is a protein that in humans is encoded by the ANGPTL3 gene.^[5][6]

ANGPTL3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 6EUA
Identifiers
Aliases	ANGPTL3, ANG-5, ANGPT5, ANL3, FHBL2, angiopoietin like 3
External IDs	OMIM: 604774; MGI: 1353627; HomoloGene: 8499; GeneCards: ANGPTL3; OMA:ANGPTL3 - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p31.3 Start 62,597,520 bp[1] End 62,606,313 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4 C6|4 45.6 cM Start 98,919,191 bp[2] End 98,934,348 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver kidney tubule metanephric glomerulus human kidney testicle gonad buccal mucosa cell Achilles tendon epithelium of colon stomach Top expressed in left lobe of liver fetal liver hematopoietic progenitor cell right kidney human fetus tail of embryo sexually immature organism blastocyst human kidney embryo embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phospholipase inhibitor activity enzyme inhibitor activity integrin binding growth factor activity heparin binding Cellular component Golgi apparatus cell surface early endosome cell projection lamellipodium extracellular region extracellular space Biological process phospholipid homeostasis positive regulation of cell migration positive regulation of lipid catabolic process lipid storage cholesterol metabolic process fatty acid metabolic process positive regulation of angiogenesis artery morphogenesis lipid homeostasis phospholipid catabolic process integrin-mediated signaling pathway negative regulation of lipoprotein lipase activity response to hormone phospholipid metabolic process cholesterol homeostasis acylglycerol homeostasis cell-matrix adhesion glycerol metabolic process negative regulation of phospholipase activity triglyceride homeostasis signal transduction lipid metabolism cell adhesion angiogenesis regulation of lipoprotein lipase activity regulation of signaling receptor activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 27329 30924 Ensembl ENSG00000132855 ENSMUSG00000028553 UniProt Q9Y5C1 Q9R182 RefSeq (mRNA) NM_014495 NM_013913 RefSeq (protein) NP_055310 NP_038941 Location (UCSC) Chr 1: 62.6 – 62.61 Mb Chr 4: 98.92 – 98.93 Mb PubMed search [3] [4]
Wikidata
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Function

The protein encoded by this gene is a member of the angiopoietin-like family of secreted factors. It is expressed predominantly in the liver, and has the characteristic structure of angiopoietins, consisting of a signal peptide, N-terminal coiled-coil domain, and the C-terminal fibrinogen (FBN)-like domain. The FBN-like domain in angiopoietin-like 3 protein was shown to bind alpha-5/beta-3 integrins, and this binding induced endothelial cell adhesion and migration. This protein may also play a role in the regulation of angiogenesis.^[5]

Angptl3 also acts as dual inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL),^[7] thereby increasing plasma triglyceride, LDL cholesterol and HDL cholesterol in mice and humans.^[7]

ANGPTL3 inhibits endothelial lipase hydrolysis of HDL-phospholipid (PL), thereby increasing HDL-PL levels.^{[citation needed]} Circulating PL-rich HDL particles have high cholesterol efflux abilities.^{[citation needed]}

Angptl3 plays a major role in promoting uptake of circulating triglycerides into white adipose tissue in the fed state,^[8] likely through activation by Angptl8, a feeding-induced hepatokine,^[9][10] to inhibit postprandial LPL activity in cardiac and skeletal muscles,^[11] as suggested by the ANGPTL3-4-8 model.^[12]

Clinical significance

In human, ANGPTL3 is a determinant factor of HDL level and positively correlates with plasma HDL cholesterol.^{[citation needed]}

In humans with genetic loss-of-function variants in one copy of ANGPTL3, the serum LDL-C levels are reduced. In those with loss-of-function variants in both copies of ANGPTL3, low LDL-C, low HDL-C, and low triglycerides are seen ("familial combined hypolipidemia").^[13]