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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)
End	62,606,313 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	98,934,348 bp
RNA expression pattern
	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
	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
	27329
	30924
	ENSG00000132855
	ENSMUSG00000028553
	Q9Y5C1
	Q9R182
	NM_014495
	NM_013913
	NP_055310
	NP_038941
	Wikidata
View/Edit Human	View/Edit Mouse

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

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]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000132855 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000028553 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: ANGPTL3 angiopoietin-like 3".
^ Conklin D, Gilbertson D, Taft DW, Maurer MF, Whitmore TE, Smith DL, et al. (December 1999). "Identification of a mammalian angiopoietin-related protein expressed specifically in liver". Genomics. 62 (3): 477–82. doi:10.1006/geno.1999.6041. PMID 10644446. S2CID 16567474.
^ ^a ^b Tikka A, Jauhiainen M (May 2016). "The role of ANGPTL3 in controlling lipoprotein metabolism". Endocrine. 52 (2): 187–93. doi:10.1007/s12020-015-0838-9. PMC 4824806. PMID 26754661.
^ Wang Y, McNutt MC, Banfi S, Levin MG, Holland WL, Gusarova V, et al. (September 2015). "Hepatic ANGPTL3 regulates adipose tissue energy homeostasis". Proceedings of the National Academy of Sciences of the United States of America. 112 (37): 11630–5. Bibcode:2015PNAS..11211630W. doi:10.1073/pnas.1515374112. PMC 4577179. PMID 26305978.
^ Zhang R (August 2012). "Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels". Biochemical and Biophysical Research Communications. 424 (4): 786–92. doi:10.1016/j.bbrc.2012.07.038. PMID 22809513.
^ Ren G, Kim JY, Smas CM (August 2012). "Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism". American Journal of Physiology. Endocrinology and Metabolism. 303 (3): E334-51. doi:10.1152/ajpendo.00084.2012. PMC 3423120. PMID 22569073.
^ Fu Z, Abou-Samra AB, Zhang R (December 2015). "A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase". Scientific Reports. 5: 18502. Bibcode:2015NatSR...518502F. doi:10.1038/srep18502. PMC 4685196. PMID 26687026.
^ Zhang R (April 2016). "The ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking". Open Biology. 6 (4): 150272. doi:10.1098/rsob.150272. PMC 4852456. PMID 27053679. Archived from the original on 2018-08-04. Retrieved 2016-04-15.
^ Musunuru K, Pirruccello JP, Do R, Peloso GM, Guiducci C, Sougnez C, et al. (December 2010). "Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia". The New England Journal of Medicine. 363 (23): 2220–7. doi:10.1056/NEJMoa1002926. PMC 3008575. PMID 20942659.

External links

Human ANGPTL3 genome location and ANGPTL3 gene details page in the UCSC Genome Browser.
Overview of all the structural information available in the PDB for UniProt: Q9Y5C1 (Angiopoietin-related protein 3) at the PDBe-KB.