“ANGPTL3”的意思、由来-开放百科全书

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.^[1]

Angptl3 also acts as dual inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL),^[3] thereby increasing plasma triglyceride, LDL cholesterol and HDL cholesterol in mice and humans.^[3]

ANGPTL3 inhibits endothelial lipase hydrolysis of HDL-phospholipid (PL), thereby increasing HDL-PL levels.{{citation needed|date=March 2018}} Circulating PL-rich HDL particles have high cholesterol efflux abilities.{{citation needed|date=March 2018}}

Angptl3 plays a major role in promoting uptake of circulating triglycerides into white adipose tissue in the fed state,^[4] likely through activation by Angptl8, a feeding-induced hepatokine,^[5]^[6] to inhibit postprandial LPL activity in cardiac and skeletal muscles,^[7] as suggested by the ANGPTL3-4-8 model.^[8]

Clinical significance

In human, ANGPTL3 is a determinant factor of HDL level and positively correlates with plasma HDL cholesterol.

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").^[9]

References

1. ^¹{{cite web | title = Entrez Gene: ANGPTL3 angiopoietin-like 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27329| accessdate = }}
2. ^{{cite journal | vauthors = Conklin D, Gilbertson D, Taft DW, Maurer MF, Whitmore TE, Smith DL, Walker KM, Chen LH, Wattler S, Nehls M, Lewis KB | title = Identification of a mammalian angiopoietin-related protein expressed specifically in liver | journal = Genomics | volume = 62 | issue = 3 | pages = 477–82 |date=December 1999 | pmid = 10644446 | doi = 10.1006/geno.1999.6041 | url = }}
3. ^¹{{cite journal | vauthors=Tikka A, Jauhiainen M | title=The role of ANGPTL3 in controlling lipoprotein metabolism | journal= Endocrine | volume=52 | issue=2 | pages=187–193 | year=2016 | pmc =4824806 | pmid = 26754661 | doi=10.1007/s12020-015-0838-9 }}
4. ^{{cite journal | vauthors = Wang Y, McNutt MC, Banfi S, Levin MG, Holland WL, Gusarova V, Gromada J, Cohen JC, Hobbs HH | title = Hepatic ANGPTL3 regulates adipose tissue energy homeostasis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 37 | pages = 11630–5 | date = Sep 2015 | pmid = 26305978 | doi = 10.1073/pnas.1515374112 | pmc=4577179}}
5. ^{{cite journal | vauthors = Zhang R | title = Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels | journal = Biochemical and Biophysical Research Communications | volume = 424 | issue = 4 | pages = 786–92 | date = Aug 2012 | pmid = 22809513 | doi = 10.1016/j.bbrc.2012.07.038 }}
6. ^{{cite journal | vauthors = Ren G, Kim JY, Smas CM | title = Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 303 | issue = 3 | pages = E334–51 | date = Aug 2012 | pmid = 22569073 | doi = 10.1152/ajpendo.00084.2012 | pmc=3423120}}
7. ^{{cite journal | vauthors = Fu Z, Abou-Samra AB, Zhang R | title = A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase | journal = Scientific Reports | volume = 5 | pages = 18502 | date = December 2015 | pmid = 26687026 | doi = 10.1038/srep18502 | pmc=4685196}}
8. ^{{cite journal | vauthors = Zhang R | title = The ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking. | journal = Open Biology | volume = 6 | issue = 4 | pages = 150272 | date = April 2016 | pmid = 27053679 | doi = 10.1098/rsob.150272 | url = http://rsob.royalsocietypublishing.org/content/6/4/150272.long | pmc=4852456}}
9. ^{{Cite journal | vauthors = Musunuru K, Pirruccello JP, Do R, Peloso GM, Guiducci C, Sougnez C, Garimella KV, Fisher S, Abreu J| doi = 10.1056/NEJMoa1002926 | title = Exome Sequencing,ANGPTL3Mutations, and Familial Combined Hypolipidemia | journal = New England Journal of Medicine | volume = 363 | issue = 23 | pages = 2220–2227 | year = 2010 | pmid = 20942659 | pmc =3008575 |display-authors=etal}}

Further reading

{{cite journal | vauthors = Miida T, Seino U, Miyazaki O, Hanyu O, Hirayama S, Saito T, Ishikawa Y, Akamatsu S, Nakano T, Nakajima K, Okazaki M, Okada M | title = Probucol markedly reduces HDL phospholipids and elevated prebeta1-HDL without delayed conversion into alpha-migrating HDL: putative role of angiopoietin-like protein 3 in probucol-induced HDL remodeling | journal = Atherosclerosis | volume = 200 | issue = 2 | pages = 329–35 |date=October 2008 | pmid = 18279878 | doi = 10.1016/j.atherosclerosis.2007.12.031 | url = }}

{{cite journal | vauthors = Moon HD, Nakajima K, Kamiyama K, Takanashi K, Sakurabayashi I, Nagamine T | title = Higher frequency of abnormal serum angiopoietin-like protein 3 than abnormal cholesteryl ester transfer protein in Japanese hyperalphalipoproteinemic subjects | journal = Clin. Chim. Acta | volume = 398 | issue = 1–2 | pages = 99–104 |date=December 2008 | pmid = 18804459 | doi = 10.1016/j.cca.2008.08.021 | url = }}

{{cite journal | author=Li C |title=Genetics and regulation of angiopoietin-like proteins 3 and 4 |journal=Curr. Opin. Lipidol. |volume=17 |issue= 2 |pages= 152–6 |year= 2007 |pmid= 16531751 |doi= 10.1097/01.mol.0000217896.67444.05 }}

{{cite journal | vauthors=Camenisch G, Pisabarro MT, Sherman D |title=ANGPTL3 stimulates endothelial cell adhesion and migration via integrin alpha vbeta 3 and induces blood vessel formation in vivo |journal=J. Biol. Chem. |volume=277 |issue= 19 |pages= 17281–90 |year= 2002 |pmid= 11877390 |doi= 10.1074/jbc.M109768200 |display-authors=etal}}

{{cite journal | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |display-authors=etal}}

{{cite journal | vauthors=Kaplan R, Zhang T, Hernandez M |title=Regulation of the angiopoietin-like protein 3 gene by LXR |journal=J. Lipid Res. |volume=44 |issue= 1 |pages= 136–43 |year= 2003 |pmid= 12518032 |doi=10.1194/jlr.M200367-JLR200 |display-authors=etal}}

{{cite journal | vauthors=Shimamura M, Matsuda M, Kobayashi S |title=Angiopoietin-like protein 3, a hepatic secretory factor, activates lipolysis in adipocytes |journal=Biochem. Biophys. Res. Commun. |volume=301 |issue= 2 |pages= 604–9 |year= 2003 |pmid= 12565906 |doi=10.1016/S0006-291X(02)03058-9 |display-authors=etal}}

{{cite journal | vauthors=Zeng L, Dai J, Ying K |title=Identification of a novel human angiopoietin-like gene expressed mainly in heart |journal=J. Hum. Genet. |volume=48 |issue= 3 |pages= 159–62 |year= 2003 |pmid= 12624729 |doi= 10.1007/s100380300025 |display-authors=etal}}

{{cite journal | vauthors=Ono M, Shimizugawa T, Shimamura M |title=Protein region important for regulation of lipid metabolism in angiopoietin-like 3 (ANGPTL3): ANGPTL3 is cleaved and activated in vivo |journal=J. Biol. Chem. |volume=278 |issue= 43 |pages= 41804–9 |year= 2004 |pmid= 12909640 |doi= 10.1074/jbc.M302861200 |display-authors=etal}}

{{cite journal | vauthors=Clark HF, Gurney AL, Abaya E |title=The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment |journal=Genome Res. |volume=13 |issue= 10 |pages= 2265–70 |year= 2003 |pmid= 12975309 |doi= 10.1101/gr.1293003 | pmc=403697 |display-authors=etal}}

{{cite journal | vauthors=Zhang Z, Henzel WJ |title=Signal peptide prediction based on analysis of experimentally verified cleavage sites |journal=Protein Sci. |volume=13 |issue= 10 |pages= 2819–24 |year= 2005 |pmid= 15340161 |doi= 10.1110/ps.04682504 | pmc=2286551 }}

{{cite journal | vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 |display-authors=etal}}

{{cite journal | vauthors=Liu T, Qian WJ, Gritsenko MA |title=Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry |journal=J. Proteome Res. |volume=4 |issue= 6 |pages= 2070–80 |year= 2006 |pmid= 16335952 |doi= 10.1021/pr0502065 | pmc=1850943 |display-authors=etal}}

{{cite journal | vauthors=Shimamura M, Matsuda M, Yasumo H |title=Angiopoietin-like protein3 regulates plasma HDL cholesterol through suppression of endothelial lipase |journal=Arterioscler. Thromb. Vasc. Biol. |volume=27 |issue= 2 |pages= 366–72 |year= 2007 |pmid= 17110602 |doi= 10.1161/01.ATV.0000252827.51626.89 |display-authors=etal}}

Function

Clinical significance

References

External links

Further reading