• 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 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: 99.03 – 99.05 Mb
PubMed search
[3]
[4]
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]
Contents
1Function
2Clinical significance
3References
4External links
5Further reading
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.
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
^ abcGRCh38: Ensembl release 89: ENSG00000132855 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000028553 - Ensembl, May 2017
^Conklin D, Gilbertson D, Taft DW, Maurer MF, Whitmore TE, Smith DL, Walker KM, Chen LH, Wattler S, Nehls M, Lewis KB (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.
^ abTikka A, Jauhiainen M (2016). "The role of ANGPTL3 in controlling lipoprotein metabolism". Endocrine. 52 (2): 187–193. doi:10.1007/s12020-015-0838-9. PMC 4824806. PMID 26754661.
^Wang Y, McNutt MC, Banfi S, Levin MG, Holland WL, Gusarova V, Gromada J, Cohen JC, Hobbs HH (Sep 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. doi:10.1073/pnas.1515374112. PMC 4577179. PMID 26305978.
^Zhang R (Aug 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 (Aug 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. 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.
^Musunuru K, Pirruccello JP, Do R, Peloso GM, Guiducci C, Sougnez C, Garimella KV, Fisher S, Abreu J, et al. (2010). "Exome Sequencing,ANGPTL3Mutations, and Familial Combined Hypolipidemia". New England Journal of Medicine. 363 (23): 2220–2227. doi:10.1056/NEJMoa1002926. PMC 3008575. PMID 20942659.
External links
Human ANGPTL3 genome location and ANGPTL3 gene details page in the UCSC Genome Browser.
Miida T, Seino U, Miyazaki O, Hanyu O, Hirayama S, Saito T, Ishikawa Y, Akamatsu S, Nakano T, Nakajima K, Okazaki M, Okada M (October 2008). "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". Atherosclerosis. 200 (2): 329–35. doi:10.1016/j.atherosclerosis.2007.12.031. PMID 18279878.
Moon HD, Nakajima K, Kamiyama K, Takanashi K, Sakurabayashi I, Nagamine T (December 2008). "Higher frequency of abnormal serum angiopoietin-like protein 3 than abnormal cholesteryl ester transfer protein in Japanese hyperalphalipoproteinemic subjects". Clin. Chim. Acta. 398 (1–2): 99–104. doi:10.1016/j.cca.2008.08.021. PMID 18804459.
Li C (2007). "Genetics and regulation of angiopoietin-like proteins 3 and 4". Curr. Opin. Lipidol. 17 (2): 152–6. doi:10.1097/01.mol.0000217896.67444.05. PMID 16531751.
Camenisch G, Pisabarro MT, Sherman D, et al. (2002). "ANGPTL3 stimulates endothelial cell adhesion and migration via integrin alpha vbeta 3 and induces blood vessel formation in vivo". J. Biol. Chem. 277 (19): 17281–90. doi:10.1074/jbc.M109768200. PMID 11877390.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Kaplan R, Zhang T, Hernandez M, et al. (2003). "Regulation of the angiopoietin-like protein 3 gene by LXR". J. Lipid Res. 44 (1): 136–43. doi:10.1194/jlr.M200367-JLR200. PMID 12518032.
Shimamura M, Matsuda M, Kobayashi S, et al. (2003). "Angiopoietin-like protein 3, a hepatic secretory factor, activates lipolysis in adipocytes". Biochem. Biophys. Res. Commun. 301 (2): 604–9. doi:10.1016/S0006-291X(02)03058-9. PMID 12565906.
Zeng L, Dai J, Ying K, et al. (2003). "Identification of a novel human angiopoietin-like gene expressed mainly in heart". J. Hum. Genet. 48 (3): 159–62. doi:10.1007/s100380300025. PMID 12624729.
Ono M, Shimizugawa T, Shimamura M, et al. (2004). "Protein region important for regulation of lipid metabolism in angiopoietin-like 3 (ANGPTL3): ANGPTL3 is cleaved and activated in vivo". J. Biol. Chem. 278 (43): 41804–9. doi:10.1074/jbc.M302861200. PMID 12909640.
Clark HF, Gurney AL, Abaya E, et al. (2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
Zhang Z, Henzel WJ (2005). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Sci. 13 (10): 2819–24. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Liu T, Qian WJ, Gritsenko MA, et al. (2006). "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry". J. Proteome Res. 4 (6): 2070–80. doi:10.1021/pr0502065. PMC 1850943. PMID 16335952.
Shimamura M, Matsuda M, Yasumo H, et al. (2007). "Angiopoietin-like protein3 regulates plasma HDL cholesterol through suppression of endothelial lipase". Arterioscler. Thromb. Vasc. Biol. 27 (2): 366–72. doi:10.1161/01.ATV.0000252827.51626.89. PMID 17110602.
This article on a gene on human chromosome 1 is a stub. You can help Wikipedia by expanding it.
28
6
$begingroup$
Per the Font of Magic feature, sorcerer can use Flexible Casting to create 5th-level spell slots at level 7, even though they are not typically available until level 9. You can transform unexpended sorcery points into one spell slot as a bonus action on your turn. The Creating Spell Slots table shows the cost of creating a spell slot of [5th level is 7] If such a sorcerer levels up while still having this 5th-level spell slot, can they choose a 5th-level spell as the spell they gain upon levelling up? The Spellcasting feature states: Additionally, when you gain a level in this class, you can choose one of the sorcerer spells you know and replace it with another spell from the sorcerer spell list, which also must be of a level for which you have spell slots.
up vote
13
down vote
favorite
1
After the 2018 errata, the disintegrate spell description now reads: A creature targeted by this spell must make a Dexterity saving throw. On a failed save, the target takes 10d6 + 40 force damage. The target is disintegrated if this damage leaves it with 0 hit points. If you were to polymorph an enemy into a rat and then disintegrate it, would the enemy be disintegrated or would it just return to its original form? I know that for Druids, it’s not an instant kill anymore, but is this the case for polymorph as well?
dnd-5e spells polymorph errata
share | improve this question
edited 18 hours ago
3
3
$begingroup$
Recently, I saw a construction of topological invariant for $pi_3(U(n))$ with $ngeq 2$ : $$ N=frac{1}{24pi^2}int_{S^3} d^3x epsilon^{ijk} Tr[(U^{-1}partial_{x_i}U)(U^{-1}partial_{x_j}U)(U^{-1}partial_{x_k}U)] , $$ where $Uin U(n)$ depends on $boldsymbol{x}=(x_1,x_2,x_3)in S^3$ , $epsilon^{ijk}$ is the Levi-Civita symbol, $i,j,k=1,2,3$ , and the duplicated indexes are summed over. It is claimed that $N$ is an integer, but why? Update 02/02/2019 I think I got an argument for $n=2$ . In this case, $U=e^{i varphi} q$ with $qin SU(2)$ . Due to the trace and the Levi-Civita symbol in $N$ , $varphi$ does not contribute to $N$ . As $Tr[q^{dagger}partial_i q]=0$ and $(q^{dagger}partial_i q)^{dagger}=-q^{dagger}partial_i q$ , $q^{dagger}partial_i q$ in geneeral has the form $q^{dagger}partia
Mixing
