Detail Information for IndEnz0005000295
IED ID IndEnz0005000295
Enzyme Type ID lipase000295
Protein Name Angiopoietin-related protein 3
Angiopoietin-like protein 3

Cleaved into: ANGPTL3
17-224
Gene Name Angptl3
Organism Mus musculus (Mouse)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse)
Enzyme Sequence MHTIKLFLFVVPLVIASRVDPDLSSFDSAPSEPKSRFAMLDDVKILANGLLQLGHGLKDFVHKTKGQINDIFQKLNIFDQSFYDLSLRTNEIKEEEKELRRTTSTLQVKNEEVKNMSVELNSKLESLLEEKTALQHKVRALEEQLTNLILSPAGAQEHPEVTSLKSFVEQQDNSIRELLQSVEEQYKQLSQQHMQIKEIEKQLRKTGIQEPSENSLSSKSRAPRTTPPLQLNETENTEQDDLPADCSAVYNRGEHTSGVYTIKPRNSQGFNVYCDTQSGSPWTLIQHRKDGSQDFNETWENYEKGFGRLDGEFWLGLEKIYAIVQQSNYILRLELQDWKDSKHYVEYSFHLGSHETNYTLHVAEIAGNIPGALPEHTDLMFSTWNHRAKGQLYCPESYSGGWWWNDICGENNLNGKYNKPRTKSRPERRRGIYWRPQSRKLYAIKSSKMMLQPTT
Enzyme Length 455
Uniprot Accession Number Q9R182
Absorption
Active Site
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity
DNA Binding
EC Number
Enzyme Function FUNCTION: Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism (PubMed:11788823, PubMed:12671033). Proposed to play a role in the trafficking of energy substrates to either storage or oxidative tissues in response to food intake (PubMed:26305978). Has a stimulatory effect on plasma triglycerides (TG), which is achieved by suppressing plasma TG clearance via inhibition of LPL activity; the function seems to be specific for the feeding conditions. The inhibition of LPL activity appears to be an indirect mechanism involving recruitment of proprotein convertases PCSK6 and FURIN to LPL leading to cleavage and dissociation of LPL from the cell surface; the function does not require ANGPTL3 proteolytic cleavage but seems to be mediated by the N-terminal domain, and is not inhibited by GPIHBP1 (PubMed:12909640, PubMed:16081640, PubMed:20581395). Can inhibit endothelial lipase, causing increased plasma levels of high density lipoprotein (HDL) cholesterol and phospholipids; the cleaved N-terminal domain is more efficient than the uncleaved proprotein (PubMed:17681148). Can bind to adipocytes to activate lipolysis, releasing free fatty acids and glycerol (By similarity). Suppresses LPL specifically in oxidative tissues which is required to route very low density lipoprotein (VLDL)-TG to white adipose tissue (WAT) for storage in response to food; the function may involve cooperation with circulating, liver-derived ANGPTL8 and ANGPTL4 expression in WAT (PubMed:26305978). Contributes to lower plasma levels of low density lipoprotein (LDL)-cholesterol by a mechanism that is independent of the canonical pathway implicating APOE and LDLR (PubMed:25954050). May stimulate hypothalamic LPL activity (PubMed:25338813). {ECO:0000250|UniProtKB:Q9Y5C1, ECO:0000269|PubMed:11788823, ECO:0000269|PubMed:12671033, ECO:0000269|PubMed:16081640, ECO:0000269|PubMed:17681148, ECO:0000269|PubMed:20581395, ECO:0000269|PubMed:25338813, ECO:0000269|PubMed:25954050, ECO:0000269|PubMed:26305978}.; FUNCTION: Involved in angiogenesis (PubMed:11877390). Binds to endothelial cells via integrin alpha-V/beta-3 (ITGAV:ITGB3), activates FAK, MAPK and Akt signaling pathways and induces cell adhesion and cell migration (By similarity). May increase the motility of podocytes. Secreted from podocytes, may modulate properties of glomerular endothelial cells involving integrin alpha-V/beta-3 and Akt signaling (By similarity). May induce actin filament rearrangements in podocytes implicating integrin alpha-V/beta-3 and Rac1 activation (PubMed:20633534, PubMed:24294595, PubMed:25710887). Binds to hematopoietic stem cells (HSC) and is involved in the regulation of HSC activity probably implicating down-regulation of IKZF1/IKAROS (PubMed:20959605). {ECO:0000250|UniProtKB:Q9Y5C1, ECO:0000269|PubMed:11877390, ECO:0000269|PubMed:20633534, ECO:0000269|PubMed:20959605, ECO:0000269|PubMed:24294595, ECO:0000269|PubMed:25710887}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Chain (2); Coiled coil (1); Compositional bias (1); Disulfide bond (2); Domain (1); Glycosylation (5); Mutagenesis (2); Region (4); Signal peptide (1)
Keywords Angiogenesis;Cell adhesion;Cell projection;Coiled coil;Disulfide bond;Glycoprotein;Heparin-binding;Lipid metabolism;Reference proteome;Secreted;Signal
Interact With
Induction INDUCTION: Down-regulated by insulin and leptin. Not regulated by nutritional status (fed/fasting) Up-regulated in podocytes by puromycin. Up-regulated after feeding in the hypothalamus. {ECO:0000269|PubMed:15336575, ECO:0000269|PubMed:15863837, ECO:0000269|PubMed:20424482, ECO:0000269|PubMed:25338813}.
Subcellular Location SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23918928}. Cell projection, lamellipodium {ECO:0000269|PubMed:25710887}. Note=Colocalized with HSPG2 and activated ITGB3 on podocytes. {ECO:0000269|PubMed:20424482, ECO:0000269|PubMed:25710887}.
Modified Residue
Post Translational Modification PTM: In part proteolytically cleaved by proprotein convertases; proposed to be involved in activation. In primary hepatocytes is intracellularily predominantly processed by FURIN and extracellularily by FURIN and PCSK6/PACE4. In 18.5 dpc embryos 75% of protein is found to be processed compared to 25 % in adults. {ECO:0000269|PubMed:17681148, ECO:0000269|PubMed:23918928}.
Signal Peptide SIGNAL 1..16; /evidence=ECO:0000255
Structure 3D
Cross Reference PDB -
Mapped Pubmed ID 11500985; 12097324; 12518032; 12672813; 15094378; 15210844; 15530921; 16141072; 16806672; 17916774; 19318355; 19542565; 20133625; 20385801; 21267068; 21677750; 23150577; 24194600; 24952961; 25170927; 26687026; 28413163; 29104012; 29183623; 29334984; 31126248; 31256934; 32646941; 33649229; 34499887;
Motif
Gene Encoded By
Mass 52,543
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda