Angptl3
entrez
30924
canonical
uniprot
Q9R182
canonical
ensembl
ENSMUSG00000028553
resolver
ensp
ENSMUSP00000030280
resolver
enst
ENSMUST00000030280
resolver
genesymbol
Angptl3
resolver
uniprot
Q3UEF5
resolver
uniprot_entry
ANGL3_MOUSE
resolver
uniprot_entry
Q3UEF5_MOUSE
resolver
amino_acid_sequence
MHTIKLFLFVVPLVIASRVDPDLSSFDSAPSEPKSRFAMLDDVKILANGLLQLGHGLKDFVHKTKGQINDIFQKLNIFDQSFYDLSLRTNEIKEEEKELRRTTSTLQVKNEEVKNMSVELNSKLESLLEEKTALQHKVRALEEQLTNLILSPAGAQEHPEVTSLKSFVEQQDNSIRELLQSVEEQYKQLSQQHMQIKEIEKQLRKTGIQEPSENSLSSKSRAPRTTPPLQLNETENTEQDDLPADCSAVYNRGEHTSGVYTIKPRNSQGFNVYCDTQSGSPWTLIQHRKDGSQDFNETWENYEKGFGRLDGEFWLGLEKIYAIVQQSNYILRLELQDWKDSKHYVEYSFHLGSHETNYTLHVAEIAGNIPGALPEHTDLMFSTWNHRAKGQLYCPESYSGGWWWNDICGENNLNGKYNKPRTKSRPERRRGIYWRPQSRKLYAIKSSKMMLQPTT
uniprot
proteins
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}.
uniprot
proteins
mass_dalton
52543
uniprot
proteins
mutagenesis
MUTAGEN 221; /note="R->A: Abolishes proteolytical cleavage."; /evidence="ECO:0000269|PubMed:20581395, ECO:0000269|PubMed:23918928"; MUTAGEN 224; /note="R->A: Abolishes proteolytical cleavage."; /evidence="ECO:0000269|PubMed:23918928
uniprot
proteins
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}.
uniprot
proteins
pubmed
10644446
uniprot
proteins
pubmed
11788823
uniprot
proteins
pubmed
11877390
uniprot
proteins
pubmed
12671033
uniprot
proteins
pubmed
12909640
uniprot
proteins
pubmed
15336575
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15863837
uniprot
proteins
pubmed
16081640
uniprot
proteins
pubmed
16508209
uniprot
proteins
pubmed
17110602
uniprot
proteins
pubmed
17681148
uniprot
proteins
pubmed
20424482
uniprot
proteins
pubmed
20581395
uniprot
proteins
pubmed
20633534
uniprot
proteins
pubmed
20959605
uniprot
proteins
pubmed
23918928
uniprot
proteins
pubmed
24294595
uniprot
proteins
pubmed
25338813
uniprot
proteins
pubmed
25710887
uniprot
proteins
pubmed
25954050
uniprot
proteins
pubmed
26305978
uniprot
proteins
sequence_length
455
uniprot
proteins
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}.
uniprot
proteins